Abstract Body (Do not enter title and authors here): Background
Extensive evidence showed lowering LDL cholesterol reduced long-term adverse cardiovascular events in primary and secondary prevention population. However, benefits need time to achieve. The association between the magnitude of LDL-C lowering and time to benefit (TTB) of clinical events is unclear.
Aim
To evaluate the association between LDL-C reduction and TTB from prevention of main adverse cardiovascular events.
Methods
Published randomized controlled trials concerning lowering LDLC agents and cardiovascular outcomes were included. Kaplan-Meier curves were extracted to reconstruct individual survival data. Hazard ratios (HRs) were calculated for the cardiovascular outcome by time following randomization. TTB was defined as initial timing with a sustained statistically significant HRs reduction. Generalized linear model was used to evaluate the association between TTB and magnitude of LDL-C reduction.
Results
A total of 236985 participants (mean age, 62.5 years;29.5% women, mean baseline LDL-C of 2.94 mmol/L [114mg/dL]) from 27 trials with 28844 major adverse cardiovascular events were included. TTB was highly correlated with LDL-C lowering (Spearman’s r=-0.61, P＜0.001). Logarithmic transformation of TTB was linearly correlated with the magnitude of LDL-C reduction (R2=0.47). The TTB for major cardiovascular events shorten 60% (95% CI, 42%-73%，P＜0.001) per 1 mmol/L (38.7mg/dL) additional reduction in LDL-C level. Shortening TTB in secondary prevention population vs primary prevention population were 59% (35%-73%) vs 72% (10%-91%) (P=0.15) per 1 mmol/L additional reduction in LDL-C level. The addition of PCSK9 inhibitor, bempedoic acid and ezetimibe to statin shorten TTB by 71% (52%-82%), 41% (27%-52%) and 27% (16%-36%), respectively.
Conclusion
Intensive LDL-C lowering further shorten the time lag to clinical benefits. Therefore, it was expected to reduce more recent risk of adverse cardiovascular events. These results can help increase clinicians' confidence in making decisions about intensive LDL-C lowering therapy to achieve earlier clinical benefit.