This randomized controlled trial evaluated the effect of dapagliflozin versus placebo on worsening heart failure or cardiovascular death in patients with heart failure and an ejection fraction above 40%. It found that dapagliflozin reduced the risk of the primary composite outcome compared to placebo, both in the overall population and in those with an ejection fraction under 60%. Dapagliflozin also reduced the risk of worsening heart failure alone. There was no significant difference in cardiovascular death or adverse events between the groups. The authors concluded that dapagliflozin lowered the risk of worsening heart failure or cardiovascular death regardless of ejection fraction.
The study evaluated the efficacy and safety of rivaroxaban compared to vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation (RHD-AF). Over 4565 patients from 24 countries were randomized to receive either rivaroxaban 20 mg daily or a vitamin K antagonist such as warfarin, with a mean follow up of 3.1 years. The primary outcome occurred in 560 patients (8.21% per year) in the rivaroxaban group and 446 patients (6.49% per year) in the vitamin K antagonist group, showing rivaroxaban to be less effective with a hazard ratio of 1.25. There were no significant
This document summarizes the cardiovascular risk of patients with type 2 diabetes mellitus (T2DM) in India and the potential benefits of SGLT2 inhibitor treatment. It finds that:
1) The majority of Indian outpatients with T2DM have at least moderate cardiovascular disease (CVD) risk, and over 35% have known CVD.
2) T2DM confers 2-4 times greater CVD risk regardless of duration, and risk increases with longer duration.
3) Empagliflozin treatment consistently reduces the risk of cardiovascular death and heart failure hospitalizations in clinical trials of patients with T2DM and atherosclerotic CVD.
4) Empagliflozin may provide additional benefits
The document discusses the concept of "metabolic memory" where the risks of diabetic complications can persist even after glucose levels have returned to normal. It provides evidence from animal and human studies in the 1980s and 2000s supporting this concept. It then summarizes findings from several major clinical trials that compared intensive glucose control to standard control and found reductions in microvascular and macrovascular outcomes with intensive control, though the benefits took years to emerge after trial completion.
Simposio ALAD Avances en la prevención y el tratamiento de la diabetes tipo 2...rdaragnez
This document summarizes research on diabetes treatment and outcomes from several long-term clinical trials. It finds that intensive glucose control early in type 2 diabetes can significantly reduce cardiovascular and renal complications long-term. However, rapidly lowering glucose in those with existing cardiovascular disease may increase mortality risk. Multifactorial treatment including blood pressure and glucose control provides substantial benefits and is recommended for all type 2 diabetes patients.
This document provides an overview of SGLT2 inhibitors (SGLT2is) for the treatment of heart failure and diabetes. It discusses key considerations for using SGLT2is such as evaluating appropriate patients, monitoring safety parameters like blood pressure and kidney function, and managing SGLT2i-associated euglycemic diabetic ketoacidosis. The document reviews clinical trial data on the benefits of SGLT2is in acute and chronic heart failure. It also presents two case studies on initiating SGLT2is during hospitalization and treating euglycemic ketoacidosis with insulin therapy.
Empagliflozin and Cardiovascular OutcomesUyen Nguyen
1) The EMPA-REG OUTCOME trial evaluated the cardiovascular outcomes of empagliflozin compared to placebo in over 7000 patients with type 2 diabetes at high risk of cardiovascular events.
2) Empagliflozin was found to significantly reduce the risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to placebo.
3) Additional benefits observed with empagliflozin included a significant reduction in all-cause mortality, cardiovascular mortality, and hospitalization for heart failure.
The document provides an overview of congestive heart failure (CHF), including its pathophysiology, diagnosis, classification, and treatment recommendations. It discusses how CHF results from neurohumoral and remodeling processes in the heart. Successful treatment requires addressing the sympathetic nervous system and renin-angiotensin-aldosterone system. Evidence shows that ACE inhibitors, beta-blockers, ARBs, and diuretics can improve outcomes when used appropriately based on the patient's stage of CHF.
The study evaluated the efficacy and safety of rivaroxaban compared to vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation (RHD-AF). Over 4565 patients from 24 countries were randomized to receive either rivaroxaban 20 mg daily or a vitamin K antagonist such as warfarin, with a mean follow up of 3.1 years. The primary outcome occurred in 560 patients (8.21% per year) in the rivaroxaban group and 446 patients (6.49% per year) in the vitamin K antagonist group, showing rivaroxaban to be less effective with a hazard ratio of 1.25. There were no significant
This document summarizes the cardiovascular risk of patients with type 2 diabetes mellitus (T2DM) in India and the potential benefits of SGLT2 inhibitor treatment. It finds that:
1) The majority of Indian outpatients with T2DM have at least moderate cardiovascular disease (CVD) risk, and over 35% have known CVD.
2) T2DM confers 2-4 times greater CVD risk regardless of duration, and risk increases with longer duration.
3) Empagliflozin treatment consistently reduces the risk of cardiovascular death and heart failure hospitalizations in clinical trials of patients with T2DM and atherosclerotic CVD.
4) Empagliflozin may provide additional benefits
The document discusses the concept of "metabolic memory" where the risks of diabetic complications can persist even after glucose levels have returned to normal. It provides evidence from animal and human studies in the 1980s and 2000s supporting this concept. It then summarizes findings from several major clinical trials that compared intensive glucose control to standard control and found reductions in microvascular and macrovascular outcomes with intensive control, though the benefits took years to emerge after trial completion.
Simposio ALAD Avances en la prevención y el tratamiento de la diabetes tipo 2...rdaragnez
This document summarizes research on diabetes treatment and outcomes from several long-term clinical trials. It finds that intensive glucose control early in type 2 diabetes can significantly reduce cardiovascular and renal complications long-term. However, rapidly lowering glucose in those with existing cardiovascular disease may increase mortality risk. Multifactorial treatment including blood pressure and glucose control provides substantial benefits and is recommended for all type 2 diabetes patients.
This document provides an overview of SGLT2 inhibitors (SGLT2is) for the treatment of heart failure and diabetes. It discusses key considerations for using SGLT2is such as evaluating appropriate patients, monitoring safety parameters like blood pressure and kidney function, and managing SGLT2i-associated euglycemic diabetic ketoacidosis. The document reviews clinical trial data on the benefits of SGLT2is in acute and chronic heart failure. It also presents two case studies on initiating SGLT2is during hospitalization and treating euglycemic ketoacidosis with insulin therapy.
