Risk of Subarachnoid Hemorrhage and Early Case Fatality Associated With Outpatient Antithrombotic Drug Use

Background and Purpose Subarachnoid hemorrhage (SAH) accounts for <7% of all strokes, but is an enormous individual and societal burden. We investigated the risk of SAH associated with prior use of antithrombotic drugs and their influence on 30-day case fatality. Methods We conducted a nested case-control study in a cohort of 13.4 million members of the German Pharmacoepidemiological Research Database. Ten controls were matched to each case hospitalized for SAH between July 2004 and November 2006 by health insurance, year of birth, and sex using risk set sampling. Exposure was assessed for the warfarin analog phenprocoumon, heparin, clopidogrel/ticlopidine, and acetylsalicylic acid. Multivariable-adjusted odds ratios (ORs) for SAH were estimated by conditional logistic regression. Risk factors for 30-day case fatality were assessed in patients with SAH by logistic regression. Results The nested case-control study included 2065 SAH cases and 20649 matched controls. The risk of SAH was significantly increased for phenprocoumon (OR, 1.7; 95% confidence interval [CI], 1.3-2.3), clopidogrel/ticlopidine (OR, 1.7; 95% CI, 1.1-2.5), and for acetylsalicylic acid use (OR, 1.5; 95% CI, 1.2-2.0), but not for outpatient heparin use (OR, 1.2; 95% CI, 0.5-2.7). The early case fatality of 22.8% was associated with an age >70 years (OR, 2.3; 95% CI, 1.8-3.1) and arterial hypertension (OR, 1.3; 95% CI, 1.0-1.6), but not with any of the antithrombotic drugs. Conclusions Outpatient antithrombotic drug use was associated with an increased risk of SAH, but no association was observed with early case fatality.