PCSK9 Inhibitors Safe, Effective in Hypercholesterolemia

PCSK9 antibodies can safely and effectively treat high cholesterol in adults while reducing mortality rates.

PCSK9 inhibitors can effectively lower LDL and lipoprotein in adults with hypercholesterolemia as well as reduce all-cause mortality, according to a study published in Annals of Internal Medicine.

The researchers also found that PCSK9 antibodies did not increase serious adverse effects, lowered increases in serum creatine kinase levels and significantly reduced total cholesterol levels.

Statins have traditionally been the first treatment option for dyslipidemia and often effectively lower LDL cholesterol levels and the risk for cardiovascular (CV) events. However, a significant amount of patients taking statins still do not achieve recommended target LDL cholesterol levels, and others cease treatment due to adverse effects.

The enzyme proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates the density of LDL cholesterol receptors in various organs, giving it a key role in lipid metabolism. The level of PCSK9 in the blood is inversely related to the number of LDL receptors. Thus, monoclonal antibodies that target PCSK9 have provided a new approach for lowering lipid levels.

The researchers in this study wanted to determine the safety and efficacy of these PCSK9 antibodies for treating hypercholesterolemia, and so they analyzed previous trials evaluating the treatment.

“The treatment of patients with hypercholesterolemia, especially those at high cardiovascular risk, can be further optimized,” researcher Eliano Pio Navarese, MD, PhD, of Henrich Heine University in Germany, said in an email interview. “PCSK9 antibodies could be a potential adjunct to standard therapy.”

Study Results

The meta-analysis included eight phase 2 and 16 phase 3 trials that compared PCSK9 antibodies with no anti-PCSK9 therapy (either placebo or ezetimibe) for the treatment of hypercholesterolemia in adults. In total, the studies included 10,159 patients.

The study had two primary clinical endpoints: all-cause mortality and CV mortality. The rate of all-cause mortality in participants treated with PCSK9 antibodies was 0.31% (19 of 6,817 participants) compared with 0.53% (21 of 3,971 participants) for those not treated with PCSK9 antibodies, according to the data.

The rate of CV mortality in participants treated with PCSK9 antibodies was 0.19% (12 of 6,817 participants) compared with 0.33% (13 of 3,972 participants) for those not treated with PCSK9 antibodies.

The secondary safety endpoints were myocardial infarction (MI), unstable angina, serum creatine kinase levels and serious adverse events. MI occurred significantly less often among those treated with PCSK9 antibodies: 0.58% (19 of 3,289 participants) compared with 1.00% (19 of 1,906 participants) in the non-treatment groups.

The rates of unstable angina were similar in the treatment groups (0.04%; 1 of 2,515 participants) and the non-treatment groups (0.08%; 1 of 1,379 participants).

Significantly fewer participants in the treatment groups had increased serum creatine kinase levels (1.96%; 121 of 6,187 participants) compared with the non-treatment groups (2.31%; 92 of 3,972 participants).