Prosthetic Heart Valves
Dipyridamole is used orally as an adjunct to coumarin anticoagulants (e.g., warfarin) in the prevention of postoperative thromboembolic complications of heart valve replacement. Because warfarin therapy alone may not completely prevent thrombosis in patients with mechanical prosthetic heart valves, dipyridamole has been used in conjunction with warfarin in an effort to reduce the risk of thrombosis in these patients. While some evidence suggests that dipyridamole used in conjunction with warfarin may be more effective in reducing postoperative thromboembolic events in patients with mechanical prosthetic heart valves than use of warfarin alone, the American College of Chest Physicians (ACCP) and other experts generally recommend the addition of low-dose aspirin (rather than dipyridamole) to warfarin therapy in such patients. Dipyridamole should not be used alone, without warfarin, for the prevention of postoperative thromboembolic complications in patients undergoing placement of mechanical prosthetic heart valves since there is no evidence to date that dipyridamole (or other platelet-aggregation inhibitors) would be effective when used alone.
Transient Ischemic Attacks and Completed Thrombotic Stroke
Extended-release dipyridamole in fixed combination with aspirin is used to reduce the risk of stroke in patients who have had transient ischemic attacks (TIAs) or completed thrombotic stroke (secondary prevention).
In a randomized, comparative, placebo-controlled study, patients who had experienced either an ischemic stroke or TIAs were assigned to receive treatment with aspirin (25 mg twice daily), extended-release dipyridamole (200 mg twice daily), aspirin plus extended-release dipyridamole (25 and 200 mg twice daily, respectively), or placebo. All active treatments reduced the risk of the primary end points of stroke (nonfatal or fatal) or stroke and/or death compared with placebo. Aspirin plus dipyridamole reduced the risk of stroke by about 23% compared with aspirin alone and by about 25% compared with dipyridamole alone at 2 years of follow-up; the effects of combined therapy on risk reductions with aspirin and dipyridamole were additive but not synergistic. Aspirin, dipyridamole, and the combination also reduced the incidence of TIAs and other vascular events in a manner consistent with these treatments' effects on the risk of stroke. None of the treatments had a statistically significant effect on the end point of death (i.e., no effect on survival). Headache and GI events were the most common adverse effects in this study, occurring more frequently in the dipyridamole-treated groups, while bleeding from the GI tract or from any site was more common in the aspirin-treated groups.
ACCP, the American Stroke Association (ASA), and the American Heart Association (AHA) recommend antiplatelet therapy for secondary prevention of ischemic atherothrombotic (noncardioembolic) stroke or TIAs in patients with prior TIAs or stroke. These experts consider the combination of aspirin and dipyridamole (25 mg aspirin/200 mg extended-release dipyridamole twice daily) an acceptable antiplatelet option for the prevention of recurrent stroke or other cardiovascular events in such patients; other options include aspirin monotherapy, cilostazol, or clopidogrel. When selecting an appropriate antiplatelet regimen for the secondary prevention of noncardioembolic stroke, factors such as the patient's individual risk for recurrent stroke, tolerance, and cost of the different agents should be considered.
Adjunct to Thallium Myocardial Perfusion Imaging
Dipyridamole is used IV as an adjunct to thallous (thallium) chloride Tl 201 myocardial stress perfusion imaging in patients unable to exercise adequately.
The sensitivity and specificity of dipyridamole-assisted thallium imaging versus coronary arteriography in the detection of coronary artery disease were determined by comparing the results of thallium imaging with those of coronary arteriography under blinded conditions. The sensitivity of dipyridamole-assisted thallium imaging (true positive thallium imaging divided by the number of patients with positive angiograms) was 85% and the specificity (true negative thallium imaging divided by the number of patients with negative angiograms) was about 50%. In a subset of patients who had exercise thallium imaging or dipyridamole-assisted thallium imaging, the sensitivity and specificity of the 2 tests were almost identical.
Dipyridamole also has been used orally to decrease platelet aggregation in a number of other thromboembolic disorders. ACCP suggests postoperative anticoagulant therapy with unfractionated heparin and antiplatelet therapy with aspirin and/or dipyridamole to reduce thromboembolic events in children with heart failure who require implantation of ventricular assist devices. However, for most thromboembolic disorders, it has not been established whether the inclusion of dipyridamole in an antithrombotic regimen substantially enhances the potential benefit compared with that of the other antithrombotic agents (e.g., aspirin) alone, and some evidence suggests that in certain disorders, it may not (e.g., for prevention of thromboembolic complications in patients surviving a myocardial infarction (MI) or following PCI, coronary artery bypass graft [CABG] surgery, lower extremity vascular reconstruction).
ACCP recommends the use of dipyridamole in combination with aspirin as an option for long-term antiplatelet therapy in patients with symptomatic carotid stenosis, including those who have undergone recent carotid endarterectomy.
There currently is no evidence that antiplatelet agents such as dipyridamole or ticlopidine have any advantage over aspirin for mortality reduction following an acute MI.
Dipyridamole has been used in the long-term therapy of chronic angina pectoris based on the premise that prolonged therapy with the drug may reduce the frequency of or eliminate anginal episodes, improve exercise tolerance, and reduce requirements for nitroglycerin. However, well-controlled clinical studies showed that long-term oral administration of dipyridamole does not prevent ECG signs of myocardial ischemia in patients with angina pectoris following exercise or decrease the frequency or severity of anginal attacks, and experts state that there is evidence and/or general agreement that dipyridamole is not useful or effective for the management of chronic angina pectoris. The drug also is not effective for the treatment of acute episodes of angina and is not a substitute for appropriate medical programs for the treatment of angina pectoris.