Brian Henry or Trish Moreis
AHA News Media Relations
Omni Rosen Hotel
NR 98-4849 (StrokeConf/CARE)
ORLANDO, Feb. 7 -- New data reveal that the cholesterol-lowering drug pravastatin (Pravachol) can significantly reduce the risk of a stroke or ministroke in people who have previously suffered a heart attack.
An analysis of the Cholesterol and Recurrent Events (CARE) study found a 32 percent reduction in strokes and a 27 percent reduction in either strokes or transient ischemic attacks (TIAs) -- "miniature" strokes, which can last from few minutes to an hour or more -- among participants treated with the drug as compared to those who received a placebo.
The results were presented here today at the American Heart Association's 23rd International Joint Conference on Stroke and Cerebral Circulation by Jonathan F. Plehn, M.D., associate professor of medicine at Dartmouth Medical School and director of the cardiac ultrasound laboratory at the Dartmouth-Hitchcock Medical Center in Lebanon, N.H.
The vast majority of strokes occur when the vessels providing blood and nutrients to the brain are blocked by cholesterol-laden plaque, which breaks free from the inner lining of the heart's coronary artery. Heart attacks result when coronary arteries are obstructed by atherosclerosis.
"The key point is that if you have a heart attack, you are at high risk of developing a stroke. If you have a stroke, you are at high risk of developing a heart attack," says Plehn. "So it makes sense to be aggressive with a strong drug to lower cholesterol in people who've had a heart attack or stroke because cholesterol reduction should reduce the amount of atherosclerosis in the coronary arteries and in the carotid arteries leading to the brain."
The new study expands upon findings from two recent drug trials. These studies examined whether lowering cholesterol in people who survived a first heart attack reduced the risk of a second attack. Both studies did find a reduced heart attack risk and evidence that lowering cholesterol also lowered a survivor's stroke risk.
Each study used a different drug from a group called HMG-CoA reductase inhibitors: simvastatin (Zocor) in the Scandinavian Simvastatin Survival Study (4S) and pravastatin in CARE. Researchers who designed 4S did not plan to test simvastatin's effectiveness in stroke, but in 1994 they reported a retrospective analysis that showed fewer strokes in patients getting simvastatin.
CARE, however, did include stroke reduction as a secondary part of its investigation. Plehn says that this part of the investigation makes the CARE stroke analysis more acceptable to statisticians. The team's initial paper in 1996 reported a 31 percent reduction in stroke, based on the reports of study investigators.
The new stroke analysis presented at the American Heart Association meeting involved a far-more detailed examination of the CARE data. The records of any patient who might have suffered a stroke were examined by two members of a special committee.
"Strokes are sometimes hard to diagnose," Plehn says. "We looked at hundreds of reported events to verify that they had indeed been strokes and not migraine headaches or something else that might appear to be strokes."
This work revealed that 128 CARE participants (52 taking pravastatin and 76 on placebo) suffered confirmed strokes during the median follow-up period of five years. The data showed a 32 percent lower risk for the drug group. A total of 216 people (92 on pravastatin and 124 on placebo) suffered either a stroke or TIA, a risk reduction of 27 percent for those getting pravastatin.
These findings held up when the team adjusted the results for age, sex, history of hypertension, cigarette smoking, diabetes, and levels of total cholesterol and "bad" LDL and "good" LDL cholesterol.
The study also yielded another tantalizing finding. In the main CARE study, researchers found that people whose "bad cholesterol" readings were below 125 mg/dl did not benefit from taking pravastatin in terms of a reduced heart-attack risk. This "threshold" effect, however, was not found in stroke patients. Study participants with LDLs under 125 had a 25 percent reduction in strokes; those with LDLs between 125 and 150 had a 28 percent lower chance of stroke; and those whose LDL levels were higher than 150 had a 44 percent lower stroke rate.
"The LDL numbers are fairly large in terms of the reduction in stroke, but because there were far fewer strokes than recurrent heart attacks, the power to detect the difference between the active therapy and the placebo was less. So none of the LDL numbers is statistically significant," says Plehn.
Nonetheless, he added, "the data are suggestive that if you have a high LDL cholesterol to start, pravastatin will make a big difference in terms of stroke reduction."
Co-authors are Jean L. Rouleau, M.D., Montreal Heart Institute; Marc A. Pfeffer, M.D., Ph.D., Eugene Braunwald, M.D., and Frank M. Sacks, M.D., Brigham and Women's Hospital, Harvard Medical School; Barry R. Davis, M.D., Ph.D., Lemuel A. Moye, M.D., Ph.D., Linda B. Piller, M.D., M.P.H., and Lara M. Simpson, M.S., University of Texas Health Science Center; Victoria Bernstein, M.D., Vancouver Hospital and Health Sciences Center, University of British Columbia, Vancouver; T. Edward Cuddy, M.D., University of Manitoba Health Sciences Center; and John D. Rutherford, M.D., University of Texas Southwestern Medical Center.
Media advisory: Dr. Plehn can be reached by calling (603) 650-6154. (Please do not publish telephone numbers.)