Empagliflozin and Cardiovascular OutcomesUyen Nguyen
1) The EMPA-REG OUTCOME trial evaluated the cardiovascular outcomes of empagliflozin compared to placebo in over 7000 patients with type 2 diabetes at high risk of cardiovascular events.
2) Empagliflozin was found to significantly reduce the risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to placebo.
3) Additional benefits observed with empagliflozin included a significant reduction in all-cause mortality, cardiovascular mortality, and hospitalization for heart failure.
The document provides an overview of congestive heart failure (CHF), including its pathophysiology, diagnosis, classification, and treatment recommendations. It discusses how CHF results from neurohumoral and remodeling processes in the heart. Successful treatment requires addressing the sympathetic nervous system and renin-angiotensin-aldosterone system. Evidence shows that ACE inhibitors, beta-blockers, ARBs, and diuretics can improve outcomes when used appropriately based on the patient's stage of CHF.
The FIGARO-DKD trial evaluated the efficacy and safety of finerenone in reducing major adverse cardiovascular events in adults with type 2 diabetes and chronic kidney disease. Over 5300 patients were randomized 1:1 to receive finerenone or placebo on top of standard renin-angiotensin-aldosterone system inhibitor therapy. Finerenone showed a statistically significant 18% relative risk reduction in the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure compared to placebo. Hyperkalemia was the most common adverse effect but occurred at a lower rate than other mineralocorticoid receptor antagonists.
The EMPEROR-Reduced Trial found that:
1) Empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure by 25% compared to placebo in patients with heart failure with reduced ejection fraction.
2) It also reduced the risk of total heart failure hospitalizations by 30% and improved kidney outcomes.
3) Empagliflozin was effective in reducing risks in patients with or without diabetes and had an acceptable safety profile.
- A study evaluated the efficacy and safety of alirocumab in adults with homozygous familial hypercholesterolemia.
- 45 patients received alirocumab and 24 received placebo for 78 weeks.
- Alirocumab reduced LDL-C levels by 24.8% compared to placebo and was well tolerated, with adverse events similar between groups.
- Alirocumab provided clinically significant LDL-C lowering in patients with homozygous familial hypercholesterolemia.
This document summarizes key information about chronic kidney disease (CKD) and cardiovascular disease (CVD). It notes that patients with CKD should be considered at the highest risk for CVD. Lower estimated glomerular filtration rate (eGFR) is associated with higher risks of coronary disease and CVD mortality. The risks of all-cause mortality are significantly higher across all levels of eGFR and proteinuria for patients with early diabetic kidney disease compared to those without. Heart failure hospitalization risk increases as kidney function declines. The development of macroalbuminuria in diabetes patients heralds a rapid decline in glomerular filtration rate. Timely protection and maintenance of kidney function can reduce CVD risks.
SGLT2 Inhibitor therapy has opened up an exciting avenue for the Physicians to manage the patients with CKD . The slide set highlights the major trials on the drug showing remarkable benefits.
The DAPA-HF trial found that among patients with heart failure and reduced ejection fraction, those who received the SGLT2 inhibitor dapagliflozin had a lower risk of hospitalization for heart failure or cardiovascular death and better symptom scores compared to placebo, regardless of the presence of diabetes. Dapagliflozin reduced the primary composite outcome of worsening heart failure or cardiovascular death across subgroups. It provided cardiovascular benefits in patients without diabetes. Adverse effects were generally uncommon and less frequent with dapagliflozin.
Ueda2015 unmet medical needs in dm dr.lobna el-toonyueda2015
This document discusses current limitations in diabetes management and unmet medical needs. It notes that standard therapeutic approaches often lead to prolonged hyperglycemia before insulin initiation. Combination therapy provides superior glycemic control compared to continued monotherapy. However, as chronic kidney disease progresses, treatment options become increasingly limited. There remains a need for antidiabetic agents that can better preserve beta cell function, address multiple disease mechanisms, aid weight control, and have fewer side effects and safety concerns especially in patients with renal impairment.
Three cases of acute myocardial infarction are presented. All three patients had type 2 diabetes and other cardiovascular risk factors like hypertension and dyslipidemia. They presented with chest pain and ST-segment changes on electrocardiogram. All underwent emergency cardiac catheterization and had stents placed in obstructed coronary arteries. Strict control of blood sugar, blood pressure, and lipids is emphasized going forward to prevent further cardiovascular complications. The role of SGLT2 inhibitors in cardiovascular and renal protection for patients with diabetes is also discussed.
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
The document summarizes evidence from several major studies on glycemic control targets in diabetes:
1. The DCCT found that intensive insulin therapy (HbA1c <6%) significantly reduced microvascular complications compared to standard therapy but was associated with higher risk of hypoglycemia.
2. The UKPDS found no glycemic threshold for reducing complications, and lower HbA1c was associated with lower risk, suggesting targeting normal levels if possible.
3. The ACCORD trial found that an HbA1c goal of <6% increased mortality risk compared to a goal of 7-7.9% without significantly reducing cardiovascular outcomes or microvascular complications.
Individualization of gly
Dabigatran vs warfain Prior to TEE Journal ClubMichael Katz
1) The document summarizes a study comparing the direct thrombin inhibitor dabigatran to warfarin for preventing thromboembolic events after cardioversion for atrial fibrillation.
2) The study found the risk of stroke and major bleeding within 30 days of cardioversion was low and comparable between the two doses of dabigatran tested and warfarin, with or without transesophageal echocardiography guidance.
3) The results suggest dabigatran is a reasonable alternative to warfarin for preventing thromboembolic events in patients requiring cardioversion for atrial fibrillation.
