Effects of Prior Antiplatelet Therapy on Mortality, Functional Outcome, and Hematoma Expansion in Intracerebral Hemorrhage: An Updated Systematic Review and Meta-Analysis of Cohort Studies

Abstract

Background and Objective: Antiplatelet therapy (APT) is widely used and believed to be associated with increased poor prognosis by promoting bleeding in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to determine whether prior APT is associated with mortality, functional outcome, and hematoma expansion in ICH patients. Methods: The PubMed, Embase, and Web of Science databases were searched for relevant published studies up to December 11, 2020. Univariate and multivariable adjusted odds ratios (ORs) were pooled using a random effects model. Cochran's chi-squared test (Cochran's Q), the I ² statistic, and meta-regression analysis were used to evaluate the heterogeneity. Meta-regression models were developed to explore sources of heterogeneity. Funnel plots were used to detect publication bias. A trim-and-fill method was performed to identify possible asymmetry and assess the robustness of the conclusions. Results: Thirty-one studies fulfilled the inclusion criteria and exhibited a moderate risk of bias. Prior APT users with intracerebral hemorrhage (ICH) had a slightly increased mortality in both univariate analyses [odds ratio (OR) 1.39, 95% CI 1.24-1.56] and multivariable adjusted analyses (OR 1.41, 95% CI 1.21-1.64). The meta-regression indicated that for each additional day of assessment time, the adjusted OR for the mortality of APT patients decreased by 0.0089 (95% CI: -0.0164 to -0.0015; P = 0.0192) compared to that of non-APT patients. However, prior APT had no effects on poor function outcome (pooled univariate OR: 0.99, 95% CI 0.59-1.66; pooled multivariable adjusted OR: 0.93, 95% CI 0.87-1.07) or hematoma growth (pooled univariate OR: 1.23, 95% CI 0.40-3.74, pooled multivariable adjusted OR: 0.94, 95% CI 0.24-3.60). Conclusions: Prior APT was not associated with hematoma expansion or functional outcomes, but there was modestly increased mortality in prior APT patients. Higher mortality of prior APT patients was related to the strong influence of prior APT use on early mortality. Systematic Review Registration:PROSPERO Identifier [CRD42020215243].

Keywords: antiplatelet therapy; functional outcome; hematoma expansion; intracerebral hemorrhage; mortality.

Figure 1

Study flowchart.

Figure 2

The risk of bias assessment of each included study (A) and weighted summary of the risk of bias (B).

Figure 3

Forest plot comparing mortality for APT vs. no APT for univariate analyses (A) and multivariable adjusted analyses (B).

Figure 4

Subgroup analyses according to assessment time in univariate analyses (A) and adjusted analyses (B). Meta-regression for the assessment time for univariate analyses (C) and multivariable adjusted analyses (D).

Figure 5

Forest plot of univariate OR (A) and multivariable adjusted OR (B) for poor function outcome in prior APT users compared to non-users. Forest plot comparing hematoma growth for APT vs. no APT in univariate analyses (C) and in multivariable adjusted analyses (D).

Figure 6

Funnel plot of (A) univariate odds ratios for mortality, (B) multivariable adjusted odds ratios for mortality, (C) univariate odds ratios for poor function outcome, (D) multivariable adjusted odds ratios for poor function outcome, (E) univariate odds ratios for hematoma growth (HG), (F) multivariable adjusted odds ratios for hematoma growth (HG), (G) results of the trim-and-fill analysis of univariate odds ratios for mortality, and (H) results of the trim-and-fill analysis of univariate odds ratios for mortality.