Enoxaparin has been shown to be effective across the spectrum of acute coronary syndromes based on multiple randomized controlled trials. For conservative management of unstable angina/NSTEMI, enoxaparin was found to be superior to unfractionated heparin in reducing the primary composite outcome of death and myocardial infarction at 1 year follow-up, with similar rates of major hemorrhage. For high risk ACS patients undergoing an early invasive strategy, enoxaparin was at least as effective as unfractionated heparin with a higher rate of minor bleeding. In STEMI patients, enoxaparin was superior to unfractionated heparin for efficacy when used with fibrinolysis or
ST elevation myocardial infarction (STEMI) results from plaque rupture or erosion leading to an occlusive thrombus. This causes myocardial cell death spreading from inner to outer layers of the heart wall. Reperfusion therapy such as primary percutaneous coronary intervention (PCI) or fibrinolytic drugs are the main treatments aimed at saving ischemic heart muscle. For PCI, the door-to-balloon time should be ≤90 minutes, while for fibrinolytics the door-to-needle time should be ≤30 minutes. General management includes intensive care monitoring, IV access, analgesia, oxygen supplementation, and investigations to guide treatment and prognosis.
This document summarizes a review on ivabradine, a drug that lowers heart rate by selectively inhibiting funny (If) channels in the sinoatrial node. It discusses the pathophysiology of elevated heart rate and heart rate control. Ivabradine is a selective If current inhibitor that reduces heart rate without affecting contractility or blood pressure. Clinical trials such as BEAUTIFUL showed ivabradine reduced rates of hospitalization for heart failure and myocardial infarction in patients with coronary artery disease and heart rates over 70 beats per minute. Ivabradine may provide benefit as an add-on to standard heart failure therapy in select patient groups.
1. This document discusses cardiovascular risks associated with cancer therapies. It highlights three main stations: risk factor assessment, surveillance during therapy, and risk stratification after therapy.
2. Different cancer treatments can cause different types of cardio-toxicity, such as anthracyclines causing heart failure, HER2 inhibitors causing drops in ejection fraction, and immune checkpoint inhibitors causing myocarditis.
3. Clinical scenarios are presented involving patients receiving various therapies who present with new cardiovascular issues, and the document discusses recommended next steps for evaluating and managing these patients.
The document summarizes the 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Key recommendations include:
- Using the ESC 0h/2h algorithm with blood sampling at 0h and 2h if an hs-cTn test with a validated 0h/2h algorithm is available.
- Considering measuring BNP or NT-proBNP for prognostic information.
- Considering prasugrel in preference to ticagrelor for NSTE-ACS patients proceeding to PCI.
- Recommending an early invasive strategy within 24h for high-risk patients based on factors like diagnosis of NSTEMI or GRACE risk score >140.
The document discusses new guidance from the 2021 Canadian Cardiovascular Society/Canadian Heart Failure Society Heart Failure Guideline Panel. It provides an overview of a webinar series on heart failure that will discuss topics such as screening and diagnosis of HFrEF and HFpEF, device therapy, and non-pharmacological management. The webinars will be presented by experts in the field. The document also provides information on proper use and citation of guideline materials from the CCS for educational or industry programs.
This document summarizes the PARADIGM-HF clinical trial which compared the angiotensin receptor-neprilysin inhibitor LCZ696 to the ACE inhibitor enalapril in patients with heart failure and reduced ejection fraction. The trial found that LCZ696 was superior to enalapril in reducing cardiovascular death and hospitalization for heart failure. Specifically, LCZ696 reduced the risk of the primary composite outcome of death from cardiovascular causes or hospitalization for heart failure by 16% compared to enalapril. LCZ696 also reduced deaths from any cause by 16% compared to enalapril.
Session 3 - Microcatheters, new developmentsEuro CTO Club
This document discusses recent developments in microcatheter technology, including new microcatheters from Asahi such as the Corsair Pro XS. It describes design features of various microcatheters like tapered shafts, braided coils, and tip configurations. New devices aim to improve trackability, torque response, and crossability. While microcatheter technology facilitates endovascular techniques, the document notes that further coordinated evolution is still needed between microcatheters and guidewires.
This document summarizes several studies on antiplatelet therapy in patients with acute coronary syndrome (ACS). It discusses the optimal P2Y12 inhibitor choice for older patients based on the Gimbel et al. study, which was a randomized trial comparing clopidogrel to ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation ACS. The trial found no significant differences in safety or efficacy outcomes between treatment groups. Modalities for switching between oral P2Y12 inhibitors are discussed, along with bleeding risks associated with ticagrelor compared to clopidogrel based on the PLATO trial. Factors favoring de-escalation of dual antiplate
ST elevation myocardial infarction (STEMI) results from plaque rupture or erosion leading to an occlusive thrombus. This causes myocardial cell death spreading from inner to outer layers of the heart wall. Reperfusion therapy such as primary percutaneous coronary intervention (PCI) or fibrinolytic drugs are the main treatments aimed at saving ischemic heart muscle. For PCI, the door-to-balloon time should be ≤90 minutes, while for fibrinolytics the door-to-needle time should be ≤30 minutes. General management includes intensive care monitoring, IV access, analgesia, oxygen supplementation, and investigations to guide treatment and prognosis.
