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

Abstract

Statin-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 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 = 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 = 0) and a favorable trend for cardiovascular events (OR = 0.79; 95% CI 0.61, 1.02; I = 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.

Incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: a systematic review and meta-analysis of cost-utility studies

“…Costeffectiveness evaluation of such newer treatments on time may positively influence the pricing and adoption of those interventions for more considerable societal benefit. 20 -524.56 (-554.24 to -494.88) --USA (11) 1-5,8,9,13,16,19 -4.33 (-92.43 O "cost effectiv*" OR "cost utility" OR "cost benefit" OR "costbenefit" OR "quality adjusted life years" OR qaly OR ly OR "life year$" OR daly OR "disability adjusted" OR "incremental cost effective ratio" OR "ICER" OR "incremental net benefit" OR inb OR "benefit ratio" OR 'cost benefit' OR 'cost minimi?ation' OR "cost-effectiveness" OR "cost effectiveness ratio" OR "cost efficiency analys?s" OR "cost utility"…”

“…Cardiovascular outcome trials with evolocumab 12 , alirocumab 17 bococozumab 16 , and inclisiran 18 proved superior to placebo at reducing major adverse cardiovascular events (MACE) among patients with elevated cardiovascular risk and on statin therapy but with no benefit on cardiovascular or all-cause mortality. Meta-analyses of randomized controlled trials (RCTs) suggest that PCSK9i effectively reduce LDL cholesterol 19,20 as well as reduction of major cardiovascular events 2,[21][22][23] and reduce the incidence of all-cause mortality compared to placebo 21 .…”

Clinical outcomes of PCSK9Is: a meta-analysis of randomized clinical trials

“…We conducted a meta-analysis looking at the clinical outcomes of PCSK9Is. Many meta-analyses (15)(16)(17)(18)(19)(20) were published comparing PCSK9Is to either placebo or other medications including (statins and ezetimibe), however to the best of our knowledge, our meta-analysis is the first on this topic to include all three RCTs available to date that are powered to assess clinical outcomes of interest (FOURIER and SPIRE 1 & 2) (7,12), while including only phase III trials. In addition to that, given the fact that statins are the standard of care in high risk patients, we opted to choose studies comparing PCSK9Is to placebo rather than statins, as it appears that PCSK9Is will play an important role as an addition rather than a replacement to the current standard of care therapy in patients at high risk for CVD.…”

Biologic therapy for dyslipidemia

“…Tato léčba je velmi dobře tolerovaná. Kromě lokální reakce v místě vpichu je výskyt nežádoucích účinků většinou srovnatelný s placebem (3,4). K dispozici máme i výsledky velkých studií, které hodnotily efekt dlouhodobé terapie monoklonálními protilátkami proti PCSK9 na výskyt hlavních KV příhod.…”