What is the course of treatment for a patient with hypertension or heart failure who cannot take Angiotensin-Converting Enzyme (ACE) inhibitors and is already taking amlodipine (Calcium Channel Blocker)?

Treatment for Hypertension or Heart Failure When ACE Inhibitors Are Not Tolerated

Switch to an angiotensin receptor blocker (ARB) as the primary alternative to ACE inhibitors in patients already taking amlodipine, using valsartan 80-320 mg daily or candesartan 4-32 mg daily as first-line options. 1

Primary Recommendation: ARB Therapy

• ARBs are the established first-line alternative when ACE inhibitors cannot be tolerated, with proven mortality and morbidity benefits in both heart failure and post-myocardial infarction patients 1
• Valsartan (160 mg twice daily) demonstrated equivalent mortality outcomes to captopril in the VALIANT trial, making it a validated ACE inhibitor substitute 1
• For heart failure patients with reduced ejection fraction (<40%), ARBs are specifically recommended when ACE inhibitor intolerance occurs 1
• Candesartan (4-32 mg daily) and valsartan (80-320 mg daily) are the ARBs with the strongest evidence base for cardiovascular outcomes 1

Additional Therapeutic Agents to Consider

Beta-Blockers (Essential Addition)

• Add one of three evidence-based beta-blockers: bisoprolol (target 10 mg daily), metoprolol succinate CR (target 200 mg daily), or carvedilol (target 50 mg daily) 1
• These agents reduce mortality in heart failure and should be titrated slowly over weeks to months, starting at low doses (bisoprolol 1.25 mg, metoprolol 12.5-25 mg, carvedilol 3.125 mg) 1
• Beta-blockers are recommended for all patients with current or prior heart failure symptoms or following myocardial infarction 1

Diuretics for Volume Management

• Thiazide or thiazide-like diuretics should be added if blood pressure remains uncontrolled or if fluid overload is present 2, 3
• Diuretics are recommended to improve symptoms, exercise capacity, and reduce heart failure hospitalizations 1

Aldosterone Antagonists

• Spironolactone (12.5-25 mg daily) or eplerenone (25 mg daily) should be added in patients with moderate-to-severe heart failure symptoms (NYHA class III-IV) who remain symptomatic despite ARB and beta-blocker therapy 1
• Requires careful monitoring: serum potassium must be <5.0 mmol/L and creatinine ≤250 mmol/L (≤2.5 mg/dL in men, ≤2.0 mg/dL in women) before initiation 1
• Check potassium and creatinine after 4-6 days; reduce dose by 50% if potassium reaches 5.0-5.5 mmol/L, and discontinue if >5.5 mmol/L 1

Alternative Option: Hydralazine-Nitrate Combination

• If both ACE inhibitors AND ARBs are not tolerated, the combination of hydralazine plus isosorbide dinitrate can be used 1
• This combination has Class I recommendation for African-American patients with moderate-severe heart failure symptoms on optimal therapy 1
• For non-African-American patients intolerant to both ACE inhibitors and ARBs, hydralazine-nitrate receives a Class IIa-IIb recommendation 1

Important Monitoring and Safety Considerations

Common Pitfalls to Avoid

• Do not combine ACE inhibitors with ARBs, as dual RAS blockade increases adverse effects (hyperkalemia, renal failure, hypotension) without additional mortality benefit 3, 4
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) if left ventricular dysfunction is present, as these have negative inotropic effects 1, 2
• NSAIDs should be avoided as they attenuate the antihypertensive effects of ARBs and can worsen renal function 3

Monitoring Parameters

• Reassess blood pressure after 2-4 weeks of any medication adjustment, targeting <130/80 mmHg 2
• Monitor serum potassium and renal function 1-2 weeks after starting ARBs or aldosterone antagonists 3
• Watch for hyperkalemia and renal dysfunction, which are shared adverse effects between ACE inhibitors and ARBs 4

Advantages of ARBs Over ACE Inhibitors

• ARBs cause significantly less cough and angioedema compared to ACE inhibitors (approximately one less case of angioedema per 500 patients) 4
• Better tolerability profile while maintaining similar efficacy for blood pressure reduction and cardiovascular outcomes 5, 6

Treatment Algorithm Summary

1. Start ARB (valsartan or candesartan at low dose) 1
2. Add or optimize beta-blocker (bisoprolol, metoprolol succinate, or carvedilol) 1
3. Add diuretic if blood pressure uncontrolled or volume overload present 2
4. Add aldosterone antagonist if heart failure symptoms persist despite above therapy and renal function/potassium are appropriate 1
5. Consider hydralazine-nitrate only if both ACE inhibitors and ARBs are not tolerated 1