Building a Case for Treating Isolated Low HDL Levels in Patients with Documented
December 15, 1997 3 minutes read
Synopsis: A total of 395 post-CABG patients with low HDL and normal LDL levels demonstrated less angiographic progression when treated with gemfibrozil compared to placebo.
Source: Frick MH, et al. Circulation 1997;96:2137-2144.
Excellent documentation exists for the morbidity and mortality benefits of lowering elevated LDL levelscertainly in those with established disease and likely in those with multiple risk factors for the development of coronary artery disease. Although epidemiologic studies have noted the association of low plasma HDL levels with an increased risk of atherosclerotic disease, evidence of treatment benefit associated with drug therapy is scanty. Three hospitals in Finland randomly treated 395 men with either gemfibrozil or placebo for an average of 32 months. The patients had undergone coronary bypass grafting 1-3 years prior to study entry. Inclusion criteria were HDL levels less than 42.5 mg/dL and LDL less than 175 mg/dL. Quantitative coronary angiography was performed at entry and at the end of the study. Treatment with 1200 mg daily of gemfibrozil resulted in an approximate 36% reduction in triglyceride levels and an increase of 21% in HDL levels, with minimal change in total or LDL cholesterol. Angiographic analysis demonstrated significantly less progression in average diameter stenosis and mean luminal diameter for native coronary arteries and reduced the development of new graft lesions in the venous bypass grafts.
COMMENT BY WILLIAM E STRAUSS, MD
So, do I believe we have proof that treatment of low HDL results in major benefits for patients with CAD? No, but we are getting there. In itself, this study doesn’t knock your socks off; the actual changes in coronary diameter between the treated and control groups, although statistically significant, were minuscule. The changes were also noted for some arterial segments, proximal to graft insertion or unrelated to the bypass graft, but not all investigated segments. However, it must be remembered that the previous angiographic "progression/regression" trials demonstrated the same findings with other treatments including the statins (i.e., small angiographic % change but dramatic clinical benefit). Whether by improving endothelial function, reversing platelet-dependent thrombotic tendencies, or plaque stabilization, something is going on.
The CLAS trial similarly demonstrated angiographic improvement for treated patients in segments proximal to graft insertions and noted subsequently that those changes were a predictor of future clinical events.1 The present study was neither large enough nor long enough to expect to note clinical benefits; however, the authors did note a marked reduction in the development of new lesions in the bypass grafts. The present study also mirrors another recent trial using fibrate drugs. The BECAIT study demonstrated less progression of lesions in MI survivors treated with bezafibrate, with attendant reduced subsequent coronary events.2 Other regression/progression trials using statins found almost identical percent luminal diameter change in patients with elevated LDLs. The latter finding suggests that it is the treatment of the individual lipoprotein abnormality that is important. Individually, each of these bits of encouraging data continues to build the case for treating patients with isolated low HDL. However, analogous to the situation a decade ago with LDL cholesterol, iron-clad proof awaits larger trials powered to demonstrate effect on clinical events. Two ongoing trials with fibrates hopefully will soon complete the story.
References
1. Azen SP, et al. Circulation 1996;93:34-41.
2. Erickson C-G, et al. Lancet 1996;347:849-853.
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