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Therapeutics

Nimodipine did not improve 6-month functional independence in acute stroke

ACP J Club. 1991 Mar-April;114:46. doi:10.7326/ACPJC-1991-114-2-046


Source Citation

TRUST Study Group. Randomized, double-blind, placebo-controlled trial of nimodipine in acute stroke. Lancet. 1990 Nov 17;336:1205-9.


Abstract

Objective

To evaluate the effectiveness of oral nimodipine, 120 mg/d, in improving functional recovery in patients with undifferentiated stroke when compared with placebo.

Design

Randomized, double-blind, placebo-controlled trial of 6 months-duration.

Setting

17 hospitals in Great Britain.

Patients

Patients were included if they showed clinical evidence of a hemiparetic stroke in the preceding 48 hours, were > 40 years of age, were functionally independent before the stroke, and were conscious and able to swallow. Patients known to have an intracranial hemorrhage or tumor were excluded. Of 4507 patients assessed, 1215 entered the study. 3 patients were lost to follow-up, and an additional 11 were not evaluated on the Barthel index.

Intervention

Nimodipine, 40 mg 3 times per day (n = 608), or matching placebo (n = 607) for 21 days.

Main outcome measure

Independence after 6 months, defined as a score of 60 or more on an activities of daily living (ADL) scale, the Barthel index.

Main results

72 patients receiving nimodipine (12%) and 65 receiving placebo (11%) were withdrawn from treatment. Reasons for withdrawal were clinical deterioration (40 patients receiving nimodipine and 28 receiving placebo); suspected adverse events (13 patients receiving nimodopine and 23 receiving placebo); and inappropriate study entry (12 patients receiving nimodopine and 11 patients receiving placebo). Data were analyzed by intention to treat. By 6 months, 55% of the nimodipine and 58% of the placebo group were independent. {Absolute risk difference 3%, 95% CI -3% to 9% (P = 0.3)}.* 070 to 1.10). 173 patients (29%) died in the nimodipine group compared with 150 (25%) in the placebo group. {absolute risk difference 4%, CI -1% to 9%, P = 0.1}.* Functional assessment scores showed a trend toward delayed recovery on nimodipine, with little difference between the 2 groups by 24 weeks. The power was 90% to detect a 10% difference in the number of patients who were functionally independent at 6 months.

Conclusion

Treatment with nimodipine, 120 mg/d, within 48 hours of stroke provided no benefit for attaining functional independence at 6 months compared with placebo.

Source of funding: Not stated.

Address for article reprint: Dr. J.J. Murphy, Department of Medicine, University Hospital, Nottingham NG7 2UH, England, UK.

*Numbers calculated from data in article.


Commentary

Although the study appeared to have high power to detect small differences in functional status, there are several reasons why it could have missed a real benefit (1). First, 76% of the patients did not have a computed tomography (CT) scan, permitting at least a 15% error rate in the diagnosis of stroke. Second, the patients were assessed by doctors, nurses, or therapists. We know that the accuracy of diagnosis of stroke is poor even for neurology residents, and the initial clinical diagnosis is wrong in 13% of patients admitted to a teaching hospital (2). Third, death and neurologic disability must be analyzed separately because of their complex interaction. The authors combined these 2 variables in a single scale. Fourth, the neurologic index used (Orgogozo score) has not been validated statistically nor undergone peer review. The results would have been more interpretable if the patients had been assessed with 1 of the tested scales, for example, the National Institutes of Health score (3).

Several studies of nimodipine are in progress or have been completed, that include CT scan confirmation of cerebral infarction. Only 1 of these showed a therapeutic benefit (4), and this may have reflected poorer status of placebo-group patients on entry. On balance, it is unclear whether there is a therapeutic role for nimodipine for patients with acute stroke.

John W. Norris, MD
Sunnybrook Health Sciences CentreToronto, Ontario, Canada


References

1. Capildeo R, Haberman S, Rose FC. Stroke trials. In: Rose FC, ed. Advances in Stroke Therapy. New York: Raven Press; 1982:53-62.

2. Norris JW, Hachinski VC. Misdiagnosis of stroke. Lancet. 1982;1:328-31.

3. Goldstein LB, Bertels C, Davis JN. Inter-rater reliability of the NIH stroke scale. Arch Neurol. 1989;46:660-2.

4. Gelmers HJ, Gorter K, de Weerdt CJ, Wiezer HJ. A controlled trial of nimodipine in acute ischemic stroke. N Engl J Med. 1988;318:203-7.