A 58-year-old man comes to the office due to progressive fatigue, dyspnea on exertion, and orthopnea. Medical history is significant for hypertension, hyperlipidemia, and a myocardial infarction 2 years ago. The patient says he has not taken his medications in several months because he was "feeling well." Blood pressure is 160/95 mm Hg and pulse is 94/min and regular. Physical examination shows bilateral lung crackles and lower extremity edema. The point of maximal impulse is displaced toward the axilla, and an S3 is heard. Serum creatinine is 0.9 mg/dL and serum potassium is 4.2 mEq/L. After this patient's condition has stabilized, long-term use of which of the following medications will most likely reduce mortality?

Question

A 58-year-old man comes to the office due to progressive fatigue, dyspnea on exertion, and orthopnea.  Medical history is significant for hypertension, hyperlipidemia, and a myocardial infarction 2 years ago.  The patient says he has not taken his medications in several months because he was "feeling well."  Blood pressure is 160/95 mm Hg and pulse is 94/min and regular.  Physical examination shows bilateral lung crackles and lower extremity edema.  The point of maximal impulse is displaced toward the axilla, and an S3 is heard.  Serum creatinine is 0.9 mg/dL and serum potassium is 4.2 mEq/L.  After this patient's condition has stabilized, long-term use of which of the following medications will most likely reduce mortality?

Quizplus · Accepted Answer

11ec160b_3b83_13e0_9249_97a7c4bb2427_MD0001_00 This patient with a previous myocardial infarction has most likely developed chronic heart failure with reduced ejection fraction (HFrEF). Appropriate pharmacologic management is important in such patients because it has been shown to reduce mortality. Much of this mortality benefit is likely related to a reduction in deleterious cardiac remodeling. Neurohormonal pathways involving norepinephrine, angiotensin II, and aldosterone all have a demonstrated role in cardiac remodeling. In particular, elevated angiotensin II and aldosterone levels increase pathologic cardiomyocyte hypertrophy and stimulate collagen deposition by fibroblasts (cardiac fibrosis). Accordingly, ACE inhibitors (eg, lisinopril), angiotensin-receptor blockers (eg, losartan), and mineralocorticoid receptor antagonists (eg, spironolactone, epleronone) reduce mortality in patients with HFrEF via a reduction in angiotensin II-mediated (and downstream aldosterone-mediated) cardiac remodeling. Beta blockers (eg, metoprolol, carvedilol) also reduce mortality in patients with chronic HFrEF, likely through similar inhibition of neurohormonal mechanisms. Potentiation of the natriuretic peptide neurohormonal pathway with angiotensin receptor-neprilysin inhibitor therapy (eg, sacubitril-valsartan) has also demonstrated mortality benefit in these patients. (Choice A) Blood pressure control is important for patients with heart failure because it slows the progression of coronary artery disease and may reduce cardiac remodeling that is triggered by increased left ventricular pressure load. However, aside from the benefit of blood pressure reduction, dihydropyridine calcium channel blockers (eg, amlodipine) provide no additional mortality benefit in patients with HFrEF. (Choice B) Digoxin is used as an adjunctive therapy in patients with HFrEF. It improves symptoms, thereby reducing the rate of hospitalization, but does not improve mortality. (Choice C) Nondihydropyridine calcium channel blockers (eg, verapamil, diltiazem) can depress cardiac contractility and are usually contraindicated in patients with HFrEF. (Choices D and E) Loop (eg, furosemide) and thiazide (eg, metolazone) diuretics reduce cardiac preload and are useful for symptomatic management of patients with HFrEF; however, these drugs do not provide a clear mortality benefit. (Choice G) Although potassium-sparing diuretics that function via blockade of mineralocorticoid receptors have shown mortality benefit for HFrEF, those that act via blockade of the epithelial sodium channel (ENaC) (eg, triamterene, amiloride) have minimal neurohormonal effects and no demonstrated benefit. Educational objective: Neurohormones (eg, norepinephrine, angiotensin II, and aldosterone) play a large role in the deleterious cardiac remodeling that occurs in heart failure with reduced ejection fraction. ACE inhibitors, angiotensin-receptor blockers, mineralocorticoid receptor antagonists, beta blockers, and angiotensin receptor-neprilysin inhibitors reduce mortality in these patients by reducing neurohormonal-mediated cardiac remodeling. __________ References: 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. (http://www.ncbi.nlm.nih.gov/pubmed/23741057)

A 58-Year-Old Man Comes to the Office Due to Progressive