Dipyridamole and headache—a pilot study of initial dose titration

Lindgren, Arne; Husted, Steen; Staaf, Gert; Ziegler, Birgitte

doi:10.1016/j.jns.2004.05.011

Cited by 28 publications

(18 citation statements)

References 7 publications

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“…A pilot study of increasing the dosing interval of one capsule at night compared with the regular recommendation as initial treatment was completed before our own study in which the secondary endpoints tended to support our own results [3]. The titration approach as in our study has been shown to cause fewer headaches than that of regular dosing.…”

Section: Discussionmentioning

confidence: 53%

“…However, it clearly showed that headache was reported more frequently for the dipyridamole-containing treatments than for aspirin or placebo during the first month of treatment only. Lindgren et al[ 3] suggested that titration with an initially lower dose of dipyridamole may be considered to reduce headache and thereby increase compliance though the differences between regular dose and titration regimens were not statistically significant. Diener [4] also observed that headachecan be prevented by gradually increasing the dose of dipyridamole over several days in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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Dose Titration to Reduce Dipyridamole-Related Headache

Chang¹,

Ryu²,

Lee³

2006

Cerebrovasc Dis

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Background: Combination of low-dose aspirin and modified-release dipyridamole (ASA+MR-DP) provides a significantly increased benefit in stroke prevention over aspirin alone. However, headaches were reported in more patients receiving dipyridamole-containing agents than in those receiving placebo. We undertook a randomized, double-blind, placebo-controlled trial to evaluate which dosing regimens of ASA+MR-DP have better tolerance. Methods: This trial randomized 146 patients with a history of ischemic cerebrovascular disease into three groups: placebo (days 1–28), reduced dose (placebo on days 1–4, ASA+MR-DP once daily before bed during days 5–14, and b.i.d. on days 15–28), and regular dose (placebo on days 1–4, and ASA+MR-DP b.i.d. on days 5–28). Using Chinese diary card, headache was assessed as mean cumulated headache (Σ frequency × intensity/occurrence days × study days) over the study period, and was graded 0–4 according to Cancer Therapy Evaluation Program, Common Toxicity Criteria, Version 2.0. Results: Intent-to-treat patients after randomization was 46 in placebo group, 45, reduced dose, and 49, regular dose. Among commonly reported adverse effects, headache of any grade occurred significantly more in the regular dose group (38.8%), as compared to the other two groups (p < 0.05). Mean cumulated headache was higher (p < 0.05) in the regular dose group than in the reduced group during days 5–14. Of 27 patients who dropped out, 15 (55.6%) were due to headache, which was substantially more in regular dose (8, 53.3%), though the difference was statistically insignificant. Conclusions: Initial reduced dose treatment with ASA+MR-DP may cause fewer headaches than regular dosing, and seems better tolerated by those susceptible to phosphodiesterase inhibitor-induced headache.

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Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Dose Titration to Reduce Dipyridamole-Related Headache

Chang¹,

Ryu²,

Lee³

2006

Cerebrovasc Dis

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“…Upward tapering of the dipyridamole dose may be helpful, 5,6 although this therapy requires further study. Adherence to medication use is an important factor to consider and is affected by costs, side effects, and frequency of dosing.…”

Section: Class III Recommendationmentioning

confidence: 99%

Update to the AHA/ASA Recommendations for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack

Adams¹,

Albers²,

Alberts³

et al. 2008

Stroke

439

290

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T he American Heart Association/American Stroke Association (AHA/ASA) Writing Committee for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack (TIA) has reviewed the results of recent trials that were published after our previous recommendations were issued. 1 Our intention in the present statement is to provide a brief review of the new data, to update specific recommendations, and to provide the reasons for any modifications. The 2 areas in which major new clinical trials have been published are (1) the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA and (2) the use of statins in the prevention of recurrent stroke.

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“…A pilot study of initial dose titration suggested that titration with an initially lower dose of dipyridamole may reduce headache and increase compliance, although the differences seen were not significant [20]. Patients were randomized to standard aspirin and dipyridamole treatment twice daily for 2 weeks or to aspirin only in the morning, and aspirin and dipyridamole in the evening for 5 days, followed by 9 days of standard aspirin and dipyridamole treatment.…”

Section: Tolerability and Safetymentioning

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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Dipyridamole and headache—a pilot study of initial dose titration

Cited by 28 publications

References 7 publications

Dose Titration to Reduce Dipyridamole-Related Headache

Dose Titration to Reduce Dipyridamole-Related Headache

Update to the AHA/ASA Recommendations for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack

Modified-Release Dipyridamole Combined with Aspirin for Secondary Stroke Prevention

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