Antiplatelet Therapy After Spontaneous Intracerebral Hemorrhage and Functional Outcomes

Santosh B. Murthy, MD, MPH; Alessandro Biffi, MD; Guido J. Falcone, MD, ScD, MPH; Lauren H. Sansing, MD, MS; Victor Torres Lopez, BS; Babak B. Navi, MD, MS; David J. Roh, MD; Pitchaiah Mandava, MD, PhD, MSEE; Daniel F. Hanley, MD; Wendy C. Ziai, MD, MPH; Hooman Kamel, MD; Jonathan Rosand, MD; Kevin N. Sheth, MD

Disclosures

Stroke. 2019;50(11):3057-3063. 

In This Article

Abstract and Introduction

Abstract

Background and Purpose: Observational data suggest that antiplatelet therapy after intracerebral hemorrhage (ICH) alleviates thromboembolic risk without increasing the risk of recurrent ICH. Given the paucity of data on the relationship between antiplatelet therapy after ICH and functional outcomes, we aimed to study this association in a multicenter cohort.

Methods: We meta-analyzed data from (1) the Massachusetts General Hospital ICH registry (n=1854), (2) the Virtual International Stroke Trials Archive database (n=762), and (3) the Yale stroke registry (n=185). Our exposure was antiplatelet therapy after ICH, which was modeled as a time-varying covariate. Our primary outcomes were all-cause mortality and a composite of major disability or death (modified Rankin Scale score 4–6). We used Cox proportional regression analyses to estimate the hazard ratio of death or poor functional outcome as a function of antiplatelet therapy and random-effects meta-analysis to pool the estimated HRs across studies. Additional analyses stratified by hematoma location (lobar and deep ICH) were performed.

Results: We included a total of 2801 ICH patients, of whom 288 (10.3%) were started on antiplatelet medications after ICH. Median times to antiplatelet therapy ranged from 7 to 39 days. Antiplatelet therapy after ICH was not associated with mortality (hazard ratio, 0.85; 95% CI, 0.66–1.09), or death or major disability (hazard ratio, 0.83; 95% CI, 0.59–1.16) compared with patients not started on antiplatelet therapy. Similar results were obtained in additional analyses stratified by hematoma location.

Conclusions: Antiplatelet therapy after ICH appeared safe and was not associated with all-cause mortality or functional outcome, regardless of hematoma location. Randomized clinical trials are needed to determine the effects and harms of antiplatelet therapy after ICH.

Introduction

The relationship between prior antiplatelet therapy (APT) and intracerebral hemorrhage (ICH) outcomes has yet to be established, with studies yielding conflicting results.[1,2] Recent studies have failed to show an association between prior single APT and mortality or major disability in large ICH cohorts,[2] although dual APT may result in higher mortality.[3] Furthermore, conflicting data on hematoma expansion[4,5] and concerns over ventriculostomy tract hemorrhage[6] with APT have contributed to the hesitancy among clinicians to reinstate APT after ICH, even in the presence of strong indications.

Nonrandomized data including our own suggest that restarting oral anticoagulation therapy after ICH is associated with a lower risk of ischemic stroke and improvement in functional outcomes.[7,8] Similarly, emerging observational data seem to favor the use of antiplatelet medications after ICH given the decreased incidence of thromboembolic events, without an apparent offsetting increase in the risk of ICH recurrence.[9,10] In fact, the RESTART (Restart or Stop Antithrombotics) randomized trial that evaluated APT resumption after ICH showed that the risk of recurrent ICH was too small to exceed the established benefits of APT for secondary prevention.[11] There is, however, a paucity of evidence on the impact of APT on functional outcomes after ICH. In a recent analysis of patients enrolled in the ERICH (Ethnic and Racial Variation in Intracerebral Hemorrhage) study, restarting APT after ICH was initially associated with worse functional outcomes at 90 days.[12] However, these findings were ultimately attributed to differences in baseline characteristics and possibly confounding by indication, and no adverse association was observed in a propensity score matched analysis subsequently.[12] In the absence of randomized trials, it is important to address the impact of APT on ICH disability. We therefore sought to leverage multiple ongoing observational studies of ICH to investigate whether APT after ICH was associated with mortality and functional outcome.

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