Associate chief physician Peking University First Hospital Beijing, China (People's Republic)
Background: Phase 3 randomized clinical trials have shown that tafolecimab significantly reduces low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] in individuals with heterozygous familial hypercholesterolemia (HeFH) or non-familial hypercholesterolemia (non-FH). To better understand the factors that may contribute to the decrease in LDL-C and Lp(a) levels, this study presents a pooled analysis of three phase 3 trials evaluating the efficacy of tafolecimab versus placebo.
METHODS AND RESULTS: This pooled analysis included patients with HeFH and non-FH from three phase 3 trials. Patients were treated with tafolecimab 450 mg every four weeks (n=494) or placebo (n=240) during the 12-week treatment period. The primary efficacy endpoint was the proportion of patients achieved LDL-C and Lp(a) reductions at week 12. Subgroup analyses of the primary endpoints were performed based on the age, gender, BMI, baseline LDL-C level, baseline statin use, baseline ezetimibe use, concomitant diseases, and other factors. Among patients with HeFH or non-FH, a significantly greater proportion of those treated with tafolecimab achieved reductions in LDL-C and Lp(a) levels compared to placebo at week 12 (tafolecimab versus placebo: 78.6% versus 29.8%, treatment difference=48.69%, P< 0.0001). Subgroup analyses indicated that LDL-C and Lp(a) reduction induced by tafolecimab were consistent across various factors, including FH classification, baseline LDC-C category, baseline PCSK9 level, baseline statin intensity, background ezetimibe use, baseline BMI, baseline weight, gender, age, concomitant disease (cardiovascular disease, cerebrovascular disease, myocardial infarction, chronic kidney disease, diabetes, dyslipidemia), and cardiovascular risk (Figure 1, Figure 2).
Conclusion: Tafolecimab is an effective treatment for lowering LDL-C and Lp(a) levels in patients with HeFH and non-FH, with consistent results across subgroups stratified by baseline LDL-C level, baseline statin intensity, background ezetimibe use, concomitant diseases, cardiovascular risk, and other factors.
