BACKGROUND: Acetylsalicylic acid (aspirin) is known to increase the risk of bleeding throughout the body. However, there is also evidence to suggest that acetylsalicylic acid may have a protective role in the formation and rupture of intracranial aneurysms. Previous studies investigating acetylsalicylic acid and subarachnoid hemorrhage (SAH) have so far provided conflicting results. AIMS: The aim of this study was to analyze the Nurse's Health Study (NHS) using serial assessments to evaluate differences in rates of SAH in those participants taking acetylsalicylic acid and those not taking acetylsalicylic acid while considering dose, frequency, and duration as well as different types of SAH. METHODS: The NHS is a prospective population-based cohort study of female nurses. Information on acetylsalicylic acid was first reported in 1980 until 2016 and included acetylsalicylic acid use, dose, frequency, and duration. All stroke cases were classified by physicians. Cox proportional-hazards regression models were used to estimate the hazard ratio (HR) associated with acetylsalicylic acid use. RESULTS: A total of 117,648 NHS participants were eligible for analysis with 357 cases of SAH observed over 4,091,239 years of follow-up. There was no association between acetylsalicylic acid use and SAH (HR = 1.02
95% confidence interval (CI) = [0.82, 1.28], p = 0.85), aneurysmal SAH (1.04
95% CI = [0.78, 1.39], p = 0.78), or idiopathic SAH (HR = 0.94
95% CI = [0.65, 1.34], p = 0.72). The number of acetylsalicylic acid tablets per week was associated with SAH (HR = 1.03
95% CI = [1.00, 1.06], p = 0.02), specifically fatal SAH (HR = 1.04 [1.00, 1.08], p = 0.03). There was no association between frequency and SAH (HR = 1.06
95% CI = [0.99, 1.13], p = 0.07). CONCLUSION: There was no evidence to support a protective association between acetylsalicylic acid and either SAH or aneurysmal SAH in female participants. In fact, there was some evidence to suggest increased SAH risk with increased acetylsalicylic acid dose in some but not all analyses. DATA ACCESS STATEMENT: Data are available by request from the Brigham and Women's Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health.