This randomized controlled trial investigated the effects of long-term simvastatin therapy in reducing mortality and coronary events in 4,444 patients with coronary artery disease. Patients received either simvastatin 20-40 mg/day or placebo. The study found that simvastatin reduced total mortality by 30%, coronary mortality by 42%, and major coronary events such as heart attack by 34% compared to placebo. Simvastatin also reduced the need for procedures like angioplasty or bypass surgery by 37% and improved long-term survival free from cardiovascular events by 26%. Simvastatin significantly lowered LDL cholesterol and total cholesterol levels.
This document is the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. It was written by a committee of experts and provides recommendations to reduce the risk of atherosclerotic cardiovascular disease through cholesterol management. The guideline covers topics such as measurements of LDL-C and other lipids, therapeutic lifestyle changes, lipid-lowering drugs including statins, and recommendations for different patient groups including those with secondary prevention of ASCVD or severe hypercholesterolemia.
The SUSTAIN-6 trial evaluated the cardiovascular safety of the GLP-1 receptor agonist semaglutide compared to placebo in patients with type 2 diabetes at high risk of cardiovascular events. Over 3,000 patients were followed for a median of 2.1 years. The trial found that semaglutide was noninferior to placebo with respect to cardiovascular safety and reduced the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke by 26% compared to placebo. Semaglutide also significantly reduced HbA1c, body weight, and systolic blood pressure.
#flozins
🫀DAPA 🆚placebo in HFpEF
Now we have a positive trial!
⬇️18% in CV☠️ death or
worsening HF among LVEF>40%
⬇️ 21%heart failure
💥Results same for LVEF> 60% 🆚LVEF<60%
1) Several early trials evaluated lipid lowering drugs such as mevastatin and lovastatin, which were isolated from fungi and shown to inhibit HMG CoA reductase. However, mevastatin was not marketed due to toxicity in dogs. Lovastatin was first marketed as Mevacor in 1987.
2) Large primary prevention trials such as WOSCOPS, AFCAPS/TexCAPS, CARDS and JUPITER demonstrated significant reductions in cardiovascular events with statin therapy compared to placebo in various populations with and without known heart disease.
3) Secondary prevention trials in patients with stable CAD such as 4S, CARE, LIPID and TNT showed that statin therapy reduces
Telmisartan is an angiotensin II receptor antagonist used to treat hypertension and lower blood pressure. It has an effective dose of 40 mg daily but can be increased to 80 mg daily. It may be combined with diuretics or amlodipine. Telmisartan has strong affinity for AT1 receptors and may have long-lasting blood pressure lowering effects with lower renal excretion. It also has superior cardioprotective properties and can improve insulin resistance in diabetic patients. Common side effects include sinus pain, back pain, and diarrhea.
- Evolocumab is a fully human monoclonal antibody that reduces LDL cholesterol levels by approximately 60% when used in addition to statin therapy.
- A large clinical trial found that evolocumab significantly reduced the risk of cardiovascular events such as heart attack and stroke in patients with cardiovascular disease. Evolocumab lowered LDL cholesterol levels to less than 70 mg/dL in 87% of patients.
- The benefits of evolocumab in reducing cardiovascular outcomes were consistent across various patient groups and baseline LDL cholesterol levels and were maintained over time with treatment. No significant safety issues were identified with evolocumab.
This document is the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. It was written by a committee of experts and provides recommendations to reduce the risk of atherosclerotic cardiovascular disease through cholesterol management. The guideline covers topics such as measurements of LDL-C and other lipids, therapeutic lifestyle changes, lipid-lowering drugs including statins, and recommendations for different patient groups including those with secondary prevention of ASCVD or severe hypercholesterolemia.
The SUSTAIN-6 trial evaluated the cardiovascular safety of the GLP-1 receptor agonist semaglutide compared to placebo in patients with type 2 diabetes at high risk of cardiovascular events. Over 3,000 patients were followed for a median of 2.1 years. The trial found that semaglutide was noninferior to placebo with respect to cardiovascular safety and reduced the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke by 26% compared to placebo. Semaglutide also significantly reduced HbA1c, body weight, and systolic blood pressure.
#flozins
🫀DAPA 🆚placebo in HFpEF
Now we have a positive trial!
⬇️18% in CV☠️ death or
worsening HF among LVEF>40%
⬇️ 21%heart failure
💥Results same for LVEF> 60% 🆚LVEF<60%
1) Several early trials evaluated lipid lowering drugs such as mevastatin and lovastatin, which were isolated from fungi and shown to inhibit HMG CoA reductase. However, mevastatin was not marketed due to toxicity in dogs. Lovastatin was first marketed as Mevacor in 1987.
2) Large primary prevention trials such as WOSCOPS, AFCAPS/TexCAPS, CARDS and JUPITER demonstrated significant reductions in cardiovascular events with statin therapy compared to placebo in various populations with and without known heart disease.
3) Secondary prevention trials in patients with stable CAD such as 4S, CARE, LIPID and TNT showed that statin therapy reduces
Telmisartan is an angiotensin II receptor antagonist used to treat hypertension and lower blood pressure. It has an effective dose of 40 mg daily but can be increased to 80 mg daily. It may be combined with diuretics or amlodipine. Telmisartan has strong affinity for AT1 receptors and may have long-lasting blood pressure lowering effects with lower renal excretion. It also has superior cardioprotective properties and can improve insulin resistance in diabetic patients. Common side effects include sinus pain, back pain, and diarrhea.
