The document discusses various antiplatelet drugs including aspirin, P2Y12 receptor antagonists like clopidogrel and prasugrel, and GPllb/llla antagonists. It provides details on the mechanisms and clinical trials of these drugs. Specifically, it summarizes that aspirin works by irreversibly inhibiting platelet COX-1 and reducing thromboxane production. Large trials showed aspirin reduces vascular events by around 25% in high risk patients. Clopidogrel and prasugrel are P2Y12 antagonists but prasugrel has faster onset and greater platelet inhibition. The TRITON trial found prasugrel more effective than clopidogrel for ACS patients
This document summarizes various trials that have evaluated antiplatelet drugs like aspirin, clopidogrel, prasugrel, ticagrelor, as well as oral anticoagulants in patients with acute coronary syndromes or those undergoing percutaneous coronary intervention. It discusses major trials such as ISIS-2, CURE, TRITON, PLATO and others that helped establish the efficacy and safety of these antiplatelet and anticoagulant drugs. It also summarizes recent trials that have evaluated shorter durations of dual antiplatelet therapy compared to longer durations.
The CAPRIE study found that clopidogrel therapy resulted in a relative risk reduction of 8.7% compared to aspirin therapy for preventing cardiovascular events in patients with atherosclerosis, with fewer gastrointestinal hemorrhages. The CURE trial found that in patients with acute coronary syndrome receiving aspirin, pretreatment with clopidogrel followed by long-term therapy reduced major cardiovascular events compared to placebo. The CLASSICS trial found that clopidogrel had superior safety and tolerability to ticlopidine for antiplatelet therapy after coronary stenting, with comparable efficacy.
Ticagrelor in acute myocardial infarctionVasif Mayan
Potential benefits of dual antiplatelet therapy beyond 1 year after an MI has not been studied
Patients with MI are at increased risk of RECURRENT ISCHAEMIC EVENTS
Intensive secondary prevention is theoretically beneficial
Finding an ideal drug with best risk-benefit ratio is a challenge
TICAGRELOR
--- Direct acting
Not a pro-drug; does not require metabolic activation
Rapid onset of inhibitory effect on the P2Y12 receptor
Greater inhibition of platelet aggregation than clopidogrel
--- Reversibly bound
Degree of inhibition reflects plasma concentration
Faster offset of effect than clopidogrel
Functional recovery of circulating platelets within ~48 hours
PLATO trial
PEGASUS TIMI trial
This document discusses antiplatelet therapy and P2Y12 platelet inhibition. It notes that dual antiplatelet therapy with aspirin and a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor is the standard treatment for patients with acute coronary syndrome. It reviews the mechanisms of action and pharmacological properties of different antiplatelet drugs. It also summarizes key trials that have evaluated antiplatelet therapies and provides recommendations from guidelines on treatment selection and duration based on a patient's risk of bleeding and thrombosis.
Central role of adenosine diphosphate P2Y12 receptor interaction in platelet activation and aggregation during occurrence of ischemic events and stent thrombosis. Clopidogrel is a pro-drug that requires conversion to its active metabolite by CYP450 enzymes, primarily CYP2C19, to irreversibly inhibit the P2Y12 receptor. There is significant variability in individual response to clopidogrel, with resistance reported in 4-44% of patients, due to factors such as CYP2C19 polymorphisms, drug-drug interactions, and clinical factors like diabetes. Both high and low levels of on-treatment platelet reactivity to ADP as measured by various assays have been associated with increased risks
Ticagrelor or prasugrel in patients with acute coronaryMANISH mohan
1) The study compared the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes.
2) A total of 4018 patients were randomly assigned to receive either ticagrelor or prasugrel.
3) The primary endpoint of death, myocardial infarction, or stroke occurred in 9.1% of patients in the ticagrelor group compared to 6.8% in the prasugrel group, showing prasugrel was superior.
1) The document discusses antiplatelet therapy for Asian patients with acute coronary syndrome (ACS) who undergo percutaneous coronary intervention (PCI), specifically comparing ticagrelor and clopidogrel.
2) The PLATO trial showed ticagrelor reduced cardiovascular events compared to clopidogrel in ACS patients but increased major bleeding risks. However, the PHILO trial of ticagrelor vs clopidogrel in Asian ACS patients found no difference in cardiovascular outcomes or major bleeding.
3) Guidelines recommend balancing bleeding risks with potential benefits when choosing antiplatelet therapy for Asians, as they may have a different therapeutic window than Caucasians. De-escalating or switching
Ticagrelor is a reversible P2Y12 inhibitor that was developed to overcome limitations of clopidogrel such as variable metabolism and slow onset of action. The PLATO trial found ticagrelor to be superior to clopidogrel in reducing cardiovascular events in ACS patients with no increase in major bleeding. The PEGASUS trial found ticagrelor reduced cardiovascular events in stable patients with prior MI compared to placebo on aspirin. However, the EUCLID trial found ticagrelor was no better than clopidogrel in reducing events in PAD patients and increased dyspnea. The TREAT trial is investigating ticagrelor vs clopidogrel after fibrinolytic therapy in STE
This document summarizes various trials that have evaluated antiplatelet drugs like aspirin, clopidogrel, prasugrel, ticagrelor, as well as oral anticoagulants in patients with acute coronary syndromes or those undergoing percutaneous coronary intervention. It discusses major trials such as ISIS-2, CURE, TRITON, PLATO and others that helped establish the efficacy and safety of these antiplatelet and anticoagulant drugs. It also summarizes recent trials that have evaluated shorter durations of dual antiplatelet therapy compared to longer durations.
The CAPRIE study found that clopidogrel therapy resulted in a relative risk reduction of 8.7% compared to aspirin therapy for preventing cardiovascular events in patients with atherosclerosis, with fewer gastrointestinal hemorrhages. The CURE trial found that in patients with acute coronary syndrome receiving aspirin, pretreatment with clopidogrel followed by long-term therapy reduced major cardiovascular events compared to placebo. The CLASSICS trial found that clopidogrel had superior safety and tolerability to ticlopidine for antiplatelet therapy after coronary stenting, with comparable efficacy.
Ticagrelor in acute myocardial infarctionVasif Mayan
Potential benefits of dual antiplatelet therapy beyond 1 year after an MI has not been studied
Patients with MI are at increased risk of RECURRENT ISCHAEMIC EVENTS
Intensive secondary prevention is theoretically beneficial
Finding an ideal drug with best risk-benefit ratio is a challenge
TICAGRELOR
--- Direct acting
Not a pro-drug; does not require metabolic activation
Rapid onset of inhibitory effect on the P2Y12 receptor
Greater inhibition of platelet aggregation than clopidogrel
--- Reversibly bound
Degree of inhibition reflects plasma concentration
Faster offset of effect than clopidogrel
Functional recovery of circulating platelets within ~48 hours
PLATO trial
PEGASUS TIMI trial
This document discusses antiplatelet therapy and P2Y12 platelet inhibition. It notes that dual antiplatelet therapy with aspirin and a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor is the standard treatment for patients with acute coronary syndrome. It reviews the mechanisms of action and pharmacological properties of different antiplatelet drugs. It also summarizes key trials that have evaluated antiplatelet therapies and provides recommendations from guidelines on treatment selection and duration based on a patient's risk of bleeding and thrombosis.
Central role of adenosine diphosphate P2Y12 receptor interaction in platelet activation and aggregation during occurrence of ischemic events and stent thrombosis. Clopidogrel is a pro-drug that requires conversion to its active metabolite by CYP450 enzymes, primarily CYP2C19, to irreversibly inhibit the P2Y12 receptor. There is significant variability in individual response to clopidogrel, with resistance reported in 4-44% of patients, due to factors such as CYP2C19 polymorphisms, drug-drug interactions, and clinical factors like diabetes. Both high and low levels of on-treatment platelet reactivity to ADP as measured by various assays have been associated with increased risks
Ticagrelor or prasugrel in patients with acute coronaryMANISH mohan
1) The study compared the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes.
2) A total of 4018 patients were randomly assigned to receive either ticagrelor or prasugrel.
