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European Heart Journal 2001 22(19):1785-1793; doi:10.1053/euhj.2001.2623
Copyright © 2001 by the European Society of Cardiology.
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Dipyridamole in chronic stable angina pectoris. A randomized, double blind, placebo-controlled, parallel group study

E Picano, on behalf of the PISA (Persantin In Stable Angina) study groupf1

Institute of Clinical Physiology, CNR, Pisa, Italy

revised January 23, 2001; accepted January 24, 2001

Abstract

Background Oral dipyridamole induces accumulation of endogenous adenosine, which in a hypoxic milieu exerts experimentally an angiogenic effect on coronary collateral circulation. A meta-analysis of 13 randomized placebo-controlled trials published between 1960 and 1992 showed evidence of benefit for dipyridamole in the treatment of angina pectoris, especially with longer duration of treatment.

Aim To assess the efficacy and safety of dipyridamole in the treatment of patients with chronic stable angina in a large scale, international, randomized, placebo-controlled, parallel group study.

Methods Four hundred patients with chronic stable angina pectoris and a positive treadmill exercise test were randomized to receive either modified release dipyridamole (200mg b.i.d. p.o., n=198) or corresponding placebo (n=202), for 24 weeks as an add-on to conventional antianginal therapy and for 4 additional weeks as monotherapy—the latter after withdrawal of standard treatment with calcium antagonists and/or beta-blockers and/or long-acting (prophylactic) nitrates.

Results Of the 198 patients randomized to dipyridamole, 134 completed the add-on and only 12 the monotherapy phase. Of the 202 patients randomized to placebo, 162 reached the add-on and only 12 the monotherapy phase. Serious adverse events occurred in 15 patients with dipyridamole and in 12 with placebo (7·6% vs 6·0,P =0·52). Increase over the baseline treadmill exercise test was similar in the treatment groups at each stage of the trial for all the main efficacy parameters: total treadmill exercise test duration; time to first anginal pain (except for a –13s difference in favour of placebo at week 24;P=0·040); time to ST segment depression >0·1mVolt (except for a +21s difference in favour of dipyridamole at week 8;P=0·024; this latter difference was totally attributable to patients with lower exercise tolerance—Bruce stage II at study entry).

Conclusion In patients with chronic stable angina treated with regular antianginal background medication, the use of oral dipyridamole is safe and well tolerated. Antianginal and antiischaemic efficacy, as assessed by exercise testing, is comparable to placebo, except for a beneficial effect on time to ischaemia after 2 months, totally attributable to patients with lower exercise tolerance at study entry.

Key Words: Adenosine, chronic stable angina, dipyridamole, therapy

f1 Correspondence: Eugenio Picano, MD, PhD, FESC, Institute of Clinical Physiology of the National Research Council, Via Moruzzi, 1, 56123 Pisa, Italy.

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