What is the appropriate captopril treatment in a patient with heart failure?

From the Guidelines

For patients with heart failure, captopril therapy should be initiated at 6.25 mg three times daily and titrated up to a target dose of 50 mg three times daily as tolerated, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

Key Considerations

• The initial daily dose of captopril is 6.25 mg three times daily, with a target dose of 50 mg three times daily, as outlined in the guideline 1.
• It is essential to monitor blood pressure, renal function, and potassium levels at initiation and with each dose increase to minimize potential side effects.
• Captopril should be part of a comprehensive heart failure regimen that typically includes beta-blockers, diuretics for fluid overload, and potentially aldosterone antagonists in appropriate patients.

Dosing and Administration

• Captopril works by inhibiting angiotensin-converting enzyme (ACE), reducing afterload and preload, decreasing ventricular remodeling, and improving survival in heart failure patients.
• Common side effects include cough, hypotension, and rarely angioedema, and if a dry cough develops and persists, consider switching to an angiotensin receptor blocker like losartan.
• Ensure patients take captopril on an empty stomach, 1 hour before meals, for optimal absorption.

Clinical Context

• The 2022 AHA/ACC/HFSA guideline emphasizes the importance of using target doses of HFrEF medications, as lower doses may not produce the same degree of clinical benefit 1.
• In clinical trials, composite event rates were lower with target doses compared with lower doses, highlighting the need for titration to the target dose as tolerated.

From the FDA Drug Label

Heart Failure - Initiation of therapy requires consideration of recent diuretic therapy and the possibility of severe salt/volume depletion In patients with either normal or low blood pressure, who have been vigorously treated with diuretics and who may be hyponatremic and/or hypovolemic, a starting dose of 6.25 or 12. 5 mg tid may minimize the magnitude or duration of the hypotensive effect For most patients the usual initial daily dosage is 25 mg tid After a dose of 50 mg tid is reached, further increases in dosage should be delayed, where possible, for at least two weeks to determine if a satisfactory response occurs. Most patients studied have had a satisfactory clinical improvement at 50 or 100 mg tid. A maximum daily dose of 450 mg of captopril should not be exceeded Captopril should generally be used in conjunction with a diuretic and digitalis. Captopril therapy must be initiated under very close medical supervision.

The appropriate captopril treatment in a patient with heart failure is to initiate therapy with consideration of recent diuretic therapy and the possibility of severe salt/volume depletion. The usual initial daily dosage is 25 mg tid, but may be started at 6.25 or 12.5 mg tid in patients who have been vigorously treated with diuretics. The dose may be increased to 50 mg tid or more, with a maximum daily dose of 450 mg, and should be used in conjunction with a diuretic and digitalis. Captopril therapy must be initiated under very close medical supervision 2.

From the Research

Captopril Treatment in Heart Failure

• The appropriate captopril treatment in a patient with heart failure is a topic of discussion in several studies 3, 4, 5, 6, 7.
• According to the Captopril in Heart Insufficient Patients Study (CHIPS), therapy with a high dose of captopril (50 mg b.i.d.) tends to improve the long-term clinical outcome of patients with mild to moderate heart failure without significantly more toxicity 3.
• The study also found that progression in heart failure seems to be favorably influenced by therapy with high dose in comparison to low dose, with a relative difference of 29% in the rates of heart failure worsening 3.
• Another study compared the safety and tolerability of recommended initial doses of enalapril and captopril in patients with heart failure, and found that both drugs were well tolerated, but enalapril significantly inhibited serum ACE activity to a greater extent than did captopril 4.
• A study on the practical issues of initiating captopril therapy in chronic heart failure found that both low and high doses of captopril produced a significant drop in blood pressure, and that the first dose-induced fall correlated significantly with subsequent dose-related reductions in blood pressure 5.
• The acute haemodynamic effects of low doses of captopril were studied in 18 patients with severe chronic heart failure, and found that graded haemodynamic improvement was noted from 1 hour and was closely associated with reduction of blood pressure 6.
• A comparative study of the first dose hypotensive effects of captopril and perindopril in patients with heart failure found that perindopril resulted in significantly less reduction in blood pressure and a lower incidence of symptomatic or asymptomatic hypotensive episodes than captopril 7.

Dosage and Administration

• The CHIPS study used a high dose of captopril (50 mg b.i.d.) and a low dose (25 mg b.i.d.) 3.
• The study on practical issues of initiating captopril therapy used a starting dose of 6.25 mg or 25.0 mg of captopril, followed by either incremental doses of 6.25, 12.5, and 25.0 mg (low dose group), or 25.0 mg 8 hourly (high dose group) 5.
• The study on the acute haemodynamic effects of low doses of captopril used increasing doses (1 mg, 2.5 mg, 6.25 mg, 12.5 mg, and 25 mg) of captopril given at 2 hour intervals 6.
• The comparative study of the first dose hypotensive effects of captopril and perindopril used a single dose of captopril 6.25 mg or perindopril 2 mg 7.

Safety and Tolerability

• The CHIPS study found that the total number of adverse events was comparable for both low and high doses of captopril, but dizziness and hypotension were a little more frequently reported in the high-dose group 3.
• The study on the safety and tolerability of recommended initial doses of enalapril and captopril found that both drugs were well tolerated 4.
• The study on practical issues of initiating captopril therapy found that no patient experienced symptomatic hypotension, and that the first dose-induced fall in blood pressure correlated significantly with subsequent dose-related reductions in blood pressure 5.
• The comparative study of the first dose hypotensive effects of captopril and perindopril found that perindopril resulted in significantly less reduction in blood pressure and a lower incidence of symptomatic or asymptomatic hypotensive episodes than captopril 7.