Background: Several randomized controlled trials of statin therapy have confirmed that every 39 mg per dL (1.00 mmol per L) reduction in low-density lipoprotein (LDL) cholesterol level is associated with a 21 percent reduction in the relative risk of cardiovascular events and a 12 percent reduction in the relative risk of cardiovascular mortality. The lowest optimal LDL cholesterol level remains unknown, and the recommended target levels differ between North American and European expert groups. Josan and colleagues reviewed the evidence for safety and effectiveness of intensive statin therapy in patients with coronary artery disease (CAD).
The Study: The meta-analysis included randomized clinical trials that compared different regimens of statin therapy intensity in adults with CAD, and that reported cardiovascular events or mortality as outcomes. Studies that used much lower doses of statins in the control group than are currently used in clinical practice were excluded. From 116 articles identified, seven trials with 29,395 patients met inclusion criteria. Two trials enrolled patients following acute coronary syndromes and five involved patients with chronic CAD. More than 70 percent of participants were men, and the average age ranged from 56 to 72 years. Baseline LDL cholesterol levels ranged from 106 to 151 mg per dL (2.74 to 3.90 mmol per L). Study medications included pravastatin (Pravachol), simvastatin (Zocor), atorvastatin (Lipitor), and lovastatin (Mevacor).
Results: In each trial, patients in the higher-intensity statin group achieved lower LDL cholesterol levels than patients in the lower-intensity statin group. The differences ranged from 15 to 39 mg per dL (0.39 to 1.00 mmol per L). About one half of the patients receiving intensive statin therapy achieved LDL cholesterol levels lower than 77 mg per dL (2.00 mmol per L). Intensive statin therapy was associated with a 25 percent reduction in mortality in patients following acute coronary syndromes, but it had no impact on mortality in patients with chronic CAD. When all seven trials were combined, intensive statin therapy had no significant impact on all-cause mortality. Intensive statin therapy was associated with significant reductions in myocardial infarction, coronary death, major cardiovascular events, and stroke in patients following acute coronary syndromes and in those with chronic CAD.
Intensive statin therapy was not associated with a significantly higher discontinuation rate from drug-related adverse events compared with less intensive statin therapy (7.8 versus 5.3 percent, respectively). In five trials, the risk of elevated aminotransferase levels was significantly increased in the intensive statin treatment group. Other adverse events, such as myopathy or rhabdomyolysis, were inconsistently reported, but they appeared to be uncommon (approximately 0.5 percent of patients) and did not occur significantly more often with intensive therapy.
Conclusion: The authors conclude that more intensive statin therapy is associated with improved outcomes in patients with established CAD. The evidence to support specific LDL cholesterol level targets is currently insufficient, and further research is needed.