Comparative Haemodynamic Responses to the First Dose of Short- and Long-acting ACE Inhibitors in Patients with Congestive Heart Failure

Summary

Background: Angiotensin Converting Enzyme inhibitors (ACEi's) confer significant mortality and morbidity benefits in all functional grades of chronic heart failure (CHF). However, physicians' concerns regarding the possible occurrence of first-dose hypotension appear to be a contributing factor to their under-utilisation in both hospital and primary care settings. We investigated whether long-acting and short-acting ACEi's differ in their haemodynamic responses to the first-dose in patients with CHF.

Method: This was a multicentre, randomised, open, two-parallel-group study of captopril 6.25 mg and perindopril 2mg. 240 patients with CHF, age 68.9 ± 8.9 years, of whom 66% were male, NYHAII—IV, with average blood pressure baseline values of 132.2 ± 16.2/78.5 ± 10.5mmHg for systolic and diastolic blood pressure, and left ventricular ejection fraction (LVEF) of 31.3 ± 7.4% received either captopril (n = 124) or perindopril (n = 116). Blood pressure was continuously monitored during the 8 h following drug intake. Minimum levels and maximum decreases in systolic, diastolic and mean arterial pressures were measured, along with the incidence of hypotensive episodes defined as mean blood pressure (MBP) fall > 20mmHg, whether symptomatic or not. Subgroups of patients distributed according to age, baseline blood pressure (BP) and LVEF were subsequently analysed.

Results: Overall, a statistically significant treatment effect in favour of perindopril was observed. First-dose hypotension was observed more frequently following captopril than perindopril administration, with lower MAP minimal levels (78.0 ± 8.9 vs. 84.5 ± 10.1 mmHg, p < 0.0001), greater maximum falls (17.6 ± 8.3 vs. 12.8 ± 7.3mmHg, p < 0.0001) and more frequent hypotensive episodes (42% vs. 15%, p < 0.0001). The incidence of at least one symptomatic episode was also significantly higher with captopril (10 patients vs. one patient, p = 0.029). Subgroup analyses according to age (< 70 years or > 70 years) or LVEF (< 30% or > 30%) reflected the main result.

Conclusion: Initiation of treatment with ACE inhibitors is associated with different haemodynamic and clinical tolerances in CHF patients, regardless of their risk for hypotension, with possible clinical implications.

Key Words::

• Chronic heart failure
• First-dose
• Hypotension
• ACE inhibitors
• Perindopril
• Captopril

Notes

* Supported by a grant from Servier Pharmaceuticals Co.