Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance

Nissen, Steven E.; Stroes, Erik S.G.; Dent-Acosta, Ricardo E; Rosenson, Robert S.; Lehman, Sam J.; Sattar, Naveed; Preiss, David; Bruckert, Éric; Češka, Richard; Lepor, Norman E.; Ballantyne, Christie M.; Gouni‐Berthold, Ioanna; Elliott, Mary; Brennan, Danielle M.; Wasserman, Scott M.; Somaratne, Ransi; Scott, Rob; Stein, Evan A.

doi:10.1001/jama.2016.3608

Cited by 460 publications

(336 citation statements)

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“…248 In another trial, 86 patients were assigned simvastatin 40 mg daily (combined with amlodipine, losartan and hydrochlorthiazide) or a matching placebo in a random sequence; muscle pain was reported more commonly on the active polypill (9 vs 1 cases), but it was not considered sufficiently troublesome to stop treatment. 249 Among 491 patients with a history of not tolerating two or more statin regimens who were randomized to receive atorvastatin 20 mg daily then placebo or placebo then atorvastatin, 250 muscle-related symptoms were reported by 43% of the patients when on atorvastatin but not on placebo versus 27% of them when on placebo but not on atorvastatin; yielding a risk ratio of 1.5 (although it has been suggested that this trial may not have been properly blinded 243 ). In a similar cross-over trial among 120 patients with a history of muscle complaints who were randomized to simvastatin 20 mg daily then placebo or placebo then simvastatin, muscle pain was reported by 36% of the patients when on simvastatin but not on placebo versus 29% of them when on placebo but not on simvastatin.…”

Section: Muscle-related Outcomes (Other Than Myopathy)mentioning

confidence: 99%

“…This idea that so-called "statin intolerance" is a common problem is being widely promulgated, not just in the medical literature [10][11][12]22,61,[71][72][73]286 but also in the public media. 186,240,287,288 In addition, the focus of new LDL-lowering agents in development (such as PCSK9 inhibitors) is shifting towards their use in patients classified as statin intolerant 152,250 in whom the reductions in LDL cholesterol would, in the absence of any background statin therapy, be larger (and, hence, their value might be perceived to be greater).…”

Section: Proven Harms Of Statin Therapy But Minimal Symptomatic Sidementioning

confidence: 99%

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Interpretation of the evidence for the efficacy and safety of statin therapy

et al. 2016

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms SummaryThis review is intended to help clinicians, patients and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomized controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment.Large-scale randomized trial evidence shows that statin therapy reduces the risk of heart attacks, ischaemic strokes and coronary revascularization procedures ("major vascular events") by about one quarter for each mmol/L reduction in low density lipoprotein (LDL) cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (e.g. atorvastatin 40 mg daily, costing about £2 per

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Section: Muscle-related Outcomes (Other Than Myopathy)mentioning

confidence: 99%

Section: Proven Harms Of Statin Therapy But Minimal Symptomatic Sidementioning

confidence: 99%

Interpretation of the evidence for the efficacy and safety of statin therapy

et al. 2016

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“…Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to substantially reduce levels of LDL-C in patients with hypercholesterolemia 11 . Evolocumab is a monoclonal antibody that inhibits PCSK9 and reduces LDL-C by $60% across populations and background therapies [12][13][14][15][16][17] . Evolocumab is currently indicated in the US as an adjunct to diet and maximally tolerated statin therapy for use in patients with heterozygous or homozygous familial hypercholesterolemia or clinical ASCVD who require additional lowering of LDL-C levels 18 .…”

