Captopril or nifedipine? Comparison of rest and exercise acute effects and long-term therapy in chronic isolated asymptomatic moderate to severe aortic regurgitation.
The effects of both single and long-term oral captopril or nifedipine treatment on cardiac parameters at rest and during exercise in patients with moderate to severe aortic regurgitation was investigated.


METHODS
Thirty-one asymptomatic patients with chronic, isolated, previously untreated, moderate to severe aortic regurgitation (AR) of mean grade 3.1 +/- 0.6, had left ventricular end-diastolic diameter (LVEDD) 64 +/- 5 mm, left ventricular end-systolic diameter (LVESD) 41 +/- 5 mm, ejection fraction (EF) 66 +/- 6% and fractional shortening (FS) 37 +/- 5% measured by echo-Doppler. Bedside Swan-Ganz measurements at rest and at peak exercise (75 W) were conducted before (baseline) and at 75-90 min after oral administration of 20 mg nifedipine. Repeat testing was performed 24 h later, at 75-90 min after oral administration of 25 mg captopril.


RESULTS
At rest, nifedipine significantly reduced systemic vascular resistance (SVR) compared with baseline (704 +/- 152 versus 880 +/- 216 dynes.s.cm-5; p < 0.0001) and captopril treatment (800 +/- 176 dynes.s.cm-5; p < 0.0001). Despite significant improvement of effective left ventricular (LV) stroke volume (LVSVef) after both nifedipine and captopril over baseline (103 +/- 20 ml), LVSVef did not differ between nifedipine and captopril (110 +/- 17 versus 110 +/- 22 ml; NS). Nifedipine significantly increased effective cardiac output (COef) from baseline (6.7 +/- 1.3 l/min) to 8.2 +/- 1.5 l/min; p < 0.0001, but this was due to an increase in heart rate (HR) (66 +/- 10 versus 75 +/- 1 beats/min; p < 0.0001). In contrast, captopril affected neither COef nor HR. In addition, captopril reduced pulmonary capillary wedge pressure (PCWP) more than nifedipine (8.7 +/- 2.5 versus 11 +/- 2.9 mmHg; p < 0.0001). At exercise, both drugs caused similar reductions in blood pressure and systemic vascular resistance (SVR). By comparison with exercise baseline, LVSVef was increased by captopril (139 +/- 24 versus 147 +/- 27 ml; p < 0.01) but was unchanged after nifedipine. Compared with baseline, nifedipine increased COef (from 14.4 +/- 2.0 to 15.5 +/- 2.1 l/min; p < 0.0001) due to a significantly higher HR, while COef and HR were unchanged after captopril. A smaller increase in PCWP was also seen after captopril than nifedipine and baseline (both p < 0.0001). After long-term therapy (33 +/- 12; range: 12 to 53 months) with captopril (75 mg/day, n = 13) or nifedipine (40 mg/day; n = 12) there was no change in LVESD, and in left ventricular EF and FS in either groups. None of the patients became symptomatic. Compared with baseline, captopril significantly reduced AR grade by 0.9 +/- 0.6 (p < 0.01), but not significantly so versus nifedipine. LVEDD was reduced in captopril patients by 4.0 +/- 2.6 mm (p < 0.0002), but not significantly so in nifedipine patients. LVEDD was normalized in five captopril patients, and in four treated with nifedipine.


CONCLUSIONS
Single captopril treatment caused a greater hemodynamic improvement than nifedipine, notably during exercise; these findings were confirmed by long-term therapy with both drugs. Therefore, captopril may delay the development of left ventricular dysfunction and thus the time for corrective surgery.
Banaszewski
M
M
National Institute of Cardiology, Warsaw, Poland.
Rydlewska-Sadowska
W
W
Rubkiewicz
S
S
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001022:Aortic Valve Insufficiency / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002216:Captopril / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D015444:Exercise; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage*; D012016:Reference Values; D012146:Rest; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D018608:Ultrasonography, Doppler; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D002216:Captopril; D009543:Nifedipine