3) The primary endpoint of death, myocardial infarction, or stroke occurred in 9.1% of patients in the ticagrelor group compared to 6.8% in the prasugrel group, showing prasugrel was superior.
1) The document discusses antiplatelet therapy for Asian patients with acute coronary syndrome (ACS) who undergo percutaneous coronary intervention (PCI), specifically comparing ticagrelor and clopidogrel.
2) The PLATO trial showed ticagrelor reduced cardiovascular events compared to clopidogrel in ACS patients but increased major bleeding risks. However, the PHILO trial of ticagrelor vs clopidogrel in Asian ACS patients found no difference in cardiovascular outcomes or major bleeding.
3) Guidelines recommend balancing bleeding risks with potential benefits when choosing antiplatelet therapy for Asians, as they may have a different therapeutic window than Caucasians. De-escalating or switching
Ticagrelor is a reversible P2Y12 inhibitor that was developed to overcome limitations of clopidogrel such as variable metabolism and slow onset of action. The PLATO trial found ticagrelor to be superior to clopidogrel in reducing cardiovascular events in ACS patients with no increase in major bleeding. The PEGASUS trial found ticagrelor reduced cardiovascular events in stable patients with prior MI compared to placebo on aspirin. However, the EUCLID trial found ticagrelor was no better than clopidogrel in reducing events in PAD patients and increased dyspnea. The TREAT trial is investigating ticagrelor vs clopidogrel after fibrinolytic therapy in STE
1) Clopidogrel (Plavix) is a drug that inhibits platelet activation and is used to prevent heart attacks and strokes. However, some patients show resistance to its effects.
2) Clopidogrel resistance can be defined biochemically by measuring platelet inhibition or clinically by poor outcomes despite treatment. Potential causes include genetic factors and drug interactions.
3) For patients undergoing stent placement, clopidogrel resistance is associated with higher risks of stent thrombosis and heart attack. Management strategies include higher loading doses, repeated loading doses based on tests of platelet function, and alternative antiplatelet drugs.
Management strategy in HF with ARNI - Recent updates Praveen Nagula
- The document discusses management strategies for heart failure with reduced ejection fraction (HFrEF), including recent updates.
- It summarizes key differences between Indian and Western HF patients, noting that Indians develop HF at a younger age and with lower ejection fractions. Prognosis is also worse for Indian patients compared to those in the West.
- Core therapies for HFrEF are discussed, including a paradigm shift with the approval of sacubitril-valsartan which has been shown to reduce cardiovascular death compared to ACE inhibitors or ARBs alone in clinical trials.
The CREDENCE trial evaluated the effect of canagliflozin vs placebo on renal outcomes in patients with type 2 diabetes and chronic kidney disease. Over 2.6 years of follow up:
1) Canagliflozin reduced the composite outcome of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death by 30% compared to placebo.
2) Canagliflozin also reduced cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure by 30% compared to placebo.
3) The trial demonstrated that canagliflozin provided renoprotective and cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease.
Sacubitril is a neprilysin inhibitor that is used in combination with valsartan for the treatment of heart failure. The combination drug sacubitril/valsartan inhibits neprilysin and blocks the angiotensin receptor. It was shown in the PARADIGM-HF trial to reduce cardiovascular death and heart failure hospitalizations compared to enalapril. Current guidelines recommend sacubitril/valsartan as a replacement for ACE inhibitors or ARBs in patients with HFrEF who are already on such therapy.
The document discusses various clinical trials related to cardiovascular diseases. It summarizes the ACCORD BP study which found that targeting a SBP of <120 mm Hg compared to <140 mm Hg in patients with type 2 diabetes did not reduce cardiovascular events. It also summarizes the HOPE trial which found that ramipril reduced cardiovascular deaths, myocardial infarction, and stroke in high-risk patients without low ejection fraction or heart failure. Finally, it summarizes the EUROPA trial which found that perindopril reduced the primary endpoint of cardiovascular mortality, non-fatal MI, and cardiac arrest in patients with stable coronary artery disease.
#flozins
🫀DAPA 🆚placebo in HFpEF
Now we have a positive trial!
⬇️18% in CV☠️ death or
worsening HF among LVEF>40%
⬇️ 21%heart failure
💥Results same for LVEF> 60% 🆚LVEF<60%
SGLT-2 inhibitors have shown promising cardiovascular and renal benefits:
1) Trials have found SGLT-2 inhibitors reduce the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease, as well as reducing heart failure hospitalizations in those with diabetes and cardiovascular risk factors.
2) Studies also show SGLT-2 inhibitors improve outcomes for patients with heart failure with reduced ejection fraction, reducing rates of heart failure hospitalization and mortality regardless of diabetes status or background heart failure therapies.
3) SGLT-2 inhibitors were also found to reduce the risk of renal death or progression to end-stage kidney disease in patients with type 2 diabetes and macroalbuminuria.
- The DAPT study was a randomized controlled trial that compared 12 versus 30 months of dual antiplatelet therapy (DAPT) consisting of aspirin and a thienopyridine after drug-eluting stent placement. Over 9,000 patients were randomized to either continue DAPT for an additional 18 months or receive a placebo. Continuing DAPT led to a significant reduction in stent thrombosis and major adverse cardiovascular events but increased the risk of moderate or severe bleeding. The study demonstrated that longer term DAPT is effective but also increases safety risks, suggesting individualized treatment based on patient risk is important.
LDL Cholesterol Target :“ Lower the Better ”Arindam Pande
Lowering LDL cholesterol provides significant cardiovascular benefits and reduces risk, even in those with low baseline LDL levels or who achieve very low LDL levels with treatment. While residual risk remains even with intensive statin therapy to lower LDL well below current target levels, risk continues to decrease as LDL is further lowered. The lower the achieved LDL level, the lower the long-term risk of major cardiovascular events and atherosclerotic progression.
The document discusses aspirin resistance, which refers to a lack of inhibition of platelet aggregation despite regular aspirin intake at recommended doses. There are three main types of aspirin resistance - type I involves no inhibition of thromboxane synthesis, type II involves altered platelet functions both in vitro and in vivo, and type III involves inhibition of thromboxane synthesis but not platelet aggregation in response to collagen. The prevalence of aspirin resistance is estimated to be between 5-15% and is associated with a higher risk of death, heart attack or stroke. Potential causes include genetic factors, non-adherence to aspirin, use of enteric-coated aspirin or proton pump inhibitors. Laboratory testing can assess platelet function and thromboxane
This document discusses PCSK9 inhibitors, which are a new class of drugs for treating hyperlipidemia. It summarizes a clinical trial that evaluated the efficacy and safety of evolocumab added to statin therapy. The trial found that evolocumab significantly reduced LDL levels compared to placebo or ezetimibe when added to moderate or high-intensity statins. Evolocumab also helped over 90% of patients achieve an LDL level under 70 mg/dL. The drug was generally well-tolerated with adverse event rates similar to the comparators. However, further outcomes studies are still needed to determine if PCSK9 inhibitors can reduce cardiovascular events.
Vymada Tablet (ARNI: Angiotensin Receptor Neprilysin Inhibitor) is an anti-hypertensive drug used in combination with Sacubitril & Valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
The document discusses dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor for patients receiving coronary stents. It addresses three questions on optimal DAPT duration: 1) Is shorter DAPT (3-6 months) as effective as 12 months for newer-generation drug-eluting stents? 2) Does longer DAPT (>12 months) reduce ischemic events more than 12 months of DAPT? 3) Does continued DAPT past 12 months benefit stable post-MI patients more than aspirin alone? The document summarizes several studies investigating these questions and guidelines on DAPT duration and choice of P2Y12 inhibitor.
The PARADIGM-HF trial compared the new drug LCZ696, which inhibits the angiotensin receptor and neprilysin, to enalapril in over 8,000 patients with heart failure. LCZ696 reduced the primary composite outcome of cardiovascular death or heart failure hospitalization more than enalapril. Specifically, LCZ696 reduced cardiovascular death alone by 20% compared to only a 15% reduction with enalapril. The benefits of LCZ696 were seen across all subgroups and it had a better side effect and tolerability profile. The results provide sufficient evidence to replace ACE inhibitors and ARBs with LCZ696 as first-line treatment for heart failure.
