Is Angioplasty Needed in Stable CAD or Will Aggressive Lipid-Lowering Therapy do as Well?
Abstract & Commentary
Synopsis: It would appear that lipid-lowering therapy should be considered in all patients with known coronary artery disease, perhaps even regardless of what the cholesterol, LDL, and HDL levels are at the time of the initiation of therapy.
Source: Pitt B, et al, for the Atorvastatin vs. Revascularization Treatment Investigators. N Engl J Med 1999;341:70-76.
There is certainly no question that percutaneous transluminal coronary angioplasty (PTCA) has been an effective form of treatment of patients afflicted with symptomatic coronary artery disease (CAD) ranging all the way from stable angina pectoris to acute myocardial infarctions. The numerous studies that have compared medical therapy with PTCA in patients with symptomatic CAD have suggested that PTCA was more effective than standard medical therapy in improving the quality of life and exercise performance.1-3 On the other hand, lipid-lowering therapy has been demonstrated to significantly reduce the incidence of overall cardiovascular mortality, overall cardiovascular events, and the need for revascularization procedures.4,5
Pitt and colleagues recently reported the results of a randomized, controlled, multicenter study comparing the outcomes of patients who received usual medical treatment and a lipid-lowering agent (atorvastatin) with the outcomes of matched patients who were first subjected to PTCA (with or without stenting) and who then received usual medical treatment including lipid-lowering therapy. This 18-month open-labeled study was performed in 341 patients with stable CAD, normal left ventricular function, asymptomatic or mild-moderate angina pectoris, and a serum level of low-density lipoprotein cholesterol (LDL) of at least 115 mg/dL who were referred for PTCA. The results demonstrated that the incidence of ischemic events was 36% lower over an 18-month period in the atorvastatin without PTCA group, but these results were not statistically significant after the reduction in events were adjusted because of the smaller number of angioplasty procedures, coronary artery bypass operations, and hospitalizations for worsening angina that occurred in the atorvastatin group. However, it should be noted that the medically treated patients had had a significantly longer period of time to a first ischemic event (P = 0.03) than did patients who were subjected to PTCA/usual care.
Comment by Harold L. Karpman, MD
Pitt et al have carefully evaluated the results obtained from the 37 medical centers in North America and Europe who participated in this study and have clearly demonstrated a 46% reduction in LDL levels in the atorvastatin group compared to an 18% reduction of LDL levels in the PTCA and usual care group; in addition, the total serum cholesterol was reduced by 37% and 10%, respectively. The mean level of LDL cholesterol was 77 mg/dL in the study group and 119 mg/dL in the PTCA/usual care group.
Even though the 36% lower incidence of ischemic events over a period of 18 months in patients treated with atorvastatin narrowly missed the level of significance after being adjusted, the final results must be considered to be most important. This is especially true because of the significantly longer time to a first ischemic event that was noted to occur in patients treated with atorvastatin when compared to the PTCA group (i.e., P = 0.03). Previous trials have suggested that the beneficial effects of lipid-lowering therapy become apparent after six or more months of therapy;4,5 a similar time delay to the onset of measurable benefits was noted in the Pitt study suggesting that these benefits occurred because of the lowering of serum lipid levels with atorvastatin. It should be recognized that a longer follow-up period would not likely demonstrate a convincingly greater benefit of angioplasty compared to lipid-lowering therapy since in most lipid-lowering trials, there has been little benefit of lipid-lowering therapy over placebo in the first two years of treatment after which time significant improvement occurs and outcome curves begin to diverge. In summary, it would appear that aggressive lowering of serum lipids is likely to diminish or prevent further progression of minimal to moderate CAD lesions and, thereby, prevent plaque rupture.6
It should be carefully recognized that this study does not provide evidence with respect to the relative value of PTCA vs. medical therapy in patients who have severe or acute symptomatology, whose quality of life has been severely affected, and/or in high-risk patients with left ventricular dysfunction, left main CAD and/or triple vessel disease, or in patients with severe angina with diminished exercise tolerance. Additional long-term trials will be required to determine whether aggressive lowering of lipid levels will compliment angioplasty in such patients by stabilizing coronary arterial lesions; however, for the time being, this paper would suggest that pharmaceutically induced lipid-lowering appears to be as safe and effective as PTCA/usual medical care in reducing the incidence of ischemic events. And, of course, if at any time symptoms were to increase or exercise performance were to deteriorate to the point where these events were to interfere with a patient’s quality of life, physicians might at that time elect to have their patients undergo revascularization with only minimal (if at all) additional risk having been incurred because of their initial decision to pharmacologically treat the patient.
Numerous studies have suggested that cholesterol lowering should be extended to patients with acute coronary conditions and that we should hasten to initiate this form of therapy rather than withholding drug therapy in order to see whether diet therapy alone will be effective in controlling the serum lipid values. Currently mounted clinical trials should soon define with certainty whether cholesterol lowering should play a role in the treatment of all patients with unstable angina and myocardial infarctions because cholesterol lowering may have immediate consequences that favorably affect coronary events. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial is currently randomizing 3000 patients with unstable angina or non-Q-wave myocardial infarction to atorvastatin or placebo beginning during the acute hospitalization and continuing for 16 weeks of follow-up. Another trial currently in the final stages of protocol development will test the effects of early vs. delayed simvastatin therapy in 4500 patients with acute coronary syndromes followed for one year. Whether the outcomes of these acute treatment trials will affect long-term therapy (i.e., drugs vs PTCA vs surgery) will almost certainly become apparent within the next several years but again, for the time being, it would appear that lipid-lowering therapy should be considered in all patients with known CAD, perhaps even regardless of what the cholesterol, LDL, and HDL levels are at the time of the initiation of therapy.7,8
Pharmaceutically induced lipid-lowering appears to be as safe and effective as PTCA/usual medical care in reducing the incidence of ischemic events.
a. True
b. False
References
1. Parisi AF, et al. N Engl J Med 1992;326:10-16.
2. Hueb WA, et al. J Am Coll Cardiol 1995;26:1600-1605.
3. Lancet 1997;350:461-468.
4. Scandinavian Simvastatin Survival Study Group. Lancet 1994;344:1383-1389.
5. Sacks FM, et al. N Engl J Med 1996;335:1001-1009.
6. Waters D. Prog Cardiovasc Dis 1994;37:107-120.
7. Waters D. Circulation 1999;99:3215-3217.
8. Dupuis J, et al. Circulation 1999;99:3227-3233.
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