While the incidence of adverse effects was significantly higher in the treatment groups (9.26%; 573 of 6,187 participants) compared with non-treatment groups (7.73%; 307 of 3,972 participants), the average discontinuation rates did not differ between the groups.

The study also had several efficacy endpoints: LDL cholesterol, HDL cholesterol, total cholesterol and lipoprotein(a). Compared with the non-treatment groups, participants treated with PCSK9 antibodies had a 47.49% reduction in LDL cholesterol, a 6.30% increase in HDL cholesterol and a 31.49% reduction in total cholesterol.

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Additionally, the treatment groups had a greater than 25% reduction in lipoprotein(a) levels compared with the non-treatment groups.

“These findings will impact the way to treat patients with hypercholesterolemia: from this meta-analysis we know now there are novel agents in the armamentarium of physicians that, when added to a statin, are able not only to further reduce the level of cholesterol but also improve survival,” said Dr. Navarese.

“Additionally, reduced level of serum creatine kinase found with PCSK9 antibodies point that these agents are also very useful in attenuating statin intolerance.”

Clinical Considerations

In a related editorial, Miguel Cainzos-Achirica, MD, and colleagues wrote that more trials with extended follow-up periods are needed to better assess the safety of PCSK9 antibodies.

Although the current meta-analysis did not find a particular increase in serious adverse effects, there are little existing data on the more long-term effects of PCSK9 antibodies. In animal models, these antibodies are potentially linked to impaired glucose metabolism, providing further incentive to test their long-term effects in humans.

Additionally, the editorial pointed out that this new therapeutic option for treating hypercholesterolemia necessitates investigating the best sequence and combination of drug therapies for various patient populations.

The editorial writers suggested that the study’s results be interpreted with “cautious enthusiasm” until further studies further explore how PCSK9 inhibitors can be used to manage hypercholesterolemia.

Navarese remains hopeful about the future of PCSK9 inhibitors. “We are entering a new era with more promising agents that soon will receive the FDA approval due to their clear cut benefits on clinical outcomes,” he said. “But for now we have yet another piece of evidence that the lower LDL cholesterol, the better.”


  1. Navarese EP et al. Ann Intern Med. 2015;doi:10.7326/2957.
  2. Cainzos-Achirica M et al. Ann Intern Med. 2015;doi:10.7326/M15-0920.