Ponencia realizada por el Prof. Alberto Zambon en la segunda sesión de CardioVascular Virtual Topic 2022, titulada Residual cardiovascular risk. What is the role of icosapent ethyl?
Beta Blockers in current cardiovascular practice Praveen Nagula
betablockers are the drug of choice for prevention of progression of heart failure with mortality benefit, after the evolution of neurohormonal regulation as pathogenesis of heart failure
This document discusses antiplatelet therapy for acute coronary syndromes. It provides information on dual antiplatelet therapy using aspirin and P2Y12 inhibitors like clopidogrel, prasugrel, and ticagrelor. It summarizes trials comparing these drugs and outlines treatment strategies and duration of dual antiplatelet therapy based on a patient's risk level. Factors influencing response to clopidogrel and the potential additional mechanisms of action of ticagrelor are also reviewed.
Statins are highly effective LDL-c lowering agents that actually reduce clinical cardiovascular events. The 2013 ACC/AHA guidelines on the management of blood cholesterol recommend high-intensity statin therapy in individuals with high cardiovascular risk as assessed by the 10-year atherosclerotic cardiovascular disease risk calculator. However, a significant number of individuals do not tolerate or respond adequately to statins, and continue to have residual risk in spite of high intensity statin therapy.
There are some exciting developments in the field of lipidology. This decade has been labeled “The PCSK9 decade”. A new class of monoclonal antibodies directed against the PCSK9 glycoproteins appears very promising in further lowering LDL cholesterol and thereby cardiovascular risk. Evolocumab and alirucomab are novel PCSK9 inhibitors that can be given subcutaneously once or twice in a month, and have the potential to reduce LDL-cholesterol to very low levels without any major adverse effects.
Other classes of drugs like Apo-B antisense oligonucleotides (mipomersen), CETP inhibitors (especially anacetrapib), microsomal transfer protein inhibitors (lomitapide) also hold some promise. The future of lipid lowering therapy looks reassuring with these new developments.
Shashikiran Umakanth presented this at the Egyptian Association of Endocrinology, Diabetes & Atherosclerosis (EAEDA) 2014 conference at Alexandria, Egypt. This conference was help in association with Endocrine Society, USA and the European Association for the Study of Diabetes (EASD).
This document summarizes different antiplatelet medications used to prevent blood clots, including aspirin, clopidogrel, prasugrel, ticagrelor, and others. Aspirin works by irreversibly inhibiting the COX-1 enzyme and blocking thromboxane A2 production. Clopidogrel and prasugrel are prodrugs that require metabolic conversion to irreversibly inhibit the P2Y12 receptor. Ticagrelor is a reversible P2Y12 inhibitor with a faster onset than clopidogrel. Clinical trials such as PLATO found ticagrelor reduced cardiovascular events compared to clopidogrel in ACS patients.
1) Clopidogrel (Plavix) is a drug that inhibits platelet activation and is used to prevent heart attacks and strokes. However, some patients show resistance to its effects.
2) Clopidogrel resistance can be defined biochemically by measuring platelet inhibition or clinically by poor outcomes despite treatment. Potential causes include genetic factors and drug interactions.
3) For patients undergoing stent placement, clopidogrel resistance is associated with higher risks of stent thrombosis and heart attack. Management strategies include higher loading doses, repeated loading doses based on tests of platelet function, and alternative antiplatelet drugs.
Management strategy in HF with ARNI - Recent updates Praveen Nagula
- The document discusses management strategies for heart failure with reduced ejection fraction (HFrEF), including recent updates.
- It summarizes key differences between Indian and Western HF patients, noting that Indians develop HF at a younger age and with lower ejection fractions. Prognosis is also worse for Indian patients compared to those in the West.
- Core therapies for HFrEF are discussed, including a paradigm shift with the approval of sacubitril-valsartan which has been shown to reduce cardiovascular death compared to ACE inhibitors or ARBs alone in clinical trials.
The CREDENCE trial evaluated the effect of canagliflozin vs placebo on renal outcomes in patients with type 2 diabetes and chronic kidney disease. Over 2.6 years of follow up:
1) Canagliflozin reduced the composite outcome of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death by 30% compared to placebo.
2) Canagliflozin also reduced cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure by 30% compared to placebo.
3) The trial demonstrated that canagliflozin provided renoprotective and cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease.
Sacubitril is a neprilysin inhibitor that is used in combination with valsartan for the treatment of heart failure. The combination drug sacubitril/valsartan inhibits neprilysin and blocks the angiotensin receptor. It was shown in the PARADIGM-HF trial to reduce cardiovascular death and heart failure hospitalizations compared to enalapril. Current guidelines recommend sacubitril/valsartan as a replacement for ACE inhibitors or ARBs in patients with HFrEF who are already on such therapy.
The document discusses various clinical trials related to cardiovascular diseases. It summarizes the ACCORD BP study which found that targeting a SBP of <120 mm Hg compared to <140 mm Hg in patients with type 2 diabetes did not reduce cardiovascular events. It also summarizes the HOPE trial which found that ramipril reduced cardiovascular deaths, myocardial infarction, and stroke in high-risk patients without low ejection fraction or heart failure. Finally, it summarizes the EUROPA trial which found that perindopril reduced the primary endpoint of cardiovascular mortality, non-fatal MI, and cardiac arrest in patients with stable coronary artery disease.
#flozins
🫀DAPA 🆚placebo in HFpEF
Now we have a positive trial!
⬇️18% in CV☠️ death or
worsening HF among LVEF>40%
⬇️ 21%heart failure
💥Results same for LVEF> 60% 🆚LVEF<60%
SGLT-2 inhibitors have shown promising cardiovascular and renal benefits:
1) Trials have found SGLT-2 inhibitors reduce the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease, as well as reducing heart failure hospitalizations in those with diabetes and cardiovascular risk factors.
2) Studies also show SGLT-2 inhibitors improve outcomes for patients with heart failure with reduced ejection fraction, reducing rates of heart failure hospitalization and mortality regardless of diabetes status or background heart failure therapies.
3) SGLT-2 inhibitors were also found to reduce the risk of renal death or progression to end-stage kidney disease in patients with type 2 diabetes and macroalbuminuria.
- The DAPT study was a randomized controlled trial that compared 12 versus 30 months of dual antiplatelet therapy (DAPT) consisting of aspirin and a thienopyridine after drug-eluting stent placement. Over 9,000 patients were randomized to either continue DAPT for an additional 18 months or receive a placebo. Continuing DAPT led to a significant reduction in stent thrombosis and major adverse cardiovascular events but increased the risk of moderate or severe bleeding. The study demonstrated that longer term DAPT is effective but also increases safety risks, suggesting individualized treatment based on patient risk is important.
LDL Cholesterol Target :“ Lower the Better ”Arindam Pande
Lowering LDL cholesterol provides significant cardiovascular benefits and reduces risk, even in those with low baseline LDL levels or who achieve very low LDL levels with treatment. While residual risk remains even with intensive statin therapy to lower LDL well below current target levels, risk continues to decrease as LDL is further lowered. The lower the achieved LDL level, the lower the long-term risk of major cardiovascular events and atherosclerotic progression.
The document discusses aspirin resistance, which refers to a lack of inhibition of platelet aggregation despite regular aspirin intake at recommended doses. There are three main types of aspirin resistance - type I involves no inhibition of thromboxane synthesis, type II involves altered platelet functions both in vitro and in vivo, and type III involves inhibition of thromboxane synthesis but not platelet aggregation in response to collagen. The prevalence of aspirin resistance is estimated to be between 5-15% and is associated with a higher risk of death, heart attack or stroke. Potential causes include genetic factors, non-adherence to aspirin, use of enteric-coated aspirin or proton pump inhibitors. Laboratory testing can assess platelet function and thromboxane
This document discusses PCSK9 inhibitors, which are a new class of drugs for treating hyperlipidemia. It summarizes a clinical trial that evaluated the efficacy and safety of evolocumab added to statin therapy. The trial found that evolocumab significantly reduced LDL levels compared to placebo or ezetimibe when added to moderate or high-intensity statins. Evolocumab also helped over 90% of patients achieve an LDL level under 70 mg/dL. The drug was generally well-tolerated with adverse event rates similar to the comparators. However, further outcomes studies are still needed to determine if PCSK9 inhibitors can reduce cardiovascular events.
