Which antihypertensive class provides the greatest morbidity and mortality benefit in a patient with hypertension and chronic congestive heart failure?

Best Antihypertensive for Heart Failure with Reduced Ejection Fraction

For patients with hypertension and chronic heart failure with reduced ejection fraction (HFrEF), an ARNI (sacubitril/valsartan) is the preferred first-line agent, followed by ACE inhibitors if ARNI is not accessible, and ARBs only if ACE inhibitors are not tolerated. 1, 2

Primary Recommendation: ARNI (Sacubitril/Valsartan)

The American College of Cardiology recommends ARNI as the preferred first-line renin-angiotensin system inhibitor for all symptomatic HFrEF patients to reduce cardiovascular death and heart failure hospitalization (Class I, Level of Evidence B-R). 1, 2

• The PARADIGM-HF trial demonstrated a 20% reduction in the composite endpoint of cardiovascular death or HF hospitalization compared to enalapril, with equal benefits for both death and hospitalization. 3, 1
• ARNI provides superior morbidity and mortality reduction compared to ACE inhibitors in head-to-head trials. 3, 1
• This should be initiated as part of four-pillar foundational therapy including a beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor. 1, 2

Second-Line: ACE Inhibitors

If ARNI is not accessible or appropriate, ACE inhibitors remain strongly recommended (Class I, Level of Evidence A) for all HFrEF patients with current or prior symptoms. 3

• Large randomized controlled trials clearly establish ACE inhibitor benefits in reducing morbidity and mortality in patients with mild, moderate, or severe HF symptoms. 3
• Preferred agents with proven mortality benefit include captopril, enalapril, lisinopril, perindopril, ramipril, and trandolapril. 3
• Start at low doses and titrate upward to target doses used in clinical trials (not just symptom-based dosing). 3

Third-Line: ARBs (Only for ACE Inhibitor Intolerance)

ARBs are recommended specifically for patients who cannot tolerate ACE inhibitors due to cough (up to 20% of patients) or angioedema (<1% but more common in Black patients and women). 3, 4

• ARBs have demonstrated mortality and hospitalization reduction in large RCTs, but should not be used as routine first-line therapy when ACE inhibitors are tolerated. 3, 4
• ARBs do not inhibit kininase and have much lower incidence of cough and angioedema compared to ACE inhibitors. 3

Critical Beta-Blocker Requirement

One of three evidence-based beta-blockers (bisoprolol, carvedilol, or metoprolol succinate) must be used in all stable HFrEF patients unless contraindicated (Class I, Level of Evidence A). 3, 2

• Beta-blockers reduce mortality and should be initiated simultaneously with ARNI or ACE inhibitors—do not wait to reach target doses of renin-angiotensin system inhibitors before starting. 3, 2
• These three specific agents have proven mortality benefit; other beta-blockers (bucindolol, short-acting metoprolol tartrate) lack this evidence. 3

What NOT to Do

The routine triple combination of ACE inhibitor + ARB + aldosterone antagonist is potentially harmful (Class III: Harm) due to increased risk of hypotension, renal dysfunction, and life-threatening hyperkalemia. 3, 4

• Do not combine ARB + ACE inhibitor routinely, as this showed increased HF hospitalizations without mortality benefit. 4
• Do not use calcium channel blockers as primary antihypertensive agents in HFrEF unless needed for angina or persistent hypertension after optimal guideline-directed medical therapy. 3

Monitoring Requirements

Check blood pressure, serum creatinine/eGFR, and serum potassium within 1-2 weeks after initiating or increasing doses of any renin-angiotensin system inhibitor or aldosterone antagonist. 1, 2, 4

• Exercise particular caution in patients with systolic BP <100 mmHg, serum creatinine >3 mg/dL, or serum potassium >5.0 mEq/L. 3, 4
• Titrate medications every 2-4 weeks, doubling doses at each step until target doses are achieved. 2, 4