ASA ISC 2006: Statin withdrawal during acute phase of stroke worsens neurologic outcome


Withdrawing statins during the acute phase of ischemic stroke is associated with worse neurologic outcomes and larger brain injury compared with acute stroke patients who remain on their statins, said Florentino Nombela, MD, at the American Stroke Association's International Stroke Conference 2006 in Kissimmee, Fla.

Clinical studies have demonstrated a neuroprotective effect in acute ischemic stroke patients on prior statin therapy.

"The potential benefit of statin therapy prior to stroke onset, as it has been previously described, can be dramatically lost if the treatment is stopped in the acute phase, even if for a brief period," said Dr Nombela, a neurologist at University Hospital de la Princesa in Madrid, Spain.

Dr Nombela conducted a prospective, open-label, randomized study of 215 patients admitted to a single center within 24 hours from symptom onset.

Eighty-nine of the patients were taking statins at the time of their stroke. These 89 patients were randomized to either statin withdrawal during the first 3 days or continued statin therapy. A third group of 126 patients not on a statin at the time of their stroke served as controls. All patients received a statin (atorvastatin, 20 mg/d) after Day 3.

Early neurologic deterioration, defined as a decrease of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) within the first 48 hours of hospital admission, was observed in 65.2% of patients who had statins withdrawn on admission, compared with 20.9% who remained on statins (P<.001). In the control group, early neurologic deterioration was experienced by 27%.

Statin withdrawal was an independent prognostic risk factor of early neurologic deterioration with an odds ratio of 9.93, Dr Nombela said.

Infarct volume at Days 4 to 7 increased by a mean of 74 cc in the group in whom statins were withdrawn compared with 26 cc in the group that remained on statins (P<.0001). By comparison, infarct volume was 53 cc in the group that was not on a statin at admission.

In other data presented here, statin treatment prior to stroke onset offered protection against stroke progression, reported Atsushi Shiraishi, MD, and colleagues at Tokyo Medical and Dental University. In their study, 523 first-ever stroke patients were evaluated within 48 hours of stroke onset. Stroke progression, defined as a worsening of more than 2 points on the NIHSS or death, occurred in 7 of 64 (10.9%) patients taking a statin before their stroke, compared with 108 of 459 (23.5%) who did not take statins prior to their stroke (P=.027).

After multivariate adjustment, statin pretreatment was associated with a significant 55% reduction in stroke progression (P=.04). The benefit of statin pretreatment appeared to be greatest in patients with large-artery atherosclerosis, although the sample size was too small to draw definitive conclusions. The investigators suggest future randomized, controlled trials to assess the utility of statins as acute stroke therapy.

In a third study, this one a retrospective chart review, patients who used lipid-lowering agents within 48 hours of admission, most often statins, had a reduction in in-hospital mortality and stroke severity following acute ischemic stroke compared with patients not using such agents, said Norina Allen, MPH, a doctoral candidate at Yale University, New Haven, Conn.

Charts from 1,256 stroke patients were reviewed. In-hospital mortality was 5.3% in patients not on lipid-lowering agents and 1.0% in patients taking lipid-lowering therapy, a reduction of 82% (adjusted OR=0.18; 95% CI, P=not given). More patients on lipid-lowering therapy had mild events compared with those not on lipid-lowering therapy.

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