The DELIVER Trial: Dapagliflozin in Heart Failure with Mildly Reduced or Pres...ddocofdera
Few pharmacologic treatment options are available for patients with heart failure with mildly reduced or preserved ejection fraction, representing about half of patients with heart failure
The SGLT2i, empagliflozin, was found to reduce the risk of cardiovascular death and heart failure hospitalization in the EMPEROR-Preserved trial
Uncertainty remains regarding efficacy in specific groups of patients with HF with mildly reduced or preserved ejection fraction:
Those in the highest part of the ejection fraction range, where there has been concern about attenuation of the treatment effect
Those with a previously reduced ejection fraction that has improved to > 40%, a group that has been excluded from prior trials Men and women age 40 years or greater
Documented diagnosis of symptomatic heart failure ( [NYHA] class II-IV) at enrollment, and a medical history of symptoms/signs of heart failure ≥ 6 weeks before enrollment with at least intermittent need for diuretic treatment (requiring recurrent intermittent dosing).
LVEF > 40% and evidence of structural heart disease (i.e. LVH or LA enlargement) documented by the most recent echo, and/or cardiac MRI within the last 12 months prior to enrollment.
NT-pro BNP ≥ 300 pg/mL at Visit 1 for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at Visit 1, NT-pro BNP must be ≥ 600 pg/mL.
Patients may be ambulatory, or hospitalized; patients must be off intravenous heart failure therapy (including diuretics) for at least 12 hours prior to enrollment and 24 hours prior to randomization. The primary outcome was a composite of worsening heart failure, which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure, or cardiovascular death.
Secondary outcomes were the total number of worsening heart failure events and cardiovascular deaths, the change from baseline in the total symptom score on the Kansas City Cardiomyopathy Questionnaire at month 8, cardiovascular death, and death from any cause.
Among patients with HF with mildly reduced or preserved ejection fraction, dapagliflozin reduced the risk of the primary composite outcome of cardiovascular death or worsening heart failure
These findings were consistent across prespecified subgroups, including those defined according to left ventricular ejection fraction, with no attenuation in the highest LVEF group
Dapagliflozin was equally effective in patients with recent HF hospitalization and those with prior reduced ejection fraction that had improved to over 40%
Serious adverse events and adverse events leading to discontinuation were similar between dapagliflozin and placebo
A comprehensive meta-analysis confirmed robust benefits of SGLT2i in HF with mildly reduced or preserved EF, including among patients with LVEF ≥60% ESC 2023 Focused update on ESC 2021 guidelines designated SGLT2 inhibitors (Dapagliflozin/Empagliflozin )as class I, level A, for the treatment of heart f
This summary outlines the key findings of the EMPA-KIDNEY trial which evaluated the effect of empagliflozin treatment on kidney disease progression and cardiovascular outcomes in patients with chronic kidney disease (CKD). The randomized, double-blind trial involved over 6,600 patients with CKD across 8 countries. Patients received either empagliflozin 10mg or placebo daily. The primary outcome of kidney disease progression or cardiovascular death occurred in 13.1% of the empagliflozin group versus 16.9% of the placebo group, representing a 28% lower risk with empagliflozin. Secondary outcomes also favored empagliflozin treatment, including lower rates of hospitalization. The benefits were
The document summarizes the SPRINT trial which compared intensive blood pressure control (target SBP <120 mm Hg) to standard treatment (target SBP 135-139 mm Hg) in patients at high risk for cardiovascular disease but without diabetes or history of stroke. The trial found that intensive treatment reduced the occurrence of heart attacks, heart failure, and death by about 25% compared to standard treatment. However, intensive treatment also increased the risk of acute kidney injury, particularly in those without chronic kidney disease at baseline. Overall, the trial demonstrated that intensive blood pressure control provides significant cardiovascular benefits for high-risk patients.
This document summarizes the key points from a lipidology conference presentation. It discusses recent guidelines and studies on cholesterol treatment, including more aggressive LDL lowering to under 70mg/dl for patients with cardiovascular disease. New tools for general cardiovascular risk prediction were presented. Treatment with high-dose statins was found to significantly reduce stroke recurrence and other outcomes for patients who had a stroke or TIA within the past 1-6 months. Immediate withdrawal of statins after acute stroke was associated with increased risks.
Oral anticoagulation with vitamin K antagonists or non-vitamin K antagonist oral anticoagulants (NOACs) is the standard of care for reducing thromboembolic risk in patients with atrial fibrillation (AF). Warfarin is effective but has limitations including a narrow therapeutic window requiring frequent monitoring and dose adjustments. NOACs have advantages over warfarin such as rapid onset, fewer drug interactions and no requirement for routine monitoring. Apixaban and edoxaban have been shown to have the lowest risk of gastrointestinal bleeding compared to other NOACs based on data from pivotal clinical trials. Dosing of NOACs requires adjustment based on renal function and bleeding risk.
This document discusses the potential benefits of combining a SGLT-2 inhibitor (SGLT2i) and DPP-4 inhibitor (DPP4i) for treatment of type 2 diabetes. It notes that SGLT2is increase glucagon levels while DPP4is inhibit glucagon release, providing a counteracting effect. The combination addresses multiple metabolic abnormalities and has synergistic effects on glycemic control, cardiovascular risk reduction, renal protection, and other benefits. Clinical evidence suggests this combination may be preferred over other therapies for patients with diabetes and cardiovascular or renal complications.
The document summarizes findings from the ACCORD clinical trial which compared an intensive glucose lowering strategy targeting an A1C less than 6.0% to a standard strategy targeting an A1C of 7.0-7.9% in adults with type 2 diabetes at high risk for cardiovascular disease. The intensive strategy resulted in lower A1C levels but also increased mortality, did not reduce the risk of major cardiovascular events, and was associated with more hypoglycemia, weight gain, and other side effects. Certain subgroups such as those with an A1C under 8% at baseline or receiving primary prevention may have experienced reduced cardiovascular risk with intensive control.
Novel Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fib...Choying Chen
This document summarizes the results of three major clinical trials that compared new oral anticoagulants to warfarin for stroke prevention in atrial fibrillation:
- The RE-LY trial found that dabigatran 110mg and 150mg were as effective or more effective than warfarin in reducing stroke and systemic embolism.
- The ROCKET-AF trial found that rivaroxaban was non-inferior to warfarin in reducing stroke and systemic embolism.
- The ARISTOTLE trial found that apixaban was superior to warfarin in reducing stroke and systemic embolism.
