http://www.theheart.org/web_slides/1144191.do
A randomized to prasugrel or clopidogrel study on TRITON-TIMI 38 with patients who have moderate- to high-risk ACS.
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) The PLATO trial compared ticagrelor to clopidogrel for prevention of cardiovascular events in patients with acute coronary syndromes. It involved over 18,000 patients across 43 countries.
2) The primary endpoint was a composite of death from vascular causes, myocardial infarction, or stroke. At 12 months, this occurred in 9.8% of ticagrelor patients compared to 11.7% of clopidogrel patients, showing ticagrelor was more effective at reducing cardiovascular events.
3) The primary safety endpoint of major bleeding at 12 months occurred in 11.6% of ticagrelor patients and 11.2% of clopidogrel patients, showing no significant
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
This document discusses clopidogrel (Plavix) metabolism and response variability. It describes how CYP2C19 polymorphisms can affect clopidogrel's conversion to its active metabolite, leading to increased risk of therapeutic failure or adverse effects. It also discusses the drug interaction between clopidogrel and proton pump inhibitors like omeprazole, which inhibits CYP2C19 and reduces clopidogrel's efficacy through the same metabolic pathway. Healthcare providers should consider a patient's CYP2C19 genotype and avoid concurrent use of clopidogrel with omeprazole or other inhibitors when possible.
1) The TRITON-TIMI 38 trial compared the antiplatelet drug prasugrel to clopidogrel in 13,608 patients with acute coronary syndrome undergoing percutaneous coronary intervention.
2) Prasugrel was found to significantly reduce the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke compared to clopidogrel, from 12.1% to 9.9%. However, prasugrel was also associated with an increased risk of bleeding.
3) In the overall study population, the superior efficacy of prasugrel in reducing ischemic events outweighed the increased risk of bleeding, representing a net clinical benefit. However, prasugrel appeared to have less benefit or
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
http://www.theheart.org/web_slides/1144191.do
A randomized to prasugrel or clopidogrel study on TRITON-TIMI 38 with patients who have moderate- to high-risk ACS.
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) The PLATO trial compared ticagrelor to clopidogrel for prevention of cardiovascular events in patients with acute coronary syndromes. It involved over 18,000 patients across 43 countries.
2) The primary endpoint was a composite of death from vascular causes, myocardial infarction, or stroke. At 12 months, this occurred in 9.8% of ticagrelor patients compared to 11.7% of clopidogrel patients, showing ticagrelor was more effective at reducing cardiovascular events.
3) The primary safety endpoint of major bleeding at 12 months occurred in 11.6% of ticagrelor patients and 11.2% of clopidogrel patients, showing no significant
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
This document discusses clopidogrel (Plavix) metabolism and response variability. It describes how CYP2C19 polymorphisms can affect clopidogrel's conversion to its active metabolite, leading to increased risk of therapeutic failure or adverse effects. It also discusses the drug interaction between clopidogrel and proton pump inhibitors like omeprazole, which inhibits CYP2C19 and reduces clopidogrel's efficacy through the same metabolic pathway. Healthcare providers should consider a patient's CYP2C19 genotype and avoid concurrent use of clopidogrel with omeprazole or other inhibitors when possible.
1) The TRITON-TIMI 38 trial compared the antiplatelet drug prasugrel to clopidogrel in 13,608 patients with acute coronary syndrome undergoing percutaneous coronary intervention.
2) Prasugrel was found to significantly reduce the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke compared to clopidogrel, from 12.1% to 9.9%. However, prasugrel was also associated with an increased risk of bleeding.
3) In the overall study population, the superior efficacy of prasugrel in reducing ischemic events outweighed the increased risk of bleeding, representing a net clinical benefit. However, prasugrel appeared to have less benefit or
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
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.
1) Gliptins like vildagliptin have less risk of hypoglycemia and weight gain compared to sulfonylureas.
2) Vildagliptin has shown beneficial effects on blood pressure and lipid levels.
3) Meta-analyses of clinical trials show that gliptins like vildagliptin have no increased cardiovascular risk compared to other antidiabetic drugs, and may have cardio-protective effects.
Empagliflozin and Cardiovascular OutcomesUyen Nguyen
1) The EMPA-REG OUTCOME trial evaluated the cardiovascular outcomes of empagliflozin compared to placebo in over 7000 patients with type 2 diabetes at high risk of cardiovascular events.
2) Empagliflozin was found to significantly reduce the risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to placebo.
3) Additional benefits observed with empagliflozin included a significant reduction in all-cause mortality, cardiovascular mortality, and hospitalization for heart failure.
Glucagon-like peptide 1 (GLP-1) is an incretin hormone that enhances glucose-dependent insulin secretion from pancreatic beta cells. GLP-1 levels are reduced in patients with type 2 diabetes. Therapeutic strategies that augment the GLP-1 pathway include GLP-1 receptor agonists such as exenatide and liraglutide, as well as dipeptidyl peptidase-4 (DPP-4) inhibitors which prevent the breakdown of endogenous GLP-1. These incretin-based therapies lower blood glucose levels with a low risk of hypoglycemia and promote weight loss, offering an important treatment option for patients with type 2 diabetes.