This document summarizes a review on ivabradine, a drug that lowers heart rate by selectively inhibiting funny (If) channels in the sinoatrial node. It discusses the pathophysiology of elevated heart rate and heart rate control. Ivabradine is a selective If current inhibitor that reduces heart rate without affecting contractility or blood pressure. Clinical trials such as BEAUTIFUL showed ivabradine reduced rates of hospitalization for heart failure and myocardial infarction in patients with coronary artery disease and heart rates over 70 beats per minute. Ivabradine may provide benefit as an add-on to standard heart failure therapy in select patient groups.
1. This document discusses cardiovascular risks associated with cancer therapies. It highlights three main stations: risk factor assessment, surveillance during therapy, and risk stratification after therapy.
2. Different cancer treatments can cause different types of cardio-toxicity, such as anthracyclines causing heart failure, HER2 inhibitors causing drops in ejection fraction, and immune checkpoint inhibitors causing myocarditis.
3. Clinical scenarios are presented involving patients receiving various therapies who present with new cardiovascular issues, and the document discusses recommended next steps for evaluating and managing these patients.
The document summarizes the 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Key recommendations include:
- Using the ESC 0h/2h algorithm with blood sampling at 0h and 2h if an hs-cTn test with a validated 0h/2h algorithm is available.
- Considering measuring BNP or NT-proBNP for prognostic information.
- Considering prasugrel in preference to ticagrelor for NSTE-ACS patients proceeding to PCI.
- Recommending an early invasive strategy within 24h for high-risk patients based on factors like diagnosis of NSTEMI or GRACE risk score >140.
The document discusses new guidance from the 2021 Canadian Cardiovascular Society/Canadian Heart Failure Society Heart Failure Guideline Panel. It provides an overview of a webinar series on heart failure that will discuss topics such as screening and diagnosis of HFrEF and HFpEF, device therapy, and non-pharmacological management. The webinars will be presented by experts in the field. The document also provides information on proper use and citation of guideline materials from the CCS for educational or industry programs.
This document summarizes the PARADIGM-HF clinical trial which compared the angiotensin receptor-neprilysin inhibitor LCZ696 to the ACE inhibitor enalapril in patients with heart failure and reduced ejection fraction. The trial found that LCZ696 was superior to enalapril in reducing cardiovascular death and hospitalization for heart failure. Specifically, LCZ696 reduced the risk of the primary composite outcome of death from cardiovascular causes or hospitalization for heart failure by 16% compared to enalapril. LCZ696 also reduced deaths from any cause by 16% compared to enalapril.
Session 3 - Microcatheters, new developmentsEuro CTO Club
This document discusses recent developments in microcatheter technology, including new microcatheters from Asahi such as the Corsair Pro XS. It describes design features of various microcatheters like tapered shafts, braided coils, and tip configurations. New devices aim to improve trackability, torque response, and crossability. While microcatheter technology facilitates endovascular techniques, the document notes that further coordinated evolution is still needed between microcatheters and guidewires.
This document summarizes several studies on antiplatelet therapy in patients with acute coronary syndrome (ACS). It discusses the optimal P2Y12 inhibitor choice for older patients based on the Gimbel et al. study, which was a randomized trial comparing clopidogrel to ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation ACS. The trial found no significant differences in safety or efficacy outcomes between treatment groups. Modalities for switching between oral P2Y12 inhibitors are discussed, along with bleeding risks associated with ticagrelor compared to clopidogrel based on the PLATO trial. Factors favoring de-escalation of dual antiplate
This document discusses several clinical studies that compare the effects of different statin drugs on cardiovascular outcomes and the progression of atherosclerosis. The STELLAR study showed that rosuvastatin more effectively lowered LDL-C and raised HDL-C than other statins. Two real-world studies found that rosuvastatin use was associated with a 28-40% lower risk of cardiovascular events compared to other statins. The METEOR study found that rosuvastatin slowed the progression of atherosclerosis whereas the ENHANCE study found that ezetimibe added to simvastatin provided no benefit.
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 EMPEROR-Reduced trial studied the effects of empagliflozin in patients with chronic heart failure with reduced ejection fraction. The trial included patients with NYHA class II-IV heart failure and an ejection fraction below 40% who were receiving standard guideline-directed medical therapy. Patients were randomly assigned to receive empagliflozin 10 mg daily or placebo and followed for a median of 16 months. The study found that empagliflozin reduced the risk of the composite primary outcome of cardiovascular death or hospitalization for heart failure compared to placebo.
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 summarizes clinical trials investigating the oral anticoagulant Xarelto for the treatment and prevention of venous thromboembolism (VTE) and arterial thromboembolism. It describes two major studies:
1) The ROCKET AF study found that once-daily Xarelto was non-inferior to warfarin for preventing strokes in atrial fibrillation patients, with lower rates of intracranial bleeding and fatal bleeding.
