Efficacy of Aspirin Plus Extended-Release Dipyridamole in Preventing Recurrent Stroke in High-Risk Populations

Sacco, Ralph L.; Sivenius, Juhani; Diener, Hans Christoph

doi:10.1001/archneur.62.3.403

Cited by 52 publications

(27 citation statements)

References 18 publications

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“…7 A post hoc analysis of the data from ESPS 2 showed that the efficacy of the dipyridamole/aspirin combination was greater in patients with the highest risk of stroke and those who had other cardiovascular diseases. 8 Thus, available information supports the efficacy of dipyridamole/aspirin combination in stroke prevention, and an ongoing clinical trial will compare the efficacy and safety of dipyridamole/aspirin and clopidogrel in stroke prevention. 9 Dipyridamole is known to inhibit the nucleoside transporter responsible for terminating the actions of adenosine.…”

Section: Discussionmentioning

confidence: 99%

Role of Adenosine and Nitric Oxide on the Mechanisms of Action of Dipyridamole

Gamboa

Abraham

Diedrich

et al. 2005

Stroke

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Background and Purpose-The combination of dipyridamole and aspirin has been shown to be more effective than aspirin alone in the secondary prevention of stroke. Dipyridamole may act by inhibiting adenosine uptake, thus potentiating its actions. Dipyridamole also inhibits cGMP-specific phosphodiesterases (PDE) and, through this mechanism, could potentiate cGMP-mediated actions of nitric oxide. Methods-To define the mechanism of action of dipyridamole, we studied the local vascular effects of adenosine, acetylcholine (NO-mediated dilation), and nitroprusside (cGMP-mediated dilation) in a double-blind study after treatment with dipyridamole/aspirin (200 mg dipyridamole/25 mg aspirin twice a day) or aspirin control for 7 days in 6 normal volunteers. Vasodilators were administered into the brachial artery in the nondominant arm in random order and forearm blood flow (FBF) was measured by venous occlusion plethysmography. Results-Adenosine at a dosage of 125 g/min increased FBF from 4.6Ϯ0.9 to 29.4Ϯ5.3 (539% increase) with dipyridamole/aspirin and from 3.9Ϯ0.8 to 12Ϯ2.5 mL/100 mL forearm/min (208% increase) with aspirin alone (Pϭ0.007). In contrast, dipyridamole/aspirin did not alter the response to acetylcholine or to nitroprusside. The magnitude of adenosine-induced vasodilation correlated with plasma dipyridamole concentrations (r 2 ϭ0.6); no correlation was observed with acetylcholine-or nitroprusside-induced vasodilation. Similar potentiation of adenosine, but not acetylcholine or nitroprusside, was observed in 7 additional subjects when adenosine, acetylcholine, and nitroprusside were given in random order before and 2 hours after a single dose of dipyridamole/aspirin. Conclusion-The

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Section: Discussionmentioning

confidence: 99%

Role of Adenosine and Nitric Oxide on the Mechanisms of Action of Dipyridamole

Gamboa

Abraham

Diedrich

et al. 2005

Stroke

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“…Individual patient data were available for 11,036 patients. Recurrent stroke was reduced by dipyridamole compared with placebo (odds ratio A post hoc analysis of data from ESPS2 indicates that the efficacy advantage of combined MR-dipyridamole-aspirin over aspirin alone is greater in higher-risk patients [18]. Annual rates of strokes and vascular events for the MR-dipyridamole-aspirin group (n = 1650) and the aspirin-only group (n = 1649) were stratified according to both risk subgroups and individual risk factors.…”

Section: Combined Mr-dipyridamole and Aspirin -Drug Evaluationmentioning

confidence: 99%

Modified-Release Dipyridamole Combined with Aspirin for Secondary Stroke Prevention

