• Intern Emerg Med · Oct 2017

    Review

    PCSK9 inhibitors for treating dyslipidemia in patients at different cardiovascular risk: a systematic review and a meta-analysis.

    • Alessandro Squizzato, Matteo Basilio Suter, Marta Nerone, Robert Patrick Giugliano, Francesco Dentali, Andrea Maria Maresca, Leonardo Campiotti, Anna Maria Grandi, and Luigina Guasti.
    • Department of Medicine and Surgery, Research Center on Dyslipidaemia, University of Insubria, U.O. Medicina Interna 1, ASST Settelaghi, Viale Borri 57, 21100, Varese, Italy. alessandro.squizzato@uninsubria.it.
    • Intern Emerg Med. 2017 Oct 1; 12 (7): 1043-1053.

    AbstractStatin-induced lowering of low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular morbidity and mortality, but many patients do not adequately reduce their LDL-C levels. Monoclonal antibodies targeting PCKS9 are currently in the advanced phase of development. We aimed to investigate the efficacy and safety of PCSK9 inhibitors in patients at different cardiovascular risk in a systematic review. Studies were searched on MEDLINE and EMBASE until January 2016. Differences in the outcomes among groups were expressed as mean differences, or pooled odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I 2 statistic. 22 RCTs and 8833 patients were included. Six studies were performed in patients affected by homozygous or heterozygous familial hypercholesterolemia, or with increased cardiovascular risk, two in patients with statin intolerance, three in statin-naïve patients, and 10 in patients unable to achieve LDL-C target with statin therapy. PCSK9 inhibitors were associated with a statistically significant reduction of LDL-C (mean = -48.8%; 95% CI -54.1, -43.4; I 2 = 94%) compared to control groups, and with a statistically significant reduction in death for any cause (OR = 0.34; 95% CI 0.17, 0.69; I 2 = 0) and a favorable trend for cardiovascular events (OR = 0.79; 95% CI 0.61, 1.02; I 2 = 0%). PCSK9 inhibitors reduce LDL-C concentration in every group explored. A significant reduction in death by all cause was observed in the PCSK9 inhibitors groups, compared with control groups, even in the short time frame studied.

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