2) The ATLAS ACS 2-TIMI 51 study found that adding 2.5 mg twice-daily Xarelto to standard antiplatelet therapy after an acute coronary syndrome reduced the composite of cardiovascular death, heart attack, and
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
The PARADIGM-HF trial compared the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan to the ACE inhibitor enalapril in patients with heart failure with reduced ejection fraction. It found that sacubitril/valsartan reduced cardiovascular mortality and heart failure hospitalizations compared to enalapril, as well as reducing overall mortality. The trial established sacubitril/valsartan as a new standard of care for treating HFrEF.
COMPARES OPTIMAL MEDICAL THERAPY WITH INVASIVE THERAPY IN A PATIENT WITH STABLE ISCHEMIC HEART DISEASE WITH MODERATE TO SEVERE MYOCARDIAL ISCHEMIA ON NON INVASIVE STRESS TESTING
LCZ696 was more effective than enalapril in reducing the risks of CV death and HF hospitalization, CV death, HF hospitalization, and all-cause mortality in patients with heart failure with reduced ejection fraction. LCZ696 also provided incremental improvements in symptoms and physical limitations. LCZ696 was better tolerated than enalapril with lower rates of symptomatic hypotension, hyperkalemia, renal impairment, and cough.
The EMPEROR-Preserved trial evaluated whether empagliflozin reduces cardiovascular death or hospitalization for heart failure in adults with either heart failure with mid-range or preserved ejection fraction. The trial randomized over 5,000 patients to empagliflozin 10 mg daily or placebo, with a median follow up of 26 months. Empagliflozin reduced the primary composite outcome of cardiovascular death or hospitalization for heart failure by 21% compared to placebo, driven mainly by a 29% lower risk of hospitalization for heart failure.
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 recent clinical trials evaluating new treatments for heart failure with reduced ejection fraction (HFrEF). It finds that sodium-glucose cotransporter-2 inhibitors (SGLT2i) like dapagliflozin and empagliflozin are now foundational therapies for HFrEF as they reduce mortality, hospitalizations, and improve outcomes. Two novel agents, vericiguat and omecamtiv mecarbil, are described as well-tolerated therapies that may provide additional benefit by reducing residual risk in select HFrEF patients. Vericiguat is now FDA-approved and recommended by guidelines for recent worsening HF, while omecamtiv me
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.
This document summarizes several studies related to sacubitril/valsartan (LCZ696):
- The TRANSITION trial found that initiating sacubitril/valsartan in hospital shortly after stabilization from acute heart failure had similar safety outcomes as initiating post-discharge. About 50% of patients achieved the top dose within 10 weeks.
- The PIONEER-HF trial showed that among patients hospitalized for acute heart failure, sacubitril/valsartan led to a greater reduction in NT-proBNP levels at 8 weeks compared to enalapril, with similar rates of adverse events.
- The landmark PARADIGM-HF trial demonstrated that sacubitril
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.
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.
This document outlines the biological functions of uric acid and its relationship to cardiovascular disease. It discusses asymptomatic hyperuricemia and how elevated uric acid levels are associated with increased risks of hypertension, chronic kidney disease, and cardiovascular disease through proinflammatory and oxidative stress mechanisms, though the relationship is not fully understood. The document provides guidelines for evaluating and managing hyperuricemia, including lifestyle modifications and pharmacologic treatment with allopurinol or febuxostat to lower uric acid levels. Allopurinol is preferred initially due to safety concerns raised about febuxostat increasing heart-related deaths.
Emergency Medical System Network for STEMI ManagementPERKI Pekanbaru
This document discusses the emergency medical system network for managing ST-elevation myocardial infarction (STEMI). It outlines the importance of rapid diagnosis through early electrocardiograms and treatment through reperfusion therapies like primary percutaneous coronary intervention (PCI) or fibrinolysis. The target is first medical contact to reperfusion within 90 minutes for primary PCI or 30 minutes for fibrinolysis. It also discusses long-term secondary prevention therapies.
This document discusses several clinical studies that compare the effects of different statin drugs on cardiovascular outcomes and the progression of atherosclerosis. The STELLAR study showed that rosuvastatin more effectively lowered LDL-C and raised HDL-C than other statins. Two real-world studies found that rosuvastatin use was associated with a 28-40% lower risk of cardiovascular events compared to other statins. The METEOR study found that rosuvastatin slowed the progression of atherosclerosis whereas the ENHANCE study found that ezetimibe added to simvastatin provided no benefit.
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 EMPEROR-Reduced trial studied the effects of empagliflozin in patients with chronic heart failure with reduced ejection fraction. The trial included patients with NYHA class II-IV heart failure and an ejection fraction below 40% who were receiving standard guideline-directed medical therapy. Patients were randomly assigned to receive empagliflozin 10 mg daily or placebo and followed for a median of 16 months. The study found that empagliflozin reduced the risk of the composite primary outcome of cardiovascular death or hospitalization for heart failure compared to placebo.
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 summarizes clinical trials investigating the oral anticoagulant Xarelto for the treatment and prevention of venous thromboembolism (VTE) and arterial thromboembolism. It describes two major studies:
1) The ROCKET AF study found that once-daily Xarelto was non-inferior to warfarin for preventing strokes in atrial fibrillation patients, with lower rates of intracranial bleeding and fatal bleeding.
