Lipid modulation and atherosclerotic events: extending the clinical spectrum with fibrates and statins

Two recently published clinical endpoint trials, Veterans Affairs Cooperative Studies Program High-density Lipoprotein Intervention Trial (VA-HIT) and Atorvastatin Versus Revascularization Treatment (AVERT), studied lipid populations and clinical subgroups not previously evaluated in prior trials. VA-HIT, which used gemfibrozil, resurrected the potential benefits of fibrates in atherosclerotic subjects after previous trials either showed nonsignificant reductions in coronary artery disease (CAD) events or raised questions regarding non-CAD events. This study also raised intriguing questions about mechanisms and reinvigorated the triglyceride-atherothrombotic debate. The latest statin trial, AVERT, helped move the potential use of statins in two directions, addressing whether more LDL-cholesterol reduction is better, and whether lipid lowering offers an alternative to revascularization in certain subgroups. Finally, the design or initiation of a number of innovative and potentially landmark statin, fibrate, or combination studies has been published, or their results made public. The focus is on current gaps in our knowledge as we move toward evidence-based medicine. These include primary and secondary prevention of CAD in the elderly, primary prevention of CAD in persons with diabetes, and primary prevention of stroke.