Statin therapy increases PCSK9 and Lp(a) levels in patients at high CV risk
Effect of atorvastatin, cholesterol ester transfer protein inhibition, and diabetes mellitus on circulating proprotein subtilisin kexin type 9 and lipoprotein(a) levels in patients at high cardiovascular riskLiterature - Arsenault BJ, Petrides F, Tabet F, et al. - J Clin Lipidol 2018; 12: 130–136
- Plasma PCSK9 and Lp(a) levels were dose-dependently increased with increasing atorvastatin doses.
- Compared with patients without T2DM, those with T2DM had higher PCSK9 (357 ± 123 vs 338 ± 115 ng/mL; P=0.0012) and lower Lp(a) levels (28 ± 32 vs 32 ± 33 mg/dL; P=0.0005).
- Regardless of T2DM status, higher atorvastatin doses were associated with higher PCSK9 levels and with higher Lp(a) levels.
After 3 months of treatment:
- Plasma PCSK9 levels significantly increased in patients treated with torcetrapib (+13.1 ± 125.3 ng/mL; +3.7%; P=0.005), but not in patients treated with placebo (+2.6 ± 127.9 ng/mL; +0.7%; P=0.39).
- Increases in PCSK9 levels with torcetrapib were statistically significant in patients with T2DM only.
- Plasma Lp(a) levels significantly decreased in patients treated with torcetrapib (-3.4 ± 10.7 mg/dL; -11.1%; P <0.0001), but not in patients treated with placebo (+0.3 ± 9.4 mg/dL; +0.1%; P=0.92).
In a sub-analysis of the ILLUMINATE study, in patients at high CV risk, PCSK9 and Lp(a) levels were dose-dependently increased by atorvastatin. The presence of T2DM was associated with higher PCSK9 levels and lower Lp(a) levels. Cholesterol ester transfer protein inhibition with torcetrapib slightly increased PCSK9 levels and decreased Lp(a) levels.