Stopping Statins After Stroke Raises Risk for Death, Dependence

Caroline Cassels

August 30, 2007 — Individuals who stop statin treatment after hospitalization for ischemic stroke have nearly a 5-fold increased risk for death or dependence within 3 months poststroke, a new study suggests.
In addition, patients who are withdrawn from statin therapy during the acute phase of stroke have almost a 9-fold increased risk for early neurologic deterioration (END) and larger infarct volumes.
"These results strongly support the recommendation to physicians to continue statin drugs during the acute phase of an ischemic stroke," the study's principal investigator, José Castillo, MD, PhD, from the University of Santiago de Compostela, in Santiago, Spain, said in a statement from the American Academy of Neurology.
Dr. Castillo added that while no protocols suggest patients should not receive statins after stroke, in many cases the drugs are discontinued to avoid bronchoaspiration, particularly in the most severe strokes. "This study clearly shows the benefits of continuing statin use," he said.
The study is published in the August 28 issue of Neurology.
The single-center analysis included 215 consecutive patients hospitalized for acute hemispheric ischemic stroke and admitted within 24 hours of symptom onset from October 2003 to May 2005.
Of these, 89 subjects who were on previous statin therapy were randomized to receive 20 mg daily of atorvastatin (administered orally or through a nasogastric tube) or were taken off statins for 3 days immediately following stroke.
Patients who had not been on statin therapy prior to admission were followed up as a reference group for secondary analysis.
From the fourth day onward, atorvastatin 20 mg daily was also administered to patients in the withdrawal group and in those who were not on previous statin treatment.
Greater Infarct Volume
The primary outcome was death or dependence at 3 months, defined as a modified Rankin Scale of greater than 2. Secondary outcomes were infarct volume and END, defined as an increase in National Institutes of Health Stroke Scale (NIHSS) of 4 points or more between time of admission and any time during the first 48 hours of hospitalization.
After 3 months, 60% (27) of those in the statin-withdrawal group had either died or were disabled to the point of dependence compared with 39% (16) of those who had continuous statin therapy.
The authors also report that infarct volume was greater in statin-withdrawal patients compared with those who remained on statin therapy.
In addition, secondary analysis revealed patients in the reference group had a higher frequency of atrial fibrillation and were less likely to have a previous history of hypercholesterolemia than randomized patients.
Statin Therapy Should Not Be Interrupted
Post hoc analysis showed no difference in the study's primary outcome among the statin-withdrawal group and the reference group. However, the researchers observed a 19-fold increased risk for END among patients who were withdrawn from statin therapy compared with referent subjects.
According to the authors, previous animal and clinical research has shown the neuroprotective effect of statins is related not only to the reduction of plasma cholesterol but also to their direct influence on improving endothelial function through the overexpression of nitric-oxide synthase, as well as their antithrombotic and anti-inflammatory effects.
While the optimal dose of statins for neuroprotection in ischemic stroke is not known, animal studies of cerebral ischemia indicate neuroprotection is more likely at lower doses.
"Our findings strongly support that previous statin therapy should not be interrupted during the acute phase of ischemic stroke. The recommendation to start on statin treatment as soon as ischemic stroke occurs needs to be investigated in further randomized trials," they write.
The study was partially supported by grants from the Spanish Ministry of Health. Dr. Castillo and coauthors José Vivancos, MD, PhD, and Antonio Dávalo, MD, PhD, are scientific advisors to Pfizer. The other study authors report no conflicts of interest.
Neurology. 2007;69:904-910. Abstract