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Original article

Maulaz AB et al. (2005) Effect of discontinuing aspirin therapy on the risk of brain ischemic stroke. Arch Neurol 62: 1217–1220   PubMed

Synopsis

Background

Owing to its antithrombotic effect, aspirin is widely used for the prevention of ischemic vascular disease; however, treatment is often interrupted, for example before surgery or as a result of drug intolerance. Aspirin withdrawal could theoretically cause a rebound prothrombotic effect, and preliminary clinical evidence suggests that aspirin discontinuation might indeed prompt an ischemic stroke.

Objective

To investigate whether the withdrawal of aspirin therapy is a risk factor for ischemic cerebrovascular disease.

Design and intervention

This retrospective, cross-sectional, single-center case–control study included 309 patients who were admitted to hospital between January 2002 and April 2004 after an ischemic stroke or transient ischemic attack (TIA) and who had received long-term antiplatelet therapy containing aspirin before their index event. Patients showing poor compliance with previous treatment for cerebrovascular or cardiovascular risk factors were excluded. The control group consisted of 309 age-matched and sex-matched outpatients with a history of stroke who had not had a stroke or TIA in the previous 6 months and who were taking long-term antiplatelet therapy containing aspirin for the secondary prevention of cerebrovascular events. The investigators collected information on the presence of cerebrovascular risk factors and on the discontinuation of aspirin therapy in the 4 weeks before the ischemic event (patients) or before participation in a telephone survey (controls).

Outcome measure

The primary outcome was the frequency of aspirin therapy discontinuation during the 4 weeks before the ischemic cerebral event or telephone interview.

Results

The two groups had similar frequencies of cerebrovascular risk factors, with the exception of coronary heart disease, which was more frequent in patients than in controls (36% vs 18%; P <0.001). During the 4 weeks before the cerebrovascular event or before interview, 13 patients (4.2%) discontinued aspirin therapy compared with 4 controls (1.3%; P = 0.03). The odds ratio for an ischemic cerebral event in the 4 weeks after aspirin interruption was 3.34 (95% CI 1.07–10.39). After adjustment for coronary heart disease, discontinuation of aspirin therapy remained a significant risk factor for a cerebrovascular event in the 4 weeks after aspirin discontinuation (odds ratio 3.4; 95% CI 1.08–10.63). The main reasons for interrupting aspirin therapy were surgery, the treating physician's decision that the therapy had no clear clinical benefit, bleeding complications, negligence, and dementia. The mean ( SD) interval between treatment withdrawal and cerebral infarction in the patient group was 9.5 ( 7) days. Cardiometabolic stroke was the most common subtype of stroke associated with aspirin cessation.

Conclusion

The findings suggest that aspirin discontinuation could increase the risk of stroke during the first 4 weeks after treatment interruption.

Commentary

Aspirin is the mainstay of primary and secondary stroke prevention. The rate of cerebrovascular events such as ischemic stroke and TIA after discontinuation of aspirin has not been clearly studied in a case-controlled fashion. Aspirin is usually discontinued before elective surgical procedures, because it increases complications by prolonging bleeding times and increasing operative blood loss.^{1, 2} Anecdotal evidence indicates that strokes can occur when patients discontinue either warfarin or aspirin. It is not clear, however, whether this apparent association is coincidence, a result of transient hypercoagulability from surgical procedures, or caused primarily by the discontinuation of antithrombotic medication.

Maulaz et al. have shed some light on this issue. The aim of their study was to find out whether more TIAs and strokes occur in patients who discontinue aspirin than in those with good aspirin compliance. Using a retrospective design, the authors compared the rate of aspirin discontinuation in a group of inpatients who had experienced a recent TIA or stroke with that in a group of outpatients who had a history of stroke or TIA, but who had not experienced a cerebrovascular event in the previous 6 months. The cerebrovascular risks in the two groups were similar but not identical, with the inpatients having a higher rate of cardiovascular disease. The reasons for aspirin discontinuation—surgery, treating physician's decision, bleeding complications, negligence or dementia—also imply that the inpatients might have been sicker and at a greater risk of stroke than the relatively stable outpatient population. The authors found a statistically significant odds radio for stroke in patients who discontinued aspirin (P <0.005), with most strokes being of cardioembolic origin. The risk estimate had a wide confidence interval, however, probably owing to the small number of stroke patients who discontinued aspirin (n = 13).

The assumed cause of the increased rate of stroke and TIA after halting aspirin is a rebound prothrombotic effect. Experimental studies quoted in the article by Maulaz et al. suggest that this effect can occur 8–21 days after halting aspirin use, and many clinicians feel that withholding aspirin for 5–7 days is risk-free when compared with the low risk of aspirin complicating procedures such as endoscopy or conventional angiography. Most concerning in the present study was the short duration of time that elapsed between the stopping of aspirin and the onset of TIA or stroke—six patients had a stroke within 5 days, and 70% of the strokes occurred in less than 10 days after discontinuation of aspirin. As this is a population-based study analyzing risk, an etiology for the observed strokes can only be surmised. The findings serve as reasonable evidence, however, that interruption of aspirin therapy should be carefully weighed against the risks, and that compliance with aspirin on the patient's part is vital. Other literature supports this view and suggests that continuation of aspirin or the rapid reintroduction of aspirin after coronary artery bypass graft surgery might in fact be beneficial.^{3, 4}

In conclusion, the findings from this retrospective study provide a preliminary indication that discontinuation of aspirin therapy might be more risky than previously supposed, and that care should be taken when aspirin is discontinued—particularly in patients with a high cardioembolic stroke risk.

Acknowledgments

The synopsis was written by Martina Habeck, Associate Editor, Nature Clinical Practice.

References

1. Amrein PC et al. (1981) Aspirin-induced prolongation of the bleeding time and perioperative blood loss. JAMA 245: 1825–1828 | Article | PubMed | ISI | ChemPort |
2. Cahill RA et al. (2005) Duration of increased bleeding tendency after cessation of aspirin therapy. J Am Coll Surg 200: 564–573 | Article | PubMed | ISI |
3. Katz J et al. (2003) Risks and benefits of anticoagulant and antiplatelet medication use before cataract surgery. Ophthalmology 110: 1784–1788 | Article | PubMed | ISI |
4. Topol EJ (2002) Aspirin with bypass surgery—from taboo to new standard of care. N Engl J Med 347: 1359–1360 | Article | PubMed | ISI |

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Subject areas under which this article appears: Stroke