Vymada Tablet (ARNI: Angiotensin Receptor Neprilysin Inhibitor) is an anti-hypertensive drug used in combination with Sacubitril & Valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
The document discusses dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor for patients receiving coronary stents. It addresses three questions on optimal DAPT duration: 1) Is shorter DAPT (3-6 months) as effective as 12 months for newer-generation drug-eluting stents? 2) Does longer DAPT (>12 months) reduce ischemic events more than 12 months of DAPT? 3) Does continued DAPT past 12 months benefit stable post-MI patients more than aspirin alone? The document summarizes several studies investigating these questions and guidelines on DAPT duration and choice of P2Y12 inhibitor.
The PARADIGM-HF trial compared the new drug LCZ696, which inhibits the angiotensin receptor and neprilysin, to enalapril in over 8,000 patients with heart failure. LCZ696 reduced the primary composite outcome of cardiovascular death or heart failure hospitalization more than enalapril. Specifically, LCZ696 reduced cardiovascular death alone by 20% compared to only a 15% reduction with enalapril. The benefits of LCZ696 were seen across all subgroups and it had a better side effect and tolerability profile. The results provide sufficient evidence to replace ACE inhibitors and ARBs with LCZ696 as first-line treatment for heart failure.
Ponencia realizada por el Prof. Alberto Zambon en la segunda sesión de CardioVascular Virtual Topic 2022, titulada Residual cardiovascular risk. What is the role of icosapent ethyl?
Beta Blockers in current cardiovascular practice Praveen Nagula
betablockers are the drug of choice for prevention of progression of heart failure with mortality benefit, after the evolution of neurohormonal regulation as pathogenesis of heart failure
This document discusses antiplatelet therapy for acute coronary syndromes. It provides information on dual antiplatelet therapy using aspirin and P2Y12 inhibitors like clopidogrel, prasugrel, and ticagrelor. It summarizes trials comparing these drugs and outlines treatment strategies and duration of dual antiplatelet therapy based on a patient's risk level. Factors influencing response to clopidogrel and the potential additional mechanisms of action of ticagrelor are also reviewed.
Statins are highly effective LDL-c lowering agents that actually reduce clinical cardiovascular events. The 2013 ACC/AHA guidelines on the management of blood cholesterol recommend high-intensity statin therapy in individuals with high cardiovascular risk as assessed by the 10-year atherosclerotic cardiovascular disease risk calculator. However, a significant number of individuals do not tolerate or respond adequately to statins, and continue to have residual risk in spite of high intensity statin therapy.
There are some exciting developments in the field of lipidology. This decade has been labeled “The PCSK9 decade”. A new class of monoclonal antibodies directed against the PCSK9 glycoproteins appears very promising in further lowering LDL cholesterol and thereby cardiovascular risk. Evolocumab and alirucomab are novel PCSK9 inhibitors that can be given subcutaneously once or twice in a month, and have the potential to reduce LDL-cholesterol to very low levels without any major adverse effects.
Other classes of drugs like Apo-B antisense oligonucleotides (mipomersen), CETP inhibitors (especially anacetrapib), microsomal transfer protein inhibitors (lomitapide) also hold some promise. The future of lipid lowering therapy looks reassuring with these new developments.
Shashikiran Umakanth presented this at the Egyptian Association of Endocrinology, Diabetes & Atherosclerosis (EAEDA) 2014 conference at Alexandria, Egypt. This conference was help in association with Endocrine Society, USA and the European Association for the Study of Diabetes (EASD).
This document summarizes different antiplatelet medications used to prevent blood clots, including aspirin, clopidogrel, prasugrel, ticagrelor, and others. Aspirin works by irreversibly inhibiting the COX-1 enzyme and blocking thromboxane A2 production. Clopidogrel and prasugrel are prodrugs that require metabolic conversion to irreversibly inhibit the P2Y12 receptor. Ticagrelor is a reversible P2Y12 inhibitor with a faster onset than clopidogrel. Clinical trials such as PLATO found ticagrelor reduced cardiovascular events compared to clopidogrel in ACS patients.
Platelets play an important role in hemostasis and thrombosis. Antiplatelet drugs like aspirin and clopidogrel are commonly used to prevent heart attacks and strokes. Aspirin works by irreversibly inhibiting the COX-1 enzyme in platelets to block thromboxane A2 production. Clopidogrel is a prodrug that irreversibly inhibits the P2Y12 receptor on platelets. Clinical trials show dual antiplatelet therapy with aspirin and clopidogrel reduces cardiovascular events in conditions like acute coronary syndrome compared to aspirin alone, though it increases bleeding risk. Newer P2Y12 inhibitors like prasugrel and ticagrelor are more potent but also associated with
Antiplatelet therapy is an important part of treatment for acute coronary syndrome. There are four main classes of antiplatelet agents: aspirin, P2Y12 receptor antagonists like clopidogrel and prasugrel, GP IIb/IIIa inhibitors like abciximab, and PAR-1 receptor antagonists like vorapaxar. Aspirin is recommended for all patients, and dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is recommended for at least 1 year following ACS depending on the treatment strategy and patient risk factors.
1. Platelets play an important role in both normal hemostasis and pathological thromboses like myocardial infarction and stroke. Antiplatelet drugs are commonly used to prevent strokes.
2. Aspirin is recommended for both primary and secondary stroke prevention. Clopidogrel and dipyridamole are also options for secondary prevention. Combination aspirin/dipyridamole may be better than aspirin alone.
3. Newer antiplatelets like ticagrelor inhibit the P2Y12 receptor more effectively than clopidogrel, but trials found no clear benefit over aspirin for acute stroke. Combining aspirin and clopidogrel long-term increases bleeding risk without
The TREAT trial compared ticagrelor to clopidogrel in patients who received fibrinolytic therapy for ST-elevation myocardial infarction (STEMI). The trial aimed to evaluate the safety of ticagrelor in this setting given concerns about bleeding risk. The primary safety outcome was major bleeding at 30 days, with major efficacy outcomes including death from cardiovascular causes, myocardial infarction or stroke. The trial found ticagrelor to be non-inferior to clopidogrel for major bleeding at 30 days. Rates of other bleeding outcomes and major cardiovascular events were also similar between the two treatments.
Antiplatelets and anticoagulation in AMISCGH ED CME
1) Aspirin, P2Y12 inhibitors (ticagrelor, prasugrel, clopidogrel), and heparin are used to treat acute myocardial infarction. Aspirin and P2Y12 inhibitors prevent platelet aggregation while heparin inhibits thrombin.
2) Clinical trials have shown that aspirin reduces mortality and reinfarction rates compared to placebo. P2Y12 inhibitors like ticagrelor and prasugrel are more effective than clopidogrel but increase bleeding risk.
3) Fibrinolytics like tenecteplase can be used when primary PCI is not available within 120 minutes to reperfuse the infarcted area through
This document summarizes a randomized controlled trial that compared clopidogrel to ticagrelor or prasugrel in 1002 patients aged 70 years or older with non-ST-elevation acute coronary syndrome. Patients were randomly assigned to receive clopidogrel or ticagrelor/prasugrel. The primary outcome was major or minor bleeding, while the co-primary outcome included mortality, myocardial infarction, stroke, and bleeding. The results found clopidogrel was associated with fewer bleeding events compared to ticagrelor/prasugrel without increasing the risk of the combined clinical outcome. The conclusion is that clopidogrel could be an alternative P2Y12 inhibitor, especially for elderly patients
This document discusses anti-platelet drugs used to treat arterial thrombi, specifically newer P2Y12 receptor antagonists. It provides details on Clopidogrel, Prasugrel, and Ticagrelor which are widely used due to being more potent than Aspirin. Clinical trials including TRITON-TIMI 38, TRILOGY-ACS and PLATO compared the drugs and found Ticagrelor and Prasugrel superior to Clopidogrel in reducing ischemic events without increasing major bleeding risk. The document concludes the drugs have differences in efficacy against stent thrombosis and risk of bleeding.