2) The ATLAS ACS 2-TIMI 51 study found that adding 2.5 mg twice-daily Xarelto to standard antiplatelet therapy after an acute coronary syndrome reduced the composite of cardiovascular death, heart attack, and
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
The PARADIGM-HF trial compared the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan to the ACE inhibitor enalapril in patients with heart failure with reduced ejection fraction. It found that sacubitril/valsartan reduced cardiovascular mortality and heart failure hospitalizations compared to enalapril, as well as reducing overall mortality. The trial established sacubitril/valsartan as a new standard of care for treating HFrEF.
COMPARES OPTIMAL MEDICAL THERAPY WITH INVASIVE THERAPY IN A PATIENT WITH STABLE ISCHEMIC HEART DISEASE WITH MODERATE TO SEVERE MYOCARDIAL ISCHEMIA ON NON INVASIVE STRESS TESTING
LCZ696 was more effective than enalapril in reducing the risks of CV death and HF hospitalization, CV death, HF hospitalization, and all-cause mortality in patients with heart failure with reduced ejection fraction. LCZ696 also provided incremental improvements in symptoms and physical limitations. LCZ696 was better tolerated than enalapril with lower rates of symptomatic hypotension, hyperkalemia, renal impairment, and cough.
The EMPEROR-Preserved trial evaluated whether empagliflozin reduces cardiovascular death or hospitalization for heart failure in adults with either heart failure with mid-range or preserved ejection fraction. The trial randomized over 5,000 patients to empagliflozin 10 mg daily or placebo, with a median follow up of 26 months. Empagliflozin reduced the primary composite outcome of cardiovascular death or hospitalization for heart failure by 21% compared to placebo, driven mainly by a 29% lower risk of hospitalization for heart failure.
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 recent clinical trials evaluating new treatments for heart failure with reduced ejection fraction (HFrEF). It finds that sodium-glucose cotransporter-2 inhibitors (SGLT2i) like dapagliflozin and empagliflozin are now foundational therapies for HFrEF as they reduce mortality, hospitalizations, and improve outcomes. Two novel agents, vericiguat and omecamtiv mecarbil, are described as well-tolerated therapies that may provide additional benefit by reducing residual risk in select HFrEF patients. Vericiguat is now FDA-approved and recommended by guidelines for recent worsening HF, while omecamtiv me
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.
This document summarizes several studies related to sacubitril/valsartan (LCZ696):
- The TRANSITION trial found that initiating sacubitril/valsartan in hospital shortly after stabilization from acute heart failure had similar safety outcomes as initiating post-discharge. About 50% of patients achieved the top dose within 10 weeks.
- The PIONEER-HF trial showed that among patients hospitalized for acute heart failure, sacubitril/valsartan led to a greater reduction in NT-proBNP levels at 8 weeks compared to enalapril, with similar rates of adverse events.
- The landmark PARADIGM-HF trial demonstrated that sacubitril
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.
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.
This document outlines the biological functions of uric acid and its relationship to cardiovascular disease. It discusses asymptomatic hyperuricemia and how elevated uric acid levels are associated with increased risks of hypertension, chronic kidney disease, and cardiovascular disease through proinflammatory and oxidative stress mechanisms, though the relationship is not fully understood. The document provides guidelines for evaluating and managing hyperuricemia, including lifestyle modifications and pharmacologic treatment with allopurinol or febuxostat to lower uric acid levels. Allopurinol is preferred initially due to safety concerns raised about febuxostat increasing heart-related deaths.
Emergency Medical System Network for STEMI ManagementPERKI Pekanbaru
This document discusses the emergency medical system network for managing ST-elevation myocardial infarction (STEMI). It outlines the importance of rapid diagnosis through early electrocardiograms and treatment through reperfusion therapies like primary percutaneous coronary intervention (PCI) or fibrinolysis. The target is first medical contact to reperfusion within 90 minutes for primary PCI or 30 minutes for fibrinolysis. It also discusses long-term secondary prevention therapies.
Secondary Prevention after ACS: Focused on Anticoagulant TherapyPERKI Pekanbaru
Dr. Nathania Marliani Kristanti, SpJP, FIHA. 3rd Pekanbaru Cardiology Update, August 25th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
Strategy to Go for Goal in Dyslipidemia with Acute Coronary Syndrome PatientsPERKI Pekanbaru
Dr. A. Fauzi Yahya, SpJP (K), FIHA, FAsCC. 3rd Pekanbaru Cardiology Update, August 24th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
1) The document discusses fibrinolytic therapy for ST-elevation myocardial infarction (STEMI). STEMI is defined as new ST elevation and biomarkers of necrosis.
2) Immediate reperfusion therapy with either primary percutaneous coronary intervention (PCI) or fibrinolysis is recommended for STEMI patients. The goals are to perform primary PCI within 90 minutes of first medical contact or give fibrinolysis within 30 minutes.
3) Several fibrinolytic agents are discussed including alteplase, reteplase, tenecteplase, and streptokinase. Their properties, dosages, and effectiveness are compared. Successful reperfusion is assessed by resolution of symptoms and ECG changes.
