Time‐Dependent Cardiovascular Treatment Benefit Model for Lipid‐Lowering Therapies

Abstract

Background With the availability of new lipid‐lowering therapy options, there is a need to compare the expected clinical benefit of different treatment strategies in different patient populations and over various time frames. We aimed to develop a time‐dependent model from published randomized controlled trials summarizing the relationship between low‐density lipoprotein cholesterol lowering and cardiovascular risk reduction and to apply the model to investigate the effect of treatment scenarios over time. Methods and Results A cardiovascular treatment benefit model was specified with parameters as time since treatment initiation, magnitude of low‐density lipoprotein cholesterol reduction, and additional patient characteristics. The model was estimated from randomized controlled trial data from 22 trials for statins and nonstatins. In 15 trials, the new time‐dependent model had better predictions than cholesterol treatment trialists’ estimations for a composite of coronary heart disease death, nonfatal myocardial infarction, and ischemic stroke. In explored scenarios, absolute risk reduction ≥2% with intensive treatment with high‐intensity statin, ezetimibe, and high‐dose proprotein convertase subtilisin/kexin type 9 inhibitor compared with high‐ or moderate‐intensity statin alone were achieved in higher‐risk populations with 2 to 5 years of treatment, and lower‐risk populations with 9 to 11 years of treatment. Conclusions The time‐dependent model accurately predicted treatment benefit seen from randomized controlled trials with a given lipid‐lowering therapy by incorporating patient profile, timing, duration, and treatment type. The model can facilitate decision making and scenario analyses with a given lipid‐lowering therapy strategy in various patient populations and time frames by providing an improved assessment of treatment benefit over time.

Keywords

• atherosclerotic cardiovascular disease
• ezetimibe
• low‐density lipoprotein cholesterol
• PCSK9 inhibitor
• statin