Clinical Question

Is a strategy of treat-to-target statin dosing noninferior to high-intensity dosing for adults with coronary artery disease (CAD)?

Bottom Line

The study found that statin dosing based on a treat-to-target low-density lipoprotein (LDL) level of 50 to 70 mg per dL (1.29 to 1.81 mmol per L) is noninferior to a high-intensity strategy to reduce adverse events in adults with established CAD. Although the authors see this as an advantage that allows a tailored approach for individual dosing variability, it also serves as some of the best evidence yet that CAD can be managed with a high-intensity strategy and patients can avoid the costs and burdens of repeated LDL testing. (Level of Evidence = 1b)

Synopsis

There is minimal evidence supporting the superiority or noninferiority of a high-intensity strategy of statin dosing vs. treating to a target LDL level. The investigators identified 4,400 adults with CAD, including stable ischemic heart disease and acute coronary syndrome. Eligible patients randomly received (concealed allocation assignment) a statin using either a strategy of a treat-to-target LDL level between 50 and 70 mg per dL or a strategy of high-intensity therapy (20 mg of rosuvastatin or 40 mg of atorvastatin daily) without a dose adjustment based on follow-up testing of LDL levels. An independent committee masked to treatment group assignment assessed outcomes. Complete follow-up occurred for 98.7% of participants at three years.

Using intention-to-treat and per-protocol analysis, the primary end point (a composite of all-cause death, myocardial infarction, stroke, and any coronary revascularization) occurred in 8.1% of the treat-to-target group and 8.7% in the high-intensity statin therapy group (nonsignificant difference, meeting the significance for noninferiority). No significant group differences occurred for multiple prespecified secondary end points, including new-onset diabetes mellitus, elevated liver enzymes, hospitalizations, end-stage renal disease, and study drug discontinuation due to intolerance.

Study design: Randomized controlled trial (single-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Outpatient (any)

Reference: Hong SJ, Lee YJ, Lee SJ, et al.; LODESTAR Investigators. Treat-to-target or high-intensity statin in patients with coronary artery disease: a randomized clinical trial. JAMA. 2023;329(13):1078-1087.