Prof. DR. Dr. Rochmad Romdoni, SpJP(K), FINASIM, FIHA, FAsCC. 3rd Pekanbaru Cardiology Update, August 24th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
La misión de UNIMINUTO es ofrecer educación superior de alta calidad a sus estudiantes y formarlos éticamente para lograr líderes que construyan. La visión es aprovechar el número de sedes para expandir el alcance educativo.
1. The document discusses acute ischemic stroke treatment and highlights the importance of timely intravenous thrombolysis administration.
2. It reviews insights on intravenous and intra-arterial thrombolysis and previews future interventional therapies for ischemic stroke.
3. The author examines a clinical trial on the use of Factor VIIa for intracerebral hemorrhage that showed it reduced hematoma growth and mortality in a dose-dependent manner, indicating a potential new treatment for spontaneous ICH.
1) The document compares the factor Xa inhibitor fondaparinux to enoxaparin for treating acute coronary syndrome, based on the OASIS-5 trial results.
2) The trial found that fondaparinux was as effective as enoxaparin for outcomes like death, MI, and ischemia, but had significantly lower rates of major bleeding at 9 days and 6 months.
3) Based on these results, fondaparinux provides an improved benefit-risk profile compared to enoxaparin for treating acute coronary syndrome.
Novedades en Cardiopatía Isquémica en los principales congresos del año
24/11/15 18:00h - 20:00h Casa del Corazón, Madrid
Intervencionismo en Cardiopatía Isquémica
Dr. Iván Núñez Gil, Hospital Universitario Clínico San Carlos (Madrid)
Survival after cardiac arrest is poor but some therapies can make a difference. This presentation discusses the evidence for therpauetic hypothermia, normoxia, management of blood pressure and early cardiac catherterisation. It also makes the case that these might be elements of a bundle of care.
Tenecteplase (TNK) has been shown to be more cost-effective than streptokinase (STK) for fibrinolytic therapy in acute myocardial infarction based on improved outcomes and fewer adverse events. Studies have demonstrated TNK saves 1-2 more lives per 100 patients treated compared to STK, with significantly lower rates of major bleeding events, cardiogenic shock, and other complications. The increased efficacy and safety of TNK can translate to cost savings by reducing the number of patients requiring blood transfusions, ICU care for shock, and overall length of hospital stay. As a single bolus agent, TNK is also easier to administer than STK or alteplase.
Presentación "Update de los estudios de ABSORB hasta 2014" del Dr. Flavio Ribichini durante la Mesa Redonda sobre Scaffolds reabsorbibles de la XXV Reunión Anual de la Sección de Hemodinámica y Cardiología Intervencionista (SHCI) de 2014 en Córdoba.
Ponencia realizada por el Dr. Montalescot y presentada por el Dr. José Antonio Gómez Hospital en la Reunión EuroIMAT 2020, celebrada en Barcelona (20 y 21 de febrero de 2020).
This document summarizes presentations given at the World Congress of Cardiology in 2006. It discusses results from the PCI ExTRACT-TIMI 25 trial showing that enoxaparin was associated with lower rates of death or heart attack compared to unfractionated heparin in patients undergoing percutaneous coronary intervention (PCI) after receiving a fibrinolytic. It also summarizes meta-analyses showing an increased risk of late stent thrombosis with drug-eluting stents compared to bare-metal stents. Faculty disclosures are provided.
Thrombus aspiration prior to primary percutaneous coronary intervention (PCI) shows the most promise for preventing distal embolization in ST-segment elevation myocardial infarction (STEMI) based on clinical trial evidence. New devices like the MGuard stent, which combines a stent and embolic protection mesh, also show potential benefits. The presentation reviewed various pharmacologic and mechanical approaches and their supporting clinical trial data, ultimately recommending thrombus aspiration as the current best therapy to reduce distal embolization in STEMI patients undergoing primary PCI.
This document provides an overview of intravenous thrombolysis for acute ischemic stroke, including available agents, safety data, and efficacy studies. It discusses the evidence for alteplase and tenecteplase, including major trials. Tenecteplase is a genetically engineered form of alteplase that requires only intravenous bolus administration. While not FDA-approved for stroke, studies suggest tenecteplase has similar efficacy to alteplase with potentially fewer bleeding complications. Ongoing trials are further evaluating tenecteplase compared to alteplase and standard treatments. The document reviews criteria for use and contraindications of tenecteplase based on acute ischemic stroke studies.
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Similar to Enoxaparin Proven Across the ACS Spectrum (20)
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1. Enoxaparin
Proven Across
the Acute Coronary Syndrome
Spectrum
Learning from current guidelines
Dr. Irwan, SpJP-FIHA
Department of Cardiology and Vascular Medicine
Faculty of Medicine, Riau University
Arifin Achmad Hospital - Pekanbaru
2. IX VII
X
II
Intrinsic pathway
(surface contact)
XII XIIa
XI
Tissue factor
IIa
Xa
XIa
IXa VIIa
VIII VIIIa
Extrinsic pathway
(tissue damage)
Xa
V Va
Fibrinogen Fibrin
Heparins and
LMWH2
Vitamin K antagonists3
Direct thrombin inhibitors4
Factor Xa inhibitors5
(Thrombin)IIa
Targets for AnticoagulantsTargets for Anticoagulants
1Adapted with permission from
Petitou M, et al. Nature. 1991;350(suppl):30-33.
