ACE Inhibitors Do Not Worsen Heart Failure
ACE inhibitors are cornerstone therapy for heart failure with reduced ejection fraction and improve—not worsen—survival, symptoms, and hospitalizations. They should be initiated in all patients with heart failure due to left ventricular systolic dysfunction unless contraindicated 1.
Evidence for Benefit, Not Harm
ACE inhibitors improve survival, symptoms, functional capacity, and reduce hospitalization in patients with moderate and severe heart failure and left ventricular systolic dysfunction 1. The extended 12-year SOLVD study demonstrated significant reduction in all-cause mortality (50.9% vs 56.4%, HR 0.86, p < 0.001) 2.
- ACE inhibitors reduce cardiovascular mortality, myocardial infarction, and heart failure hospitalizations in both asymptomatic and symptomatic left ventricular dysfunction 2
- They delay or prevent the development of symptomatic heart failure in asymptomatic patients with left ventricular systolic dysfunction 1
- ACE inhibitors reduce the risk of myocardial infarction and sudden death (Class I, Level A recommendation) 1
When ACE Inhibitors Can Cause Problems (Not Worsening of Heart Failure Itself)
While ACE inhibitors do not worsen heart failure as a disease process, they can cause adverse effects that require management:
Important adverse effects include cough, hypotension, renal insufficiency, hyperkalemia, syncope, and angioedema 1. These are medication side effects, not worsening of the underlying heart failure.
Absolute Contraindications
- Bilateral renal artery stenosis (Class III, Level A) 1
- History of angioedema during previous ACE inhibitor therapy (Class III, Level A) 1
Situations Requiring Specialist Consultation
Proper Initiation and Titration Algorithm
Start at low doses and titrate to target doses used in clinical trials, not based on symptomatic improvement alone 1:
| ACE Inhibitor | Starting Dose | Target Dose |
|---|---|---|
| Captopril | 6.25 mg TID | 50-100 mg TID |
| Enalapril | 2.5 mg BID | 10-20 mg BID |
| Lisinopril | 2.5-5.0 mg daily | 30-35 mg daily |
| Ramipril | 2.5 mg daily | 5 mg BID or 10 mg daily |
| Trandolapril | 1.0 mg daily | 4 mg daily |
Monitoring Requirements
Regular monitoring of renal function is essential 1:
- Before initiation, 1-2 weeks after each dose increment, and at 3-6 month intervals 1
- When ACE inhibitor dose is increased or other medications affecting renal function are added (aldosterone antagonists, ARBs) 1
- More frequent measurements in patients with past or present renal dysfunction or electrolyte disturbances 1
Combination with Other Therapies
ACE inhibitors should be given as initial therapy in the absence of fluid retention 1. In patients with fluid retention, ACE inhibitors should be given together with diuretics (Class I, Level B) 1.
Higher doses provide greater benefit: The ATLAS trial showed that high-dose lisinopril reduced the combined outcome of all-cause mortality and heart failure hospitalization by 15% compared to low-dose (p < 0.001), with a 24% reduction in heart failure hospitalization (p = 0.002) 2.
Common Pitfalls to Avoid
Cough is common in heart failure patients and may be due to pulmonary edema or underlying lung disease, not necessarily the ACE inhibitor 3. ACE inhibitor-induced cough rarely requires treatment discontinuation 3.
Asymptomatic hypotension or small increases in serum creatinine do not require dose reduction or discontinuation 1. Changes in systolic and diastolic blood pressure and increases in serum creatinine are usually small in normotensive patients 1.
Angiotensin receptor blockers may be used as an effective alternative in patients who develop cough or angioedema on an ACE inhibitor (Class I, Level A) 1.