Statin therapy reduced the risk of cardiac death and coronary revascularization in patients with acute MI who had baseline low-density lipoprotein cholesterol (LDL-C) levels below 70 mg/dl, researchers reported in the Oct. 11 issue of the Journal of the American College of Cardiology. The study had serious shortcomings, according to an accompanying editorial, but the findings support conducting a placebo-controlled clinical trial.
Results have been mixed in trials designed to assess the benefits of LDL-lowering drugs for patients with acute coronary syndromes (ACS) with baseline levels of LDL-C below 70 mg/dl, the therapeutic threshold set in guidelines set by the American College of Cardiology and American Heart Association. Ki Hong Lee, MD, of Chonnam National University Hospital in Gwangju, South Korea, and colleagues designed an observational study to try to shed light on the issue for patients with acute MI with baseline LDL-C levels below 70 mg/dl.
“In real clinical practice, physicians often encounter patients with ACS with LDL-C levels below 70 mg/dl,” they wrote. “What is the physicians’ optimal choice for these patients?”
Lee and colleagues identified 1,054 patients with AMI who had enrolled in the Korean Acute Myocardial Infarction Registry between November 2005 and December 2007. They were divided into two groups: a statin group in which 607 patients were administered statins for at least one month after discharge and a non-statin group, in which 447 patients did not receive statins. The primary end point was the composite of major adverse cardiac events at one year.
All patients received a 300-mg loading dose of aspirin, 300- to 600-mg loading dose of clopidogrel (Plavix, Bristol-Myers Squibb, Sanofi Aventis) and heparin. The maintenance dose regime was 100 mg a day of aspirin and 75 mg a day for clopidogrel administered for six or more months. The statin group received statins for at least one month; after one month, statin administration was at the discretion of the physician.
The researchers found that statin therapy significantly reduced the risk of the composite primary endpoint during the 12-month follow-up. Cardiac death occurred in 4 percent of the statin group compared with 7.5 percent of the non-statin group; 6.8 percent of the statin group experienced coronary revascularization compared with 10 percent of the non-statin group. There were no differences in the risk of the composite of all-cause death, recurrent MI and repeated PCI.
Subgroup analyses suggested statins offered benefits to certain patient populations, they reported. “This finding indicates that statin therapy might be considered in patients with ACS who do not have a history of diabetes mellitus, hypertension or dyslipidemia,” they wrote. “They often are regarded as low-risk patients and are less likely to be prescribed statins.”
In an accompanying editorial, John C. LaRosa, MD, of the SUNY Downstate Medical Center in Brooklyn, N.Y., pointed out several limitations in the study. The study was observational, he noted, rather than being a randomized trial, included only index lipid levels, and those index levels may not have been representative.
But he concluded the study was “provocative,” and taken in the context of other trials the findings give weight to the concept of a clinical trial of statin therapy with a placebo arm. “[It] might still be ethically acceptable, although careful monitoring of LDL levels (with statin intervention if LDL levels rose above current LDL targets) would be required,” LaRosa wrote. “[S]uch a trial might address the interesting question of whether achievement of very low LDL levels would obviate the need to aggressively modify other risk factors.”