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Dipyridamole increases adenosine levels and augments coronary collateralization in patients with coronary ischemia. This pilot study tested whether a 6-month course of sustained-release dipyridamole/aspirin improves coronary flow reserve and left ventricular systolic function in patients with ischemic cardiomyopathy. Six outpatients with coronary artery disease and left ventricular ejection fraction (LVEF) <40% were treated with sustained-release dipyridamole 200 mg/aspirin 25 mg twice daily for 6 months. Myocardial function and perfusion, including coronary sinus flow at rest and during intravenous dipyridamole-induced hyperemia, were measured using velocity-encoded cine magnetic resonance stress perfusion studies at baseline, 3 months, and 6 months. There was no change in heart failure or angina class at 6 months. LVEF increased by 39%±64% (31.0%±13.3% at baseline vs 38.3%±10.7% at 6 months; P=.01), hyperemic coronary sinus flow increased more than 2-fold (219.6±121.3 mL/min vs 509.4±349.3 mL/min; P=.01), and stress-induced relative myocardial perfusion increased by 35%±13% (9.4%±3.4% vs 13.9%±8.5%; P=.004). Sustained-release dipyridamole improved hyperemic myocardial blood flow and left ventricular systolic function in patients with ischemic cardiomyopathy.