Statin Use Was not Associated with Less Vasospasm or Improved Outcome after Subarachnoid Hemorrhage

To the Editor: The study by Kramer et al. (1) addresses the potential influence of statin therapy after aneurysmal subarachnoid hemorrhage (SAH). This was a retrospective, nonrandomized study comparing the incidence of cerebral vasospasm (detected with computed tomographic angiography), clinical vasospasm, and unfavorable outcome at 6 weeks (measured with the Glasgow Outcome Scale) between those receiving daily simvastatin (80 mg for 14 days [n = 71]), or not (n = 79), after aneurysmal SAH. The authors concluded that statin therapy was not associated with any measurable difference in end points when compared with a similar cohort observed over a 2-year period (1). The authors pointed out that the study was neither a randomized trial nor a matched-controlled study. Hence, the results need to be interpreted with caution. The most important concern relates to the use of historical controls, in that they are known to be prone to many potential biases. Indeed, despite a neutral clinical gain over time, the authors observed significant changes in the management of the culprit aneurysms and the vigilance for detecting vasospasm over the time course of their investigations. Many other confounders may have been missed, and not all of their patients underwent computed tomographic angiography to detect vasospasm. The sample size was small, even though it included the largest number of prospective statin users observed after aneurysmal SAH. Other potential influencing factors were not considered: sepsis, immediate postoperative deficits, hydrocephalus, ventriculitis, and the use of endovascular angioplasty, all of which may have altered the outcome significantly (2,3). Differences in mortality and long-term outcome also were not defined. Thus, the findings may simply reflect a study design that cannot be expected to identify an influence of a given therapy unless that influence is extremely strong. Any positive influence of a single therapy on the complex causes of a poor clinical outcome after aneurysmal SAH is always likely to be relatively small. Nonetheless, given the simplicity, impeccable safety record, short duration of treatment, and very low cost for statin therapy, a small effect is worth pursuing. The closing statement that the influences of statin therapy in aneurysmal SAH can only be determined by means of a large, multicenter, randomized, controlled trial is, of course, correct. Indeed, recruitment for such a study is currently being conducted (SimvaSTatin for Aneurysmal Subarachnoid Haemorrhage [STASH] study; British Heart Foundation SP/08/003; trial size, n = 1600; UK EudraCT 2006-000-277-30, USA Food and Drug Administration IND 75893, Canada CDHA-RS/2007-117). Once completed, STASH will be the largest trial of its type examining the effect of a drug therapy (simvastatin, 40 mg) on clinical outcome (as assessed by the modified Rankin Scale at 6 months) after aneurysmal SAH (4). We would be delighted if Kramer et al. would consider joining us in recruiting to what will hopefully prove a definitive study on the subject (see http://www.stashtrial.com for information on center participation, recruitment details, and trial progress). Ming-Yuan Tseng Peter J. Hutchinson Carole L. Turner Marek Czosnyka Hugh K. Richards John D. Pickard Peter J. Kirkpatrick Cambridge, England

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