Statins in acute coronary syndromes: do the guideline recommendations match the evidence?
On the basis of the evidence obtained from observational studies, randomized controlled trials and their meta-analyses, current guidelines recommend initiating high-dose statin therapy pre-discharge regardless of the baseline low-density lipoprotein (LDL) level in patients with acute coronary syndromes (ACS). Careful review of the evidence indicates that early initiation of high-dose statin therapy reduces recurrent ischemia and may reduce revascularization, but does not confer benefit in terms of hard clinical outcomes such as death or myocardial infarction in any of the randomized controlled trials, and may be associated with increased liver and muscle-related adverse outcomes leading to increased withdrawal and suboptimal long-term adherence. A mortality benefit is apparent in pooled analyses of randomized controlled trials only at long-term (24-month) but not short-term (4-month) follow-up. The critical role of the timing of initiation of therapy (early vs. late) on the benefit-risk profile of statin treatment has not been systematically assessed. It is unclear whether the clinical benefits are attributable to lipid-lowering or lipid-lowering-independent effects. Finally, an optimal LDL threshold for initiating treatment or target LDL level for treatment in ACS remains yet to be defined. On the basis of these observations, and despite a compelling pathophysiologic rationale, the justification for current Class I, Level of Evidence: A recommendation for statin therapy in patients with ACS remains open to question.
Morrissey
Ryan P
RP
Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Diamond
George A
GA
Kaul
Sanjay
S
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000789:Angina, Unstable / Q000188:drug therapy; D008078:Cholesterol, LDL / Q000187:drug effects; D019317:Evidence-Based Medicine; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D055118:Medication Adherence; D009203:Myocardial Infarction / Q000188:drug therapy; D017410:Practice Guidelines as Topic
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors