In a large clinical trial, patients with recent myocardial infarction and heart failure were randomized to a study medication or placebo. The average left ventricular ejection fraction of the study subjects was 33%. Most patients in both groups were concomitantly treated with a beta blocker and an angiotensin system inhibitor, in addition to the study medication or placebo. The long-term, all-cause mortality curves are shown in the image below, with the solid line representing the study medication and the dashed line representing the placebo. The difference between the curves is statistically significant. Which of the following medications most likely was used in the clinical trial?

Question

In a large clinical trial, patients with recent myocardial infarction and heart failure were randomized to a study medication or placebo.  The average left ventricular ejection fraction of the study subjects was 33%.  Most patients in both groups were concomitantly treated with a beta blocker and an angiotensin system inhibitor, in addition to the study medication or placebo.  The long-term, all-cause mortality curves are shown in the image below, with the solid line representing the study medication and the dashed line representing the placebo.  The difference between the curves is statistically significant.  Which of the following medications most likely was used in the clinical trial?

Quizplus · Accepted Answer

Explanation: 11ec25c8_d23d_e02a_bc81_ef01fef31fbf_MD0003_00 The following medications have been shown to improve long-term mortality in patients with heart failure with reduced ejection fraction (HFrEF) (ie, left ventricular [LV] systolic dysfunction): Angiotensin system inhibitors: Angiotensin receptor-neprilysin inhibitors (eg, sacubitril-valsartan) have demonstrated the greatest mortality benefit among these agents. ACE inhibitors (eg, lisinopril) and angiotensin II receptor blockers alone (eg, losartan, valsartan) have also demonstrated mortality benefit. Beta blockers (eg, metoprolol, carvedilol) Mineralocorticoid receptor antagonists (eg, spironolactone, eplerenone) Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (eg, dapagliflozin, empagliflozin) Typically, patients with HFrEF initially are given an angiotensin system inhibitor, a beta blocker, and a loop diuretic (eg, furosemide). A mineralocorticoid receptor antagonist is added for patients with LV ejection fraction ≤35% and persistent heart failure symptoms. Mineralocorticoid receptor antagonists block the deleterious cardiac remodeling effects of aldosterone and have been shown to improve overall survival and reduce hospitalizations in these patients. (Choices A and C) Calcium channel blockers (eg, amlodipine, diltiazem) have not been shown to provide symptomatic or mortality benefit in patients with HFrEF and have no direct role in management. (Choice B) Digoxin is sometimes used as a supplementary agent for symptom control in patients with HFrEF. It reduces the rate of hospitalization for heart failure but has not been shown to improve mortality. (Choice E) Hydrochlorothiazide typically is not used in management of heart failure. Loop diuretics (eg, furosemide) are used frequently, sometimes in combination with metolazone (a thiazide diuretic). These diuretics improve symptoms and reduce hospitalizations in patients with HFrEF but have not been shown to improve mortality. (Choice F) Ranolazine is an effective antianginal agent, commonly used in patients with angina symptoms that are refractory to other agents (eg, beta blockers, long-acting nitrates). Ranolazine has no direct role in management of HFrEF. Educational objective: Medications shown to improve mortality in patients with heart failure with reduced ejection fraction include angiotensin system inhibitors, beta blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors. References: 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. (http://www.ncbi.nlm.nih.gov/pubmed/33446410) The effect of spironolactone on morbidity and mortality in patients with severe heart failure: randomized aldactone evaluation study investigators. (http://www.ncbi.nlm.nih.gov/pubmed/10471456) Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. (http://www.ncbi.nlm.nih.gov/pubmed/16053953)

In a Large Clinical Trial, Patients with Recent Myocardial Infarction