ABSTRACT & COMMENTARY
Synopsis: Aggressive lowering of moderately elevated LDL cholesterol levels reduces graft occlusion in patients who have undergone bypass surgery.
Source: The Post Coronary Artery Bypass Graft Trial Investigators. N Engl J Med 1997;336:153-162.
A total of 1351 patients who had undergone bypass surgery with saphenous vein bypasses 1-11 years previously and who had moderately elevated LDL cholesterol levels (130-175 mg/dL at baseline) were randomly assigned in a factorial design to either aggressive lowering of LDL cholesterol (to a target of 60-85 mg/dL) by up to 80 mg of lovastatin per day plus up to 8 g of cholestyramine daily if needed vs. moderate reduction (to a target of 130-140 mg/dL) by means of 2.5-5.0 mg of lovastatin daily. Low-dose anticoagulation with warfarin was similarly compared to placebo. The primary outcomes were angiographic, with angiography repeated a mean of 4.3 years post-randomization. The mean LDL cholesterol level achieved in the aggressively treated cohort was 93-97 mg/dL vs. 132-136 mg/dL in the moderately treated group. This resulted in a 31% reduction in the likelihood of graft progression or occlusion (P < 0.001). Although the study was not powered to detect clinical events, this angiographic outcome translated into a 29% reduction in the need for revascularization procedures in the aggressively treated group. Low-dose anticoagulation demonstrated no effect different from placebo.
COMMENT BY WILLIAM E. STRAUSS, MD
Over approximately the last three decades, hundreds of thousands of patients have undergone coronary artery bypass graft surgery each and every year. Many tens of thousands have even now undergone redo operations. The Achilles heel of such surgery has been the likelihood of stenosis of the vein grafts. By the end of the first year, 20% of grafts are occluded, with approximately 3%/year additional closure.1 Thus, by 10 years, 50% of all bypassed segments may be occluded. Just as well-recognized is the fact that the cholesterol level post-operatively is intimately correlated with long-term success. Patients who had occluded grafts had cholesterol levels, or any of its components, that were elevated compared to those with patent grafts.2 This most recent study completes the case for the patient post-bypass surgery, just as the 4S and CARE trials have for the post-myocardial infarction patient3,4aggressive lowering of elevated cholesterol (or LDL levels) is associated with impressive impact.
But, why discuss such studies in Internal Medicine Alert, a publication primarily aimed at primary care givers? Because those several million patients who have undergone bypass surgery can’t be, and are not being, followed by cardiologists, let alone "preventive cardiology or lipid specialists." As a cardiologist, I may see a patient post-operatively once, if even that. Thus, this absolutely vital, but long-term, need to monitor and attack the patient’s cholesterol falls to you. What this study does is provide the proof that these efforts are worthwhile and important. Just as important, but just as "unsexy," is the need to get your surgical patients who smoke to stop smoking, since doing so will affect their survival as much as whether or not they even have the surgery!5 Sometimes, in our interest to embrace the "high tech," we lose sight of the impact such basic issues as smoking and cholesterol can have.
References
1. Sharma GVRK, Hosa M. Factors influencing saphenous vein graft patency. Card Surg State Art Rev 1986;1:125-128.
2. Campeau L, et al. Relation of risk factors to the development of atherosclerosis in saphenous vein bypass grafts and the progression of disease in the native circulation. N Engl J Med 1984;311:1329-1332.
3. Sacks M, et al. The effect of pravastatin on coronary events after myocardial infarction on patients with average cholesterol levels. N Engl J Med 1996; 335:1001-1009.
4. Scandinavian Simvastatin Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: The 4S study. Lancet 1994;344: 1388-1389.
5. Cavender JB, et al. Effects of smoking on survival and morbidity in patients randomized to medical therapy in the coronary artery surgery study: 10-year follow up. J Am Coll Cardiol 1992;20:287-294.
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