Withdrawing Aspirin Significantly Increases Stroke Risk

Aspirin cessation in adults at high risk of cerebrovascular disease increases the risk of stroke and TIA. Withdrawing aspirin significantly increases the risk of stroke, according to the results of a case-control study. "Aspirin, or acetylsalicylic acid, is widely used to prevent ischemic vascular disease," write Alexandre Balzano Maulaz, MD, from Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, and colleagues. "Clinical and experimental data suggest that a rebound effect occurs four or fewer weeks after interruption of aspirin therapy."

Cases consisted of 309 patients with ischemic stroke (IS) or transient ischemic attack (TIA) undergoing long-term aspirin treatment before their index event, and 309 control subjects who had not had an IS in the previous six months were matched for age, sex, and antiplatelet therapy. The investigators compared the frequency of aspirin therapy discontinuation during the four weeks before a cerebral ischemic event in patients and during the four weeks before interview in control subjects.

Both groups had a similar frequency of risk factors, except for coronary heart disease (CHD), which was more prevalent in IS or TIA patients (36% vs 18%; P < .001). Thirteen IS or TIA patients and four control subjects had discontinued aspirin. After adjustment in a multivariable model, aspirin interruption yielded an odds ratio for IS or TIA of 3.4 (95% confidence interval, 1.08 – 10.63; P < .005).

"These results highlight the importance of aspirin therapy compliance and give an estimate of the risk associated with the discontinuation of aspirin therapy in patients at risk for IS, particularly those with coronary heart disease," the authors write.
Study limitations include those inherent to a case-control design, risk of a selection bias toward control subjects with higher health awareness, possible underestimation of the frequency of aspirin therapy discontinuation or of the delay between treatment cessation and cerebral infarct, inability to exclude the possibility that aspirin dosage may be important in the development of the rebound phenomenon, and differing indications for taking aspirin in the two groups.

"The discontinuation of aspirin therapy could increase the risk of IS in patients with multiple cardiovascular risk factors, mainly in those with CHD, and we should be aware of the indications, adverse effects, and potential complications of stopping aspirin use," the authors conclude. "Preoperative withholding of antiplatelet drug therapy in patients with ischemic heart disease may not always be the best solution and requires further study."

Arch Neurol. 2005;1217-1220

Practice Notes: Aspirin works as an anticoagulant through higher levels of inhibition of thromboxane A2 than prostacyclin. However, cessation of aspirin may leave the patient at risk of decreased prostacyclin production within the microvasculature.

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