The use of statins to lower cholesterol levels has been considered effective long-term therapy in reducing deaths and ischemic cardiovascular events in patients with stable coronary heart disease; the benefit is evident after approximately two years of therapy. The highest rates of death and recurrent ischemic events, however, occur during the early period after an acute coronary event. The effect of early intervention with statins in reducing the occurrence of these events in patients with unstable angina or acute myocardial infarction remains undetermined. Schwartz and colleagues conducted a randomized, double-blind study to determine if early intervention with a statin immediately after an acute coronary syndrome reduces death and nonfatal ischemic events.
The trial was conducted from May 1997 to September 1999 at 122 clinical centers in Europe, North America, South Africa and Australia. Adult patients (18 years and older) who presented with unstable angina or a non–Q-wave myocardial infarction were enrolled. In Poland and South Africa, patients were excluded if the serum total cholesterol level at screening exceeded 310 mg per dL (8 mmol per L); at all other sites, the cholesterol level exclusion criterion was 270 mg per dL (7 mmol per L). Other exclusion criteria, in part, were evidence of Q-wave acute myocardial infarction within the previous four-week period, a recent history of coronary artery bypass surgery within the previous three months, severe congestive heart failure or concurrent therapy with other lipid-lowering agents. Patients were randomized with stratification by center to receive 80 mg daily of atorvastatin or matching placebo and were monitored for ischemic events for 16 weeks. All patients were counseled to promote compliance with the National Cholesterol Education Program Step I diet. Laboratory testing was performed at baseline and at weeks 6 and 16.
|Event||Placebo (%)||Atorvastatin (%)|
|Death and/or nonfatal acute MI||169 (10.9)||155 (10.1)|
|Death||68 (4.4)||64 (4.2)|
|Nonfatal acute MI||113 (7.3)||101 (6.6)|
|Resuscitated cardiac arrest||10 (0.6)||8 (0.5)|
|Recurrent symptomatic myocardial ischemia with objective evidence and emergency rehospitalization||130 (8.4)||95 (6.2)|
|Any outcome||269 (17.4)||228 (14.8)|
Of the 3,086 patients enrolled, 1,538 were randomized to receive atorvastatin and 1,548 to receive placebo. Compliance was 86 percent in the atorvastatin group and 88 percent in the placebo group. At baseline, serum lipid levels were nearly identical in both groups (124 mg per dL [3.2 mmol per L]). At week 16, low-density lipoprotein (LDL) cholesterol levels had increased by an adjusted mean of 12 percent (to 135 mg per dl [3.5 mmol per L]) in the placebo group and decreased by 40 percent (to 72 mg per dL [1.9 mmol per L]) in the atorvastatin group. Triglycerides similarly increased by a mean of 9 percent in the placebo group but decreased by a mean of 16 percent in the atorvastatin group. Changes in high-density lipoprotein cholesterol levels were considered minor.
The accompanying table shows the occurrence of primary outcomes, showing that the risk of recurrent symptomatic myocardial ischemia was significantly less in the atorvastatin group than in the placebo group (absolute risk reduction of 2.2 percent and reduction in relative risk of 26 percent). The investigators report a 2.6 percent absolute reduction and a 16 percent relative reduction in the combined primary end points. Of secondary end points, the effect on stroke was significant. Nonfatal stroke was lower in the atorvastatin group than the placebo group (nine and 22, respectively). When fatal and nonfatal strokes were combined, 12 (0.8 percent) strokes occurred in the atorvastatin group versus 24 (1.6 percent) in the placebo group. The change in LDL cholesterol was not significantly associated with the occurrence of one of the main outcome measures. Although the number of stroke events was small, the authors suggest that atorvastatin may also produce beneficial effects on cerebrovascular events within the 16-week post-event period.
The authors conclude that intervention with atorvastatin (80 mg daily) initiated 24 to 96 hours following an acute coronary event reduces the risk of recurrent, symptomatic ischemic events.