1) Multiple trials have evaluated various oral antiplatelet agents for reducing mortality in patients with acute coronary syndromes. The ISIS-2 trial showed aspirin reduces mortality in STEMI patients with no increased bleeding risk.
2) Clopidogrel, prasugrel, ticagrelor, and cangrelor are P2Y12 receptor antagonists used in addition to aspirin. They differ in reversibility, activation pathway, onset and offset of action, and drug interactions. Trials have shown these agents reduce ischemic events when added to aspirin.
3) Later trials evaluated higher doses of antiplatelet agents or administering them in alternative ways like crushing tablets. While some strategies led
Role of antiplatelets in cardiovascular diseases.pptxMohamedSabry35679
The document summarizes information about antiplatelet drugs, including their definition, mechanism of action, role in different diseases, and major clinical trials. Antiplatelet drugs prevent and inhibit platelet activation and aggregation to interfere with thrombus formation. The principal classes are cyclooxygenase inhibitors like aspirin, and P2Y12 receptor blockers that inhibit the ADP pathway such as clopidogrel, prasugrel, and ticagrelor. Major trials like CAPRIE, CHARISMA, and Prevention of Cardiovascular Events compared antiplatelet regimens in coronary diseases and found some regimens reduced events more than aspirin alone with increased bleeding risks. Optimal medical therapy alone was found sufficient
This document summarizes a study comparing long-term outcomes of clopidogrel versus aspirin monotherapy after percutaneous coronary intervention (PCI). The study included over 5,400 patients who received dual antiplatelet therapy for 6-18 months after PCI. Patients were then randomized to clopidogrel or aspirin monotherapy. After a median follow up of 5.8 years, the primary endpoint occurred in 12.8% of clopidogrel patients and 16.9% of aspirin patients, showing clopidogrel reduced risk. Secondary endpoints including thrombosis and bleeding were also lower with clopidogrel. The study concludes clopidogrel provides significant relative risk reduction compared to aspirin for long-term
This randomized clinical trial compared adjunctive cilostazol versus double dose clopidogrel after drug-eluting stent implantation. The trial involved 3,755 patients randomized to either triple antiplatelet therapy with cilostazol or double dose clopidogrel dual antiplatelet therapy for 1 month. The primary endpoint of cardiac death, MI, stent thrombosis, stroke, or major bleeding within 1 month occurred in 1.2% of the triple therapy group and 1.4% of the double dose clopidogrel group, demonstrating noninferiority of triple therapy. On treatment platelet reactivity was lower in the triple therapy group. The trial demonstrated that triple antiplatelet therapy was noninferior to double
This document discusses antiplatelet therapies used in patients presenting with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PPCI). It summarizes the evidence for aspirin, clopidogrel, prasugrel, and ticagrelor in reducing mortality and cardiovascular events in STEMI patients. Current guidelines recommend a clopidogrel 600mg loading dose or prasugrel or ticagrelor prior to PPCI based on randomized controlled trials demonstrating their efficacy.
This document discusses antiplatelet and anticoagulant treatments for stroke prevention in the context of valvular heart disease, non-valvular heart disease, and atrial fibrillation. It classifies antiplatelet drugs and describes the mechanisms and uses of aspirin, clopidogrel, ticlopidine, dipyridamole, abciximab, eptifibatide, tirofiban, vorapaxar and various oral anticoagulants including warfarin, acenocoumarol, dabigatran, rivaroxaban, apixaban and edoxaban. It also outlines guidelines for initiating and transitioning between different antico
Newer antiplatelet drugs like prasugrel and ticagrelor have shown better outcomes than clopidogrel in reducing heart attacks and deaths in ACS patients. Prasugrel reduced risk by 24% compared to clopidogrel but increased bleeding risk, so it is not recommended for those over 75, under 60kg, or with stroke history. Ticagrelor provided faster, more consistent platelet inhibition than clopidogrel and reduced deaths and heart attacks in the PLATO trial, though it increased non-CABG bleeding and dyspnea. Guidelines recommend aspirin plus a P2Y12 inhibitor like clopidogrel, prasugrel or ticagrelor for ACS patients
- A study evaluated the efficacy and safety of alirocumab in adults with homozygous familial hypercholesterolemia.
- 45 patients received alirocumab and 24 received placebo for 78 weeks.
- Alirocumab reduced LDL-C levels by 24.8% compared to placebo and was well tolerated, with adverse events similar between groups.
- Alirocumab provided clinically significant LDL-C lowering in patients with homozygous familial hypercholesterolemia.
1) Platelet activation plays a key role in acute coronary syndromes (ACS) such as unstable angina. Markers of platelet activation such as CD62, fibrinogen levels, and GP IIb/IIIa receptor expression are significantly higher in unstable angina compared to stable angina.
2) There is wide variability in individual patient response to the antiplatelet drug clopidogrel, with up to 30% showing resistance. This variability is due to genetic and environmental factors that influence clopidogrel metabolism and platelet receptor binding.
3) Guidelines recommend dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor such as clopidogrel in ACS, with higher loading
Clopidogrel is a prodrug that requires metabolic activation. Genetic polymorphisms in CYP2C19, the enzyme responsible for activating clopidogrel, can result in clopidogrel resistance in some patients. Clopidogrel resistance is defined as inadequate inhibition of platelet aggregation despite standard clopidogrel dosing and is associated with worse clinical outcomes. The prevalence of clopidogrel resistance varies internationally and locally, ranging from 5-67%. Methods to identify resistance include measuring platelet reactivity before and after treatment. Strategies to overcome resistance include increasing clopidogrel dose, switching to newer P2Y12 inhibitors like ticagrelor and prasugrel, or genetic testing to guide therapy
This document provides guidance on publishing a scientific manuscript in a peer-reviewed journal. It discusses factors to consider when choosing a journal such as scope, impact, policies and accessibility. It also covers preparing the manuscript by addressing authorship, guidelines, style and potential reuse of content. The submission process involves getting feedback, registering online, and writing a cover letter that pitches the importance and novelty of the work. Peer review involves the possibility of rejection, which the author says is a common experience that should not be taken personally, and work may be resubmitted elsewhere.
This document provides an overview of the IMRAD structure for scientific manuscripts and research articles. It defines IMRAD as the standard structure with four sections: Introduction, Methods, Results, and Discussion. Checklists are then provided to help ensure each section contains the necessary elements. The introduction defines the research problem or hypothesis, methods describes how the study was conducted, results presents the findings, and discussion interprets the results and draws conclusions. Adhering to IMRAD helps clearly communicate the research process and findings to readers.
This document discusses important aspects of scientific writing such as titles, abstracts, and keywords. It explains that titles should summarize the main idea and attract readers. Abstracts are important summaries that influence editors and readers. They should describe the purpose, design, findings, and conclusions of the study. Keywords ensure papers are discoverable in databases and search engines. They must be chosen carefully from common vocabularies to accurately represent the paper's subject.
This document provides an overview of scientific writing. It defines scientific writing as technical writing aimed at peers in a scientific field. Publication is important for disseminating knowledge, facilitating collaboration and archiving information. Characteristics of good scientific writing include being clear, simple, neutral, concise, logically structured, accurate and objective. The peer review process involves experts in a field evaluating ideas and determining publication or funding. Key elements of a scientific paper are the title, abstract, introduction, methods, results, discussion and references. The document outlines best practices for writing scientifically, including choosing the right journal and reference manager, and revising extensively.
The document provides instructions for using various medical devices including inhalers, blood pressure monitors, peak flow meters, insulin pens and syringes, glucose testing devices, and eye drops. It describes the proper techniques for operating each device and highlights key points such as rotating injection sites and priming insulin pens. The intended learning objectives are for students to understand how to counsel patients on using these common medical devices and dosage forms.
