Continue Statins After Ischemic Stroke to Minimize Mortality and Dependency

SANTIAGO DE COMPOSTELA, Spain, Aug. 27 -- Ischemic stroke patients already taking statins should be continued on the drugs during the acute phase, clinicians here recommended.
Among 89 such patients, those who were withdrawn from the drugs for the first three days after admission had a nearly five-fold risk for death or dependency compared with patients who were continued on atorvastatin (Lipitor), reported José Castillo, M.D., of the University of Santiago de Compostela, and colleagues.
"Our findings strongly support that previous statin therapy should not be interrupted during the acute phase of ischemic stroke," they wrote in the August 28 issue of Neurology.
And, they said, "The recommendation to start on statin treatment as soon as ischemic stroke occurs needs to be investigated in further randomized clinical trials."
Many stroke patients, especially those with severe strokes, are taken off oral medications in the first days of an acute stroke to prevent the possibility of bronchoaspiration, the authors noted.
To see whether this practice might have a deleterious effect on statin users, the authors identified 89 statin users from a series of 215 consecutive patients admitted within 24 hours of an acute hemispheric ischemic stroke.
The statin users were randomly assigned to either statin withdrawal for the first three days after admission (46 patients) or to immediate treatment with atorvastatin 20 mg/day (43 patients).
The primary study outcome was a composite of death or dependency at three months, with dependency defined as a score greater than 2 on the modified Rankin Scale.
Secondary endpoints included early neurologic deterioration, defined as an increase of four or more points in the NIH Stroke Scale score between admission and any time during the first 48 hours of hospitalization, and infarct volume from days four through seven.
The authors also conducted a secondary analysis in which outcome variables were compared with those for nonrandomized patients who had not previously received statin therapy (126 patients).
They found that 60% of the statin users randomized to withdrawal had a modified Rankin Scale score greater than 2, compared with only 39% of those continued on statins (P=0.043).
In addition, 65.2% of those withdrawn from statins had early neurologic deterioration, compared with 20.9% of those continued on statins (P<0.0001).
Patients in the statin-withdrawal group also had significantly greater infarct volume (median 74 mL, range 45 to 126) compared with the non-withdrawal groups (median 26 mL, range 12 to 70, P=0.002).
After adjusting for age and baseline stroke severity, statin withdrawal was associated with a 4.66-fold increase (1.46 to 14.91) in the risk of death or dependency, a 8.67-fold increase (3.05 to 24.63) in the risk of early neurologic deterioration, and an increase in mean infarct volume of 37.63 mL (SE 10.01; P<0.001), the researchers found.
When they compared the patients in the statin withdrawal group with controls who had never taken the drugs, they found that statin withdrawal was associated with a 19.01-fold increase (range 1.96 to 184.09) in the risk of early neurologic deterioration and an increase in mean infarct volume of 43.51 mL (SE 21.91; P=0.048).
The researchers speculated that the neuroprotective effects of statins may be related to their ability to induce over-expression of endothelial nitric oxide synthase, resulting in an improvement in vascular endothelial function, as well as an increase in expression of tissue plasminogen activator (tPA), and reduction in thrombogenesis.
"Statins also reduce the levels of proinflammatory cytokines and decrease the expression of adhesion molecules," they wrote. "In fact, in the Cholesterol and Recurrent Events (CARE) study, a reduction in the levels of C-reactive protein has been reported."
"In this context," they said, "and given the greater prominence of cytotoxic effects after cerebral ischemia, it is not surprising that statin withdrawal has a deleterious effect on the prognosis of ischemic stroke patients."
They acknowledged that the study was limited by a lack of repeat cholesterol measurements during the acute stroke phase, and by controversies over the optimal dosage of atorvastatin when the goal is neuroprotection.
The study was partially supported by grants from the Spanish Ministry of Health. Dr. Castillo and two of his co-authors are scientific advisors to Pfizer, maker of Lipitor. Co-author Antonio Dávalos, M.D. is a member of the Writing Committee for the Pfizer-funded SPARCL trial. The rest of the authors reported no conflicts of interest. Primary source: NeurologySource reference: Blanco M et al. "Statin treatment withdrawal in ischemic stroke: A controlled randomized study." Neurology 2007; 69: 904-910.