- Evolocumab is a fully human monoclonal antibody that reduces LDL cholesterol levels by approximately 60% when used in addition to statin therapy.
- A large clinical trial found that evolocumab significantly reduced the risk of cardiovascular events such as heart attack and stroke in patients with cardiovascular disease. Evolocumab lowered LDL cholesterol levels to less than 70 mg/dL in 87% of patients.
- The benefits of evolocumab in reducing cardiovascular outcomes were consistent across various patient groups and baseline LDL cholesterol levels and were maintained over time with treatment. No significant safety issues were identified with evolocumab.
PCSK9 inhibitors are a new class of drugs for lowering LDL cholesterol by inhibiting the PCSK9 protein. They have been shown to reduce LDL levels by 40-72% as monotherapy or in combination with statins. While clinical trials have demonstrated excellent safety and efficacy, their high cost remains a limitation. Current guidelines recommend PCSK9 inhibitors as a second-line option for patients who cannot reach LDL goals despite maximal statin therapy or who are statin intolerant.
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.
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
This document provides guidelines and recommendations for lipid management:
1. It summarizes the 2013 ACC/AHA guidelines and 2016 ACC expert consensus, focusing on proven therapy rather than arbitrary lipid targets. Lifestyle changes like diet and exercise are encouraged for all.
2. Statins are recommended for four major groups to reduce ASCVD risk. High, moderate, and low intensity statin therapies are defined based on average LDL-C reduction.
3. For patients who are truly statin intolerant or require additional lowering, the document provides guidance on use of non-statin therapies like ezetimibe, basing selection on risk level and comorbidities.
The document provides an overview of the Standards of Care in Diabetes - 2023 guidelines. It includes 17 sections that cover various aspects of diabetes care, treatment goals, and quality evaluation tools. The sections include classification and diagnosis of diabetes, prevention or delay of type 2 diabetes, medical evaluation and assessment of comorbidities, facilitating positive health behaviors, glycemic targets, pharmacologic treatment approaches, management of cardiovascular disease and other complications, and more. The guidelines are intended to provide clinicians, patients, and other stakeholders with an evidence-based framework for diabetes care and management.
1) Statins are highly effective in reducing LDL-C and cardiovascular risk, playing a cornerstone role in lipid management. They work by inhibiting HMG-CoA reductase.
2) Atorvastatin has been extensively studied in large trials and shown to significantly reduce major cardiovascular events when doses are increased from 10 mg to 80 mg.
3) Studies in India found that high dose atorvastatin (80 mg) was well tolerated and more effective at reducing LDL-C and hs-CRP than lower doses in ACS patients. However, many ACS patients in India were not receiving statins as recommended.
Ponencia realizada por el Prof. Alberto Zambon en la segunda sesión de CardioVascular Virtual Topic 2022, titulada Residual cardiovascular risk. What is the role of icosapent ethyl?
Anticoagulation in atrial fibrillationMashiul Alam
This document discusses anticoagulation for atrial fibrillation (AF). It covers the epidemiology and pathophysiology of AF, as well as the risks of stroke. It describes scoring systems like CHADS2 and CHA2DS2-VASc that are used to determine stroke risk and recommend antithrombotic therapy. Newer oral anticoagulants like apixaban, dabigatran and rivaroxaban are discussed and compared to warfarin. Guidelines for anticoagulation in various clinical scenarios involving AF are provided, such as with stable ischemic heart disease, intracoronary stents, acute coronary syndrome, and cardioversion.
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.
SGLT-2 inhibitors have shown promising cardiovascular and renal benefits:
1) Trials have found SGLT-2 inhibitors reduce the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease, as well as reducing heart failure hospitalizations in those with diabetes and cardiovascular risk factors.
2) Studies also show SGLT-2 inhibitors improve outcomes for patients with heart failure with reduced ejection fraction, reducing rates of heart failure hospitalization and mortality regardless of diabetes status or background heart failure therapies.
3) SGLT-2 inhibitors were also found to reduce the risk of renal death or progression to end-stage kidney disease in patients with type 2 diabetes and macroalbuminuria.
This document provides information on hyperlipidemia including the transport and metabolism of lipids, causes of hyperlipidemia, screening guidelines, treatment goals, and treatment options. It describes how chylomicrons transport dietary fats through the lymphatic system to the liver where they are converted to LDL, which transports cholesterol to cells. HDL transports excess cholesterol from cells back to the liver. It lists various genetic and acquired causes of elevated lipids and guidelines for screening and treatment targets based on cardiovascular risk factors. Lifestyle modifications and drug classes used to treat hyperlipidemia are also summarized.
Angiotensin receptor-neprilysin inhibition(ARNI):The New Fronteir ?drucsamal
1) LCZ696, which inhibits neprilysin and blocks angiotensin receptors, reduced the risks of cardiovascular death and heart failure hospitalization compared to enalapril in patients with heart failure with reduced ejection fraction.
2) LCZ696 also reduced the risks of all-cause mortality and worsened heart failure compared to enalapril.