All three new oral anticoagulants were associated with
The AALL1331 trial compared blinatumomab to chemotherapy as consolidation therapy after re-induction in pediatric patients with first relapse B-cell acute lymphoblastic leukemia. The open-label, randomized controlled trial found that blinatumomab significantly improved disease-free survival compared to chemotherapy, with 3-year disease-free survival rates of 45% for blinatumomab versus 27% for chemotherapy. Blinatumomab was generally well-tolerated though adverse events included cytokine release syndrome and neurotoxicity. The results support using blinatumomab as consolidation therapy to bridge pediatric B-ALL patients to hematopoietic stem cell transplant.
Coronary artery disease remains the leading cause of death in the US. Acute coronary syndromes are caused by a sudden reduction in coronary blood flow due to atherosclerosis. There are three presentations of ACS: unstable angina, NSTEMI, and STEMI. Treatment involves stabilizing the patient, risk stratification, and determining reperfusion strategy which may involve fibrinolysis, PCI, or CABG. Long term management focuses on preventative therapies including antiplatelets, statins, beta blockers, ACE inhibitors, and other secondary prevention medications.
The FIGARO-DKD trial evaluated the efficacy and safety of finerenone in reducing major adverse cardiovascular events in adults with type 2 diabetes and chronic kidney disease. Over 5300 patients were randomized 1:1 to receive finerenone or placebo on top of standard renin-angiotensin-aldosterone system inhibitor therapy. Finerenone showed a statistically significant 18% relative risk reduction in the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure compared to placebo. Hyperkalemia was the most common adverse effect but occurred at a lower rate than other mineralocorticoid receptor antagonists.
The EMPEROR-Reduced Trial found that:
1) Empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure by 25% compared to placebo in patients with heart failure with reduced ejection fraction.
2) It also reduced the risk of total heart failure hospitalizations by 30% and improved kidney outcomes.
3) Empagliflozin was effective in reducing risks in patients with or without diabetes and had an acceptable safety profile.
- A study evaluated the efficacy and safety of alirocumab in adults with homozygous familial hypercholesterolemia.
- 45 patients received alirocumab and 24 received placebo for 78 weeks.
- Alirocumab reduced LDL-C levels by 24.8% compared to placebo and was well tolerated, with adverse events similar between groups.
- Alirocumab provided clinically significant LDL-C lowering in patients with homozygous familial hypercholesterolemia.
This document summarizes key information about chronic kidney disease (CKD) and cardiovascular disease (CVD). It notes that patients with CKD should be considered at the highest risk for CVD. Lower estimated glomerular filtration rate (eGFR) is associated with higher risks of coronary disease and CVD mortality. The risks of all-cause mortality are significantly higher across all levels of eGFR and proteinuria for patients with early diabetic kidney disease compared to those without. Heart failure hospitalization risk increases as kidney function declines. The development of macroalbuminuria in diabetes patients heralds a rapid decline in glomerular filtration rate. Timely protection and maintenance of kidney function can reduce CVD risks.
SGLT2 Inhibitor therapy has opened up an exciting avenue for the Physicians to manage the patients with CKD . The slide set highlights the major trials on the drug showing remarkable benefits.
The DAPA-HF trial found that among patients with heart failure and reduced ejection fraction, those who received the SGLT2 inhibitor dapagliflozin had a lower risk of hospitalization for heart failure or cardiovascular death and better symptom scores compared to placebo, regardless of the presence of diabetes. Dapagliflozin reduced the primary composite outcome of worsening heart failure or cardiovascular death across subgroups. It provided cardiovascular benefits in patients without diabetes. Adverse effects were generally uncommon and less frequent with dapagliflozin.
Ueda2015 unmet medical needs in dm dr.lobna el-toonyueda2015
This document discusses current limitations in diabetes management and unmet medical needs. It notes that standard therapeutic approaches often lead to prolonged hyperglycemia before insulin initiation. Combination therapy provides superior glycemic control compared to continued monotherapy. However, as chronic kidney disease progresses, treatment options become increasingly limited. There remains a need for antidiabetic agents that can better preserve beta cell function, address multiple disease mechanisms, aid weight control, and have fewer side effects and safety concerns especially in patients with renal impairment.
Three cases of acute myocardial infarction are presented. All three patients had type 2 diabetes and other cardiovascular risk factors like hypertension and dyslipidemia. They presented with chest pain and ST-segment changes on electrocardiogram. All underwent emergency cardiac catheterization and had stents placed in obstructed coronary arteries. Strict control of blood sugar, blood pressure, and lipids is emphasized going forward to prevent further cardiovascular complications. The role of SGLT2 inhibitors in cardiovascular and renal protection for patients with diabetes is also discussed.
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
The document summarizes evidence from several major studies on glycemic control targets in diabetes:
1. The DCCT found that intensive insulin therapy (HbA1c <6%) significantly reduced microvascular complications compared to standard therapy but was associated with higher risk of hypoglycemia.
2. The UKPDS found no glycemic threshold for reducing complications, and lower HbA1c was associated with lower risk, suggesting targeting normal levels if possible.
3. The ACCORD trial found that an HbA1c goal of <6% increased mortality risk compared to a goal of 7-7.9% without significantly reducing cardiovascular outcomes or microvascular complications.
Individualization of gly
Dabigatran vs warfain Prior to TEE Journal ClubMichael Katz
1) The document summarizes a study comparing the direct thrombin inhibitor dabigatran to warfarin for preventing thromboembolic events after cardioversion for atrial fibrillation.
2) The study found the risk of stroke and major bleeding within 30 days of cardioversion was low and comparable between the two doses of dabigatran tested and warfarin, with or without transesophageal echocardiography guidance.
3) The results suggest dabigatran is a reasonable alternative to warfarin for preventing thromboembolic events in patients requiring cardioversion for atrial fibrillation.
