Frequency of Intracranial Hemorrhage With Low-Dose Aspirin in Individuals Without Symptomatic Cardiovascular Disease

Abstract

IMPORTANCE Use of low-dose aspirin for the primary prevention of cardiovascular events remains controversial because increased risk of bleeding may offset the overall benefit. Among major bleeding events, intracranial hemorrhage is associated with high mortality rates and functional dependency. OBJECTIVE To assess the risk of intracranial hemorrhage associated with low-dose aspirin among individuals without symptomatic cardiovascular disease. DATA SOURCES PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1966 to October 30, 2018. STUDY SELECTION Randomized clinical trials that compared low-dose aspirin (daily dose Յ100 mg) vs control and recorded the end points of intracranial hemorrhage separately for active treatment and control groups were included. DATA EXTRACTION AND SYNTHESIS A random-effect estimate was computed based on the Mantel-Haenszel method. Relative risk with 95% CI was used as a measure of aspirin vs control on risk of intracranial hemorrhage. MAIN OUTCOMES AND MEASURES The main outcomes were any intracranial hemorrhage, intracerebral hemorrhage, subdural or extradural hemorrhage, and subarachnoid hemorrhage, for aspirin vs control. RESULTS The search identified 13 randomized clinical trials of low-dose aspirin use for primary prevention, enrolling 134 446 patients. Pooling the results from the random-effects model showed that low-dose aspirin, compared with control, was associated with an increased risk of any intracranial bleeding (8 trials; relative risk, 1.37; 95% CI, 1.13-1.66; 2 additional intracranial hemorrhages in 1000 people), with potentially the greatest relative risk increase for subdural or extradural hemorrhage (4 trials; relative risk, 1.53; 95% CI, 1.08-2.18) and less for intracerebral hemorrhage and subarachnoid hemorrhage. Patient baseline features associated with heightened risk of intracerebral hemorrhage with low-dose aspirin, compared with control, were Asian race/ethnicity and low body mass index. CONCLUSIONS AND RELEVANCE Among people without symptomatic cardiovascular disease, use of low-dose aspirin was associated with an overall increased risk of intracranial hemorrhage, and heightened risk of intracerebral hemorrhage for those of Asian race/ethnicity or people with a low body mass index.

Biomarker Application for Precision Medicine in Stroke

“…Such answers can be delivered only through recruitment of entire populations (e.g., Framingham [24] or Baseline [25] studies), though studies in stroke-prone populations (e.g., hypertensive, obese) based on global statistical analysis are also needed [26]. More recently, reports of increased risk of adverse events with aspirin when used for cardiovascular disease prevention in patients without symptomatic cardiovascular disease [27] highlight the need for patient-individualized interventions. Better identification of patients who could suffer from stroke within a whole population would have a tremendous impact on healthcare, as the new algorithm would better identify high-risk stroke groups on the level of individual patients.…”

Ethnic Differences in Oral Antithrombotic Therapy

“…In a meta-analysis of low-dose aspirin for primary prevention, investigators report a more profound increased risk of intracerebral hemorrhage in Asians compared with non-Asians. The relative risk (RR) of intracerebral hemorrhage in the Asian-populations trials was 1.84 (95% CI, 1.04–3.27; 2 trials), whereas in the non-Asian population trials the risk increase was insignificant (RR, 1.14; 95% CI, 0.89–1.46; 8 trials) 25) Likewise, gastrointestinal (GI) bleeding, a clinically relevant adverse effect by aspirin, 26) 27) occurred more often in East Asians. This can be mostly attributed to the higher prevalence of Helicobacter pylori infection and the genetic variation in relation to cytochrome P450 (CYP450) polymorphism.…”

Canadian Stroke Best Practice Recommendations, seventh edition: acetylsalicylic acid for prevention of vascular events

“…In the 3 aforementioned trials (ASPREE, 3 In a systematic review and meta-analysis designed specifically to examine the risk of intracranial hemorrhage associated with the use of ASA, Huang and colleagues 19 included the results of 13 RCTs (n = 134 446) that comprised individuals without pre-existing symptomatic cardiovascular diseases (e.g., coronary artery disease, stroke or peripheral artery disease). The trials compared low-dose ASA (≤ 100 mg/d for ≥ 6 mo) versus placebo or no treatment, and examined intracranial bleeding outcomes exclusively.…”