3) Patients receiving LCZ696 experienced greater improvements in quality of life and functional status measures compared to those receiving enalapril.
This document summarizes the history and mechanisms of action of SGLT2 inhibitors, a class of diabetes medications. Key points include:
- SGLT2 inhibitors work by blocking glucose reabsorption in the kidney, inducing glucosuria and lowering blood glucose levels.
- Several large clinical trials demonstrated SGLT2 inhibitors effectively lower HbA1c and blood glucose with a low risk of hypoglycemia compared to other diabetes medications.
- Beyond glycemic control, SGLT2 inhibitors provide additional benefits like weight loss, blood pressure reduction, and improved cardiac outcomes.
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 recently had an acute coronary syndrome.
2) Patients receiving ezetimibe/simvastatin had a lower rate of major cardiovascular events (32.7% vs 34.7%) over a median follow-up of 6 years, demonstrating the additional clinical benefit of further lowering LDL-C with ezetimibe.
3) Ezetimibe/simvastatin also reduced the rate of the composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to
This document summarizes a thesis on PCSK9 inhibitory drugs as a potential new treatment for patients with hypercholesterolemia. It begins with an introduction to cholesterol and hypercholesterolemia. It then discusses current treatments like statins, the role of LDL receptors and how PCSK9 inhibits their function, raising LDL levels. The document outlines clinical trials of PCSK9 inhibitors that dramatically lower LDL levels with minimal side effects. It concludes that PCSK9 inhibitors show promise as a new treatment that can improve outcomes for patients with hypercholesterolemia.
The Role of SGLT 2 Inhibitors and GLP 1 Receptor Agonists and DPP 4 InhibitorsPHAM HUU THAI
This document discusses the role of SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors in managing type 2 diabetes. It provides background on the pathophysiology and progression of type 2 diabetes and limitations of older drug classes. It then describes the mechanisms and roles of the newer drug classes like SGLT-2 inhibitors in promoting urinary glucose excretion and GLP-1 agonists and DPP-4 inhibitors in augmenting the body's own incretin response. It also discusses ongoing cardiovascular outcome trials and FDA approvals of these newer agents.
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment optionsahvc0858
Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Chan Wan Xian
Cardiologist, Echocardiologist
Heart Failure Intensivist
Asian Heart & Vascular Centre
www.ahvc.com.sg
This document discusses lipid lowering drugs and the management of hyperlipidemia. It covers the pathways of lipid transport and inherited forms of hyperlipidemia. It discusses statins as the primary drug treatment and their mechanisms of action and clinical trial results demonstrating their efficacy in reducing cardiovascular events. It also briefly discusses other lipid lowering agents such as fibrates, nicotinic acid, and resins.
The document discusses treatment of hypertensive patients who also have dyslipidemia. It describes a case study of a 57-year-old man with prior myocardial infarction, uncontrolled hypertension, and elevated LDL cholesterol. Clinical trials show that intensive statin therapy to achieve lower LDL levels reduces cardiovascular risks more than moderate statin therapy. The Heart Protection Study also found that simvastatin reduced cardiovascular events in high-risk patients, regardless of baseline LDL level.
1. Chronic kidney disease (CKD) is associated with a significantly higher risk of cardiovascular disease (CVD) mortality. CVD is the leading cause of death in CKD patients.
2. Lipid abnormalities are common in CKD and contribute to increased CVD risk. Statins are generally safe and effective for lowering lipid levels in CKD, and may help slow CKD progression as well as reduce proteinuria.
3. Other lipid lowering agents like fibrates and omega-3 fatty acids may benefit CKD patients, especially those with high triglyceride levels, but require monitoring for side effects. Multiple clinical trials are exploring optimal treatment strategies for dyslipidemia in CKD.
1. Chronic kidney disease (CKD) is associated with a significantly higher risk of cardiovascular disease (CVD) mortality. CVD is the leading cause of death in CKD patients.
2. Lipid abnormalities are common in CKD and contribute to increased CVD risk. Statins are generally safe and effective for lowering lipid levels in CKD, and may help slow CKD progression as well as reduce proteinuria.
3. Other lipid lowering agents like fibrates and omega-3 fatty acids may benefit CKD patients, especially those with high triglyceride levels, but require monitoring for side effects. New drugs continue to be studied to provide more comprehensive cardioprotection for those with CKD.
PCSK9 inhibitors are a new class of drugs for lowering LDL cholesterol by inhibiting the PCSK9 protein. They have been shown to reduce LDL levels by 40-72% as monotherapy or in combination with statins. While clinical trials have demonstrated excellent safety and efficacy, their high cost remains a limitation. Current guidelines recommend PCSK9 inhibitors as a second-line option for patients who cannot reach LDL goals despite maximal statin therapy or who are statin intolerant.
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.
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
This document provides guidelines and recommendations for lipid management:
1. It summarizes the 2013 ACC/AHA guidelines and 2016 ACC expert consensus, focusing on proven therapy rather than arbitrary lipid targets. Lifestyle changes like diet and exercise are encouraged for all.
2. Statins are recommended for four major groups to reduce ASCVD risk. High, moderate, and low intensity statin therapies are defined based on average LDL-C reduction.
3. For patients who are truly statin intolerant or require additional lowering, the document provides guidance on use of non-statin therapies like ezetimibe, basing selection on risk level and comorbidities.