2Hirsh J, et al. Chest. 2001;119(suppl):64S-94S.
3Hirsh J, Fuster V. Circulation. 1994;89:1449-1468.
4Weitz JI, Hirsh J. Chest. 2001;119(suppl):95S-107S.
5Herbert JM, et al. Cardiovasc Drug Rev. 1997;15:1.
3.
4.
5. Enoxaparin in ACS
Conservative UA/NSTEMI
High risk UA/STEMI
High risk UA/NSTEMI + early invasive
(PCI)
Conservative STEMI
STEMI + Elective PCI
STEMI + Primary PCI
6.
7. ENOXAPARIN in
conservative ACS
In the TIMI 11B and ESSENCE trials,
meta-analysis showed :
• the primary composite outcome was
significantly lower in patients treated
with enoxaparin compared with UFH
after 1 year of follow-up.
• no significant differences in the rates
of major hemorrhage between
enoxaparin and UFH in either trial or
in the pooled data.
• there was an increased rate of minor
hemorrhage with enoxaparin.
8. INTERACT:
• Among patients treated with eptifibatide in the setting of
high risk non-ST elevation ACS, administration of
enoxaparin is associated with improves outcomes
compared to currently recommended therapy (UF Heparin)
based on better safety and efficacy
A to Z
• In patients with high-risk NSTE-ACS treated with
AGGRASTAT®† (tirofiban, MSD) and ASA, enoxaparin is an
effective noninferior alternative
to UFH
• Overall rates of bleeding, transfusion, and
thrombocytopenia were low in both heparin groups given
AGGRASTAT and ASA
Slide 8
Adapted from Blazing MA et al JAMA 2004;292(1):55–64.
†Registered trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.
Enoxaparin in high risk ACS
9. ENOXAPARIN in
high risk + early invasive ACS
SYNERGY
• Efficacy — not superior but at least as
effective as UFH in the overall population (met
criteria for non inferiority)
• Minor bleeding — more frequent with
enoxaparin
• An overview of all recent RCTs comparing
enoxaparin and UFH shows a consistent effect
across the management spectrum
10. Study N Death or MI at 30 days Major bleeds
ESSENCE ’97 3,171
TIMI 11B ’99 3,910
ACUTE II ’02 525
INTERACT ’03 746
A TO Z ’04 3,620
SYNERGY ’04 9,974
ALL 21,946
0 2010
Incidence (%)
10.1 vs. 11.0
0.5 21
OR (95% CI)
0.91 (0.83 – 0.99)
0 105
Incidence (%)
3.9 vs 3.7
0.1 101
OR (95% CI)
1.1 (0.96 – 1.3)
0.5 21 10102 ∞ 102 10 1
NNT (95% CI)
113 (61 – 1,438)
Enox
+
UFH
+
Enox
+
UFH
+
Enox
+
UFH
+
Randomized Trial
Totality of clinical evidence for
Enoxaparin should lead to level A
Bassand JP, et al. Eur Heart J. 28:1598-1660.
ESC and ACC/AHA NSTE MI ACS GuidelinesESC and ACC/AHA NSTE MI ACS Guidelines
UFHUFH
EnoxaparinEnoxaparin
11. ENOXAPARIN in STEMI
ASSENT-3
• “In view of the present data and the ease of
administration, enoxaparin might be considered an
attractive alternative anticoagulant treatment when
given in combination with tenecteplase”.
EXTRACT-TIMI 25
● Among STEMI patients undergoing PCI following fibrinolysis,
ENOX was superior to UFH for efficacy with similar safety
- significantly less death or re MI
- both delayed onset and lower incidence of PCI
- no difference in bleeding
- less stroke
12. On behalf of, A. Shui, A.J. Jacob, N. Gotcheva, L.
Polonetsky, E.M. Antman, E. Braunwald, and the
ExTRACT-TIMI 25 Investigators. EHJ in press
Enoxaparin vs UFH with Fibrinolysis
for STEMI in Pts ≥ 75 years
compared with < 75 years
13. STEMI < 6 h
Lytic eligible
Lytic choice by MD
(TNK, tPA, rPA, SK)
ENOX
< 75 y: 30 mg IV bolus
SC 1.0 mg / kg q 12 h (Hosp DC)
≥ 75 y: No bolus
SC 0.75 mg / kg q 12 h (Hosp DC)
CrCl < 30: 1.0 mg / kg q 24 h
Double-blind, double-dummy
ASA
Day 30
1°°°° Efficacy Endpoint: Death or Nonfatal MI
1°°°° Safety Endpoint: TIMI Major Hemorrhage
Protocol Design
UFH
60 U / kg bolus (4000 U)
Inf 12 U / kg / h (1000 U / h)
Duration: at least 48 h
Cont’’’’d at MD discretion
14. Main Results
Primary Endpoint:
Death or non-fatal re-MI by 30 days
Main Secondary Endpoint:
Death, non-fatal re-MI, urgent
revascularization by 30 days
12.0
9.9
UFH UFH
ENOX ENOX
14.5
11.7
Days Days
%% RR = 0.83
p = 0.000003
RR = 0.81
p = 0.000001
N Engl J Med 2006;354:1477-88.
