Why is captopril (angiotensin-converting enzyme inhibitor) no longer commonly used?

From the Guidelines

Captopril is not entirely obsolete but its use has significantly declined in favor of newer angiotensin-converting enzyme (ACE) inhibitors and other agents like angiotensin receptor-neprilysin inhibitors (ARNI) due to its less favorable pharmacokinetic profile and higher incidence of side effects. The primary reasons for this decline include its short duration of action, requiring multiple daily doses, and a higher incidence of side effects such as taste disturbances and skin rash compared to newer ACE inhibitors like lisinopril or enalapril 1. Additionally, captopril must be taken on an empty stomach to ensure proper absorption, complicating patient adherence.

When considering the management of heart failure with reduced ejection fraction (HFrEF), the use of ACE inhibitors, angiotensin receptor blockers (ARBs), or ARNI is recommended to reduce morbidity and mortality 1, 2. While captopril, as an ACE inhibitor, has been shown to reduce morbidity and mortality in patients with HFrEF, its use is now more limited due to the availability of newer agents with more favorable profiles. The 2017 ACC/AHA/HFSA focused update on the management of heart failure emphasizes the benefits of ACE inhibitors, ARBs, and ARNI in patients with chronic HFrEF, with a preference for ARNI over ACE inhibitors in appropriate patients due to its superior reduction in cardiovascular death or HF hospitalization 1.

Key points to consider in the use of captopril and other ACE inhibitors include:

• Starting at low doses and titrating upward to doses shown to reduce the risk of cardiovascular events in clinical trials.
• Giving with caution to patients with low systemic blood pressures, renal insufficiency, or elevated serum potassium.
• Being aware of the potential for angioedema, which occurs in less than 1% of patients but more frequently in blacks and women.
• Avoiding use in pregnant or planning-to-become-pregnant patients.
• Recognizing that ACE inhibitors also inhibit kininase and increase levels of bradykinin, which can induce cough but may contribute to beneficial vasodilation.

In summary, while captopril is still an option for certain clinical scenarios, particularly where its rapid onset of action is beneficial, its overall use has decreased in favor of newer, more convenient, and potentially more effective agents for the management of heart failure and hypertension, as supported by recent guidelines and evidence 1, 2.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Reasons for Decreased Use of Captopril

• The provided studies do not directly address why captopril is not used anymore, but they do discuss its efficacy and side effects in various treatments 3, 4, 5, 6, 7.
• Captopril was found to be effective in treating hypertension and congestive heart failure, but it also had potential side effects such as agranulocytosis, dysgeusia, and reduced renal function 3, 5, 6.
• The development of other angiotensin-converting enzyme (ACE) inhibitors may have led to a decrease in captopril's use, as these new drugs may have improved efficacy or safety profiles 4, 7.
• The studies provided are from the 1980s and 1990s, and it is possible that more recent research has led to a reevaluation of captopril's use in clinical practice.

Side Effects and Safety Concerns

• Captopril was associated with several side effects, including skin rashes, proteinuria, and neutropenia 3, 5, 6.
• The incidence of these side effects was generally low, but they could be serious in some cases 4, 6.
• The safety concerns associated with captopril may have contributed to its decreased use in favor of other treatments with more favorable safety profiles.

Clinical Applications and Efficacy

• Captopril was found to be effective in treating hypertension, congestive heart failure, and myocardial infarction 3, 4, 5, 6, 7.
• The drug was shown to improve cardiac performance, reduce systemic vascular resistance, and increase exercise tolerance in patients with heart failure 5.
• Captopril also demonstrated a survival benefit in patients with myocardial infarction, particularly those at high risk of mortality 7.