The DELIVER Trial: Dapagliflozin in Heart Failure with Mildly Reduced or Pres...ddocofdera
Few pharmacologic treatment options are available for patients with heart failure with mildly reduced or preserved ejection fraction, representing about half of patients with heart failure
The SGLT2i, empagliflozin, was found to reduce the risk of cardiovascular death and heart failure hospitalization in the EMPEROR-Preserved trial
Uncertainty remains regarding efficacy in specific groups of patients with HF with mildly reduced or preserved ejection fraction:
Those in the highest part of the ejection fraction range, where there has been concern about attenuation of the treatment effect
Those with a previously reduced ejection fraction that has improved to > 40%, a group that has been excluded from prior trials Men and women age 40 years or greater
Documented diagnosis of symptomatic heart failure ( [NYHA] class II-IV) at enrollment, and a medical history of symptoms/signs of heart failure ≥ 6 weeks before enrollment with at least intermittent need for diuretic treatment (requiring recurrent intermittent dosing).
LVEF > 40% and evidence of structural heart disease (i.e. LVH or LA enlargement) documented by the most recent echo, and/or cardiac MRI within the last 12 months prior to enrollment.
NT-pro BNP ≥ 300 pg/mL at Visit 1 for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at Visit 1, NT-pro BNP must be ≥ 600 pg/mL.
Patients may be ambulatory, or hospitalized; patients must be off intravenous heart failure therapy (including diuretics) for at least 12 hours prior to enrollment and 24 hours prior to randomization. The primary outcome was a composite of worsening heart failure, which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure, or cardiovascular death.
Secondary outcomes were the total number of worsening heart failure events and cardiovascular deaths, the change from baseline in the total symptom score on the Kansas City Cardiomyopathy Questionnaire at month 8, cardiovascular death, and death from any cause.
Among patients with HF with mildly reduced or preserved ejection fraction, dapagliflozin reduced the risk of the primary composite outcome of cardiovascular death or worsening heart failure
These findings were consistent across prespecified subgroups, including those defined according to left ventricular ejection fraction, with no attenuation in the highest LVEF group
Dapagliflozin was equally effective in patients with recent HF hospitalization and those with prior reduced ejection fraction that had improved to over 40%
Serious adverse events and adverse events leading to discontinuation were similar between dapagliflozin and placebo
A comprehensive meta-analysis confirmed robust benefits of SGLT2i in HF with mildly reduced or preserved EF, including among patients with LVEF ≥60% ESC 2023 Focused update on ESC 2021 guidelines designated SGLT2 inhibitors (Dapagliflozin/Empagliflozin )as class I, level A, for the treatment of heart f
This summary outlines the key findings of the EMPA-KIDNEY trial which evaluated the effect of empagliflozin treatment on kidney disease progression and cardiovascular outcomes in patients with chronic kidney disease (CKD). The randomized, double-blind trial involved over 6,600 patients with CKD across 8 countries. Patients received either empagliflozin 10mg or placebo daily. The primary outcome of kidney disease progression or cardiovascular death occurred in 13.1% of the empagliflozin group versus 16.9% of the placebo group, representing a 28% lower risk with empagliflozin. Secondary outcomes also favored empagliflozin treatment, including lower rates of hospitalization. The benefits were
The document summarizes the SPRINT trial which compared intensive blood pressure control (target SBP <120 mm Hg) to standard treatment (target SBP 135-139 mm Hg) in patients at high risk for cardiovascular disease but without diabetes or history of stroke. The trial found that intensive treatment reduced the occurrence of heart attacks, heart failure, and death by about 25% compared to standard treatment. However, intensive treatment also increased the risk of acute kidney injury, particularly in those without chronic kidney disease at baseline. Overall, the trial demonstrated that intensive blood pressure control provides significant cardiovascular benefits for high-risk patients.
This document summarizes the key points from a lipidology conference presentation. It discusses recent guidelines and studies on cholesterol treatment, including more aggressive LDL lowering to under 70mg/dl for patients with cardiovascular disease. New tools for general cardiovascular risk prediction were presented. Treatment with high-dose statins was found to significantly reduce stroke recurrence and other outcomes for patients who had a stroke or TIA within the past 1-6 months. Immediate withdrawal of statins after acute stroke was associated with increased risks.
Oral anticoagulation with vitamin K antagonists or non-vitamin K antagonist oral anticoagulants (NOACs) is the standard of care for reducing thromboembolic risk in patients with atrial fibrillation (AF). Warfarin is effective but has limitations including a narrow therapeutic window requiring frequent monitoring and dose adjustments. NOACs have advantages over warfarin such as rapid onset, fewer drug interactions and no requirement for routine monitoring. Apixaban and edoxaban have been shown to have the lowest risk of gastrointestinal bleeding compared to other NOACs based on data from pivotal clinical trials. Dosing of NOACs requires adjustment based on renal function and bleeding risk.
This document discusses the potential benefits of combining a SGLT-2 inhibitor (SGLT2i) and DPP-4 inhibitor (DPP4i) for treatment of type 2 diabetes. It notes that SGLT2is increase glucagon levels while DPP4is inhibit glucagon release, providing a counteracting effect. The combination addresses multiple metabolic abnormalities and has synergistic effects on glycemic control, cardiovascular risk reduction, renal protection, and other benefits. Clinical evidence suggests this combination may be preferred over other therapies for patients with diabetes and cardiovascular or renal complications.
The document summarizes findings from the ACCORD clinical trial which compared an intensive glucose lowering strategy targeting an A1C less than 6.0% to a standard strategy targeting an A1C of 7.0-7.9% in adults with type 2 diabetes at high risk for cardiovascular disease. The intensive strategy resulted in lower A1C levels but also increased mortality, did not reduce the risk of major cardiovascular events, and was associated with more hypoglycemia, weight gain, and other side effects. Certain subgroups such as those with an A1C under 8% at baseline or receiving primary prevention may have experienced reduced cardiovascular risk with intensive control.
Novel Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fib...Choying Chen
This document summarizes the results of three major clinical trials that compared new oral anticoagulants to warfarin for stroke prevention in atrial fibrillation:
- The RE-LY trial found that dabigatran 110mg and 150mg were as effective or more effective than warfarin in reducing stroke and systemic embolism.
- The ROCKET-AF trial found that rivaroxaban was non-inferior to warfarin in reducing stroke and systemic embolism.
- The ARISTOTLE trial found that apixaban was superior to warfarin in reducing stroke and systemic embolism.