The document provides an overview of the Standards of Care in Diabetes - 2023 guidelines. It includes 17 sections that cover various aspects of diabetes care, treatment goals, and quality evaluation tools. The sections include classification and diagnosis of diabetes, prevention or delay of type 2 diabetes, medical evaluation and assessment of comorbidities, facilitating positive health behaviors, glycemic targets, pharmacologic treatment approaches, management of cardiovascular disease and other complications, and more. The guidelines are intended to provide clinicians, patients, and other stakeholders with an evidence-based framework for diabetes care and management.
1) Statins are highly effective in reducing LDL-C and cardiovascular risk, playing a cornerstone role in lipid management. They work by inhibiting HMG-CoA reductase.
2) Atorvastatin has been extensively studied in large trials and shown to significantly reduce major cardiovascular events when doses are increased from 10 mg to 80 mg.
3) Studies in India found that high dose atorvastatin (80 mg) was well tolerated and more effective at reducing LDL-C and hs-CRP than lower doses in ACS patients. However, many ACS patients in India were not receiving statins as recommended.
Ponencia realizada por el Prof. Alberto Zambon en la segunda sesión de CardioVascular Virtual Topic 2022, titulada Residual cardiovascular risk. What is the role of icosapent ethyl?
Anticoagulation in atrial fibrillationMashiul Alam
This document discusses anticoagulation for atrial fibrillation (AF). It covers the epidemiology and pathophysiology of AF, as well as the risks of stroke. It describes scoring systems like CHADS2 and CHA2DS2-VASc that are used to determine stroke risk and recommend antithrombotic therapy. Newer oral anticoagulants like apixaban, dabigatran and rivaroxaban are discussed and compared to warfarin. Guidelines for anticoagulation in various clinical scenarios involving AF are provided, such as with stable ischemic heart disease, intracoronary stents, acute coronary syndrome, and cardioversion.
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.
SGLT-2 inhibitors have shown promising cardiovascular and renal benefits:
1) Trials have found SGLT-2 inhibitors reduce the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease, as well as reducing heart failure hospitalizations in those with diabetes and cardiovascular risk factors.
2) Studies also show SGLT-2 inhibitors improve outcomes for patients with heart failure with reduced ejection fraction, reducing rates of heart failure hospitalization and mortality regardless of diabetes status or background heart failure therapies.
3) SGLT-2 inhibitors were also found to reduce the risk of renal death or progression to end-stage kidney disease in patients with type 2 diabetes and macroalbuminuria.
This document provides information on hyperlipidemia including the transport and metabolism of lipids, causes of hyperlipidemia, screening guidelines, treatment goals, and treatment options. It describes how chylomicrons transport dietary fats through the lymphatic system to the liver where they are converted to LDL, which transports cholesterol to cells. HDL transports excess cholesterol from cells back to the liver. It lists various genetic and acquired causes of elevated lipids and guidelines for screening and treatment targets based on cardiovascular risk factors. Lifestyle modifications and drug classes used to treat hyperlipidemia are also summarized.
Angiotensin receptor-neprilysin inhibition(ARNI):The New Fronteir ?drucsamal
1) LCZ696, which inhibits neprilysin and blocks angiotensin receptors, reduced the risks of cardiovascular death and heart failure hospitalization compared to enalapril in patients with heart failure with reduced ejection fraction.
2) LCZ696 also reduced the risks of all-cause mortality and worsened heart failure compared to enalapril.
3) Patients receiving LCZ696 experienced greater improvements in quality of life and functional status measures compared to those receiving enalapril.
This document summarizes the history and mechanisms of action of SGLT2 inhibitors, a class of diabetes medications. Key points include:
- SGLT2 inhibitors work by blocking glucose reabsorption in the kidney, inducing glucosuria and lowering blood glucose levels.
- Several large clinical trials demonstrated SGLT2 inhibitors effectively lower HbA1c and blood glucose with a low risk of hypoglycemia compared to other diabetes medications.
- Beyond glycemic control, SGLT2 inhibitors provide additional benefits like weight loss, blood pressure reduction, and improved cardiac outcomes.
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 recently had an acute coronary syndrome.
2) Patients receiving ezetimibe/simvastatin had a lower rate of major cardiovascular events (32.7% vs 34.7%) over a median follow-up of 6 years, demonstrating the additional clinical benefit of further lowering LDL-C with ezetimibe.
3) Ezetimibe/simvastatin also reduced the rate of the composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to
This document summarizes a thesis on PCSK9 inhibitory drugs as a potential new treatment for patients with hypercholesterolemia. It begins with an introduction to cholesterol and hypercholesterolemia. It then discusses current treatments like statins, the role of LDL receptors and how PCSK9 inhibits their function, raising LDL levels. The document outlines clinical trials of PCSK9 inhibitors that dramatically lower LDL levels with minimal side effects. It concludes that PCSK9 inhibitors show promise as a new treatment that can improve outcomes for patients with hypercholesterolemia.
