High-Dose Statin May Not Be Enough To Protect Acute Coronary Patients


STOCKHOLM — Patients with acute coronary syndrome who are treated with a high-dose statin and other standard medications still have a high, 13% rate of cardiac events during follow-up, which suggests a need for more interventions to further lower event rates.

“Patients are not fully protected by a statin, aspirin, clopidogrel, an angiotensin-converting enzyme inhibitor, and a β-blocker. They need other treatments, too,” Dr. Kausik K. Ray said at the annual congress of the European Society of Cardiology. In his analysis of more than 2,000 patients who received 80 mg of atorvastatin (Lipitor) daily in a recent major trial, Dr. Ray suggested that more diligent control of diabetes, raising the serum levels of HDL cholesterol, and anti-inflammatory treatment might push down event rates even more.

The data came from the intensive-treatment arm of 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 atorvastatin daily) or moderate (40 mg pravastatin daily) lipid-lowering regimen. The results showed that patients whose LDL cholesterol levels dropped below 70 mg/dL had better outcomes during 2 years of follow-up, compared with patients who had higher levels of LDL cholesterol.

The new analysis focused entirely on the patients who received 80 mg atorvastatin daily. During the first 4 months of treatment, 124 patients in this group died or had a myocardial infarction or unstable angina; the remaining 1,939 patients had no events. Beyond the first 4 months, another 140 patients had events and 1,777 were event free. A multivariate analysis showed that the serum level of HDL cholesterol at baseline was a significant predictor of early events. For every 1 mg/dL rise in the HDL cholesterol level, the risk of an event during the first 4 months fell by 3%, reported Dr. Ray, a cardiologist at Brigham and Women's Hospital in Boston. Other significant determinants of early risk were age and smoking.

A second analysis showed that the 4-month serum levels of hemoglobin (Hb) A1c and C-reactive protein (CRP) were significant predictors of late events. For every 1% rise in the level of HbA1c, the risk of a late event rose by 28%. For every 1 log rise in the serum level of CRP, the risk rate rose by 25%, said Dr. Ray. Other determinants of late risk were age, gender, and the serum level of LDL cholesterol at 4 months.

Better diabetes control and a reduction in HbA1c is a strategy that can be used in the clinic right now, commented Dr. Elliott Antman, director of the coronary care unit at Brigham and Women's Hospital. He noted that the average HbA1c level in patients with events was 6.1%, compared with an average 5.7% level in those with no events.

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