1. Resistant Hypertension, complications, Target organ damage2. newly diagnosed stage-1 hypertension, rationale of use of ARB and comparison of Azilsartan with other ARBs3. Hypertension with bronchial asthma 4. Hypertension with Diabetes Mellitus with proteinuria5. Hypertension , Diabetes and IHD6. Gestational Hypertension , rationale of use of drugs7. Hypertension , Diabetes , ACS8. Hypertension, Diabetes and Syndrome X9. Hypertension and special situations
Dapagliflozin is an SGLT2 inhibitor that has shown benefits in managing type 2 diabetes and reducing cardiovascular outcomes. The document summarizes results from several key studies on dapagliflozin. The DECLARE-TIMI trial showed that dapagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure compared to placebo in patients with type 2 diabetes with high cardiovascular risk. The DAPA-HF trial found that dapagliflozin reduced the risks of worsening heart failure or cardiovascular death compared to placebo in patients with heart failure regardless of diabetes status. Dapagliflozin also improved outcomes related to heart failure in the DEFINE-HF trial.
Dipeptidyl peptidase inhibitors(DPP-IV): A deep insightRxVichuZ
This presentation deals with DPP-IV inhibitors, that are implicated for use in diabetes mellitus. Generalized pharmacology, including a precise insight into individual drugs have been elucidated.
This document summarizes the results of a post-hoc analysis of the TWILIGHT trial to evaluate the safety and efficacy of ticagrelor monotherapy versus ticagrelor plus aspirin in patients who underwent complex percutaneous coronary intervention (PCI). The analysis found that in patients who underwent complex PCI, ticagrelor monotherapy was associated with a lower risk of clinically relevant bleeding compared to ticagrelor plus aspirin, without increasing the risk of ischemic events. Specifically, ticagrelor monotherapy resulted in a 46% lower risk of BARC type 3 or higher bleeding. There were no significant differences in rates of death, myocardial infarction, or stroke between the two treatment groups in either complex or non-
Her2Neu positive breast cancer is comprises of about 15-20% of all breast cancer. Among them quite a few number of patients present as de novo metastasis . In this presentation you ll find a guide how to manage it with relevant evidences. Presentation is meant for Oncology trainees.
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.
Rivaroxaban has shown benefits beyond antiplatelet therapy alone in reducing cardiovascular events. The COMPASS trial found that in patients with chronic coronary artery disease or peripheral artery disease, rivaroxaban plus aspirin reduced the composite of cardiovascular death, stroke, and myocardial infarction by 24% compared to aspirin alone. It also reduced mortality by 18% and ischemic stroke by 42%. Patients with multiple risk factors such as diabetes, chronic kidney disease, or heart failure derived the greatest benefits. However, use of anticoagulants remains lower than guidelines recommend due to overestimation of bleeding risks and underestimation of thrombotic risk.
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.
Este documento descreve um projeto para capacitar e certificar pelo menos um profissional da empresa PM Consultoria como Project Management Professional (PMP). O projeto inclui análise de requisitos, estudo para a certificação, treinamento em gerenciamento de projetos, cadastramento no PMI e simulados para a prova de certificação. O objetivo é atender a uma cláusula contratual e garantir a manutenção de um importante contrato que representa 35% do faturamento anual da empresa.
DUAL ANTIPLATELET THERAPY IN CORONARY ARTERY DISEASE.Sumedh Ramteke
This document summarizes guidelines for therapy in coronary artery disease from the 2017 ESC guidelines. It discusses various antiplatelet therapies including aspirin, clopidogrel, prasugrel, ticagrelor, and cilostazol. For each drug, it provides information on mechanisms of action, pharmacokinetics, major clinical trials, cautions, and when to stop before surgery. It also briefly mentions the SAFARI-STEMI trial which found no superiority of radial over femoral access for primary PCI in STEMI 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.
1) The IMPROVE-IT trial investigated whether adding ezetimibe to simvastatin therapy provides additional cardiovascular benefit compared to simvastatin monotherapy in 18,144 high-risk patients who had an acute coronary syndrome.
2) At a median follow-up of 6 years, combination ezetimibe/simvastatin therapy resulted in a statistically significant 9% relative risk reduction in major cardiovascular events compared to simvastatin alone.
3) Combination therapy also significantly reduced the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke by 10% compared to simvastatin monotherapy.
Eversion or standard carotid endarterectomy local or general anesthesia does ...uvcd
1) This document discusses different techniques for carotid endarterectomy (CEA), including eversion endarterectomy (EEA) versus standard CEA with patchplasty, and whether general (GA) or local anesthesia (LA) makes a difference.
2) Meta-analyses and randomized trials like the GALA trial found no significant differences in stroke or death rates between EEA versus CEA, or between GA versus LA.
3) The conclusions are that the choice of surgical technique and anesthesia method depends on surgeon and patient factors, with completion imaging advisable, but overall the scientific evidence shows no difference in outcomes between the various options.
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.
1) Gliptins like vildagliptin have less risk of hypoglycemia and weight gain compared to sulfonylureas.
2) Vildagliptin has shown beneficial effects on blood pressure and lipid levels.
3) Meta-analyses of clinical trials show that gliptins like vildagliptin have no increased cardiovascular risk compared to other antidiabetic drugs, and may have cardio-protective effects.
