Stroke prevention: might vitamin D be safer than statins?

Abstract

Drs. Paliani and Ricci [1] recommend statin therapy in both primary and secondary prevention of stroke. However, although statin treatment might be effective in the prevention of stroke in patients with known coronary-artery disease but without a history of cerebrovascular disease, its role in the secondary prevention of stroke raises some serious concerns [2]. Indeed, a closer look at the results of the Stroke Prevention with Aggressive Reduction in Cholesterol (SPARCL) trial [3], the only study specifically designed to investigate the role of high-dose statin therapy in the secondary prevention of stroke, should question the safety of statin therapy in patients with a history of cerebrovascular disease. The well publicized effect of highdose statin on stroke recurrences in the SPARCL trial reaches significance only with the merging of fatal and nonfatal outcomes. In fact, as compared with placebo, the use of high-dose atorvastatin in accurately selected patients who had a stroke or TIA is associated with a nonsignificant 13% risk reduction of nonfatal stroke during a 5-year follow-up, without improving overall survival (five more deaths in the statin arm), and with 66% increase in the relative risk of hemorrhagic stroke among the patients receiving the statin drug. The latter outcome is neither unlikely a chance finding, nor it could be related to the fact that the SPARCL study not only included patients with ischemic stroke as an entry event, but also patients with hemorrhagic stroke. A sensitivity analysis excluding all patients with a hemorrhagic stroke as an entry event in the SPARCL trial finds that statin treatment is still associated with an increased risk of hemorrhagic stroke [4]. In a subgroup of patients with a history of cerebrovascular disease enrolled in the Heart Protection Study, which did not include patients with hemorrhagic stroke, a similar increased risk of hemorrhagic stroke during follow-up is demonstrated [4]. Furthermore, in the same SPARCL trial, high-dose atorvastatin fails to significantly reduce nonfatal stroke recurrences in every subgroup of studied patients [2], such as men and women, individuals older than 65 years, and patients with and without carotid stenosis. Of concern, despite in the trial design, among the primary efficacy parameters, it was reported that every effort should have been made to determine whether strokes were ischemic or hemorrhagic [3], this worrisome statin side-effect was never reported in any secondary analysis [2]. Finally, Drs. Paliani and Ricci [1] highlight that in combination with other preventive strategies, such as blood pressure-lowering and antithrombotic treatment, in the prevention of stroke, we should also focus on lipid-lowering therapies, beyond statins. However, this approach may distract from other safer tools for the prevention and treatment of stroke. In this setting, an emerging role is related to the vitamin D status. Mounting evidence suggests that vitamin D deficiency is associated with an increased risk of stroke [5]. This notion is supported by studies showing that several risk factors for cerebrovascular events are associated with low 25-hydroxyvitamin D levels L. Mascitelli (&) Comando Brigata Alpina ‘‘Julia’’, Medical Service, 8 Via S. Agostino, 33100 Udine, Italy e-mail: lumasci@libero.it