Dipyridamole

Observational studies

The incidence of major adverse reactions to dipyridamole was determined in a multicenter retrospective study, involving 73 806 patients who underwent intravenous dipyridamole stress imaging in 59 hospitals and 19 countries [ ]. The main conclusion was that the risk of serious dipyridamole-induced adverse effects is very low, a conclusion that is in line with other reports [ ], and comparable to that reported for exercise testing in a similar patient population. Combined major adverse events among the entire patient population included 7 cardiac deaths (0.95 per 10 000), 13 non-fatal myocardial infarctions (1.76 per 10 000), 6 non-fatal sustained ventricular dysrhythmias (0.81 per 10 000) (ventricular tachycardia in 2 and ventricular fibrillation in 4), 9 transient cerebral ischemic attacks (1.22 per 10 000), 1 stroke, and 9 severe cases of bronchospasm (1.22 per 10 000). Minor non-cardiac adverse effects were less frequent among the elderly and more frequent in women and patients taking maintenance aspirin.

Comparative studies

Dipyridamole is a vasodilator and can cause hypotension, which can lead to myocardial ischemia in patients with coronary artery disease [ ]. The effect of dipyridamole has been studied to determine whether it reduces the blood pressure after cerebral ischemia of presumed arterial origin more than 6 months after the start of treatment) [ ]. Patients were randomized to aspirin combined with dipyridamole, usually in a modified-release formulation (n = 325) or aspirin alone (n = 341). After exclusion of those who did not adhere to therapy, 273 remained in the combination group and 318 in the group on aspirin alone. Common reasons for non-adherence were headache and gastrointestinal complaints; dizziness and cardiac symptoms (palpitation or angina pectoris) also occurred; some switched to oral anticoagulation. There was no clinically important reduction in blood pressure.

The results of other studies of aspirin plus dipyridamole versus aspirin alone for secondary prevention of vascular events after ischemic stroke of presumed arterial origin have been inconsistent. In a randomized single-blind trial patients were given aspirin (30–325, median 75, mg/day) with (n = 1363) or without (n = 1376) dipyridamole 200 mg bd (83% modified-release) within 6 months of a transient ischemic attack or minor stroke of presumed arterial origin [ ]. The primary outcome was the composite of deaths from all vascular causes, non- fatal stroke, non-fatal myocardial infraction, or major bleeding complications, whichever happened first. Primary analysis was by intention to treat. The mean follow up was 3.5 years. There were fewer primary outcome events in the patients who took the combination of aspirin plus dipyridamole (hazard ratio = 0.80; 95% CI = 0.66, 0.98; absolute risk reduction 1.0% per year, 95% CI = 0.1, 1.8). Addition of these data to a meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infraction of 0.82 (95% CI = 0.74, 0.91). Patients taking aspirin plus dipyridamole discontinued the trial medication more often than those taking aspirin alone (470 versus 184), mainly because of headache.

Placebo-controlled studies

The efficacy and safety of dipyridamole have been assessed in patients with chronic stable angina in a large-scale, international, randomized, placebo-controlled, parallel-group study, in which 400 patients with chronic stable angina pectoris and a positive treadmill exercise test were randomized to receive either modified-release dipyridamole (200 mg bd orally; n = 198) or 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 channel blockers and/or beta-blockers and/or long-acting (prophylactic) nitrates [ ]. Of the 198 patients randomized to dipyridamole, 134 completed the add-on phase but only 12 completed the monotherapy phase. Of the 202 patients randomized to placebo, 162 reached the add-on phase but only 12 reached the monotherapy phase. There were serious adverse events in 15 patients who took dipyridamole and 12 who took placebo (7.6% versus 6.0%). These included chest pain, angina pectoris, and non-cardiac adverse effects, such as diarrhea, nausea, and headache.