What Factors Determine Treatment Outcome in Aneurysmal Subarachnoid Hemorrhage in the Modern Era? A Post Hoc STASH Analysis

Background

The management of aneurysmal subarachnoid hemorrhage (aSAH) has changed dramatically in the last few decades with the publication of a few major studies, including ISAT (International Subarachnoid Aneurysm Trial, the International Cooperative Study on the Timing of Aneurysm Surgery Study). The aim of this study is to analyze the outcome of patients with aSAH based on a contemporary series, identify the risk factors for poor outcome, and focus on patients with good-grade aSAH (to match the ISAT cohort).

Methods

Baseline demographic and outcome data (modified Rankin Scale) were available for the 803 patients recruited from the STASH (Simvastatin in Aneurysmal Subarachnoid Haemorrhage) trial for post hoc analysis, using a χ² test or 2-sample t test. Logistic regression analysis was performed to assess the risk factors for poor outcome at 6 months. Propensity matched analysis comparing coiling and clipping, and subgroup analysis of good-grade patients (World Federation of Neurosurgical Societies grade I–II) were also performed.

Results

Logistic regression analysis showed that the treatment modality (i.e., coiling or clipping) was not associated with poor outcome at 6 months (P = 0.839). The risk factors associated with poor outcome at 6 months were poor admission World Federation of Neurosurgical Societies grade (P < 0.0001), Fisher grade on initial computed tomography scan (P = 0.013), and the development of delayed cerebral ischemia (P < 0.0001). Subgroup analysis for good-grade patients only showed that 82% of patients after coiling and 78% of patients after clipping were classed as good outcome at 6 months (P = 0.181).

Conclusions

In the current era of aSAH management, apart from patients' admission status, SAH blood load and the development of delayed cerebral ischemia, treatment modality with either coiling or clipping was not associated with poor outcome difference at 6 months.

Introduction

The management of aneurysmal subarachnoid hemorrhage (aSAH) has changed dramatically in the last few decades. The International Cooperative Study on the Timing of Aneurysm Surgery was the first large-scale prospective observational study to look at the issue of timing, and it also addressed factors that influenced outcome at 6 months stratified by Glasgow Outcome Scale. With 3521 patients recruited of 8879 patients with SAH between 1980 and 1983,1, 2 75% of those admitted within 3 days were in good condition, with a 58% good recovery at 6 months, and 25% death rate. Initial bleed, vasospasm, and rebleeding were the major causes of death and disability. Several key prognostic factors identified included admission Glasgow Coma Scale score (75% who were alert on admission had good recovery, compared with 11% who were comatose) and age (only 26% of those aged between 70 and 87 years had a good outcome). The results also showed that at 6 months, 69% who had surgery had good outcome, and alert patients preoperatively had a favorable prognosis if operated on between days 0 and 3 or after day 10. Subgroup analysis then showed that 71% versus 62% of patients operated on between days 0 and 3 versus days >10 had good recovery (P < 0.01).³

This study confirmed that older, poor-grade patients with preexisting medical conditions have a bleak prognosis. It also prompted an international change on the timing to early surgery for good-grade patients.

The International Subarachnoid Aneurysm Trial (ISAT)4, 5, 6 was the first large-scale randomized trial of endovascular coiling versus microsurgical clipping of ruptured aneurysms. Of the initial 9559 patients screened, 2143 were randomized, and a statistically significant outcome difference (using modified Rankin Scale [mRS]) of 7% was found at 1 year in favor of coiled patients. Of the enrolled patients, 88% had good grades (World Federation of Neurosurgical Societies [WFNS] class I or II), 95% had anterior circulation aneurysm, and 90% had aneurysms smaller than 10 mm. The trial result has since been generalized to most patients with aSAH in many parts of the world, with over 90% of cerebral aneurysms managed by endovascular coiling in many neurosurgical centers in the United Kingdom.7, 8

With technological advances over the last 2 decades, changing practice in the management of patients with aSAH, the increasing proportion of patients coiled, and improvements in both microsurgical and endovascular techniques, there is a need to reassess the factors determining patients' outcome in a contemporary series.

The STASH (Simvastatin in Aneurysmal Subarachnoid Haemorrhage) trial was an international, multicenter, parallel group, double-blinded, randomized phase 3 trial. It was designed to determine whether simvastatin 40 mg could improve the long-term outcome of patients with aSAH. A total of 803 patients were recruited from 35 neurosurgical units (23 in the United Kingdom and 12 sites outside the United Kingdom) between January 2007 and February 2013. Details of the study were described in a previous report.⁹

The aim of the present study was to analyze the STASH cohort to identify risk factors for poor outcome and to compare the outcome between those managed by neurosurgical clipping and endovascular coiling, focusing on patients with good-grade aSAH (in line with the ISAT cohort).