Diener

2005

Aging Health

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Patients suffering from transient ischemic attack (TIA) or ischemic stroke have a high risk of suffering a first or recurrent stroke, with an annual risk of between 5 and 15%. The European Stroke Prevention Study (ESPS)2 was a randomized, double-blind, placebocontrolled trial involving 6602 patients with TIA or stroke comparing aspirin alone (50 mg daily), modified-release (MR) dipyridamole alone (200 mg twice daily), aspirin plus dipyridamole, and placebo. The 2-year relative risk reduction of stroke in the aspirin plus MR-dipyridamole group (37.0%) was significantly higher than in either the aspirin group (18.1%) or the MR-dipyridamole group (16.3%). The results of the comparison between aspirin plus MR-dipyridamole versus placebo confirmed the findings of ESPS1. The results of ESPS2 were at odds with all prior trials with dipyridamole alone or in association with aspirin, but it was also the only trial sufficiently powered to show a significant difference. For this reason, a meta-analysis was performed based on a systematic review of individual patient data from randomized controlled trials involving dipyridamole in patients with prior ischemic stroke or TIA. Recurrent stroke was reduced by dipyridamole compared with placebo, and by combined aspirin and dipyridamole versus aspirin alone, dipyridamole alone or placebo. In two post hoc analyses the efficacy of aspirin plus extended-release dipyridamole was compared with aspirin alone for the prevention of recurrent stroke among high-risk groups. Stroke models from the Framingham Study and the Stroke Prognostic Instrument II were applied to subjects in ESPS2 to assign patients to risk groups. Compared with aspirin alone, aspirin plus MR-dipyridamole demonstrated a more pronounced efficacy in reducing the risk for stroke and vascular events among patients younger than 70 years of age, with hypertension, or prior stroke; current smokers; and those with any prior cardiovascular disease. Another model (Essen risk score) showed that patients with a high risk of recurrent stroke show a much greater benefit from aspirin plus MR-dipyridamole compared with aspirin monotherapy than patients with a low risk.Annually, 15 million people worldwide suffer a stroke, of whom 5 million die and 5 million are permanently disabled [1]. The age-related incidence of stroke is declining in many developed countries, largely as a result of the control of risk factors such as high blood pressure and smoking. The absolute number of strokes continue to increase because of the aging population. For example, stroke is the biggest single cause of disability in the UK. People who have an ischemic stroke or transient ischemic attack (TIA) are at high risk of a second stroke [2], although this risk ranges from approximately 5% to around 20% per year [3,4]. The recurrence risk is highest in the first few days after a TIA or stroke and declines with time. Such second strokes often cause substantial disability and greatly reduce quality of life.Evidence-based improvements to the prevention of second...

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“…17 A post hoc subgroup analysis of ESPS-2 has shown that the treatment benefit associated with aspirin/ER-DP is particularly great among certain high-risk patients. 18 Patients with a history of hypertension, MI, TIA, or stroke prior to the index event, or any CVD, as well as patients who were smokers at baseline, showed greater benefit than low-risk patients when aspirin/ER-DP was compared with aspirin alone. 18 …”

Section: Dipyridamole Plus Aspirinmentioning

confidence: 92%

“…18 Patients with a history of hypertension, MI, TIA, or stroke prior to the index event, or any CVD, as well as patients who were smokers at baseline, showed greater benefit than low-risk patients when aspirin/ER-DP was compared with aspirin alone. 18 …”

Section: Dipyridamole Plus Aspirinmentioning

confidence: 92%

Prevention of vascular events in patients with cerebrovascular disease: Efficacy and appropriate duration of antiplatelet therapy

Habib

2006

Clinical Cardiology

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Summary:Antiplatelet therapy has shown consistent benefit in the prevention of secondary stroke. The paucity of head-tohead studies of different antiplatelet regimens, assessment of comparative efficacy, and optimal treatment duration requires evaluation and comparison of clinical studies that vary extensively in design and follow-up. Evidence for aspirin benefit in secondary stroke prevention is strong, but existing studies provide little guidance with regard to treatment duration. The efficacy of clopidogrel in secondary event prevention is significantly greater than that of aspirin for patients with a history of peripheral artery disease, but does not differ from that of aspirin for patients with a history of stroke or myocardial infarction. Relative to clopidogrel alone, the addition of aspirin to clopidogrel results in increased risk for life-threatening bleeding episodes similar in absolute magnitude to the reduction of secondary event risk in patients with stroke. Benefits associated with clopidogrel occur early in the course of therapy; few data support clopidogrel use for longer than 1 year after stroke. Monotherapy with extended-release dipyridamole (ER-DP) provides reduction in secondary stroke risk similar to aspirin; however, the combination of aspirin plus ER-DP significantly reduces risk relative to either agent alone. Compared with placebo and monotherapy with either agent, risk reduction for the aspirin plus ER-DP combination continued through 24 months, with no concomitant increase in bleeding risk. Additional clinical studies should provide needed comparisons of efficacy and guidance with regard to optimal duration of therapy.

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Efficacy of Aspirin Plus Extended-Release Dipyridamole in Preventing Recurrent Stroke in High-Risk Populations

Cited by 52 publications

References 18 publications

Role of Adenosine and Nitric Oxide on the Mechanisms of Action of Dipyridamole

Role of Adenosine and Nitric Oxide on the Mechanisms of Action of Dipyridamole

Modified-Release Dipyridamole Combined with Aspirin for Secondary Stroke Prevention

Prevention of vascular events in patients with cerebrovascular disease: Efficacy and appropriate duration of antiplatelet therapy

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