Cholesterol reduction yields clinical benefit. A new look at old data

Area of Science:

• Cardiovascular Medicine
• Clinical Trials
• Meta-Analysis

Background:

• Ongoing debate regarding the net benefit of cholesterol-lowering interventions.
• Need to differentiate effects of cholesterol reduction from intervention-specific impacts.

Purpose of the Study:

• To meta-analyze randomized trials (>2 years) to assess relationships between cholesterol lowering, coronary heart disease (CHD) mortality, non-CHD mortality, and total mortality.
• To evaluate intervention-specific effects independent of cholesterol reduction.

Main Methods:

• Meta-analysis of 35 randomized trials with durations exceeding 2 years.
• Analytical approach to separate cholesterol-lowering effects from intervention-specific effects.

Main Results:

• A 10% reduction in cholesterol correlated with a 13% decrease in CHD mortality (P < .002) and a 10% decrease in total mortality (P < .03).
• Cholesterol lowering did not impact non-CHD mortality.
• Fibrates increased non-CHD and total mortality by approximately 30% (P < .01) and 17% (P < .02), respectively.
• Hormones increased CHD mortality in men by 27% (P < .04), non-CHD mortality by 55% (P < .03), and total mortality by 33% (P < .01).
• Diet, resins, niacin, statins, and partial ileal bypass showed no specific adverse effects independent of cholesterol lowering.

Conclusions:

• Cholesterol lowering itself demonstrates a beneficial effect on mortality.
• Specific interventions, notably fibrates and hormones, are associated with increased risks of non-CHD and total mortality, with hormones also increasing CHD mortality.