Can PCSK9 Inhibitors Improve Hypercholesterolemia Outcomes?

While cautioning that further research is needed, study authors have found that PCSK9 inhibitors dramatically lower LDL cholesterol and could have a mortality benefit for adults with hypercholesterolemia.

In an effort to assess the efficacy and safety of PCSK9 antibodies for this patient population, researchers combined data from 24 phase 2 and 3 randomized, controlled trials involving 10,159 patients, comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia. Two investigators independently extracted data on study characteristics and lipid and clinical outcomes, and rated risk of bias of trials. Pre-specified primary end points were all-cause and cardiovascular mortality.

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PCSK9 inhibitors conferred a 55% reduction in mortality, according to the authors. They note, however, that absolute mortality rates were very low—0.31% with PCSK9 inhibitors compared to 0.53% among controls—with a statistically significant reduction in myocardial infarction. Overall, those treated with PCSK9 inhibitors had a 47% reduction in LDL cholesterol, relative to all controls. In comparison to ezetimibe, PCSK9 inhibitors affected a 36% reduction in LDL cholesterol.

The findings figure to impact the way patients with hypercholesterolemia are treated, says lead study author Eliano Pio Navarese, MD, PhD, from the department of internal medicine in the division of cardiology, pulmonology and vascular medicine at Heinrich Heine University.

“We now know there are novel agents in the armamentarium of physicians that, when added to a statin, are able to not only further reduce the level of cholesterol, but improve survival,” says Navarese. “This is therefore the sign that we are going to optimize the treatment of patients with hypercholesterolemia, especially those at high cardiovascular risk.”

In addition, this meta-analysis finds that PCSK9 antibodies are beneficial in reducing serum creatinkinase levels, which “would make these agents very useful in patients intolerant to a statin” as well, says Navarese.

Therefore, “these agents will fit both in combination with a statin and when used along,” he says. “We are entering a new era with more promising agents that will soon receive the FDA approval due to their clear-cut benefits on clinical outcomes. This large meta-analysis has clearly shown this for the first time.”

—Mark McGraw


Navarese E, Kołodziejczak M, et al. Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis. Ann Intern Med. 2015.