Empagliflozin and Cardiovascular OutcomesUyen Nguyen
1) The EMPA-REG OUTCOME trial evaluated the cardiovascular outcomes of empagliflozin compared to placebo in over 7000 patients with type 2 diabetes at high risk of cardiovascular events.
2) Empagliflozin was found to significantly reduce the risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to placebo.
3) Additional benefits observed with empagliflozin included a significant reduction in all-cause mortality, cardiovascular mortality, and hospitalization for heart failure.
Glucagon-like peptide 1 (GLP-1) is an incretin hormone that enhances glucose-dependent insulin secretion from pancreatic beta cells. GLP-1 levels are reduced in patients with type 2 diabetes. Therapeutic strategies that augment the GLP-1 pathway include GLP-1 receptor agonists such as exenatide and liraglutide, as well as dipeptidyl peptidase-4 (DPP-4) inhibitors which prevent the breakdown of endogenous GLP-1. These incretin-based therapies lower blood glucose levels with a low risk of hypoglycemia and promote weight loss, offering an important treatment option for patients with type 2 diabetes.
1. Resistant Hypertension, complications, Target organ damage2. newly diagnosed stage-1 hypertension, rationale of use of ARB and comparison of Azilsartan with other ARBs3. Hypertension with bronchial asthma 4. Hypertension with Diabetes Mellitus with proteinuria5. Hypertension , Diabetes and IHD6. Gestational Hypertension , rationale of use of drugs7. Hypertension , Diabetes , ACS8. Hypertension, Diabetes and Syndrome X9. Hypertension and special situations
Dapagliflozin is an SGLT2 inhibitor that has shown benefits in managing type 2 diabetes and reducing cardiovascular outcomes. The document summarizes results from several key studies on dapagliflozin. The DECLARE-TIMI trial showed that dapagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure compared to placebo in patients with type 2 diabetes with high cardiovascular risk. The DAPA-HF trial found that dapagliflozin reduced the risks of worsening heart failure or cardiovascular death compared to placebo in patients with heart failure regardless of diabetes status. Dapagliflozin also improved outcomes related to heart failure in the DEFINE-HF trial.
Dipeptidyl peptidase inhibitors(DPP-IV): A deep insightRxVichuZ
This presentation deals with DPP-IV inhibitors, that are implicated for use in diabetes mellitus. Generalized pharmacology, including a precise insight into individual drugs have been elucidated.
This document summarizes the results of a post-hoc analysis of the TWILIGHT trial to evaluate the safety and efficacy of ticagrelor monotherapy versus ticagrelor plus aspirin in patients who underwent complex percutaneous coronary intervention (PCI). The analysis found that in patients who underwent complex PCI, ticagrelor monotherapy was associated with a lower risk of clinically relevant bleeding compared to ticagrelor plus aspirin, without increasing the risk of ischemic events. Specifically, ticagrelor monotherapy resulted in a 46% lower risk of BARC type 3 or higher bleeding. There were no significant differences in rates of death, myocardial infarction, or stroke between the two treatment groups in either complex or non-
Her2Neu positive breast cancer is comprises of about 15-20% of all breast cancer. Among them quite a few number of patients present as de novo metastasis . In this presentation you ll find a guide how to manage it with relevant evidences. Presentation is meant for Oncology trainees.
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.
Rivaroxaban has shown benefits beyond antiplatelet therapy alone in reducing cardiovascular events. The COMPASS trial found that in patients with chronic coronary artery disease or peripheral artery disease, rivaroxaban plus aspirin reduced the composite of cardiovascular death, stroke, and myocardial infarction by 24% compared to aspirin alone. It also reduced mortality by 18% and ischemic stroke by 42%. Patients with multiple risk factors such as diabetes, chronic kidney disease, or heart failure derived the greatest benefits. However, use of anticoagulants remains lower than guidelines recommend due to overestimation of bleeding risks and underestimation of thrombotic risk.
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.
Este documento descreve um projeto para capacitar e certificar pelo menos um profissional da empresa PM Consultoria como Project Management Professional (PMP). O projeto inclui análise de requisitos, estudo para a certificação, treinamento em gerenciamento de projetos, cadastramento no PMI e simulados para a prova de certificação. O objetivo é atender a uma cláusula contratual e garantir a manutenção de um importante contrato que representa 35% do faturamento anual da empresa.
DUAL ANTIPLATELET THERAPY IN CORONARY ARTERY DISEASE.Sumedh Ramteke
This document summarizes guidelines for therapy in coronary artery disease from the 2017 ESC guidelines. It discusses various antiplatelet therapies including aspirin, clopidogrel, prasugrel, ticagrelor, and cilostazol. For each drug, it provides information on mechanisms of action, pharmacokinetics, major clinical trials, cautions, and when to stop before surgery. It also briefly mentions the SAFARI-STEMI trial which found no superiority of radial over femoral access for primary PCI in STEMI 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.
1) The IMPROVE-IT trial investigated whether adding ezetimibe to simvastatin therapy provides additional cardiovascular benefit compared to simvastatin monotherapy in 18,144 high-risk patients who had an acute coronary syndrome.
2) At a median follow-up of 6 years, combination ezetimibe/simvastatin therapy resulted in a statistically significant 9% relative risk reduction in major cardiovascular events compared to simvastatin alone.
3) Combination therapy also significantly reduced the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke by 10% compared to simvastatin monotherapy.
