Aspirin and Risk of Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (aSAH) remains a morbid and lethal condition. Despite an increase in the number of unruptured intracranial aneurysms treated with endovascular techniques or microsurgical clipping, the incidence of aSAH is relatively unchanged in many countries including the United States. It seems as if risk factor modification such as smoking cessation has more impact on prevention of aSAH than treatment of unruptured aneurysms. For many patients with an unruptured aneurysm, the decision whether to pursue invasive therapy or continued observation with risk factor modification is challenging. Although antiplatelets and antithrombotic agents have been widely used in the prevention of thromboembolism and stroke, their effects on prevention of aSAH are not well established. There have been several recent studies that have suggested that the use of low-dose aspirin may reduce the risk of aSAH. Hasan et al first reported the protective role of aspirin against the risk of aSAH, finding that aspirin use 3× per week was associated with significantly reduced adjusted odds of aSAH. The authors hypothesized that the protective effect was secondary to modulation of the inflammatory pathways that have been implicated in the pathogenesis of aneurysm development and rupture. As a widely used and commonly available medication with an acceptable safety profile and dosing regimen, aspirin may be a promising treatment option for this indication. However, this evidence is conflicting with some studies suggesting that aspirin may be associated with increased risk of aSAH after short-term use. It seems that the beneficial effects of aspirin, if any, on the risk of aSAH is dependent on the duration of aspirin use and the prescribed dosing regimen. Given that aspirin use has the potential to increase the amount of subarachnoid blood after an aneurysm rupture, it is absolutely critical to establish the nature of the relationship between regular aspirin use and risk of aSAH. The evidence base on the role of aspirin in preventing aSAH remains unclear. Background and Purpose—Recent studies have suggested that the use of low-dose aspirin may reduce the risk of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to evaluate any association between aspirin use and risk of aSAH based on the literature, and whether this is influenced by duration or frequency of aspirin use. Methods—A search of electronic databases was done from inception to September 2016. For each study, data on risk of aSAH in aspirin versus nonaspirin users were used to generate odds ratios and 95% confidence intervals, and combined using inverse variance–weighted averages of logarithmic odds ratios in a random-effects models. Results—From 7 included studies, no significant difference was noted between aspirin use of any duration or frequency and nonaspirin users (odds ratio, 1.00; 95% confidence interval, 0.81–1.24; P=0.99). We found a significant association between short-term use of aspirin (<3 months) and the risk of aSAH (odds ratio, 1.61; 95% confidence interval, 1.20– 2.18; P=0.002). No significant difference was found in terms of risk of aSAH for 3 to 12 months, 1 to 3 years, and >3 years of durations of use. No significant association was found between infrequent aspirin use (≤2× per week) or frequent use (≥3× per week) with risk of aSAH. Conclusions—Current evidence suggests that short-term (<3 months) use of aspirin is associated with increased risk of aSAH. Limitations include substantial heterogenity of the included studies. The role of long-term aspirin in reducing risk of aSAH remains unclear and ideally should be addressed by an appropriately designed randomized controlled trial. (Stroke. 2017;48:1210-1217. DOI: 10.1161/STROKEAHA.116.015674.)