Section: Introductionmentioning

confidence: 99%

Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context

Tóth

Danese²,

Villa

et al. 2017

Journal of Medical Economics

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Aim: To estimate real-world cardiovascular disease (CVD) burden and value-based price range of evolocumab for a US-context, high-risk, secondary-prevention population. Materials and methods: Burden of CVD was assessed using the UK-based Clinical Practice Research Datalink (CPRD) in order to capture complete CV burden including CV mortality. Patients on standard of care (SOC; high-intensity statins) in CPRD were selected based on eligibility criteria of FOURIER, a phase 3 CV outcomes trial of evolocumab, and categorized into four cohorts: high-risk prevalent atherosclerotic CVD (ASCVD) cohort (n ¼ 1448), acute coronary syndrome (ACS) (n ¼ 602), ischemic stroke (IS) (n ¼ 151), and heart failure (HF) (n ¼ 291) incident cohorts. The value-based price range for evolocumab was assessed using a previously published economic model. The model incorporated CPRD CV event rates and considered CV event reduction rate ratios per 1 mmol/L reduction in low-density lipoprotein-cholesterol (LDL-C) from a meta-analysis of statin trials by the Cholesterol Treatment Trialists Collaboration (CTTC), i.e. CTTC relationship. Results: Multiple-event rates of composite CV events (ACS, IS, or coronary revascularization) per 100 patient-years were 12.3 for the high-risk prevalent ASCVD cohort, and 25.7, 13.3, and 23.3, respectively, for incident ACS, IS, and HF cohorts. Approximately one-half (42%) of the high-risk ASCVD patients with a new CV event during follow-up had a subsequent CV event. Combining these real-world event rates and the CTTC relationship in the economic model, the value-based price range (credible interval) under a willingness-to-pay threshold of $150,000/quality-adjusted life-year gained for evolocumab was $11,990 ($9,341-$14,833) to $16,856 ($12,903-$20,678) in ASCVD patients with baseline LDL-C levels !70 mg/dL and !100 mg/dL, respectively. Conclusion: Real-world CVD burden is substantial. Using the observed CVD burden in CPRD and the CTTC relationship, the cost-effectiveness analysis showed that, accounting for uncertainties, the expected value-based price for evolocumab is higher than its current annual cost, as long as the payer discount off list price is greater than 20%. ARTICLE HISTORY

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“…dose of administration, polarity of the compound, degradation pathways) and the concomitant use of other drugs, which may account for most of the muscle-related adverse events reported with statins [19]. However, in a significant proportion of patients, musclerelated statin-intolerance cannot be objectively documented by physicians and, therefore, it is frequently set as a psychosomatic disorder [20]. Inappropriate prescribing (e.g.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of adherence to lipid lowering therapy on LDL-cholesterol in patients with very high cardiovascular risk: A real-world evidence study in primary care

et al. 2017

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a b s t r a c tBackground and aims: Despite management guidelines advocating statin/ezetimibe use in very high cardiovascular risk (CV) conditions, adherence to this therapy is still suboptimal and LDL-C target attainment unsatisfactory. We aimed to investigate the level of adherence to statin/ezetimibe and LDL-C target achievement rates in an unselected very high CV risk population in primary care setting in Italy. Methods: We performed a retrospective population-based study using the Health Search IMS Health Longitudinal Patient Database (HSD), including adult patients at very high CV risk, newly treated with statin, ezetimibe or their combination, with 3 and 6 months of follow-up. Results: Although the large majority of patients had previous major CV events (99.9%), only 61% and 55.14% resulted adherent (Proportion of Days Covered, PDC 80%) after 3 and 6 months, respectively. High adherence entailed almost a three times higher probability to reach the therapeutic LDL-C target (3 months: OR ¼ 2.26 [95% [CI]: 1.88 to 2.72]; 6-months: OR ¼ 2.74 [95% CI: 2.27 to 3.31]). The odds to treat to LDL-C target was greater for simvastatin-ezetimibe fixed combination, simvastatin, atorvastatin and rosuvastatin, in decreasing order. Finally, poor adherence was slightly more prevalent among patients treated with less effective statins, and at both low and maximal dosage regimens.Conclusions: This population-based study showed that adherence to statin therapy is poor even among patients who have already experienced a CV event. Failure to achieve recommended LDL-C levels appears imputable to the use of moderate doses and low to standard efficacy statins.

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Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance

Cited by 460 publications

References 14 publications

Interpretation of the evidence for the efficacy and safety of statin therapy

Interpretation of the evidence for the efficacy and safety of statin therapy

Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context

Effectiveness of adherence to lipid lowering therapy on LDL-cholesterol in patients with very high cardiovascular risk: A real-world evidence study in primary care

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