Eversion or standard carotid endarterectomy local or general anesthesia does ...uvcd
1) This document discusses different techniques for carotid endarterectomy (CEA), including eversion endarterectomy (EEA) versus standard CEA with patchplasty, and whether general (GA) or local anesthesia (LA) makes a difference.
2) Meta-analyses and randomized trials like the GALA trial found no significant differences in stroke or death rates between EEA versus CEA, or between GA versus LA.
3) The conclusions are that the choice of surgical technique and anesthesia method depends on surgeon and patient factors, with completion imaging advisable, but overall the scientific evidence shows no difference in outcomes between the various options.
This document summarizes a study of 56 cases of carotid body tumors (CBTs) conducted by Dr. Amr Gad of Cairo University. It provides background on CBTs and discusses the patients, techniques, outcomes, and complications of surgical resection. Key points include:
- CBTs arise from paraganglionic cells and account for over 50% of neck tumors.
- Vascular reconstruction was required in 10 cases (17.85%) due to the high risk of injury to the carotid artery during resection.
- Postoperative complications occurred in 12 cases (21.43%), including transient neurological deficits in 2 cases (3.57%) and permanent deficits in 2 other cases.
- Care
In most cases evar substituted conventional repaire for ruptured aaa whyuvcd
The document discusses the increasing use of endovascular aneurysm repair (EVAR) to treat ruptured abdominal aortic aneurysms (rAAA) instead of open repair. EVAR is considered less invasive, resulting in less blood loss, shorter hospital stays, and lower mortality compared to open repair. While evidence comes from heterogeneous studies and a single-arm trial of 34 patients treated with the Anaconda device showed 91% treatment success but 30-day mortality of 17%, EVAR is increasingly used for rAAA due to the potential advantages over open repair. Randomized controlled trials are still needed to provide higher quality evidence.
Impact of contralateral carotid or vertebral artery occlusion in patients und...uvcd
1) The study analyzed the risk of early neurologic complications in patients undergoing carotid endarterectomy (CEA) or carotid artery stenting (CAS) based on the presence of contralateral carotid occlusion (CCO) or vertebral artery occlusion (VAO).
2) CCAS was associated with significantly higher rates of early neurologic complications (8.1% vs 2.6%) and stroke (6.8% vs 1.3%) compared to CEA.
3) For CEA patients, CCO and a history of stroke were independent risk factors for early neurologic complications, but CCO was not a risk factor for stroke.
This document discusses acute traumatic aortic rupture, summarizing that it is a life-threatening surgical emergency caused by blunt trauma from motor vehicle accidents or falls. It can be diagnosed using CT scans or TEE ultrasound and treated either through open surgical repair requiring bypass and clamping, or endovascular stent grafting which avoids thoracotomy. While endovascular repair has advantages of less invasiveness and shorter procedure time, open repair may be necessary for injuries of the ascending aorta and there is limited long-term data on endovascular techniques. Complication and mortality rates were found to be lower for endovascular repair compared to open surgery in studies of patients at the Deutsches Herzzentrum Berlin.
Creative endovascular procedures for ischemic limb salvageuvcd
The document discusses creative endovascular procedures for treating ischemic limb salvage. It describes various techniques including creative arteriography, guidance, access approaches, pathways, and techniques. Retrograde ascending approaches, double approaches, subintimal dissection, wire rendezvous, loop techniques, and trans-collateral techniques are presented. The goal is to obtain direct blood flow to the foot in a creative manner by being flexible and combining different techniques. Recommendations include planning strategies, adapting to each situation, using multi-level work, alternating and combining techniques, being inventive, and only attempting what can be done safely.
Combined carotid and coronary disease the strategy should beuvcd
1. Combined carotid and coronary artery disease presents challenges in determining the optimal treatment strategy. Performing carotid endarterectomy and coronary artery bypass grafting simultaneously or in stages both carry risks.
2. Factors such as the severity of stenosis in the carotid and coronary arteries, and a patient's surgical risk profile must be considered. High grade stenosis in both territories typically warrants staged procedures to avoid complications.
3. Preventing embolic sources, maintaining adequate cerebral perfusion and temperature, and using monitoring techniques can help reduce risks of central nervous system injuries during combined or staged carotid and cardiac surgeries. Close evaluation of individual patient characteristics is important for surgical planning.
3. GP = glycoprotein; PAR = protease-activated receptor; TP = thromboxane A2 / prostaglandin H2.
Storey RF. Curr Pharm Des. 2006;12:1255-1259.
