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Published Online
on June 11, 2009

Stroke. 2009
Published online before print June 11, 2009, doi: 10.1161/STROKEAHA.109.552760
A more recent version of this article appeared on August 1, 2009
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Submitted on March 16, 2009
Accepted on May 5, 2009

Withdrawal of Statins and Risk of Subarachnoid Hemorrhage

Roelof Risselada MD*; Huub Straatman MSc; Fop van Kooten MD, PhD; Diederik W.J. Dippel MD, PhD; Aad van der Lugt MD, PhD; Wiro J. Niessen PhD; Azadeh Firouzian MSc; Ron M.C. Herings PhD; and Miriam C.J.M. Sturkenboom PharmD, PhD

From the Departments of Medical Informatics (R.R., W.J.N., A.F., M.C.J.M.S.), Neurology (F.v.K., D.W.J.D.), Radiology (A.v.d.L., W.J.N., A.F.), and Epidemiology (M.C.J.M.S.), and iBMG (R.M.C.H.), Erasmus MC, Rotterdam, the Netherlands; PHARMO Institute (H.S., R.M.C.H.), Utrecht, the Netherlands; and the Faculty of Applied Sciences (W.J.N.), Delft University of Technology, the Netherlands.

* To whom correspondence should be addressed. E-mail: r.risselada{at}erasmusmc.nl.

Background and Purpose—Vascular endothelium, which can be affected by statins, is believed to play a substantial role in subarachnoid hemorrhage (SAH). Our objective was to estimate the association between use and withdrawal of statins and the risk of SAH.

Methods—We conducted a population-based case–control study within the PHARMO database. A case was defined as a person hospitalized for SAH (ICD-9-CM code 430) in the period January 1, 1998 to December 31, 2006. Ten randomly chosen controls were matched to each case on age, gender, and calendar date.

Results—During the study period 1004 incident cases of SAH were identified. Current use of statins did not significantly decrease the risk of SAH (OR=0.77, 95% CI 0.55 to 1.07). The odds ratio for recent withdrawal compared to nonusers was 1.62 (95% CI 0.96 to 2.73). Compared to current use, recent withdrawal was associated with an increased risk of SAH (OR=2.34, 95% CI 1.35 to 4.05). Interaction analysis showed that the effect of statin withdrawal was highest in patients who had also recently stopped antihypertensive drugs (OR=6.77, 95% CI 2.10 to 21.8).

Conclusions—Current use of statins seems to lower the risk of SAH, although the reduction was not significant in new users. Statin withdrawal increased the risk of SAH by a factor 2, even more in patients who had also recently stopped their antihypertensive treatment.


Key words: subarachnoid hemorrhage • case–control study • 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors • statins • withdrawal