Lower incidence of cerebral infarction correlates with improved functional outcome after aneurysmal subarachnoid hemorrhage

Abstract

Despite an undisputed association between vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH), there is debate if this association implies causality. It has been suggested that cerebral infarction is a better outcome measure than vasospasm in clinical trials and observational studies. To further investigate the relationship between infarction and outcome, we performed a systematic review and meta-analysis of all randomized, double-blind, placebo-controlled trials that studied the efficacy of pharmaceutical preventive strategies in SAH patients, and had both cerebral infarction and clinical outcome as outcome events. Effect sizes were expressed in (pooled) risk ratio (RR) estimates with corresponding 95% confidence intervals (CIs). Sensitivity analyses were performed for studies with a low risk of bias and for those who reported outcome at 3 months after SAH. Twenty-four studies including 8,552 patients were included. Pharmaceutical treatments decreased the incidence of both cerebral infarction (RR: 0.83; 95% CI: 0.74 to 0.93) and of poor functional outcome (RR: 0.92; 95% CI: 0.86 to 0.98). The sensitivity analyses did not change the results essentially. These data suggest that the previously observed association between cerebral infarction and functional outcome implies causality, and that cerebral infarction is a better outcome measure than vasospasm in clinical trials and observational studies.

Figure 1

(Pooled) risk ratio (RR) estimates for patients on pharmaceutical treatment to have cerebral infarction. CI, confidence interval.

Figure 2

(Pooled) risk ratio (RR) estimates for patients on pharmaceutical treatment to have poor clinical outcome. CI, confidence interval.

Figure 3

Funnel plot for outcome measure cerebral infarction (A) and functional outcome (B). The name funnel plot arises from the fact that precision of the estimated intervention effect increases as the size of the study increases. Effect estimates from small studies will therefore scatter more widely at the y-axis, with the spread narrowing among larger studies. In the absence of bias, the plot should approximately resemble a symmetrical funnel. If there is bias, from for example publication bias or studies with low methodological quality, this will lead to an asymmetrical appearance of the funnel plot (Higgins and Green, 2008).