Platelet İnhibisyonu
Thromboxane
A2
5HT
P2Y 12
ADP ADPADP
5HT
PLATELET
ACTIVATION
P2Y 1
5HT 2A
PAR-1
PAR-4
Dense
granule
Thrombin
generation
Shape
change
aIIb b3
aIIb b3
Fibrinogen
aIIb b3
Aggregation
Amplification
Alpha
granule
Coagulation factors
Inflammatory mediators
TP a
Coagulation
GPVI
Collagen
ATPATP
P2X 1
ASPIRIN
x TICLOPIDINE
CLOPIDOGREL
PRASUGREL
ACTIVE
METABOLITE
x TICAGRELOR
CANGRELOR
GP IIb/IIIa ANTAGONISTS
xx
SCH 530348
E5555
x
TERUTROBAN
x
HEPARINS
FONDAPARINUX
BIVALIRUDIN
RIVAROXABAN
APIXABAN
DABIGATRAN Thrombin
x
4. KV RİSK AZALSIN KOMPLİKASYON AZALSIN
The Most Successful Technology Comes
From the Clinical Pull, as Opposed to a
Technical Push
• Klopidogrel
• Ticagrelol
• Plasugrel
5. Tikagrelor
• Yeni bir kimyasal sınıf:
– Siklo-pentil-triazolo-primidinler
(CPTP).1
• Doğrudan etki gösterir:
– Ön ilaç değildir ve metabolik aktivasyon
gerektirmez).1
• Doğrudan P2Y12 reseptörlerine
bağlanır ve trombosit aktivasyonunu ve
agregasyonunu önlemek üzere
reseptörle geri dönüşümlü olarak
etkileşir.2
• ENT-1 transporter inhibisyonu3
– Lokal adenozin konsantrasyon artışı
1. Husted S, et al. Eur Heart J. 2006;27:1038-47. 2. Gurbel PA, et al. Expert Opin Drug Metab Toxicol. 2009;5(8):989-1004. 3. Van Giezen
JJ, et al. J Thromb Haemost. 2009;7:1556-65.
Trombosit
üzerindeki P2Y12
reseptörü
Tikagrelor
ADP bağlanma bölgesi
515901011-EKİM-2014-BRILINTA
Doğrudan P2Y12 reseptörlerine
bağlanır ve trombosit aktivasyonunu
ve agregasyonunu önlemek üzere
reseptörle geri dönüşümlü olarak
etkileşir.2
6. Klinik Farmakoloji: Tikagrelor ve
Klopidogrel
1. Gurbel PA, et al. Circulation 2009;120:2577-85. 2. BRILINTA Ürün Bilgisi. 3. PLAVIX Ürün bilgisi.
515901011-EKİM-2014-BRILINTA
7. Kararlı durumdaki KAH olgularında 180 mg tikagrelor yükleme dozu
Kararlı durumdaki KAH olgularında 600 mg klopidogrel yükleme dozu
1. Gurbel PA, et al. Circulation 2009;120:2577-85.
Tikagrelor ile elde edilen anlamlı fark,
yükleme dozundan sonraki 24 saat boyunca korunur.1
Yükleme dozu
Tikagrelor (n=54)
Klopidogrel (n=50)
Plasebo (n=12)
İlk 24 Saatte Trombosit Agregasyon İnhibisyonu (%)1
*P<0.0001 (klopidogrele kıyasla)
515901011-EKİM-2014-BRILINTA
8. PLATO çalışmasının hasta popülasyonu
“geniş bir AKS spektrumu”
STEMİ
Primer PKG
Fibrinolitik ilaç önerisi
UA/NSTEMİ
Başlangıçta
İnvazif Tedavi
PKG
Revaskülarizasyon yok
KABG
Başlangıçta
Non-invazif Tedavi
PKG
KABG
Revaskülarizasyon
yok
1. James S, et al. Am Heart J 2009;157:599-605.
AKS Hastası
Primer PKG için
sadece STEMİ hastaları
düşünülmüştür.
9. PLATO Çalışması Tasarımı1,2
Primer etkililik
sonlanımı:
Kardiyovasküler
ölüm, Mİ ve
inme bileşimi
Primer
güvenlilik
sonlanımı:
Toplam PLATO
majör kanama
N=18,624
AKS’li hastalar
(UA, NSTEMİ
ya da STEMİ)
1. James S, et al. Am Heart J 2009;157:599-605. 2. Wallentin L, et al. N Engl J Med 2009;361:1045-57.
Tikagrelor (n=9,333)
180-mg yükleme dozu 90 mg 2x1 + ASA idame dozu
Klopidogrel (n=9,291)
300-mg yükleme dozu 75 mg 1x1 + ASA idame dozu
<24 saat 1. Ay 3. Ay 6. Ay 9. Ay 12. AyTarama
Vizit 2 Vizit 3 Vizit 4 Vizit 5 Vizit 6
Randomizasyon
PLATO Çalışmasının Tasarımı1,2
Daha önce klopidogrel ile tedavi edilmemiş olan hastalarda 300 mg yükleme dozunda klopidogrel verilmesine göz yumuldu,
buna ek olarak araştırmacının kararına göre ek 300 mg daha verilmesine izin verildi.
515901011-EKİM-2014-BRILINTA
10. 1. Yılda Primer Bileşik Sonlanım Noktası
Her iki grupta da ASA kullanıldı. İnme açısından tedavi grupları arasında fark yoktur.
ARR: Mutlak risk azalması, RRR: Rölatif risk azalması; NNT: Tedavi edilmesi gereken hasta sayısı
Tikagrelor ile klopidogrele göre erken dönemde sağlanan mutlak
risk azalması 1 yıllık tedavi süresince devam eder.1
%11.7
%9.8
1. Wallentin L, et al. N Engl J Med 2009;361:1045-57.
%1.9
ARR
%16
RRR
Tikagrelor (n=9333)
Klopidogrel (n=9291)
HR %95 GA P değeri
0.84 0.77-0.92 <0.001
NNT=54
515901011-EKİM-2014-BRILINTA
11. PLATO Etkililik Sonuçları
• PLATO çalışmasında, tikagrelor 1 yılda KV ölüm, Mİ ya da inme bileşik
sonuçlarını klopidogrele kıyasla anlamlı olarak azalttı (ARR %1.9, RRR %16,
P<0.001, NNT=54).1,2
• Tikagrelor KV mortaliteyi klopidogrele kıyasla anlamlı olarak azalttı.