33% RRR in reMI by 48 h (P=0.002)
19% RRR in Death/MI by 72 h (P<0.001)
12% RRR in by 48 h (P=0.02)
15. Pharmacokinetics
Age <75 years
(N=60)
Age ≥75 years
(N=13)
P-value
AntiXa clearance (L/hr) 0.794 0.654 0.049
Area under curve 0-12hr IU x h/L 9839 4532 <0.001
Area under curve at steady state IU x h/L 10,000 8197 0.005
16. Day 30 UFH ENOX RRR ARD NNT
Effects of enoxaparin vs
unfractionated heparin
Stratified by age
17. TIMI major bleeding
Stratified by age
1.1
1.9
3.3
2.9
0
1
2
3
4
5
< 75 years
n = 17,814
≥ 75 years
n = 2513
%Events
Unfractionated heparin Enoxaparin
ARD 0.8%
RR 1.67 (1.31-2.13)
p=<0.0001
ARD 0.4%
RR 1.15 (0.74-1.78)
p=0.53
18. ExTRACT TIMI 25
• The Enox strategy as implemented in
ExTRACT-TIMI 25 is preferred to the
standard UFH strategy in both younger and
older patients treated with fibrinolysis.
19. Slide 19
Enoxaparin in the Cath. Lab. Replacing UFH
Is there enough evidence based trial ?
20. ATOLL
An international randomized study
comparing IV enoxaparin to IV UFH in primary PCI
G. Montalescot, M. Cohen, P. Goldstein,
K. Huber, C. Pollack, U. Zeymer, E. Vicaut
for the ATOLL investigators
G. MONTALESCOT, DISCLOSURE: Research Grants (to the Institution) from Abbott Vascular, Bristol Myers
Squibb, Boston Scientific, Centocor, Cordis, Eli-Lilly, Fédération Française de Cardiologie, Fondation de France,
Guerbet Medical, INSERM, Medtronic, Pfizer, Sanofi-Aventis Group, Société Française de Cardiologie;
Consulting or Lecture Fees from Accumetrics, Astra-Zeneca, Bayer, Biotronik, Boehringer-Ingelheim, Bristol-
Myers Squibb, Daichi-Sankyo, Eisai, Eli-Lilly, Menarini, MSD, Novartis, Portola, Sanofi-Aventis Group, Schering-
Plough , Servier and The Medicines Company.
ATOLL: Acute STEMI Treated with primary PCI and intravenous enoxaparin Or UFH to
Lower ischemic and bleeding events at short- and Long-term follow-up
(Investigator-driven study)
ESC,Stockholm-August30,2010–Hotlinesession
21. Intravenous 0.5mg/kg Enoxaparin
Time (hours)
Anti-XaIU/mL
0 2 4 6 8 10 12 14 16 18 20
0
0.4
0.8
1.2
0.5 mg/kg IV
1 mg/kg SC
•Choussat et al (elective PCI)
•Miller et al (ACS-PCI)
•Carnendran et al (elective PCI)
•STEEPLE (elective PCI)
•PROTECT –TIMI30 (ACS-PCI)
•Silvain et al (elective PCI)
•FINESSE (primary PCI)
•Brieger et al. (Primary PCI)
PD experience Clinical experience
Choussat et al. JACC. 2002;40:1943-50.
Miller L. J Invasive Cardiol. 2002;14:247-50
Carnendran et al. J Invasive Cardiol. 2003;15:235-8.
Montalescot et al. N Engl J Med. 2006;355:1006-17.
Gibson et al. JACC. 2006;47:2364-2373
Silvain et al. JACC. 2010;55:617-25
Montalescot et al. JACC Cardiovasc Interv. 2010;3:203-12
Brieger et al. Catheter Cardiovasc Interv. 2010 [in press]Sanchez-Pena P. Br J Clin Pharmacol. 2005;60:364-73.
22. Intravenous enoxaparin vs. UFH in PCI
57%
Major Bleeding
(p=0.004)
23%
Death or re-MI
(p<0.001)
Montalescot G et al. N Engl J Med 2006;355:1006 –17
Gibson MC et al. J Am Coll Cardiol 2007;49:2238–46
?