The Role of SGLT 2 Inhibitors and GLP 1 Receptor Agonists and DPP 4 InhibitorsPHAM HUU THAI
This document discusses the role of SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors in managing type 2 diabetes. It provides background on the pathophysiology and progression of type 2 diabetes and limitations of older drug classes. It then describes the mechanisms and roles of the newer drug classes like SGLT-2 inhibitors in promoting urinary glucose excretion and GLP-1 agonists and DPP-4 inhibitors in augmenting the body's own incretin response. It also discusses ongoing cardiovascular outcome trials and FDA approvals of these newer agents.
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment optionsahvc0858
Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Chan Wan Xian
Cardiologist, Echocardiologist
Heart Failure Intensivist
Asian Heart & Vascular Centre
www.ahvc.com.sg
This document discusses lipid lowering drugs and the management of hyperlipidemia. It covers the pathways of lipid transport and inherited forms of hyperlipidemia. It discusses statins as the primary drug treatment and their mechanisms of action and clinical trial results demonstrating their efficacy in reducing cardiovascular events. It also briefly discusses other lipid lowering agents such as fibrates, nicotinic acid, and resins.
The document discusses treatment of hypertensive patients who also have dyslipidemia. It describes a case study of a 57-year-old man with prior myocardial infarction, uncontrolled hypertension, and elevated LDL cholesterol. Clinical trials show that intensive statin therapy to achieve lower LDL levels reduces cardiovascular risks more than moderate statin therapy. The Heart Protection Study also found that simvastatin reduced cardiovascular events in high-risk patients, regardless of baseline LDL level.
1. Chronic kidney disease (CKD) is associated with a significantly higher risk of cardiovascular disease (CVD) mortality. CVD is the leading cause of death in CKD patients.
2. Lipid abnormalities are common in CKD and contribute to increased CVD risk. Statins are generally safe and effective for lowering lipid levels in CKD, and may help slow CKD progression as well as reduce proteinuria.
3. Other lipid lowering agents like fibrates and omega-3 fatty acids may benefit CKD patients, especially those with high triglyceride levels, but require monitoring for side effects. Multiple clinical trials are exploring optimal treatment strategies for dyslipidemia in CKD.
1. Chronic kidney disease (CKD) is associated with a significantly higher risk of cardiovascular disease (CVD) mortality. CVD is the leading cause of death in CKD patients.
2. Lipid abnormalities are common in CKD and contribute to increased CVD risk. Statins are generally safe and effective for lowering lipid levels in CKD, and may help slow CKD progression as well as reduce proteinuria.
3. Other lipid lowering agents like fibrates and omega-3 fatty acids may benefit CKD patients, especially those with high triglyceride levels, but require monitoring for side effects. New drugs continue to be studied to provide more comprehensive cardioprotection for those with CKD.
The document summarizes key findings from the LIFE study, a large clinical trial that compared losartan to atenolol for reducing cardiovascular risk in hypertensive patients with left ventricular hypertrophy. The main findings were:
1) Losartan reduced the primary composite endpoint of cardiovascular death, stroke or myocardial infarction by 13% compared to atenolol, with comparable blood pressure reduction in both groups.
2) Secondary analyses found losartan reduced risks for several individual components of the primary endpoint including stroke and heart failure hospitalizations.
3) Losartan provided greater regression of left ventricular hypertrophy compared to atenolol based on electrocardiogram and echocardiogram assessments
1) Contrast induced nephropathy (CIN) is a serious complication of cardiac procedures and can lead to acute renal failure, increased mortality, and long term renal dysfunction.
2) Many risk factors increase a patient's likelihood of developing CIN, including pre-existing renal insufficiency, diabetes, older age, hypotension, and the volume and osmolality of contrast agent used.
3) Preventive strategies aim to reduce renal ischemia and oxidative stress through hydration with intravenous fluids like sodium bicarbonate or sodium chloride, as well as pharmacological interventions including N-acetylcysteine. Larger clinical trials are still needed to determine the most effective prevention protocols.
The success of neurohormonal blockade: looking back – looking forward: Beta-b...drucsamal
- The document summarizes the history of beta-blocker treatment for heart failure, from early studies in the 1970s showing potential benefits to large randomized controlled trials in the 1990s and 2000s firmly establishing mortality reduction.
- Key trials included MDC (1993) showing reduced mortality and heart transplantation, CIBIS-II (1999) showing reduced mortality with bisoprolol, MERIT-HF (1999) showing reduced mortality with metoprolol CR/XL, and COPERNICUS (2001) showing reduced mortality, hospitalizations, and worsening heart failure with carvedilol.
- Meta-analyses demonstrated a consistent mortality reduction of approximately 35% associated with beta-blocker use in
Mr. B is a 68-year-old man who presented with acute chest pain and was found to have ST depression on ECG and elevated troponin. His TIMI risk score was 4, indicating a 20% risk of adverse events in the next 14 days. His GRACE risk score was 144, indicating risks of 3% in-hospital death or 17% in-hospital death or MI. Guidelines recommend an invasive strategy for patients like Mr. B with NSTEMI based on randomized controlled trials showing reduced rates of death and MI compared to conservative management, especially in higher risk patients. Optimal timing of angiography is within 24 hours of presentation based on trials such as TIMACS and ISAR-CO
This study evaluated the impact of low circulating levels of the thyroid hormone triiodothyronine (T3) on prognosis in 573 patients with heart disease. The study found that patients with low T3 levels had higher rates of death and cardiac death at 31 days and 12 months. Low T3 was an independent predictor of mortality in multivariate analysis and correlated with shorter survival times. The results suggest low T3 is directly implicated in the progression of cardiac disease and prognosis, rather than just a marker of poor prognosis. Further research is needed to determine if low T3 contributes directly to impaired cardiac function.