(ARR %1.1, RRR %21 , P=0.001).1,2
– KV ölüm ve Mİ riski anlamlı olarak azaldı.1,2
– İnme riskinde anlamlı fark oluşmadı.1,2
• Klopidogrel karşısında tikagrelor ile mutlak risk azalması erken başlar ve
1 yıllık tedavi süresince artarak devam eder.1,2
1. Wallentin L, et al. N Engl J Med 2009;361:1045-57. 2. Wallentin L, et al. N Engl J Med 2009;361:1045-57. Supplement.
Özet
515901011-EKİM-2014-BRILINTA
12. Tikagrelor ile klopidogrel arasında toplam majör kanama oranları
açısından istatistiksel fark görülmemiştir.1
PLATO’datanımlanantoplam
majörkanama(%)
1. Wallentin L, et al. N Engl J Med 2009;361:1045-57.
İlk Doz Sonrası (Gün)
10
5
0
15
0 60 120 180 240 300 360
%11.2
%11.6
1. Yılda Majör Kanama Oranı
Her iki grupta da ASA kullanıldı.
Tikagrelor (n=9333)
Klopidogrel (n=9291)
HR %95 GA P değeri
1.04 0.95-1.13 0.43
Benzermajör
kanamaoranı
Tikagrelor ile KABG dışı majör ve girişimle ilgisi olmayan majör ve minör kanama nedeniyle tedaviyi bırakma oranları
klopidogrelden anlamlı derecede yüksekti.1
515901011-EKİM-2014-BRILINTA
13. Tikagrelor ile toplam ölümcül/yaşamı tehdit edici kanama sıklığında
klopidogrele göre artış oluşmamıştır.1
PLATO Çalışmasında Görülen Kanama Olayları
Tikagrelor (n=9235)
Klopidogrel (n=9186)
1. Wallentin L, et al. N Engl J Med 2009;361:1045-57.
Her iki grupta da ASA kullanıldı.
Tikagrelor ile KABG dışı majör ve girişimle ilgisi olmayan majör ve minör kanama nedeniyle tedaviyi bırakma oranları klopidogrelden anlamlı
derecede yüksekti.1
p=0.03
p=0.03
%11,6
%11,2
%7,9
%7,7
%4,5
%3,8
%2,8
%2,2
%8,9 %8,9
%5,8 %5,8
%0,2 %0,3
515901011-EKİM-2014-BRILINTA
14. PLATO çalışmasında dispne, tikagrelor ile
klopidogrele göre daha sık gözlenmiştir.1
• Tikagrelor ile ilişkili dispnenin şiddeti büyük ölçüde hafif-orta düzeyde gözlenmiş ve
etkinliği azalmamıştır.1
• Dispne olgularının çoğu (%87) tedaviden sonraki erken dönemde görülen tek epizod
olarak gerçekleşmiştir.1
• Dispne tikagrelor alanların %0,14’ü, klopidogrel alanların ise %0,02’side ciddi advers
olay olarak bildirilmiştir.1
• Solunum fonksiyonları üzerinde herhangi bir advers etkiye yol açmamıştır.1
İstenmeyen etki olarak dispne insidansı (%) 13.8 7.8 <0.001
Dispne nedeniyle tedaviyi yarım bırakan hastalar (%) 0.9 0.1 <0.001
Tikagrelor
(n=9235)
Klopidogrel
(n=9186)
P değeriPLATO Çalışmasında Dispne
1. Wallentin L, et al. N Engl J Med 2009;361:1045-57.
515901011-EKİM-2014-BRILINTA
16. PLATO KABG: Hasta Akışı
134 hasta randomize
edilmedi
18.624 hasta randomize
edildi
KABG-dışı:
16.725 hasta
KABG: 1899 hasta
Ameliyattan ≤7 gün
öncesi son çalışma
ilacı kullanımı: 1261
hasta
Klopidogrel ile tedavi edilen
629 hasta
Tikagrelor ile tedavi edilen
632 hasta
Tüm hastalar (n=18.758)
1. Held C, et al. J Am Coll Cardiol 2011;57:672-84.
515901011-EKİM-2014-BRILINTA
17. %7.9
%4.1
1. Yılda Kardiyovasküler Ölüm Riski1
Tikagrelor (n=632)
Klopidogrel (n=629)
HR %95 GA P değeri
0.52 0.32-0.85 0.009
Tikagrelor, KABG ile tedavi edilen olgularda kardiyovasküler ölüm
oranını klopidogrele göre %48(RR) azaltmıştır.1
0 1 2 3 4 5 6 7 8 9 10 11 12
KABG işleminden sonraki aylar
K-Mhesaplanmışoran(%)
