Effect of HMGcoA Reductase Inhibitors on Stroke
ABSTRACT & COMMENTARY
Source: Bucher HC, et al. Effect of HMGcoA reductase inhibitors on stroke. A meta-analysis of randomized, controlled trials. Ann Intern Med 1998;128:89-95.
Neurology Alert has previously reviewed the apparent effectiveness in lowering serum cholesterol by various members of the HMGcoA (3-hydroxy-3-methylglutaryl coenzyme A) family of reductase inhibitors. Several reported analyses have shown a favorable influence of lowering the risk of fatal or nonfatal myocardial infarction by lowering serum cholesterol, but, until the present, no study has provided strong evidence that lowering serum cholesterol levels protects against nonfatal or fatal strokes. The study by Bucher et al now provides a favorable report in this regard.
The authors, from the Kantonsspital Basel, Switzerland, and McMaster University, Hamilton, Ontario, report a meta-analysis of the topic drawn from 28 large, appropriately randomized, controlled trials reported by October 1996. Participants included 49,477 persons taking HMGcoA vs. 56,636 controls. Neither group had a history of stroke, but both groups contained patients with previous episodes of myocardial ischemic disease. Patients with cardiac transplants were excluded. Knowledge of randomization was meticulously hidden until final analysis. Incidents of nonfatal and fatal stroke were amalgamated because of the relatively few fatal strokes in either arm. Trial outcome of reductase inhibitors was compared to trials of fibrates, resins, and dietary interventions.
The overall risk ratio for first nonfatal or fatal stroke was 0.95. Persons receiving HMGcoA had a favorable risk ratio of 0.76 (P = 0.01), lower than that of all other cholesterol-lowering interventions (risk ratio, 1.02). Indeed, none of the latter were significantly different from the norm.
For death from coronary heart disease (CHD), the risk ratio for all collected trials was 0.87. HMGcoA again showed a reduced incidence for death from CHD of 0.69, significantly different (P = 0.003) from baseline and from all other trials employing other cholesterol lowering agents.
The risk for overall mortality was 0.94 for the entire study group. With HMGcoA reductase inhibitors, the risk for death from all causes dropped to 0.90 (P = 0.03).
COMMENTARY
The apparent lack of relationship between elevated cholesterol levels and stroke has puzzled neurologists in the past and inhibited their efforts to take serious target at cholesterol in their patients. This important paper firmly indicates the value of providing HMGcoA to patients with even moderate elevations of serum cholesterol. This study, at least, indicates that other agents produce few preventive successes and the HMGcoA group of drugs apparently does not induce an abnormally high frequency of hemorrhagic stroke. Several different specific forms of HMGcoA reductase inhibitors are presently on the market, all effectively lowering cholesterol blood levels, as tabulated in Neurology Alert (1997;15:61-62). Of the group, it appears that Baycol may have the strongest cholesterol-reducing effect in a short time, but whether this makes a difference remains to be seen. -fp
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