Time to benefit of intensive lipid lowering therapy in individuals with cardiovascular disease

BACKGROUND

The timing of the clinical benefit of intensive lipid-lowering therapy in reducing major adverse cardiovascular events (MACE) in individuals with established cardiovascular disease (CVD), both before and after the advent of novel medications (proprotein convertase subtilisin/kexin type 9 inhibitor [PCSK9i] and ezetimibe) in 2010, is unclear.

OBJECTIVE

To evaluate the time to benefit (TTB) from intensive lipid-lowering therapy.

METHODS

The investigators systematically searched for randomized controlled trials evaluating intensive lipid-lowering therapy. The primary outcome was MACE. Utilizing reconstructed individual participant data, Weibull survival curves were fitted to estimate the TTB for specific absolute risk reduction thresholds (0.002, 0.005, and 0.01).

RESULTS

Seven trials randomizing 92,180 adults aged between 58.2 and 63.6 years were identified. A TTB of 19.6 months (95% CI: 12.3–31.4) of intensive lipid-lowering was needed to prevent 1 MACE per 100 patients. Before 2010, when statin was the only option, a TTB for high-intensity statin therapy of 15.2 months (95% CI: 6.52–35.5) was needed. After 2010, the TTB for PCSK9i-based, ezetimibe-based intensive lipid-lowering on a background of statin therapy was 17.7 (95% CI: 12.2–25.6) and 47.3 (95% CI: 20.4–110) months, respectively.

CONCLUSION

In contemporary practice, to prevent 1 MACE in 100 individuals with established CVD, a TTB of 17.7 and 47.3 months was needed for PCSK9i-based and ezetimibe-based intensive lipid-lowering therapy on a background of statin therapy, respectively. The observed variations across different drug regimens highlight the need for a personalized approach to treatment decisions.