8
7
6
5
4
3
2
1
0
1. Held C, et al. J Am Coll Cardiol 2011;57:672-84.
515901011-EKİM-2014-BRILINTA
18. PLATO KABG alt grubunda KABG ilişkili kanama açısından tikagrelor ve
klopidogrel arasında istatistiksel fark gösterilmemiştir.1
NS = istatistiksel olarak anlamlı değil
1. Held C, et al. J Am Coll Cardiol 2011;57:672-84.
NS
NS
NS
NS
NS
0
K-Mhesaplanmışoran(yıllık%)
Majör KABG
ile ilişkili
kanama
10
20
30
40
50
60
70
80
100
90
KABG ile
ilişkili TIMI
majör
kanama
KABG ile
ilişkili TIMI
minör
kanama
KABG ile ilişkili
GUSTO
şiddetli
kanama
KABG ile ilişkili
ölümcül
kanama
81.2 80.1
59.3 57.6
21.0
21.6
10.6 12.2
0.8 1.0
Tikagrelor (n=632)
Klopidogrel (n=629)
PLATO KABG Çalışmasında KABG ile İlişkili Kanama1
515901011-EKİM-2014-BRILINTA
19. Tikagrelorun AKS Tedavisindeki Kullanım
Endikasyonları
Tikagrelorun ASA ile eşzamanlı kullanımı,
tıbbi gözetimdeki hastalar ve PKG veya KABG ile tedavi edilen hastalar da dahil olmak üzere,
akut koroner sendromlu (kararsız anjina, NSTEMİ veya STEMİ) hastalarda
trombotik olayların (kardiyovasküler ölüm, Mİ ve inme) önlenmesinde endikedir.1
1. BRILINTA Ürün Bilgisi.
Kararsız anjina
NSTEMİ
STEMİ
Medikal
Tedavi
PKG KABG
TEDAVİYE GÖRETANIYA GÖRE
515901011-EKİM-2014-BRILINTA
20. Plasugrel
• Thienopyridine
• Aktif metaboliti aracığı ile etki
eder
• IPA düzeylerini hızla yükseltir.
• Klopidogrele yanıtı düşük
olanlarda da etkili
21. Prasugrel Compared to Clopidogrel in Patients
with Acute Coronary Syndromes Undergoing PCI
with Stenting:
the TRITON - TIMI 38 Stent Analysis
Stephen D. Wiviott, Elliott M. Antman, Ivan Horvath,
Matyas Keltai, Jean-Paul R. Herrman, Frans van de Werf,
William Downey, Benjamin M. Scirica, Sabina A. Murphy,
Carolyn H. McCabe, Eugene Braunwald
STENT ANALYSIS
22. Çalışma Dizaynı
Çift Kör
AKS (STEM, UA/NSTEMI) & Elektif PCI
ASA
PRASUGREL
60 mg yükleme/ 10
mg idame
KLOPIDOGREL
300 mg yükleme/ 75 mg
idame
1o sonlanım: KV ölüm, MI, İnme
2o sonlanım: Stent Trombozu
Güvenlik sonlanımları: TIMI major kanama, Hayati tehdid edici kanama
Tedavi Süresi: 6-15 ay
N= 13,608
Wiviott SD, Antman EM et al AHJ 2006
27. Sonuç
Stent takılan hastalarda PRASUGREL tedavisi
KLOPIDOGREL ile karşılaştırıldığında:
•Stent Trombozunda anlamlı azalma
•Stent, Stent Trombozu, işlem tipinden ve erken ya
da geç sonuçlardan bağımsız
Daha az iskemik olay, daha çok kanama
28. Diyabetik Alt Grup
0
2
4
6
8
10
12
14
16
18
0 30 60 90 180 270 360 450
HR 0.70
P<0.001
Days
Sonlanım(%)
KV Ölüm / MI / İnme
TIMI Major
KABG dışı kanama
NNT = 46
N=3146
17.0
12.2
Prasugrel
Klopidogrel
Prasugrel
Klopidogrel 2.6
2.5
29. TRITON Klinik Fayda
Kanama Alt Grupları
Toplam
>=60 kg
< 60 kg
< 75
>=75
Yok
Var
0.5 1 2
Geçirilmiş
SVO/TİA
Yaş
Kg
Risk (%)
+ 37
-16
-1
-16
+3
-14
-13
Prasugrel Lehine Clopidogrel Lehine
HR
Pint = 0.006
Pint = 0.18
Pint = 0.36
Post-hoc analiz
30.
31. Ticagrelor Akut Koroner
Sendrom tedavisinde
Plasugrel’den üstün müdür?
32,893 hasta verisinden meta-
analiz (dolaylı karşılaştırma)
32. • Head-to-head comparison of prasugrel vs.
ticagrelor showed no significant differences in
the risk of death (OR=1.22 [0.96-1.55],
p=0.106), myocardial infarction (OR=0.89 [0.75-
1.06], p=0.202), stroke (OR=1.19 [0.77-1.84],
p=0.441), MACE (OR=0.99 [0.86-1.13],
p=0.862), stent thrombosis (OR=0.71 [0.47-
1.09], p=0.115).
Sonuçlar
34. Cangrelor
• Direkt reversibl kısa etkili ( yarılanma ömrü 3
dk)
• Champion Çalışmaları 11 145 hasta
• Periprosedürel trombotik komplikasyonlar
daha az
• Cerrahi gereken durumlarda oral antiplatet
tedavi kesilmesi gerektiğinde kullanımı faydalı
olabilir.
