Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome

Murphy, Sabina A.; Cannon, Christopher P.; Blazing, Michael A.; Giugliano, Robert P.; White, Jennifer A.; Lokhnygina, Yuliya; Reist, Craig J.; Im, KyungAh; Bohula, Erin A.; Isaza, Daniel; López‐Sendón, José; Dellborg, Mikael; Kher, Uma; Tershakovec, Andrew M.; Braunwald, Eugene

doi:10.1016/j.jacc.2015.10.077

Cited by 187 publications

(84 citation statements)

References 23 publications

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“…Lowering LDL-C levels has been shown to reduce the risk of CVD events in several interventional and epidemiologic studies [11–13,37–39]; that holds for both statin [40,41] and non-statin therapies [42,43]. The evolocumab CV outcomes trial, Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) [16], demonstrated that the addition of evolocumab to SoC is associated with a reduced incidence of major CVD events.…”

Section: Methodsmentioning

confidence: 99%

Cost-effectiveness of evolocumab in treatment of heterozygous familial hypercholesterolaemia in Bulgaria: measuring health benefit by effectively treated patient-years*

Borissov¹,

Urbich

Georgieva³

et al. 2017

Journal of Market Access & Health Policy

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Background: An elevated level of low-density lipoprotein cholesterol (LDL-C) constitutes one of the most important modifiable risk factors for cardiovascular disease (CVD). Individuals with heterozygous familial hypercholesterolaemia (HeFH) are particularly vulnerable to CVD events. The addition of evolocumab to statins has shown marked reductions in LDL-C levels. The objective of this analysis is to demonstrate the clinical and economic value of LDL-C lowering with evolocumab from the Bulgarian public health care perspective. Methods: A disease-specific measure of health benefit was devised: Effectively treated patient-years (ETPYs) combine length of life with the likelihood of attaining best-practice recommendations on LDL-C lowering. “Effective treatment” was defined as a reduction in LDL-C levels of ≥50%. A Markov cohort state-transition model was adapted, considering a life-long treatment duration. Demographics, baseline characteristics and efficacy data were taken from the RUTHERFORD-2 trial. The model uses the relationship between LDL-C lowering and reduced CVD event rates observed in the meta-analyses conducted by the Cholesterol Treatment Trialists’ Collaboration. Outcomes and costs (from year 2015) were discounted at an annual rate of 5%. Sensitivity analyses were conducted to assess uncertainty surrounding the results. Results: The total incremental costs of evolocumab added to statins versus statins alone are BGN 120,329 while adding 9.30 ETPYs over lifetime. These results imply an incremental cost per ETPY of BGN 12,937 (US$ 7,215; € 6,604). The use of evolocumab is associated with a relative reduction in the CVD event rate by 38% (18% per 1 mmol/L). Conclusions: Adding evolocumab to statins may be considered cost-effective in light of an additional expense per patient-year gained in which individuals with HeFH receive effective treatment under the terms of international prevention guidelines. ETPYs are an intuitive and clinically meaningful measure of patient benefit that, in relation to costs, can support health care decision-making that considers quality of care.

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Section: Methodsmentioning

confidence: 99%

Cost-effectiveness of evolocumab in treatment of heterozygous familial hypercholesterolaemia in Bulgaria: measuring health benefit by effectively treated patient-years*

Borissov¹,

Urbich

Georgieva³

et al. 2017

Journal of Market Access & Health Policy

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“…Reductions in total primary endpoint events, driven by reductions in myocardial infarction and stroke, more than doubled the number of events prevented compared with examining only the first event. The number of cardiovascular deaths remained similar between treatment groups [70].…”

