Combination Antiplatelet Therapy Associated With Higher Mortality After ICH Than Single Antiplatelet Therapy

Antiplatelet therapy (APT) is associated with increased risk of intracerebral hemorrhage (ICH), though data about the association between APT use and mortality risk after ICH are limited.

In a study published in Stroke, Nadeem I. Khan, MD, from the Department of Neurology at the Southern Illinois University School of Medicine in Springfield, and co-authors assessed mortality and other post-ICH outcomes associated with prior APT use in patients with ICH in a real-world setting. They found that patients who received combination APT – but not single APT – at the time of ICH diagnosis had a higher mortality risk, compared with patients who were not receiving APT.

“These findings provide important insights into the risks associated with prior APT use among … patients with ICH,” the authors wrote, adding that the results suggest “a threshold effect” in which platelet-function inhibition affects outcome.

The investigators identified 82,576 patients not on oral anticoagulant therapy from 1,574 sites from the Get With The Guidelines®-Stroke registry database – an ongoing, voluntary, continuous registry and performance-improvement initiative for stroke care – between October 2012 and March 2016.

Prior to ICH diagnosis, patients were:

  • not receiving APT (n=54,299; 65.8%)
  • receiving single APT (n=24,331; 29.5%)
  • receiving combination APT (n=3,946; 4.8%)

The median age of patients not receiving APT was 64 years, and it was 76 years in the single- and combination-APT groups (ranges not provided). The most common APT used in the single-APT group was aspirin.

The researchers detected a modest increase in in-hospital mortality in patients who were receiving APT, compared with those who were not (24% vs. 23%; odds ratio [OR] = 1.05; 95% CI 1.01-1.10; p=0.012).

Between patients in the single- and combination-APT groups, the risk of in-hospital mortality was higher in the combination group (23% and 30%, respectively). See TABLE 1 for more outcomes.

The researchers found no statistically significant difference in in-hospital mortality among patients who were not on any APT, compared with those on single APT, but mortality was higher among patients receiving combination APT, compared with no APT (OR=1.5; 95% CI 1.39-1.63). This association persisted even after the researchers adjusted for the National Institutes of Health Stroke Scale score (OR=1.49; 95% CI 1.33-1.67; p<0.0001). See TABLE 2 for more outcomes.

The authors noted that future trials should evaluate whether patients with ICH on combination APT would benefit from restoring platelet function.

The study is limited by its retrospective design. Missing data, including patients’ comorbidity scores, may also have had a confounding effect on the study results.

The authors report research funding from Boehringer Ingelheim, Portola, Pfizer, and CSL Behring.


Khan NI, Siddiqui FM, Goldstein JN, et al. Association between previous use of antiplatelet therapy and intracerebral hemorrhage outcomes. Stroke. 2017;48:1810-7.