Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions
Reductions in Lipids and Major CV Events
Circulation; 2016 Dec 13; Ray, Ginsberg, et al
Greater percentage reductions in low-density lipoprotein cholesterol (LDL-C) and lower on-treatment LDL-C were associated with a lower incidence of major adverse cardiovascular events (MACE), including at very low levels of LDL-C, a recent study found. Data were pooled from 10 double-blind trials including 4,974 patients (6,699 patient-years follow-up), with participants randomized to alirocumab 75/150 mg every 2 weeks or control for 24 to 104 weeks, added to background statin therapy in 8 trials. Researchers found:
- 33.1% of the pooled cohort achieved average LDL-C <50 mg/dL.
- 104 patients experienced MACE.
- For every 39 mg/dL lower achieved LDL-C, the risk of MACE was 24% lower (aHR, 0.76).
- Percent reductions in LDL-C from baseline were inversely correlated with MACE rates (HR, 0.71).
Ray KK, Ginsberg HN, Davidson MH, et al. Reductions in atherogenic lipids and major cardiovascular events. Circulation. 2016;134:1931-1943. doi:10.1161/CIRCULATIONAHA.116.024604.
PCSK-9 inhibitors are monoclonal antibodies that target an enzyme, PCSK-9, which degrades LDL receptors on the liver. The LDL receptors remove LDL cholesterol from the blood. By blocking PCSK-9 from degrading the LDL receptor, more receptors are available to remove LDL cholesterol from the blood, resulting in lower LDL cholesterol levels. It is clear that PCSK-9 inhibitors are potent cholesterol lowering drugs that can often achieve a greater than 50% lowering of LDL-cholesterol when either given alone, or when given in addition to a statin.1 What remains to be seen is if this lowering, often below an LDL-cholesterol level of 50 mg/dL, will yield positive cardiovascular benefit. This meta-analysis of 10 randomized trials suggest that PCSK-9 inhibitors do reduce major adverse cardiac events. —Neil Skolnik, MD