Statin Therapy in Ischemic Stroke Patients with Atrial Fibrillation: Efficacy and Safety Outcomes

Abstract Background The efficacy and safety of statins for secondary prevention in patients who have experienced a cardioembolic stroke are not well-defined. However, previous observational data reported hyperlipidemia as a risk factor for both ischemic and bleeding complications in patients with AF and previous stroke. Based on these premises, we conducted a sub-analysis of the RAF and RAF-NOAC studies to evaluate the efficacy and safety of statins in secondary prevention in patients with acute ischemic stroke and AF. Methods We combined patient data from the RAF and RAF-NOAC studies, prospective observational studies conducted across Stroke Units in Europe, the United States, and Asia from January 2012 to June 2016. We included consecutive patients with AF who suffered an acute ischemic stroke with a follow-up of 90 days. Our outcomes were the combined endpoint, including stroke, transient ischemic attack, systemic embolism, symptomatic intracerebral hemorrhage, and major extracranial bleeding. Furthermore, both ischemic and hemorrhagic outcomes were evaluated separately. Results A total of 1.742 patients were included (46% male), and 898 (52%) received statins after the index event. At multivariable analysis, statin use was statistically associated with age (OR 0.92, 95% CI 0.97 - 0.99, p = 0.001), male sex (OR 1.35, 95% CI 1.07 - 1.70, p = 0.013), anticoagulation (OR 2.53, 95% CI 1.90 - 3.36, p <0.0001), hyperlipidemia (OR 5.52, 95% CI 4.28 - 7.12, p <0.0001), paroxysmal AF (OR 1.40, 95% CI 1.12 - 1.75, p = 0.003), leukoaraiosis (OR 1.39, 95% CI 1.11 - 1.75, p = 0.004) and heart failure (OR 0.72, 95% CI 0.53 - 0.98, p = 0.034). Statin use was not associated with the combined outcome event (OR 0,81, 95% CI 0,56 – 1,19, p = 0.286) and ischemic outcome event (OR 1,13, 95% CI 0,71 – 1,82, p = 0.604) while was associated with a lower risk of hemorrhagic outcome event (OR 0,49, 95% CI 0,27 – 0,88, p = 0.016). Conclusions Our data show that statins seem to protect against global bleeding events in cardioembolic stroke patients; this may be due to the pleiotropic effect of statins. More data are warranted to confirm these findings.