39. Cerrahi Öncesi-Sonrası
2014 ESC/EACTS
Tikagrelor, Klopidogrel 5 gün,
Plasugrel 7 gün
Cerrahi sonrası kanama riski
kalmadığında tekrar başla
Eğer klinik durum uygunsa ve
Iskemik risk yüksek değilse
44. • Elektif PCI DA YUKSEK RİSKLİ GRUPTA (LM
STENT YADA DİYABETİK) KLAS 2 B PLASUGREL
YADA TICAGRELOR
45. Fig. 2 Management of prasugrel and ticagrelor before an elective surgery.
Fanny Bonhomme , Pierre Fontana , Jean-Luc Reny
How to manage prasugrel and ticagrelor in daily practice
European Journal of Internal Medicine, Volume 25, Issue 3, 2014, 213 - 220
http://dx.doi.org/10.1016/j.ejim.2014.01.016
46. Fig. 1 Comparative pharmacokinetics of oral P2Y12 inhibitors. t inhibition : time to peak platelet inhibition.
Fanny Bonhomme , Pierre Fontana , Jean-Luc Reny
How to manage prasugrel and ticagrelor in daily practice
European Journal of Internal Medicine, Volume 25, Issue 3, 2014, 213 - 220
http://dx.doi.org/10.1016/j.ejim.2014.01.016
47. Fig. 3 Example of a protocol for bridging therapy in patients scheduled for an invasive procedure with a moderate/high bleeding risk
associated with a high thrombotic risk. Adapted from <ce:cross-ref refid="bb0380" id="cf0005"> [76]</ce:cross-ref> . Aspi...
Fanny Bonhomme , Pierre Fontana , Jean-Luc Reny
How to manage prasugrel and ticagrelor in daily practice
European Journal of Internal Medicine, Volume 25, Issue 3, 2014, 213 - 220
http://dx.doi.org/10.1016/j.ejim.2014.01.016
48.
49.
50.
51.
52.
53. • Tedavi seçimi, başlangıç zamanı,
kombinasyonları ve tedavi süresi
• Klinik duruma (Stabil KAH, NSTE-AKS, STEMI)
ve tedavi seçeneğine (PCI, AKBG) göre
• En fazla fayda, en az zarar dengesi hastadan
hastaya değişir.
54. Stabil Koroner Hastalarında PCI
• ASA
• Yükleme dozu 150-300 mg
• ≥ 75 mg irrevesibl platelet siklooksijenaz
1(COX-1) için yeterli
• Optimal fayda-zarar oranı ideali: 75-150
mg/gün
55. • Klopidogrel
• Yükleme dozu: 300-600 mg
• İdame doz: 75 mg/günlük
• GRAVITAS çalışması: yüksek riskli hastalarda doz
artırmının faydası yok
• Dual Tedavi (ASA+Klopidogrel)
• BMS: En az 1 ay
• PARIS çalışması:
56. • Dual Tedavi (ASA+Klopidogrel)
• BMS: En az 1 ay
• DES: 6 ay
• Kanama riski yüksekse daha erkeb kesilebilir.
• Ömür boyu ASA
• Yüksek riskli hastalarda > 6 ay?
60. Plasugrel
• Yükleme dozu: 60 mg
• İdame: 10 mg
• P2Y12 receptör irreversibl blokajı/inhibisyonu
• Daha hızlı daha Yüksek etki
• TRINITRON-TIMI 38
• Kardiovasküler olay daha az
• Kanama riski daha yüksek
61. • Klopidogrel altında stent trombozunda
Plasugrel
• Daha önce TIA, inme öyküsü varsa kontrendike
• 75 yaş üstü hastalarda önerilmez
• Mutlaka gerekli ise 5 mg idame
62. • Ticagrelor
• Yükleme: 180 mg
• İdame: 90 mgx2
• Siklopentiltriazolopirimidin
• Reversibl P2Y12 inhibitörü
• PLATO çalışması
• Daha yüksek etki daha fazla kanama
63. • TIMI Major AKBG dışı kanama plasugrel ile
aynı, klopidogrelden daha fazla
• TIMI Majot AKBG ilişkili kanama
klopidogrelden daha az
64. Klopidogrel
• Sitokrom P450 – ireversibl P2Y12 blokajı
• Daha yavaş etki
• CURRENT-OASIS Çift dozun belirgin bir
üstünlüğü yok
65. ST Elevasyonlu MI
• Dual antiplatelet tedavi
• ASA 150-300 mg ve İdame 75-100 mg
• Plasugrel ya da Ticagrelor tercih sebebi
• Plasugrel Klopidogrel TRINITRON- TIMI 38
• Ticagrelor Klopidogrel PLATO
66. PLATO ve TRITON Çalışma Tasarımları1,2
1. James S, et al. Am Heart J 2009;157:599-605. 2. Wiviott SD et al. Am Heart J. 2006;152:627–635.
515901011-EKİM-2014-BRILINTA
67. PLATO ve TRILOGY Çalışma Tasarımları1,2
1. James S, et al. Am Heart J 2009;157:599-605. 2. Roe MT. N Eng J Med 2012;367(14):1297-309.
515901011-EKİM-2014-BRILINTA