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European Heart Journal 1994 15(3):389-393;
Copyright © 1994 by the European Society of Cardiology.
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© 1994 The European Society of Cardiology

Once daily felodipine in preventing ergonovine-induced myocardial ischaemia in Prinzmetal's variant angina

M. CHIMIENTI, M. S. NEGRONI, E. PUSINERI, M. B. REGAZZI*, L. INGLESE, C. KLERSY and L. DE AMBROGGI

"E. Malan" University Cardiovascular Centre, S. Donato Hospital, S. Donato Milanese Pavia, Italy
*Department of Clinical Pharmacology, S. Matteo Hospital Pavia, Italy

Received 2 August 1993; revised 12 October 1993; .

Correspondence Marcello Chimienti, MD, Centro Cardiovascolare E. Malan, Ospedale Clinicizzato S. Donato, Via Morandi 30, 20097 S. Donato Milanese, Italy

Abstract

The efficacy of extended-release felodipine in preventing ergonovine-induced myocardial ischaemia was assessed in 14 patients (12 male, two female, aged 56±7 years) with Prinzmetal's variant angina. Four of the patients had normal coronary arteries, eight had one-vessel and two had two-vessel disease. The ergonovine test was performed once in basal conditions and twice 5 days after beginning the oral administration of felodipine 20 mg o.d., 4 and 24 h after the last administration. During a continuous 6-lead ECG recording, ergonovine was injected at doses of 25, 50, 100, 200, and 400 µg at 5 min intervals. Blood samples for felodipine plasma concentrations were drawn at the time of the tests.

The basal ergonovine test was positive in all 14 patients (seven with anterior and seven with inferior ST segment elevation >0•1 m V) at a mean ergonovine dose of 162±138 µg. The test was repeated 4 h after the last felodipine administration and was negative in 13 patients (93%), but 24 h after the last drug administration, eight patients (57%) had a positive test response (five with anterior, three with inferior ST segment elevation) at a higher ergonovine dose than at baseline (150 vs 97 µg, P=0•042). The only dtfferences between patients with a negative and a positive test were the mean values of the left ventricular end-diastolic pressure (9•3 vs 14•9 mmHg, P=0•002) and the ergonovine doses used in the baseline tests (250 vs 97 µg, P=0•034). The mean felodipine plasma level 4 h after dosing was 18•0±12•2 nmol. l–1; 24 h post-dosing plasma concentrations were generally very low (<3 nmol. l–1 in eight cases). No acute side effects were observed during the trial.

In conclusion, extended-release felodipine, given once daily, appears to be highly effective in preventing ergonovine-induced ischaemia in patients with Prinzmetal's variant angina, maintaining good efficacy even 24 h post-dosing.

Key Words: Ergonovine test • felodipine • Prinzmetal's variant angina


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