All three new oral anticoagulants were associated with
Similar to Final_ASandler_Dapag_HFpEF_JC.docx (20)
The AALL1331 trial compared blinatumomab to chemotherapy as consolidation therapy after re-induction in pediatric patients with first relapse B-cell acute lymphoblastic leukemia. The open-label, randomized controlled trial found that blinatumomab significantly improved disease-free survival compared to chemotherapy, with 3-year disease-free survival rates of 45% for blinatumomab versus 27% for chemotherapy. Blinatumomab was generally well-tolerated though adverse events included cytokine release syndrome and neurotoxicity. The results support using blinatumomab as consolidation therapy to bridge pediatric B-ALL patients to hematopoietic stem cell transplant.
Coronary artery disease remains the leading cause of death in the US. Acute coronary syndromes are caused by a sudden reduction in coronary blood flow due to atherosclerosis. There are three presentations of ACS: unstable angina, NSTEMI, and STEMI. Treatment involves stabilizing the patient, risk stratification, and determining reperfusion strategy which may involve fibrinolysis, PCI, or CABG. Long term management focuses on preventative therapies including antiplatelets, statins, beta blockers, ACE inhibitors, and other secondary prevention medications.
This document summarizes the background, objectives, methods, and endpoints of the MENDS2 trial, a randomized controlled trial comparing dexmedetomidine to propofol for sedation in mechanically ventilated adults with sepsis. The trial aims to test whether dexmedetomidine results in better short-term outcomes, such as fewer days of delirium or coma and more ventilator-free days, and long-term outcomes like survival and cognition at 6 months compared to propofol. The trial plans to enroll approximately 420 patients and randomize them 1:1 to receive either dexmedetomidine or propofol infusion titrated to light sedation. The primary outcome is the number of days alive
This document summarizes the epidemiology, pathophysiology, presentation, diagnosis and treatment of acute decompensated heart failure (ADHF). Some key points:
1. ADHF is a leading cause of hospitalization and mortality worldwide, with high readmission rates. Risk factors include non-adherence to medications and acute infections.
2. Presentation depends on the degree of pulmonary congestion and systemic perfusion. Diagnosis is made clinically based on symptoms and objective data like chest x-ray and BNP levels.
3. Initial treatment focuses on relieving congestion with diuretics. Vasodilators may be used in hypertensive patients. Inotropes and vasopress
Parkinson's disease is a neurodegenerative disorder characterized by three key points:
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Final mab DI question presentation.docxAnnaSandler4
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Final_ASandler_Dapag_HFpEF_JC.docx
1. Anna Sandler, PharmD Candidate ‘23
09.22.2022
1
BACKGROUND
Title Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in Heart Failure
with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. Published
online August 27, 2022:NEJMoa2206286. doi:10.1056/NEJMoa2206286
Background Heart failure (HF) is a progressive condition in which the heart is unable to
pump blood efficiently to the rest of the body.
HF can stem from impaired cardiac contraction, or impaired ventricular
relaxation and compliance, the latter of which is typically associated with a
preserved the left ventricular ejection fraction (LVEF).
Approximately 6 million Americans adults ≥ 20 years old have HF, and
roughly 50% have HFpEF.1
While the incidence of HF with a reduced ejection fraction (HFrEF) has
decreased, there has been an increased incidence of HFpEF.2,3
HFpEF leads to increased morbidity and mortality; five-year mortality may
be as high as 50%.3,4
There are currently no mortality-benefiting therapies in HFpEF.
With newer studies and proposed benefits5,6
, the 2022 American Heart
Association (AHA) HF guidelines2
list sodium-glucose cotransporter-2
(SGLT2) inhibitors as reasonable agents in symptomatic HFpEF (Class of
recommendation, 2a).
Definitions by LVEF:
o HFrEF: LVEF ≤ 40%
o Heart failure with mildly reduced EF (HFmEF): LVEF 41-49%
o HFpEF: LVEF ≥ 50%
SGLT2 inhibitor: Empagliflozin (Jardiance ® )7
o Indications: Diabetes mellitus type II (T2DM), HF
o Dosing in HF: 10 mg by mouth (PO) once daily
o Adverse effects (AEs): Hypovolemia, genitourinary (GU) fungal
infections, urinary tract infections, pyelonephritis, euglycemic
ketoacidosis, dyslipidemia
o Contraindications (CIs)/Warnings: Lower limb amputation? ,
dialysis patients, eGFR < 20 mL/min/1.73m2
o Pharmacokinetics/Pharmacodynamics (PK/PD):
Volume of distribution (Vd): 73.8 L
Time to peak: ~1.5 hours
Metabolism: Mainly via glucuronidation
Half-life elimination (t1/2): 12.4 hours
Excretion: ~55% urine, ~41% feces
SGLT2 inhibitor: Dapagliflozin (Farxiga ® )8
o Indications: T2DM, CKD (adjunct to first-line therapies), HFrEF,
HFpEF (off-label)
o Dosing in HF: 10 mg PO daily
o AEs: AKI, hypovolemia, GU infections, dyslipidemia,
o CIs/warnings: Dialysis patients, eGFR < 30 mL/min/1.73m2
o PK/PD:
Bioavailability: 78%
Time to peak: 2 hours
Metabolism: Mainly via glucuronidation, minor CYP-
mediated metabolism
2. t1/2: ~12.9 hours
Excretion: ~75% urine, 21% feces
Previous trials 2019: Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
(DAPA-HF trial9
)
Phase three, randomized controlled trial assessing worsening HF or
cardiovascular (CV) death in patients with NYHA class II-IV HF and a
LVEF ≤ 40% treated with dapagliflozin or matching placebo.
Primary outcome: dapagliflozin- 386 patients (16.3%); placebo-502
(21.2%); hazard ratio (HR), 0.74; 95% confidence interval (CI), 0.65-
0.85; P<0.001. Significant reductions in both hospitalizations and CV
death.
Limitations: Exclusion of LVEF > 40%, low representation of existing
comorbidities
2021: Empagliflozin in Heart Failure with a Preserved Ejection Fraction
(EMPEROR-Preserved trial)10
Double-blind randomized controlled trial evaluating the effect of
empagliflozin versus (vs.) matching placebo on CV death or hospitalization
for HF in patients with NYHA class II-IV HF and a LVEF >40%.
Primary outcome: empagliflozin-415 patients (13.8%); placebo- 511
(17.1%); HR, 0.79; 95% CI, 0.69-0.90; P< 0.001.