Section: Previous Clinical Experience With Simvastatinezetimibe Combimentioning

confidence: 80%

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

Ferreira

Silva

2016

Am J Cardiovasc Drugs

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Statin-ezetimibe combinations are a potentially advantageous therapeutic option for high-risk patients who need additional lowering of low-density lipoprotein cholesterol (LDL-C). These combinations may overcome some of the limitations of statin monotherapy by blocking both sources of cholesterol. Recently, a fixed-dose combination with atorvastatin, one of the most extensively studied statins, was approved and launched in several countries, including the USA. Depending on atorvastatin dose, this combination provides LDL-C reductions of 50-60%, triglyceride reductions of 30-40%, and highdensity lipoprotein cholesterol (HDL-C) increases of 5-9%. Studies comparing the lipid-lowering efficacy of the atorvastatin-ezetimibe combination with the alternatives of statin dose titration or switching to a more potent statin consistently showed that combination therapy provided greater LDL-C reduction, translating into a greater proportion of patients achieving lipid goals. Simvastatinezetimibe combinations have been shown to reduce the incidence of major atherosclerotic events in several clinical settings to a magnitude that seems similar to that observed with statins for the same degree of absolute LDL-C lowering. The atorvastatin-ezetimibe combination has also been shown to induce the regression of coronary atherosclerosis measured by intravascular ultrasound in a significantly greater proportion of patients than atorvastatin alone. Atorvastatin-ezetimibe combinations are generally well tolerated. Previous concerns of a possible increase in the incidence of cancer with ezetimibe were dismissed in large trials with long follow-up periods. In this paper, we examine the rationale for an atorvastatin-ezetimibe combination, review the evidence supporting it, and discuss its potential role in the management of dyslipidemia. Key PointsStatin-ezetimibe combinations are a realistic treatment option for patients who do not achieve low-density lipoprotein cholesterol (LDL-C) targets while receiving statin monotherapy and for patients prone to dose-dependent statin side effects.The IMPROVE-IT trial was the first to demonstrate a reduction in cardiovascular events with ezetimibe.Recently, combination therapy with atorvastatin plus ezetimibe was also associated with greater coronary plaque regression than atorvastatin alone.

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“…5 Prevention of recurrent cardiovascular events can have important implications for cardiovascularrelated healthcare resource use and associated costs, which are expected to rise with the increase in elderly populations, obesity, and diabetes mellitus. 3 We performed a health economic study alongside the IMPROVE-IT trial to examine the impact of simvastatin-ezetimibe combination therapy compared with simvastatin-placebo on the rate of cardiovascular-related hospitalizations and associated costs, both in the overall trial population and in various clinically relevant subgroups.…”

Section: Pokharel Et Al Impact Of Ezetimibe On CV Hospitalization Andmentioning

confidence: 99%

Impact of Ezetimibe on the Rate of Cardiovascular-Related Hospitalizations and Associated Costs Among Patients With a Recent Acute Coronary Syndrome

Pokharel

Chinnakondepalli

Vilain

et al. 2017

Circ: Cardiovascular Quality and Outcomes

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Background— Ezetimibe, when added to simvastatin therapy, reduces cardiovascular events after recent acute coronary syndrome. However, the impact of ezetimibe on cardiovascular-related hospitalizations and associated costs is unknown. Methods and Results— We used patient-level data from the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) to examine the impact of simvastatin–ezetimibe versus simvastatin–placebo on cardiovascular-related hospitalizations and related costs (excluding drug costs) over 7 years follow-up. Medicare Severity–Diagnosis Related Groups were assigned to all cardiovascular hospitalizations. Hospital costs were estimated using Medicare reimbursement rates for 2013. Associated physician costs were estimated as a percentage of hospital costs. The impact of treatment assignment on hospitalization rates and costs was estimated using Poisson and linear regression, respectively. There was a significantly lower cardiovascular hospitalization rate with ezetimibe compared with placebo (risk ratio, 0.95; 95% confidence interval, 0.90–0.99; P =0.031), mainly attributable to fewer hospitalizations for percutaneous coronary intervention, angina, and stroke. Consequently, cardiovascular-related hospitalization costs over 7 years were $453 per patient lower with ezetimibe (95% confidence interval, −$38 to −$869; P =0.030). Although all prespecified subgroups had lower cost with ezetimibe therapy, patients with diabetes mellitus, patients aged ≥75 years, and patients at higher predicted risk for recurrent ischemic events had even greater cost offsets. Conclusions— Addition of ezetimibe to statin therapy in patients with a recent acute coronary syndrome leads to reductions in cardiovascular-related hospitalizations and associated costs, with the greatest cost offsets in high-risk patients. These cost reductions may completely offset the cost of the drug once ezetimibe becomes generic, and may lead to cost savings from the perspective of the healthcare system, if treatment with ezetimibe is targeted to high-risk patients. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique Identifier: NCT00202878

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Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome

Cited by 187 publications

References 23 publications

Cost-effectiveness of evolocumab in treatment of heterozygous familial hypercholesterolaemia in Bulgaria: measuring health benefit by effectively treated patient-years*

Cost-effectiveness of evolocumab in treatment of heterozygous familial hypercholesterolaemia in Bulgaria: measuring health benefit by effectively treated patient-years*

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

Impact of Ezetimibe on the Rate of Cardiovascular-Related Hospitalizations and Associated Costs Among Patients With a Recent Acute Coronary Syndrome

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