ORLANDO, FLA. — Intensive statin treatment produced a bigger benefit in elderly patients at high risk for coronary artery disease than in younger patients, based on a new analysis from the PROVE IT-TIMI 22 study.
Intensive statin treatment that lowered serum levels of LDL cholesterol to less than 70 mg/dL was also safe in elderly patients, leading to no increased rate of liver enzyme or muscle abnormalities, Kausik K. Ray, M.D., said at the annual meeting of the American College of Cardiology.
These findings show that the updated guidelines of the National Cholesterol Education Program, which suggested lowering LDL-cholesterol levels to less than 70 mg/dL in patients with a very high risk of coronary disease, are applicable to patients aged at least 70 years, said Dr. Ray, a cardiologist at Brigham and Women's Hospital in Boston.
To assess the role of age in intensive LDL-cholesterol reduction, Dr. Ray and his associates used data collected in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial (N. Engl. J. Med. 2004;350:1495–504).
That study randomized more than 4,000 patients with acute coronary syndrome to treatment with either an intensive (80 mg of atorvastatin daily) or moderate (40 mg of pravastatin daily) lipid-lowering regimen, and showed that patients whose LDL-cholesterol levels dropped below 70 mg/dL had better outcomes during 2 years of follow-up than patients who had higher levels of LDL cholesterol.
The new analysis focused on the 3,784 patients (91% of the total study cohort) who were free from MI, unstable angina, or death 30 days after they started treatment. This group included 634 patients aged at least 70 years, and 3,150 patients younger than 70.
During the remaining 23 months of follow-up, patients aged 70 or older who were in the intensive-treatment group had a 20% reduced risk of death, MI, or unstable angina compared with similarly aged patients in the moderate-treatment group. The benefit from aggressive treatment was virtually identical in younger patients. Those younger than 70 years in the aggressive arm had a 21% drop in events compared with similarly aged patients in the moderate-treatment group.
The outcomes also were assessed by focusing on how patients fared if their LDL-cholesterol level dropped below 70 mg/dL after the first 30 days of treatment, regardless of which treatment arm they were in. By this measure, older patients got more bang for their statin buck than did younger patients.
Among the older patients, those whose cholesterol had dropped below 70 mg/dL after the first 30 days of treatment had a 13.5% rate of death, MI, or unstable angina during the following 23 months. In contrast, older patients whose LDL-cholesterol level was 70 mg/dL or higher after the first 30 days had a 21.5% event rate, a statistically significant 8% absolute difference, Dr. Ray reported.
In contrast, among younger patients, those whose LDL-cholesterol level dropped below 70 mg/dL had a subsequent 8.1% event rate, compared with a 10.4% rate among younger patients who failed to achieve this LDL-cholesterol target. The difference between these groups was also statistically significant, but the absolute difference was only 2.3%.
The incidence of abnormal liver-function tests, an aspartate aminotransferase level at three times or more above the upper limit of normal, occurred in 2% of all patients regardless of their age. The incidence of elevations in creatinine kinase, a marker of muscle abnormalities, was 6% in younger patients and 3% in older patients.