Limitations: Primary outcome driven by statistically significant reductions
in HF hospitalization, unknown whether benefits are consistent across
entire LVEF range11
, high discontinuation rates (23%)
Gap in Knowledge Whether the benefits of SGLT2 inhibitors are consistent at higher LVEFs is
yet to be elucidated.
GENERAL STUDY OVERVIEW
Objective Test whether dapagliflozin would reduce the risk of worsening HF or CV death
in patients with a mildly reduced or preserved ejection fraction
Trial design Phase 3, international, multicenter, double-blind, randomized controlled trial
Null Hypothesis Dapagliflozin does not reduce the risk of worsening HF and CV death among
patients with a LVEF of > 40%.
Funding Source AstraZeneca
METHODS
Inclusion criteria ≥ 40 years old
NYHA class II-IV HF with symptoms ≥ 6 weeks before enrollment & at least an
intermittent need for diuretics
LVEF > 40% and structural heart disease
Ambulatory or hospitalized patients; off intravenous HF therapy for ≥ 12 hours
prior to enrollment
Exclusion criteria Receipt of SGLT2 inhibitor within 4 weeks prior to randomization
Prior intolerance to an SGLT2 inhibitor
T1DM
Systolic blood pressure (SBP) < 95 mmHg during first two visits
SBP ≥ 180 mmHg
eGFR < 25 mL/min/1.73 m2
Myocardial infarction, unstable angina, coronary revascularization, atrial
fibrillation ablation or recent valve repair/replacement within 12 weeks prior to
enrollment
Stroke or transient ischemic attack within 12 weeks prior to enrollment
Severe pulmonary disease (e.g., COPD requiring home oxygen or a recent
exacerbation)
Heart failure due to infiltrative cardiomyopathy, active myocarditis, genetic
hypertrophic cardiomyopathy
Pregnant or breastfeeding individuals
3. Anna Sandler, PharmD Candidate ‘23
09.22.2022
3
Interventions + Control Screening period: August 2018 – December 2020
Patients randomized 1:1 to receive dapagliflozin 10 mg once daily or matching
placebo
Randomization with stratification based on T2DM status
Other medications could be continued
Study visits: day 30, day 120, and every 120 days thereafter
Median duration of follow-up (years): 2.3; interquartile range (IQR): 1.7-2.8
Primary + Secondary
Endpoints
Primary Endpoint: Composite: Worsening HF or CV death
Statistical Test: Cox proportional-hazards model stratified by
diabetes status
Performed concurrently in the overall
population AND in patients with a LVEF <
60%
Total significance alpha (α) split: α1= 0.038 for
LVEF < 60%; α2= 0.024 for overall population
Secondary
Endpoint(s):
Change from baseline in total symptom score on
the Kansa City Cardiomyopathy Questionnaire
(KCCQ) at month 8
o Minimally clinically important difference:
5 points12
CV death
Death from any cause
Statistical Test: KCCQ: Descriptive statistics
Safety Endpoint(s) Endpoint: Amputations
Diabetic ketoacidosis
Hypoglycemic events
Renal adverse events (AEs)
Fourier’s Gangrene
Statistical Test: Descriptive statistics
Additional Statistical
Analyses
All efficacy analyses completed in the intention-to-treat (ITT) population
Testing for significance was done in a hierarchical fashion from the primary
outcome to the secondary outcomes
Power analysis: 6100 patients 1117 events & 93% power 20% risk
reduction in worsening HF or CV death
RESULTS
Total enrollment Overall population: n= 6263; dapagliflozin: n=3131; placebo; n=3132
LVEF < 60%: n=4372; dapagliflozin: n=2200; placebo: n=2172
Total discontinuation rate: 14%
Baseline characteristics
(overall population)
Groups well-balanced
Mean age (years): ~72
Female (%): ~43-44
Asian (%): ~20
Black (%): ~2
White (%): ~71
North America (%): ~14
Latin America (%): ~19
Europe or Saudi Arabia (%): ~48
4. NYHA II (%): ~75
NYHA III (%): ~25
NYHA IV (%): 0.3
LVEF ≤ 49: ~34%
LVEF 50-59: ~36%
LVEF ≥ 60: ~30%
Prior LVEF ≤ 40: ~19%
T2DM (%): ~45
Hypertension (%): ~89%
Prior hospitalization for HF (%) ~41%
History and baseline ECG atrial fibrillation or flutter (%): ~56 and ~42
respectively
Loop diuretic (%): ~77
Beta-blocker (%): ~83
Mineralocorticoid receptor antagonist (%): ~43
ACE inhibitor (%): ~37
Angiotensin receptor blocker (%): ~37
Mean eGFR (mL/min/1.73 m2
) (+/- standard deviation): 61 +/- 19
Primary Outcome:
Worsening HF or CV death
no. events, (%)
Overall population: Dapagliflozin: 512 (16.4); placebo: 610 (19.5); HR 0.82,
95% CI 0.73-0.92; P< 0.001 Number needed to treat (NNT) ~ 33
LVEF < 60%: HR 0.83, 95% CI 0.73-0.95; P=0.009, NNT ~34
Secondary Outcome:
Worsening HF no. events,
(%)
Overall population: Dapagliflozin: 368 (11.8); placebo: 455 (14.5); HR 0.79,
95% CI 0.69-0.91; NNT ~38
LVEF < 60%: HR 0.77, 95% CI 0.66-0.91; NNT ~33
Secondary Outcome: CV
death no. events, (%)
Overall population: Dapagliflozin: 231 (7.4); placebo: 261 (8.3); HR 0.88, 95%
CI 0.74-1.05
LVEF < 60%: HR, 0.95; 95% CI 0.78-1.16
Secondary Outcome:
Change KCCQ total score
Overall population: Mean score change at month 8: 2.4, 95% CI 1.5-3.4
Safety/AEs Dapagliflozin: n- 3126; placebo: n=3127
Adverse events (AEs) similar between two groups
Any serious AE (%): ~44-46
AEs leading to discontinuation (%): ~6
AE leading to interruption of treatment (%): ~14-15
Any amputation (%): 0.6-0.8
Probable or definite diabetic ketoacidosis (%): dapagliflozin-0.1; placebo- 0
Major hypoglycemic event (%): 0.2
AUTHORS’ CONCLUSIONS
Dapagliflozin resulted in a lower risk of worsening HF or CV death than placebo. There was no appreciable
difference in benefits between patients with a LVEF ≥ 60% and those with a LVEF of < 60%, or in other
subgroups. The incidence of AEs was similar to that observed in the placebo group. The trial was not powered to
assess the effect of dapagliflozin on CV death alone and had specific inclusion and exclusion criteria that limited
generalizability of the findings. Data support use of an SGLT2 inhibitor in patients with HF, regardless of LVEF.
