1. From a systematic review, proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies significantly reduced LDL cholesterol levels and all-cause mortality without an increase in serious adverse events.
2. PCSK9 antibodies were also associated with a decreased risk for myocardial infarction in patients with dyslipidemia.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Dyslipidemia affects millions of Americans and contributes to coronary artery disease. Although statin drugs are the first-line treatment for patients with high cholesterol, they are not without risk of adverse events. Recently, antibodies to the enzyme proprotein convertase subtilisin/kexin type 9 (PCSK9) have been shown to effectively lower LDL cholesterol in some clinical trials. To investigate the overall safety and efficacy, the authors performed a systematic review of these trials of PCSK9 antibodies for the treatment of dyslipidemia. From this, PCSK9 antibodies significantly lowered all-cause mortality compared to control treatment (i.e., either placebo or ezetimibe). There was also a 50% reduction in LDL cholesterol levels in patients taking PCSK9 antibodies as opposed to control. Additionally, the risk of myocardial infarction was significantly lower in patients taking PCSK9 antibodies. There was no significant difference in the incidence of adverse events between the two treatment groups. This study is limited in that it analyzed study-level, rather than patient-level, data, and the follow-up period varied widely among the trials included in the review. Overall, these findings suggest that PCSK9 antibodies are potentially a viable treatment strategy for patients with dyslipidemia.
In-Depth [systematic review]: The authors searched several online sources for phase 2 or 3 clinical trials comparing PCSK9 antibodies to either placebo or ezetimibe. Twenty-four studies that included a total of 10,159 patients met these criteria and were chosen for the meta-analysis. The findings demonstrated that PCSK9 antibodies significantly reduced all-cause mortality compared to non-PCSK9 treatments (OR, 0.45; p = 0.015); however, there was no significant difference between the groups with respect to cardiovascular mortality (OR 0.50; p = 0.084). There was a significant 47.49% mean difference in reduction of LDL cholesterol for patients taking PCSK9 antibodies as opposed to those who did not (95% CI -69.64% to -25.35%; p < 0.001). Treatment with PCSK9 antibodies also significantly reduced the risk for myocardial infarction, with rates of 0.58% in patients taking PCSK9 and 1.00% in patients who did not (OR 0.49; p = 0.03). There was no significant difference in the incidence of serious adverse events between the two treatment groups, with the rates of adverse events being 9.26% in PCSK9 patients and 7.73% in non-PCSK9 patients (OR 1.01; p = 0.879).
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