High cholesterol secondary prevention

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753; Associate Editor(s)-In-Chief: Kashish Goel, M.D.

Overview

Patients with coronary heart disease or newly diagnosed acute coronary syndrome are at a high risk of recurrent coronary events. In addition to modification of lifestyle factors, LDL lowering has been shown to reduce recurrent events, cardiovascular deaths and all-cause mortality in these patients. According to the NCEP ATP III guidelines, LDL cholesterol of < 100 mg/dL is the goal in patients with CHD and CHD risk equivalents. The NCEP recommendations are mentioned here, in addition to recent evidence.

Therapy goals

NCEP ATP III guidelines recommended a LDL goal < 100 mg/dL for CHD or CHD risk equivalents, however drug therapy was considered optional between a LDL of 100 to <130 mg/dL. An update by the NCEP committee in 2004 based on new trial data recommended starting drug therapy simultaneously with therapeutic lifestyle changes in CHD patients with LDL < 100 mg/dL. An optional goal of LDL < 70 mg/dL was recommended in high risk patients.

LDL lowering for secondary prevention

The role of LDL lowering in patients with CHD or CHD risk equivalents is well established. Multiple trials have shown that addition of statin therapy to secondary risk reduction reduces all-cause mortality (13-30%), cardiovascular mortality (18-42%), major cardiovascular events (24-35%), revascularization (24-37%). Four major clinical trials have compared statins to placebo directly.

• Scandinavian Simvastatin Survival Study (4S) trial (1994): One of the first trial to evaluate the role of statin therapy in secondary prevention. Treatment with simvastatin was associated with a significant reduction in all-cause mortality, cardiovascular mortality, major coronary events, revascularizations and stroke in 4444 patients during a mean follow-up of 5.4 years.
• Cholesterol and Recurrent Events (CARE) trial (1996): In this study involving 4159 patients with myocardial infarction, treatment with pravastatin significantly reduced the risk of fatal/non-fatal myocardial infarctions and revascularizations without any significant effect on all-cause mortality or mortality from non-cardiovasular causes. This study showed that LDL lowering therapy is beneficial in coronary heart disease patients with average cholesterol levels.
• Long Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial (1998): Pravastatin therapy reduced coronary heart disease mortality, overall mortality and all cardiovascular outcomes in 9014 patients with a history of myocardial infarction or unstable angina during a mean follow-up of 6.1 years.
• Heart Protection Study (HPS):

Intensive versus moderate lowering of LDL

There is no clear consensus for intensive LDL lowering based on the available data. The data supporting intensive versus moderate LDL lowering in CHD patients will be reviewed here. In addition, recently FDA issued a black box warning about the increased risk of myopathy with high dose Simvastatin (80 mg) in patients who were never on it. This warning was based on the SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) trial which showed a significantly increased risk of myopathic complications in the patients treated with simvastatin 80 mg as compared to 20 mg dose.