This document discusses age-related physiological changes and functional decline in multiple body systems. It outlines that overall body system function declines with age and that specific organs like the cardiovascular, pulmonary, central nervous, renal, liver, immune, gastrointestinal, and endocrine systems are most affected. For each system, it describes both anatomical changes like decreased kidney size and functional changes like lower maximal oxygen consumption that occur with aging and can impact health and disease presentation in older adults.
This presentation introduces critical appraisal and how to evaluate evidence and websites. Critical appraisal involves a balanced assessment of the strengths and weaknesses of research by considering the research process, results, and both quantitative and qualitative aspects. It is important to critically appraise research to determine the validity, reliability, and applicability. When evaluating evidence, the presenter outlines 10 steps to appraise purpose, background, methods, population, participants, data, analysis, interpretations, conclusions, and enjoyment. Key criteria for evaluating websites include source, authority, objectivity, currency, and coverage.
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
Pictorial and detailed description of patellar instability with sign and symptoms and how to diagnose , what investigations you should go with and how to approach with treatment options . I have presented this slide in my 2nd year junior residency in orthopedics at LLRM medical college Meerut and got good reviews for it
After getting it read you will definitely understand the topic.
Know the difference between Endodontics and Orthodontics.Gokuldas Hospital
Your smile is beautiful.
Let’s be honest. Maintaining that beautiful smile is not an easy task. It is more than brushing and flossing. Sometimes, you might encounter dental issues that need special dental care. These issues can range anywhere from misalignment of the jaw to pain in the root of teeth.
Discover the benefits of homeopathic medicine for irregular periods with our guide on 5 common remedies. Learn how these natural treatments can help regulate menstrual cycles and improve overall menstrual health.
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Giloy in Ayurveda - Classical Categorization and SynonymsPlanet Ayurveda
Giloy, also known as Guduchi or Amrita in classical Ayurvedic texts, is a revered herb renowned for its myriad health benefits. It is categorized as a Rasayana, meaning it has rejuvenating properties that enhance vitality and longevity. Giloy is celebrated for its ability to boost the immune system, detoxify the body, and promote overall wellness. Its anti-inflammatory, antipyretic, and antioxidant properties make it a staple in managing conditions like fever, diabetes, and stress. The versatility and efficacy of Giloy in supporting health naturally highlight its importance in Ayurveda. At Planet Ayurveda, we provide a comprehensive range of health services and 100% herbal supplements that harness the power of natural ingredients like Giloy. Our products are globally available and affordable, ensuring that everyone can benefit from the ancient wisdom of Ayurveda. If you or your loved ones are dealing with health issues, contact Planet Ayurveda at 01725214040 to book an online video consultation with our professional doctors. Let us help you achieve optimal health and wellness naturally.
Are you looking for a long-lasting solution to your missing tooth?
Dental implants are the most common type of method for replacing the missing tooth. Unlike dentures or bridges, implants are surgically placed in the jawbone. In layman’s terms, a dental implant is similar to the natural root of the tooth. It offers a stable foundation for the artificial tooth giving it the look, feel, and function similar to the natural tooth.
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdfRahul Sen
Time-lapse embryo monitoring is an advanced imaging technique used in IVF to continuously observe embryo development. It captures high-resolution images at regular intervals, allowing embryologists to select the most viable embryos for transfer based on detailed growth patterns. This technology enhances embryo selection, potentially increasing pregnancy success rates.
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdfOsvaldo Bernardo Muchanga
GASTROINTESTINAL INFECTIONS AND GASTRITIS
Osvaldo Bernardo Muchanga
Gastrointestinal Infections
GASTROINTESTINAL INFECTIONS result from the ingestion of pathogens that cause infections at the level of this tract, generally being transmitted by food, water and hands contaminated by microorganisms such as E. coli, Salmonella, Shigella, Vibrio cholerae, Campylobacter, Staphylococcus, Rotavirus among others that are generally contained in feces, thus configuring a FECAL-ORAL type of transmission.
Among the factors that lead to the occurrence of gastrointestinal infections are the hygienic and sanitary deficiencies that characterize our markets and other places where raw or cooked food is sold, poor environmental sanitation in communities, deficiencies in water treatment (or in the process of its plumbing), risky hygienic-sanitary habits (not washing hands after major and/or minor needs), among others.
These are generally consequences (signs and symptoms) resulting from gastrointestinal infections: diarrhea, vomiting, fever and malaise, among others.
The treatment consists of replacing lost liquids and electrolytes (drinking drinking water and other recommended liquids, including consumption of juicy fruits such as papayas, apples, pears, among others that contain water in their composition).
To prevent this, it is necessary to promote health education, improve the hygienic-sanitary conditions of markets and communities in general as a way of promoting, preserving and prolonging PUBLIC HEALTH.
Gastritis and Gastric Health
Gastric Health is one of the most relevant concerns in human health, with gastrointestinal infections being among the main illnesses that affect humans.
Among gastric problems, we have GASTRITIS AND GASTRIC ULCERS as the main public health problems. Gastritis and gastric ulcers normally result from inflammation and corrosion of the walls of the stomach (gastric mucosa) and are generally associated (caused) by the bacterium Helicobacter pylor, which, according to the literature, this bacterium settles on these walls (of the stomach) and starts to release urease that ends up altering the normal pH of the stomach (acid), which leads to inflammation and corrosion of the mucous membranes and consequent gastritis or ulcers, respectively.
In addition to bacterial infections, gastritis and gastric ulcers are associated with several factors, with emphasis on prolonged fasting, chemical substances including drugs, alcohol, foods with strong seasonings including chilli, which ends up causing inflammation of the stomach walls and/or corrosion. of the same, resulting in the appearance of wounds and consequent gastritis or ulcers, respectively.
Among patients with gastritis and/or ulcers, one of the dilemmas is associated with the foods to consume in order to minimize the sensation of pain and discomfort.
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdf
Updates on Antiplatelet Therapy
1. Balamurugan Tangiisuran, PhD
Discipline of Clinical Pharmacy
School of Pharmaceutical Sciences
Universiti Sains Malaysia
b.tangiisuran@gmail.com
M.PHARM PROGRAMME 2015/16
(FCP 557)
2.
3. Antiplatelet drugs
Antiplatelet drugs
Acetylsalicylic
acid (aspirin)
P2Y12
antagonists
Dipyridamole GPIIb/IIIa
antagonists
Used widely
in patients
at risk of
thromboembolic
disease
Beneficial in the
treatment and
prevention of ACS
and the prevention
of thromboembolic
events
Secondary
prevention in
patients following
stroke, often in
combination with
aspirin
Administered
intravenously, are
effective during
percutaneous
coronary
intervention (PCI)
4. The Most Plausible Mechanism Of Aspirin In
Reducing Risks Of CV Disease
• Aspirin irreversibly acetylates the active site of
cyclooxygenase (COX)-1, which is required for
the production of thromboxane A2, a
powerful promoter of platelet aggregation
Vane JR. Inhibition of prostaglandin synthesis as a mechanism of
action of aspirin like drugs. Nat New Biol. 1971;231:232-5
5. The Most Plausible Mechanism Of Aspirin In
Reducing Risks Of CV Disease
• Rapid absorption of aspirin occurs in the
stomach and upper intestine
• Peak plasma concentration being achieved 15-
20 minutes after administration
• The peak inhibitory effect on platelet
aggregation is apparent approximately one
hour post-administration
6. The Most Plausible Mechanism Of Aspirin In
Reducing Risks Of CV Disease
• Aspirin produces the irreversible inhibition of
the enzyme cyclo-oxygenase and therefore
causes irreversible inhibition of platelets for
the rest of their lifespan (? days)
7. Evolution of Antiplatelet (AP) Therapy Trials
Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:71
Year No Of Trials No Of Patients
1988 25 25,000
1997 194 212,000
AP vs control (135,000)
Different AP (77,000)