23. ATOLL Trial design
STEMI Primary PCI
1°°°° EP: Death, Complication of MI, Procedure Failure, Major Bleeding
Main 2°°°° EP: Death, recurrent MI / ACS, Urgent Revascularization
30 days
Randomization as early as possible (MICU +++)
Real life population (shock, cardiac arrest included)
No anticoagulation and no lytic before Rx
Similar antiplatelet therapy in both groups
ENOXAPARIN IV
0.5 mg/kg
with or without GPIIbIIIa
UFH IV
50-70 IU with GP IIbIIIa
70-100IU without GP IIbIIIa
(Dose ACT-adjusted)
IVRS
Primary PCI
ENOXAPARIN SC UFH IV or SC
27. Conclusions
• This multinational randomized study,
includes 910 patients recruited over 2 years,
that shows a 17% RRR close to significance
(P= 0.07) on an innovative efficacy/safety
composite primary endpoint and was
significant on all the major secondary
standard endpoints used in ACS such as
the triple endpoint (Death, MI,
Revascularization)
• Lovenox® confirming it as a better
alternative to UFH in all ACS settings.
28. Enoxaparin benefit vs UFH
IV enoxaparin 0.5 mg/kg for PCI
• 1 shot ± GP IIb/IIIa inhibitors
• no ACT monitoring
• stable anticoagulation for 2 hours
(duration of PCI)
29. 29
What are the Guidelines telling us
for UA, NSTEMI & STEMI ?
ESC
&
ACCF / AHA
33. ESC guidelines 2012
(AMI - STEMI)
33
Recommendations Class Level
An injectable anticoagulant must be used in primary PCI. I C
Enoxaparin (with or without routine GP IIb/IIIa blocker) may be preferred over UFH. IIb B
Fondaparinux is not recommended for primary PCI. III B
The use of fibrinolysis before planned primary PCI is not recommended. III A
Recommendations Class Level
The anticoagulant can be :
* Enoxaparin i.v. followed by s.c. (using the regimen described below) (preferred over UFH). I A
* UFH given as a weight-adjusted i.v. bolus & infusion. I C
In patients treated with streptokinase, fondaparinux i.v. bolus followed by s.c. dose 24 h later. IIa B
Antithrombin co-therapy with fibrinolysis
Tabel 12 :
Periprocedural antithrombotic medication in primary PCI
Anticoagulants
UFH with or without routine GP IIb/IIIa blocker must be used in patients not receiving bivalirudin or
enoxaparin.
I C
Tabel 13 :
Fibrinolytic therapy
Bivalirudin (with use of GP IIb/IIIa blocker restricted to bailout) is recommended over UHF & GP IIb/IIIa
blocker.
I A
Anticoagulation is recommended in STEMI patients treated with lytics until revascularization (if
performed) or for the duration of hospital stay up to 8 days. I C
34. ESC guidelines 2012
(AMI - STEMI)
34
Enoxaparin 0.5 mg/kg i.v. bolus.
In patients <75 years of age :
In patients >75 years of age :
In patients with creatinine clearance of <30 mL/min, regardles of age :
the s.c. doses are given once every 24 h.
Enoxaparin Same dose as with fibrinolytic therapy.
With primary PCI
Tabel 16 :
Doses of antiplatelet & antithrombin co-therapies
Doses of antithrombin co-therapies
Enoxaparin
No adjusment of bolus dose. Following thrombolysis, in patients with creatinin
clearance <30 mL/min, the s.c. doses are given once every 24 h.
Enoxaparin
With fibrinolytic therapy
Tabel 18 :
Recommendation
30 mg i.v. bolus followed 15 min later by 1 mg/kg s.c. every 12 h until hospital discharge
for a maximum of 8 days. The first two doses should not exceed 100 mg.
no i.v. bolus; start with s.c. dose of 0.75 mg/kg with a maximum of 75 mg for the first
two s.c. doses.
Initial dosing of antithrombotic agents in patients with chronic kidney disease
(estimated creatinine clearance <60 mL/min)
Without reperfusion therapy
39. Key points
- Loading dose for all P2Y12 inhibitors is recommended (Class I-A)
- 600 mg loading recommended for clopidogrel
- Limitations imposed on prasugrel
- Issue of compliance posed against ticagrelor
40. Key points
Enoxaparin
-An additional dose of 0.3 mg/kg IV enoxaparin should be
administered at the time of PCI to patients who have received fewer
than 2 therapeutic subcutaneous doses (eg, 1 mg/kg) or received the
last subcutaneous enoxaparin dose 8 to 12 hours before PCI. (Class
I-B)
-Performance of PCI with enoxaparin may be reasonable in patients
either treated with ““““upstream”””” subcutaneous enoxaparin for
UA/NSTEMI or who have not received prior antithrombin therapy and
are administered IV enoxaparin at the time of PCI. (Class IIb-B)
-UFH should not be given to patients already receiving therapeutic
subcutaneous enoxaparin. (Class III-B: HARM)
Fondaparinux
-Fondaparinux should not be used as the sole anticoagulant to
support PCI. An additional anticoagulant with anti-IIa activity should
be administered because of the risk of catheter thrombosis. (Class
III-C: HARM)
41. Enoxaparin Proven Across
the ACS Spectrum
Conservative UA/NSTEMI
* TESMA 1997
High risk UA/STEMI
* A TO Z 2004
High risk UA/NSTEMI + early invasive (PCI)
* SYNERGY 2004
Conservative STEMI
* EXTRACT TIMI25 2005
STEMI + Elective PCI
* STEEPLE 2006
STEMI + Primary PCI
* ATOLL 2010