CRITIQUE/DISCUSSION
Patient Population Strengths: Large number
International trial
Inclusion of patients hospitalized for HF
Inclusion of patients who previously had a LVEF <40%
Larger representation of NYHA III patients
5. Anna Sandler, PharmD Candidate ‘23
09.22.2022
5
Limitations: Less representations of lower eGFRs
Exclusion of patients with recent (within 12 weeks) acute
coronary syndromes (e.g., coronary revascularization,
stroke) and those with higher BMIs
Intervention Strengths: Quadruple-blinded
Randomization with stratification by diabetes status
Limitations: Did not stratify by region or eGFR, which the EMPEROR-
preserved trial did
Endpoints Strengths: Clinically meaningful endpoints consistent with prior trials
Limitations: Underpowered to detect mortality benefits
Statistics Strengths: Analyses conducted in the ITT population
Implementation of a dual primary analysis
Use of hierarchical testing
Sensitivity analysis to account for COVID-19 as a
competing risk for non-CV death
Limitations: Did not analyze the primary outcome in those with a
LVEF ≥ 60% (Only subgroup analysis)
CONCLUSION AND RECOMMENDATIONS
Presenter’s Discussion and
Conclusion
The results in the DELIVER trial confirmed previous hospitalization and symptom
improvement benefits revealed in EMPEROR-preserved, and the benefits were
consistent in patients with an ejection fraction of less than 60%. The DELIVER trial
was a well-designed trial that had a more inclusive population, including
hospitalized patients and more patients with NYHA class III HF. Moreover, this
trial was unique in that it employed a dual primary analysis to compare treatment
effects between the overall population and patients with an ejection fraction less
than 60%. Noteworthy limitations include being underpowered to detect mortality
benefits and the fact that results were not analyzed in patients with an ejection
fraction of 60% or greater. Nevertheless, the benefits from this trial are clinically
important as hospitalization is a main driver of mortality in the disease. 13,14
Improvement in symptoms as noted by the KCCQ score results is equally
informative; poor quality of life has been linked to high hospitalization and
mortality rates.15
In the future it would be worth studying the long-term effects
SGLT2 inhibitors with longer follow-up times.
Application to Patient Care SGLT2 inhibitors may be appropriate to initiate in hospitalized patients with
HFmEF, or HFpEF, but may also be initiated after discharge. Hypotension is often a
limiting factor for initiating any blood pressure reduction therapies shortly after
admission for acute decompensated heart failure, and initiation with a less potent
agent such as an SGLT2 inhibitor may therefore be added inpatient for early
benefits.
6. References:
1. Virani SS, Alonso A, Aparicio HJ, et al. Heart Disease and Stroke Statistics—2021 Update: A Report From the
American Heart Association. Circulation. 2021;143(8). doi:10.1161/CIR.0000000000000950
2. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart
Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on
Clinical Practice Guidelines. Circulation. 2022;145(18). doi:10.1161/CIR.0000000000001063
3. Zhou L, Guo Z, Wang B, et al. Risk Prediction in Patients With Heart Failure With Preserved Ejection Fraction
Using Gene Expression Data and Machine Learning. Front Genet. 2021;12:652315.
doi:10.3389/fgene.2021.652315
4. Shah KS, Xu H, Matsouaka RA, et al. Heart Failure With Preserved, Borderline, and Reduced Ejection
Fraction. J Am Coll Cardiol. 2017;70(20):2476-2486. doi:10.1016/j.jacc.2017.08.074
5. Lopaschuk GD, Verma S. Mechanisms of Cardiovascular Benefits of Sodium Glucose Co-Transporter 2
(SGLT2) Inhibitors: A State-of-the-Art Review. JACC Basic Transl Sci. 2020;5(6):632-644.
doi:10.1016/j.jacbts.2020.02.004
6. Joshi SS, Singh T, Newby DE, Singh J. Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of
action in heart failure. Heart. 2021;107(13):1032-1038. doi:10.1136/heartjnl-2020-318060
7. Product Information: JARDIANCE(R) oral tablets, empagliflozin oral tablets. Published online 2022.
8. Product Information: FARXIGA(R) oral tablets, dapagliflozin oral tablets. Published online 2020.
9. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced
Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303
10. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N
Engl J Med. 2021;385(16):1451-1461. doi:10.1056/NEJMoa2107038
11. Butler J, Packer M, Filippatos G, et al. Effect of empagliflozin in patients with heart failure across the spectrum
of left ventricular ejection fraction. Eur Heart J. 2022;43(5):416-426. doi:10.1093/eurheartj/ehab798
12. Spertus JA, Jones PG, Sandhu AT, Arnold SV. Interpreting the Kansas City Cardiomyopathy Questionnaire in
Clinical Trials and Clinical Care. J Am Coll Cardiol. 2020;76(20):2379-2390. doi:10.1016/j.jacc.2020.09.542
13. Nanayakkara S, Patel HC, Kaye DM. Hospitalisation in Patients With Heart Failure With Preserved Ejection
Fraction. Clin Med Insights Cardiol. 2018;12:117954681775160. doi:10.1177/1179546817751609
14. Setoguchi S, Stevenson LW, Schneeweiss S. Repeated hospitalizations predict mortality in the community
population with heart failure. Am Heart J. 2007;154(2):260-266. doi:10.1016/j.ahj.2007.01.041
15. Heo S, Lennie TA, Okoli C, Moser DK. Quality of life in patients with heart failure: ask the patients. Heart
Lung J Crit Care. 2009;38(2):100-108. doi:10.1016/j.hrtlng.2008.04.002