8. Aspirin in the treatment of CVD
• Pts with prior occlusive, aspirin, prevents ~25%
of serious vascular events, including significant
reductions on MI, stroke, and CVD death
• All these patients have 10-year risks of CHD of
20% or more based on the Framingham risk score
recommended by the US NHLBI
AntiThrombotic Trialists Collaboration. Lancet, 2002
9. Benefit of Aspirin on Risk of Stroke
• 158 trials total 3,522 nonfatal and 1,424
fatal strokes after randomization
• Aspirin, reduced stroke by about 25%,
regardless of whether the patient entered the
trial with prior MI, stroke, TIA, or other high-
risk conditions
AntiThrombotic Trialists Collaboration. Lancet, 2002
10. Benefit of Aspirin on Risk of Stroke
• Aspirin increases the absolute risk of
hemorrhagic stroke by 3 per 10,000 treated
patients
• The upper bound of the 95% confidence
interval is less than 1 per 1000 treated
patients
AntiThrombotic Trialists Collaboration. Lancet, 2002
11. ISIS-2 Collaborative Group Lancet. 1988 Aug 13;332: 349-60.
Second International Study of Infarct Survival
12. Aspirin
• Debate concerning the optimal dose
• Risk of bleeding is dose-dependent
• CURE Trial – No evidence of greater efficacy at
higher dose but incidence of bleeding
increased with dose, lowest at doses up to
100mg
13. Aspirin
• CURRENT-OASIS 7 Trial
• Randomised 25,087 pts with ACS to low-dose (75-
100mg/day) or high-dose aspirin (300-
325mg/day)
• No difference in the rate of cumulative primary
end point of CV death, MI or stroke or in TIMI
major bleeding
• High-dose aspirin associated with higher risk of
minor bleeding (p=0.04) and GI bleeding (p=0.05)
Mehta et al. NEJM. 2010;363:930-42.
14. Dose-Dependent Side Effects of Aspirin
The 5 Year UK-TIA Trial of about 2400
Warlow C. et al. BMJ, 1988
Side Effects Placebo 300 mg 1200 mg
GI Symptoms 25% 29% 39%
GI bleeding
requiring transfusion 1.6% 2.6% 4.9%
15. Possible Additional Beneficial Mechanisms of
Action of Higher Doses of Aspirin on CVD
• Enhance nitric oxide formation
• Decrease inflammation
• Stabilize endothelial function
Hennekens CH, Sechenova, O, Hollar D, Serebruany VL. Dose of Aspirin in the Treatment and
Prevention of Cardiovascular Disease: Current and Future Directions. JCPT 2006.
Hennekens CH, et al. A randomized trial of aspirin at usual clinical doses and increased nitric oxide
formation in humans. JCPT 2010.
16. P2Y12 ADP - Receptor Antagonists
• Currently available – ticlopidine, clopidogrel,
prasugrel, ticagrelor, cangrelor
• Under investigation
– Elinogrel
• Dual antiplatelet is recommended for all
patients with ACS during acute phase and for
12 months, unless CI
Wright et al. Circulation. 2011;123:2022-60
17. Clopidogrel
• Irreversible thienopyridine inhibitor of the
platelet P2Y12 ADP receptor
• CURE trial – NSTE-ACS
• COMMIT/CCS-2 and CLARITY-TIMI 28 trial –
STEMI patients
– Confirmed the superiority of dual antiplatelet
therapy (A+C vs A alone)
Chen et al. Lancet 2005;366:1607-21
Sabatine et al. NEJM 2005;352:1179-89
18. Clopidogrel
Chen et al. Lancet 2005;366:1607-21
Sabatine et al. NEJM 2005;352:1179-89CURE Trial Investigators NEJM. 2001;345: 494-502
19. Second Chinese Cardiac Study: COMMIT
• Randomized, double-blind, 2x2 factorial trial
of clopidogrel and metoprolol
• 45,852 patients within 24 hours of onset of
symptoms of suspected AMI
• Randomization in clopidogrel arm to daily
75mg clopidogrel + 162mg aspirin (22,960) or
placebo +160mg aspirin(22,891)
COMMIT Collaborative Group. Lancet 2005; 366: 1607-1621.
20. COMMIT Collaborative Group. Lancet 2005; 366: 1607-1621.
COMMIT Clopidogrel Arm:
Primary Outcomes
End point Clopidogrel,
n=22 961 (%)
Placebo,
n=22 891 (%)
Odds ratio
CI)
P value
Death/MI/stroke 9.2 10.1 0.91
(0.86-0.97)
0.002
Death from any
cause
7.5 8.1 0.93
(0.87-0.99)
0.03
21. COMMIT: Major Bleeding
COMMIT Collaborative Group. Lancet 2005; 366: 1607-1621.
Bleeding Clopidogrel (%) Placebo
(%)
Excess per
1000
p
Any major
bleed
0.58 0.55 0.4 0.59
22. Limitation of Clopidogrel
1. Slow onset of action – max platelet
inhibition occurs
–at least 6 h after standard LD (300mg)
–only after 3-5 d at standard daily oral dose
(75mg)
–Pro-drug two-step biotransformation to
its active metabolite
23. Limitation of Clopidogrel
2. Slow reversal of platelet inhibition
–at least 5 day needed for recovery of
platelet function after drug discontinuation
–Important in patient requiring urgent CABG
or non-cardiac surgery
24. Limitation of Clopidogrel
3. Platelet inhibition is an average 30-40% at
steady state, mainly of poor bioavailability
–Only 15% of the absorbed pro-drug
available for metabolisation by hepatic
CYP450 enzymes to active metabolites
25. Limitation of Clopidogrel
4. There is considerable inter-patient variability
in the response to clopidogrel increased
risk of the re-occurrence of ischaemic events
5. Clopidogrel and PPI interaction
27. Clopidogrel & PPI
• In several studies, omeprazole decreases
pharmacodynamic effect of clopidogrel on
surrogate markers such as platelet
aggregation
• Studies of the other individual PPIs have not
shown such effects
28. Clopidogrel & PPI
• Observational studies patients prescribed
clopidogrel have small but significant effects
of all 5 PPIs on increased rates of CV events in
clopidogrel users
29. Clopidogrel & PPI
• RCT - clopidogrel users randomized to
omeprazole have no increased risk of CV
events
• FDA suggests that health care providers avoid
prescribing omeprazole, esomeprazole, or
cimetidine to patients receiving clopidogrel
30. Clopidogrel & PPI
• Can use one of the other PPIs (e.g.,
pantoprazole, rabeprazole) and
• Separate the PPI and clopidogrel by around
14-18 hrs
– prescribing the PPI before breakfast and
clopidogrel at bedtime
– PPI at dinner and clopidogrel at lunchtime
31. Prasugrel
• Oral, irreversible tienopyridine inhibitor of
platelet P2Y12 ADP receptor
• Prodrug – rapidly absorbed and requires in
vivo metabolism to form its active metabolite
• Faster onset of action than clopidogrel and
greater platelet inhibition with less variability
of response
• Genetic plymorphism that limit effectiveness
of clopidogrel do not affect prasugrel
Mega et al. Lancet 2010;376:1312-19
32. Prasugrel
• Biotransformed in liver by rapid hydrolysis
and oxidation mainly by CYP31 and CYP2B6
• Peak conc reached 30 min after oral dosing
and max platelet inhibition occurs about 2h
after LD of 60mg
33. Prasugrel
• Phase III TRITON-TIMI 38 Trial
– Prasugrel > efficious than clopidogrel in
population with STEMI or NSTE-ACS
undergoing PCI
– 13,608 subjects to prasugrel (LD 60mg, MD
10mg/day) or clopidogrel (LD 300mg, MD
75mg/day), with low-dose aspirin for 6-
15mths
Wiviott et al. NEJM 2007;357:2001-15
34. Prasugrel
• Phase III TRITON-TIMI 38 Trial
– Net clinical benefit including efficacy and
safety end point was in favour of prasugrel
– prevented 23 non-fatal MI at the
expense of 5 additional major bleeding
events per 1000 treated patients
Wiviott et al. NEJM 2007;357:2001-15
37. Prasugrel
• Post-hoc subgroup analysis TRITON-TIMI 38
Trial
– Efficacy of Prasugrel was offset by a higher risk of
bleeding in 3 categories of pts:
• Age ≥ 75 years (HR 0.99, 95%CI 0.81-1.21;p=0.92)
• Weight < 60kg (HR 1.03, 0.69-1.53;p=0.89)
• Previous stroke or TIA (HR 1.54, 1.02-2.32;p=0.04)
Wiviott et al. NEJM 2007;357:2001-15
Montalescot et al. Lancet 2009;373:723-31
38. Prasugrel
• Post-hoc subgroup analysis TRITON-TIMI 38
Trial
– Pt with DM and those with STEMI undergoing PCI
obtained considerable clinical benefit with
reduction in rate of ischemic event and non
increase in bleeding risk (10 vs. 12.4%; HR 0.79,
0.65-0.97;p=0.02)
Wiviott et al. NEJM 2007;357:2001-15
Montalescot et al. Lancet 2009;373:723-31
40. Prasugrel
• Prasugrel approved for STEMI and for NSTE-
ACS patients undergoing PCI BUT CI...
