Effectiveness of treat-to-target cholesterol-lowering interventions on cardiovascular disease and all-cause mortality risk in the community-dwelling population: a target trial emulation

Abstract Little is known about the long-term effectiveness of risk-based treat-to-target cholesterol-lowering interventions on cardiovascular risk. Here, we show the emulated effectiveness of guideline-recommended low-density and non-high-density lipoprotein cholesterol-lowering interventions using the absolute risk reduction (ARR) and the restricted mean event-free time-based number needed to treat (NNT). With 5,375 participants, the 29-year risks for cardiovascular disease (CVD), all-cause mortality, and atherosclerotic CVD were 18.6%, 25.6%, and 17.7%, respectively. Long-term treat-to-target interventions showed significant reductions in CVD (ARR −2.3%, 95%CI −3.4% to −0.8%; NNT 115), all-cause mortality (−3.0%, −4.3% to −1.8%; 95), and atherosclerotic CVD (−2.6%, −3.5% to −1.2%; 104). Such effects appear more pronounced in women, smokers, and those with body mass index < 24 kg/m² or higher adherence rates.