BackgroundThe proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low‐density lipoprotein cholesterol (LDL‐C) when added to statin therapy in patients who need additional LDL‐C reduction.Methods and ResultsWe conducted a systematic review and network meta‐analysis of randomized trials of lipid‐lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid‐lowering therapies that enrolled patients requiring further LDL‐C reduction while on maximally tolerated medium‐ or high‐intensity statin, of which 15 could be relevant for inclusion in LDL‐C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms. PCSK9 inhibitors significantly reduced LDL‐C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (−74.1%; 95% credible interval −79.81% to −68.58%), alirocumab 75 mg (−20.03%; 95% credible interval −27.32% to −12.96%), and alirocumab 150 mg (−13.63%; 95% credible interval −22.43% to −5.33%) at ≥12 weeks. Treatment differences were similar in direction and magnitude for PCSK9 inhibitor monthly dosing. Adverse events were similar between PCSK9 inhibitors and control. Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe.Conclusions PCSK9 inhibitors added to medium‐ to high‐intensity statin therapy significantly reduce LDL‐C in patients requiring further LDL‐C reduction. The network meta‐analysis showed a significant treatment difference in LDL‐C reduction for evolocumab versus alirocumab.

In a U.S. setting, rates of persistence and compliance over 12 months were higher among women initiating denosumab compared with those initiating other osteoporosis therapies.

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PurposeStatins are the first-choice pharmacological treatment for patients with hypercholesterolemia and at risk for cardiovascular disease; however, a minority of patients experience statin-associated symptoms (SAS) and are considered to have reduced statin tolerance. The objective of this study was to establish how patients with SAS are identified and managed in clinical practice in Austria, Belgium, Colombia, Croatia, the Czech Republic, Denmark, Portugal, Switzerland, Russia, Saudi Arabia, Turkey, and the United Arab Emirates.MethodsA cross-sectional survey was conducted (2015–2016) among clinicians (n = 60 per country; Croatia: n = 30) who are specialized/experienced in the treatment of hypercholesterolemia. Participants were asked about their experience of patients presenting with potential SAS and how such patients were identified and treated.ResultsMuscle-related symptoms were the most common presentation of potential SAS (average: 51%; range across countries [RAC] 17–74%); other signs/symptoms included persistent elevation in transaminases. To establish whether symptoms are due to statins, clinicians required rechallenge after discontinuation of statin treatment (average: 77%; RAC 40–90%); other requirements included trying at least one alternative statin. Clinicians reported that half of high-risk patients with confirmed SAS receive a lower-dose statin (average: 53%; RAC 43–72%), and that most receive another non-statin lipid-lowering therapy with or without a concomitant statin (average: 65%; RAC 52–83%).ConclusionsThe specialists and GPs surveyed use stringent criteria to establish causality between statin use and signs or symptoms, and persevere with statin treatment where possible.Electronic supplementary materialThe online version of this article (doi:10.1007/s10557-017-6727-0) contains supplementary material, which is available to authorized users.