This case report describes a 44-year-old man who developed methemoglobinemia during a transesophageal echocardiogram (TEE). He presented with right foot pain and was found to have gas in the soft tissue on x-ray. After his transmetatarsal amputation, he had persistent fevers and a TEE was ordered. During the TEE, after receiving benzocaine spray and sedation, his oxygen saturation dropped and he became cyanotic. He was treated for narcotic/benzocaine induced respiratory depression with flumazenil and naloxone but his condition did not improve. He was found to have a methemoglobin level of 31% and responded well to meth
The document discusses strategies for screening and preventing heart attacks. It argues that current risk factor-based approaches are inadequate due to high prevalence of risk factors and low predictive value. It proposes using noninvasive tests like coronary calcium scoring and carotid intima-media thickness measurements as the initial screening step. The document also outlines future directions for the SHAPE initiative, including repeated screening with trajectory tests and the potential roles of genetic and functional testing. The overall goal is to establish standardized screening for heart attacks in a similar manner to screening guidelines for cancers.
This document discusses the cardiorenal syndrome (CRS), which refers to the bidirectional relationship between heart and kidney diseases where dysfunction in one organ can induce dysfunction in the other. It describes the five subtypes of CRS and risk factors. It also discusses biomarkers that may help earlier diagnosis and management strategies including avoiding nephrotoxic drugs and maintaining euvolaemia. Contrast-induced nephropathy is also summarized, including risk factors, proposed pathogenesis, and strategies to reduce risk such as hydration protocols and pharmacological interventions.
- Liver resection (LR) and liver transplantation (LTx) are two treatment options for hepatocellular carcinoma (HCC). This study compares outcomes of 282 patients receiving LR and 187 receiving LTx.
- Patients who received LTx had a higher perioperative mortality rate compared to LR patients (18.1% vs 4.5%), mainly due to sepsis, multiple organ failure, and vascular complications. Late mortality was higher in LR patients and mainly due to tumor recurrence.
- Recurrence rates were significantly higher after LR (47.4% vs 9%), and survival after recurrence was also lower with LR. Factors associated with recurrence and survival included tumor characteristics such as α-fetoprotein levels,
The document discusses the role of imaging coronary calcium using electron beam tomography (EBT) scans. It provides evidence that EBT calcium scores are strongly correlated with the amount of atherosclerotic plaque buildup. It also shows that higher EBT calcium scores are associated with significantly higher risks of future cardiovascular events, with risk increasing progressively as calcium scores rise. EBT calcium scoring more accurately predicts cardiovascular risk than traditional risk models like Framingham and can reclassify a person's risk level in about half of intermediate-risk individuals.
This document discusses several studies related to atrial fibrillation and anticoagulation therapy:
1. A study of over 13,000 AF patients found higher baseline BNP levels were associated with increased risk of AF progression and major adverse cardiovascular events.
2. A direct comparison of dabigatran, rivaroxaban, and apixaban found apixaban and rivaroxaban had comparable safety and effectiveness to dabigatran in real-world practice, though major bleeding occurred more frequently with apixaban and rivaroxaban.
3. A study of NOAC safety in obese patients undergoing electrical cardioversion found no incidents of stroke, suggesting NOACs may be safe
This document lists potential conflicts of interest for the author, including honoraria from several pharmaceutical companies (ZS Pharma, Relypsa, Alexis) and speaker bureaus (Astute). It also notes that the author is a partner in multiple dialysis units and a vascular access center owned by Davita.
1) Diabetes is now the leading cause of end-stage renal disease (ESRD) in the United States, surpassing other causes like hypertension.
2) Diabetic nephropathy follows a typical progression from increased kidney function to protein in the urine to declining kidney function over many years.
3) Tight control of blood pressure, blood sugar, and use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can slow the progression of diabetic nephropathy.
Pioglitazone and rimonabant are emerging atherosclerosis drugs that show promise. Pioglitazone reduces neointima formation after coronary stenting and decreases endpoints in diabetes patients. Rimonabant reduces weight, insulin resistance, and metabolic syndrome risk factors, and increases smoking cessation rates. Lp-PLA2 inhibitors, like SB-480848, decrease plasma and plaque Lp-PLA2 activity levels and may represent a link between lipid metabolism and inflammation.
The REACH Registry study found that beta-blockers do not reduce the risk of cardiovascular events like death, heart attack, or stroke in stable outpatients with or without coronary artery disease. However, beta-blockers were found to lower the risk of secondary outcomes in patients who had a heart attack within the past year. The study followed over 45,000 patients for 4 years on average and compared outcomes in patients taking beta-blockers to those not taking them.
2006 orvieto, workshop interattivo. la terapia elettrica dello scompenso card...Centro Diagnostico Nardi
This document discusses cardiac resynchronization therapy (CRT). It begins by explaining how heart failure can cause delayed and disorganized electrical activation and contraction of the ventricles. CRT aims to resynchronize ventricular activation and contraction by pacing both ventricles simultaneously. Studies presented show that CRT acutely improves hemodynamics, reduces mitral regurgitation, and increases exercise capacity. Long-term trials found that CRT improves symptoms and quality of life, reverses ventricular remodeling, and reduces the combined risk of death and heart failure hospitalizations compared to medical therapy alone in patients with moderate to severe heart failure, left ventricular dysfunction, and a prolonged QRS duration.
