ACUTE AND LONG-TERM EFFICACY OF PERINDOPRIL IN SEVERE CHRONIC CONGESTIVE-HEART-FAILURE

To assess the short- and long-term hemodynamic efficacy of perindopril , 15 patients (12 men and women) diagnosed with congestive heart failu re were treated with oral perindopril (4 mg daily) for 3 months in ass ociation with digitalis and diuretic maintenance therapy. Patients wer e in New York Heart Association (NYHA) functional classes III and IV. Underlying cardiopathy was ischemic (6 patients), hypertensive (5 pati ents), valvular (2 patients), and dilated cardiomyopathy (2 patients). Hemodynamics, angiotensin-converting enzyme (ACE) activity, and perin doprilat (the active metabolite of perindopril) blood titration were m easured at 2 periods, Acute assessment was performed over 2 titration days on oral perindopril 2 mg (day 1) and 4 mg (day 2); measurements w ere performed at rest and at 0, 1, 4, 6, 8, 12, and 24 hours. Chronic assessment was performed after 3 months of treatment with oral perindo pril, 4 mg daily. During the study, 1 patient withdrew due to low syst olic blood pressure (<100 mm Hg) and 3 severely impaired patients died due to a worsening of heart failure during the study. Among the 11 re maining patients, 6 were symptomatically improved. On 4 mg perindopril administration, hemodynamic improvement was similar for peak values a t both day 2 and at 3 months. At day 2, compared with baseline, cardia c index increased by 21% (p < 0.05) and pulmonary capillary wedge pres sure (PCWP) and mean arterial pressure (MAP) decreased by 54% and by 2 1%, respectively (p < 0.01). Similarly, at 3 months, cardiac index inc reased by 37% (p < 0.001) and PCWP and MAP decreased by 41% and 19%, r espectively (p < 0.01). At both evaluation times, hemodynamic changes were correlated to serum ACE activity and perindoprilat plasma concent ration, mostly between hours 3 and 12. There was no significant change s in heart rate or plasma creatinine concentration and no clinical sid e effects. In conclusion, our study indicates beneficial short-term he modynamic efficacy of perindopril 4 mg; this efficacy persisted over 3 months in patients with severe congestive heart failure,