• TRILOGY – ACS is an trial comparing the
relative efficacy and safety of prasugrel and
clopidogrel in medically managed patients
with high-risk NSTE-ACS
Chin et al. Am Heart J 2010;160:16-22
41. TRILOGY - ACS
• Prasugrel is not superior to clopidogrel in
NSTE myocardial infarction and unstable
angina in patients without revascularisation
Roe et al. NEJM 2012;367:1297-309.
44. Ticagrelor
• Oral non-thienopyridine direct and reversible P2Y12
receptor antagonist
• Not a pro-drug
• More rapid onset of action, relatively rapid
reversibility and greater potency and consistency of
platelet inhibition than clopidogrel
Chin et al. Am Heart J 2010;160:16-22
45. Ticagrelor
• Phase III PLATO trial
– 18,624 pts with STEMI or STE-ACS
– Randomised: ticagrelor (LD 180mg and MD
90mg BID), or clopidogrel (LD 300-600mg and
MD 75mg/day)
– Primary end point , composite of CV death, MI
and stroke after 1 year follow up, was reduced
(9.8 vs. 11.7%; HR 0.84. 0.77-0.92; p<0.001)
Wallentin et al. NEJM 2009;361:1045-57
50. Ticagrelor
• SE: Dyspnoea and bradyarrhythmias – for few
days of treatment
• Not influenced by genetic polymorphism
• Dec 2010 – European Medicines Agency
approved for patient presenting with ACS
regardless managed medically or undergo PCI
or CABG
Wallentin et al. NEJM 2009;361:1045-57
51. Ticagrelor
• PEGASUS-TIMI 54 Trial – pts with previous
ACS (12-36mths before) randomised to
ticagrelor 60/90mg BID or placebo on top of
aspirin(75-150mg)
• Examine long term efficacy and safety of
ticagrelor after ACS
Wallentin et al. NEJM 2009;361:1045-57
52. Cangrelor
• Non-thienopyridine ADP-receptor antagonist
• Potent, parenteral, reversible and selective
inhibitor of P2Y12 receptor
• Intravenously and does not require any
metabolism
Akers et al. J Clin Pharmacol 2010;50:27-35
53. Cangrelor
• Onset of action is immediate (within
minutes) and platelet function normalises
within 60 mins of the discontinuation of the
infusion
• CHAMPION-PCI and CHAMPION-PLATFORM
– Both Ended prematurely because the
interim analysis did not reveal sufficient
evidence of clinical effectiveness
Akers et al. J Clin Pharmacol 2010;50:27-35
56. New targets for platelet inhibition:
The role of PAR-1 inhibitors
• Despite effective inhibition of the thromboxane-A2
and ADP-Receptor pathway, platelet can still be
activated by thrombin receptor stimulation
• Recurrence of ischemic events in patients with ACS
despite dual antiplatelets
• Blocking platelet thrombin receptor PAR-1
(protease-activated receptor-1) may lead to greater
inhibition
Akers et al. J Clin Pharmacol 2010;50:27-35
57. New targets for platelet inhibition:
The role of PAR-1 inhibitors
• Thrombin receptor antagonists are novel class of
antiplatelet agents that inhibits thrombin-mediated
platelet activation
• Currently under clinical trial : Vorapaxar and
Atopaxar
• Potent, oral competitive and selective PAR-1
antagonists
TRACER. Am Heart J 2009;158:327-34
Morrow et al. Am Heart J 2009;158:335-41
58. New targets for platelet inhibition:
The role of PAR-1 inhibitors
• Safety and efficacy of Vorapaxar in addition
to standard of care therapies two Phase III
trials:
– TRA-CER in the setting of high-risk ACS
– TRA-2P TIMI 50 for secondary prevention
TRACER. Am Heart J 2009;158:327-34
Morrow et al. Am Heart J 2009;158:335-41
59. Thrombolytic drugs – pharmacokinetics
The plasma half-life of the third generation
drugs is 14-45 minutes, allowing
administration as a single or double
intravenous bolus
This is in contrast to second generation t-PA,
which with a half-life of 3-4 minutes, must
be administered an initial bolus followed by
infusion
60. Thrombolysis in patients with acute MI
Thrombolysis in patients with ischaemic stroke
Thrombolysis of (sub)acute peripheral arterial
thrombosis
Thrombolysis in patients with acute massive
pulmonary embolism
Thrombolysis of occluded haemodialysis shunts
Thrombolytic drugs – major use
61. Thrombolytic drugs – major drawbacks
Treatment is limited to acute in-hospital
treatment
There is a high risk of bleeding inherent in
this treatment
Patients using anticoagulants are
contraindicated for treatment with
thrombolytics
62. Conclusion
STEMI
Treated with urgent PCI
Has pt a history of CVA
or TIA or cerebral bleed?
Is pt >75 years or <
60kg?
No to
all
Yes to
any
Medically managed – no
PCI procedure
Aspirin 75mg OD long term
with Prasugrel 10mg OD for
12mths
Aspirin 75mg OD long term
with Clopidogrel 75mg daily for
12 mths
Aspirin 75mg OD long term
with Clopidogrel 75mg daily for
28 days
63. Conclusion
NSTE ACS
and
Unstable
angina
Aspirin 75mg daily
long term with
Clopidogrel 75mg
for 12mths
Important:
•Aspirin - prescribe
dispersible aspirin
•The duration of antiplatelet
treatments must be stated
clearly on all discharge
letters
64. Conclusion
PCI with
Drug
Eluting
Stents
(DES)
Elective
Procedures
Aspirin 75mg daily long term
with Clopidogrel 75mg for
12mths
Important:
•Premature D/C of clopidogrel with
aspirin increases risk of stent
thrombosis.PCI with
Drug Bare
Metal
Stents
(BMS)
Elective
Procedures
Aspirin 75mg daily long term
with Clopidogrel 75mg for
28 days
65. Conclusion
Secondary Prevention
Stable Angina
(unless PCI planned)
Aspirin 75mg daily long term
Primary Prevention of
cardiovascular Events
Routine antiplatelet therapy for primary
prevention is not recommended.
Consider aspirin 75mg daily on an individual basis
Type 2 Diabetes
Age 50+ and BP <145/90
Age <50 and CV risk factors
Secondary prevention – Aspirin 75mg daily long
term
Primary prevention - See primary prevention of
cardiovascular Events
66. Conclusion
Secondary Prevention:
Ischaemic Stroke
Aspirin 300mg daily for 14 days
THEN: Clopidogrel 75mg daily long term
• If clopidogrel CI or not tolerated Aspirin 75mg daily plus
dipyridamole MR 200mg twice daily long term
• If both clopidogrel and aspirin CI or not tolerated
dipyridamole MR 200mg twice daily long term
Secondary Prevention:
TIA
Aspirin 75mg daily plus dipyridamole MR 200mg twice
daily long term
• If aspirin CI or not tolerated Dipyridamole MR 200mg twice
daily long term
• If dipyridamole CI or not tolerated Aspirin 75mg daily
monotherapy long term