Similar to Scandinavian Simvastatin Survival Study (4S) (20)
2. ObjectivesObjectives
• Randomized trial of cholesterol lowering inRandomized trial of cholesterol lowering in
4,444 patients with CAD: The Scandinavian4,444 patients with CAD: The Scandinavian
Simvastatin Survival Study.Simvastatin Survival Study.
• To investigate whether long-term simvastatinTo investigate whether long-term simvastatin
therapy reduces total mortality and coronarytherapy reduces total mortality and coronary
events in post-MI and or angina patients withevents in post-MI and or angina patients with
total cholesterol between 212-309 mg/dL.total cholesterol between 212-309 mg/dL.
The Lancet, Vol 344, November 19, 1994The Lancet, Vol 344, November 19, 1994
3. DesignDesign
• Double-blind, randomized, placebo-controlledDouble-blind, randomized, placebo-controlled
− 94 centers in 5 countries94 centers in 5 countries
− 4,444 men and women 35 to 70 years of age4,444 men and women 35 to 70 years of age
− Inclusion Criteria: Prior MI and/or anginaInclusion Criteria: Prior MI and/or angina
pectorispectoris
− Total Cholesterol:Total Cholesterol: 212-309 mg/dL212-309 mg/dL
− Follow-up: until 440 deaths occurred.Follow-up: until 440 deaths occurred.
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4. EndpointsEndpoints
• Primary:Primary: Total MortalityTotal Mortality
• Secondary:Secondary: Major adverse coronary eventsMajor adverse coronary events
• Coronary deathsCoronary deaths
• Nonfatal MIsNonfatal MIs
• Tertiary:Tertiary: Effect on:Effect on:
• PTCA/CABG proceduresPTCA/CABG procedures
• Survival without atheroscleroticSurvival without atherosclerotic
event (event-free survival)event (event-free survival)
• Any coronary eventAny coronary event
• Non-MI acute CHD eventsNon-MI acute CHD events
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5. Treatment ScheduleTreatment Schedule
Simvastatin 20 mg/day orSimvastatin 20 mg/day or
matching placebomatching placebo
Increased to 40 mg/day if TC exceededIncreased to 40 mg/day if TC exceeded
200 mg/dL200 mg/dL
Study Goal:Study Goal:
TC 116-200 mg/dLTC 116-200 mg/dL
The Lancet, Vol 344, November 19, 1994The Lancet, Vol 344, November 19, 1994
6. Dosage TitrationDosage Titration
The Lancet, Vol 344, November 19, 1994The Lancet, Vol 344, November 19, 1994
2 0 m g / d a y
6 3 %
4 0 m g / d a y
3 7 %
2 , 2 2 1
s i m v a s t a t i n 2 0 m g / d a y
2 , 2 2 3
p l a c e b o p a t i e n t s
4 , 4 4 4
r a n d o m i z e d p a t i e n t s
7. Baseline CharacteristicsBaseline Characteristics
M e a n a g e (y e a rs )-m e n 5 8 .1 5 8 .2
M e a n a g e (y e a rs )-w o m e n 6 0 .5 6 0 .5
A n g in a o n ly 2 1 % 2 1 %
M I o n ly 6 2 % 6 3 %
B o th a n g in a a n d M I 1 7 % 1 6 %
H y p e rte n s io n 2 6 % 2 6 %
S m o k e r 2 7 % 2 4 %
T C (m g /d L ) 2 6 0 2 6 0
L D L (m g /d L ) 1 8 0 1 8 0
PlaceboPlacebo
(n=2223)(n=2223)
SimvastatinSimvastatin
(n=2221)(n=2221)
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8. Primary Endpoint: Overall SurvivalPrimary Endpoint: Overall Survival
80
82
84
86
88
90
92
94
96
98
100
0 1 2 3 4 5 6
Simvastatin
Placebo
Years since randomizationYears since randomization
%Surviving%Surviving
30%
risk reduction
p = 0.0003
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10. Cardiovascular MortalityCardiovascular Mortality
Coronary 189 111 42%
-Definite acute MI 63 30
-Probable acute MI 5 5
-Sudden death 78 46
-Other 43 30
Cerebrovascular 12 14
Other cardiovascular 6 11
All cardiovascularAll cardiovascular 207207 136136 35%35%
Cause of deathCause of death
PlaceboPlacebo
(n=2223)(n=2223)
SimvastatinSimvastatin
(n=2221)(n=2221)
RiskRisk
ReductionReduction
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11. All Cause MortalityAll Cause Mortality
C o ro n a ry 1 8 9 1 1 1 4 2 %
N o n c o ro n a ry
v a s c u la r
1 8 2 5
N o n -c a rd io v a s c u la r 4 9 4 6
-C a n c e r 3 5 3 3
-S u ic id e 4 5
-T ra u m a 3 1
-O th e r 7 7
Cause of deathCause of death
PlaceboPlacebo
(n=2223)(n=2223)
SimvastatinSimvastatin
(n=2221)(n=2221)
RiskRisk
ReductionReduction
All DeathsAll Deaths 256256 182182 30%30%
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12. Causes of DeathCauses of Death
111
1314
3335
2518
189
Placebo Simvastatin
Other Cancer Other Cardiovascular Coronary
11.5%11.5%
8.2%8.2%
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13. 60
70
80
90
100
0 1 2 3 4 5 6
Simvastatin
Placebo
Coronary Death and Nonfatal MICoronary Death and Nonfatal MI
Years since randomizationYears since randomization
%ofpatientswithoutevents%ofpatientswithoutevents
34%34%
Risk ReductionRisk Reduction
p<0.00001p<0.00001
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14. Need for PTCA/CABGNeed for PTCA/CABG
70
75
80
85
90
95
100
0 1 2 3 4 5 6
Simvastatin
Placebo
Years since randomizationYears since randomization
%ofpatientswithout%ofpatientswithout
PTCA/CABGPTCA/CABG
37%37%
RiskRisk
ReductionReduction
p<0.00001p<0.00001
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15. Endpoint by GenderEndpoint by Gender
12.8
6
29.4
21.7
8.5
6.6
20.5
14.5
0
5
10
15
20
25
30
35
Male Female Male Female
Total Mortality Major Coronary Events
%Incidence
Placebo
Simvastatin
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16. Endpoints by AgeEndpoints by Age
8.1
14.8
27.6 28.3
5.2
11
17.6
21
0
5
10
15
20
25
30
35
<60 yrs >60 yrs <60 yrs >60 yrs
Total Mortality Major Coronary Events
%Incidence
Placebo
Simvastatin
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17. Event-Free SurvivalEvent-Free Survival
50
60
70
80
90
100
110
0 1 2 3 4 5 6
Simvastatin
Placebo
Survival without atherosclerotic eventSurvival without atherosclerotic event
Years since randomizationYears since randomization
%ofpatientsalivewithout%ofpatientsalivewithout
anatheroscleroticeventanatheroscleroticevent
26%26%
RiskRisk
ReductionReduction
p<0.00001p<0.00001
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19. Changes in Lipoprotein LevelsChanges in Lipoprotein Levels
-25
-35
8
-10
1 1
7 7
-50
-40
-30
-20
-10
0
10
20
TC LDL HDL TGs
%Change
Simvastatin
Placebo
Simvastatin vs placebo, at study endSimvastatin vs placebo, at study end
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20. Safety ProfileSafety Profile
N o n fa ta l c a n c e r 6 1 5 7
A S T 3 x U L N 2 3 2 0
A L T 3 x U L N 3 3 4 9
C P K 1 0 x U L N 1 6
R h a b d o m y o lis is 0 1
# of patients with# of patients with
PlaceboPlacebo
(n=2223)(n=2223)
SimvastatinSimvastatin
(n=2221)(n=2221)
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21. Summary of Key End-point ResultsSummary of Key End-point Results
Simvastatin BetterSimvastatin Better
Total mortalityTotal mortality
CAD mortalityCAD mortality
Major coronaryMajor coronary
eventsevents
PTCA/CABGPTCA/CABG
Event-freeEvent-free
survivalsurvival
0.20.2 0.40.4 0.60.6 0.80.8 1.01.0 1.21.2
p=0.0003p=0.0003
p<0.00001p<0.00001
p<0.00001p<0.00001
p<0.00001p<0.00001
p<0.00001p<0.00001
Relative risk (95% CI)Relative risk (95% CI)
Reduced Increased
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Placebo BetterPlacebo Better
22. • Overall Riskof Death 30% Only trial to date with cholesterol lowering agent to definitively
showreduction in total or coronary mortality
• Riskof CoronaryDeath 42% Cardiovascular disease is theworld’s leading cause of death
accounting for one-fourth of all deaths
• Riskof MajorCoronary
Events 34%
Includes death from coronary disease and non-fatal heart attacks
• Riskof Revascularization
Procedures 37%
Includes percutaneous coronary angioplasties (PTCA) andcoronary
artery bypass grafts (CABG).
• Event-freeSurvival 26% Finished the study without suffering any coronary events orother
atheroscleotic events such as stroke
• LDL Cholesterol
38%*
Human atherosclerotic plaques primarily contain LDL cholesterol
• HDL Cholesterol
8%*
Highconcentrations of HDL may protect against coronary heart
disease.
• Total Cholesterol
28%*
Simvastatin is the most effective cholesterol-lowering agentavailable
at recommended doses
EndpointEndpoint CommentComment
Relative RiskRelative Risk
* After 6 weeks of treatment with 20mg* After 6 weeks of treatment with 20mg
23. 4S Summary4S Summary
• Improved survivalImproved survival
• Reduced coronary mortalityReduced coronary mortality
• Reduced major coronary eventsReduced major coronary events
• Reduced need for PTCA and CABGReduced need for PTCA and CABG
Improved event-free survivalImproved event-free survival
• Substantially reduced TC and LDLSubstantially reduced TC and LDL
Compared with Placebo, Simvastatin:Compared with Placebo, Simvastatin:
The Lancet, Vol 344, November 19, 1994The Lancet, Vol 344, November 19, 1994