The economic impact of hypercholesterolemia and mixed dyslipidemia: A systematic review of cost of illness studies.

Hypercholesterolemia is a clinically relevant condition with an ascertained role in atherogenesis. In particular, its presence directly correlates to the risk of atherosclerotic cardiovascular disease (ASCVD). As known, cardiovascular diseases pose a significant economic burden worldwide; however, a clear picture of the economic impact of ASCVD secondary to hypercholesterolemia is lacking. This study aiming at conducting a systematic review of the current literature to assess the economic impact of familial hypercholesterolemia (FH), non-familial hypercholesterolemia (non-FH) or mixed dyslipidemia. A literature search was performed in Medline/PubMed and Embase database up to September 1st, 2020, exploring evidence published from 2010. The literature review was conducted in accordance with PRISMA guidelines. To be included the studies must be conducted on people who have been diagnosed with familial hypercholesterolemia, non-familial hypercholesterolemia or mixed dyslipidemia, and report data/information on costs attributable to these conditions and their sequelae. A total of 1260 studies were retrieved. After reading the titles and abstract, 103 studies were selected for full reading and eight met the criteria for inclusion. All but one studies were published in the American continent, with the majority conducted in US. An observational design with a prevalence approach were used and all estimated the economic burden of CVD. Direct cost estimates as annual average health expenditure on all population, ranging from $17 to $259 million. Few studies assessing the economic impact of hypercholesterolemia are available in the literature and new researches are needed to provide a more updated and reliable picture. Despite this scarceness of evidence, this review adds important data for future discussion on the knowledge of the economic impact of hypercholesterolemia and costs of care associated to this condition, with important implication for public health researches and novel therapies implementation.

Cost and consequence analysis of the Healthy Choices at Work programme to prevent non-communicable diseases in a commercial power plant, South Africa.

BACKGROUND: The workplace is an ideal setting for the implementation of a health promotion programmes to prevent non-communicable diseases (NCD). There are limited resources assigned to workplace health promotion programmes in low-and middle-income countries (LMIC). AIM: This study aimed to conduct a cost and consequence analysis of the Healthy Choices at Work programme. SETTING: This study was conducted at a commercial power plant in South Africa. METHODS: Incremental costs were obtained for the activities of the Healthy Choices at Work programme over a two-year period. A total of 156 employees were evaluated in the intervention, although the effect was experienced by all employees. An annual health risk factor assessment at baseline and follow up evaluated the consequences of the programme. RESULTS: The total incremental costs over the two-year period accumulated to $4015 for 1743 employees. The cost per employee on an annual basis was $1.15 and was associated with a -10.2mmHg decrease in systolic blood pressure, -3.87mmHg in diastolic blood pressure, -0.45mmol/l in total cholesterol and significant improvement in harmful alcohol use, fruit and vegetable intake and physical inactivity (p 0.001). There was no correlation between sickness absenteeism and risk factors for NCDs. CONCLUSION: The cost to implement the multicomponent HCW programme was low with significant beneficial consequences in transforming the workplace environment and reducing risks factors for NCDs. Findings of this study will be useful for small, medium and large organisations, the national department of health, and similar settings in LMICs.

Cost-Effectiveness of Alirocumab in Patients With Acute Coronary Syndromes: The ODYSSEY OUTCOMES Trial.

BACKGROUND: Cholesterol reduction with proprotein convertase subtilisin-kexin type 9 inhibitors reduces ischemic events; however, the cost-effectiveness in statin-treated patients with recent acute coronary syndrome remains uncertain. OBJECTIVES: This study sought to determine whether further cholesterol reduction with alirocumab would be cost-effective in patients with a recent acute coronary syndrome on optimal statin therapy. METHODS: A cost-effectiveness model leveraging patient-level data from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was developed to estimate costs and outcomes over a lifetime horizon. Patients (n = 18,924) had a recent acute coronary syndrome and were on high-intensity or maximum-tolerated statin therapy, with a baseline low-density lipoprotein cholesterol (LDL-C) level ≥70 mg/dl, non-high-density lipoprotein cholesterol ≥100 mg/dl, or apolipoprotein B ≥80 mg/l. Alirocumab 75 mg or placebo was administered subcutaneously every 2 weeks. Alirocumab was blindly titrated to 150 mg if LDL-C remained ≥50 mg/dl or switched to placebo if 2 consecutive LDL-C levels were <15 mg/dl. Incremental cost per quality-adjusted life-year (QALY) was determined with the addition of alirocumab versus placebo and, based on clinical efficacy findings from the trial, was stratified by baseline LDL-C levels ≥100 mg/dl and <100 mg/dl. RESULTS: Across the overall population recruited to the ODYSSEY OUTCOMES trial, using an annual treatment cost of US$5,850, the mean overall incremental cost-effectiveness ratio was US$92,200 per QALY (base case). The cost was US$41,800 per QALY in patients with baseline LDL-C ≥100 mg/dl, whereas in those with LDL-C <100 mg/dl the cost per QALY was US$299,400. Among patients with LDL-C ≥100 mg/dl, incremental cost-effectiveness ratios remained below US$100,000 per QALY across a wide variety of sensitivity analyses. CONCLUSIONS: In patients with a recent acute coronary syndrome on optimal statin therapy, alirocumab improves cardiovascular outcomes at costs considered intermediate value, with good value in patients with baseline LDL-C ≥100 mg/dl but less economic value with LDL-C <100 mg/dl. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402).

Hidden Burden of Electronic Health Record-Identified Familial Hypercholesterolemia: Clinical Outcomes and Cost of Medical Care.

Background Familial hypercholesterolemia ( FH ), is a historically underdiagnosed, undertreated, high-risk condition that is associated with a high burden of cardiovascular morbidity and mortality. In this study, we use a population-based approach using electronic health record ( EHR )-based algorithms to identify FH . We report the major adverse cardiovascular events, mortality, and cost of medical care associated with this diagnosis. Methods and Results In our 1.18 million EHR- eligible cohort, International Classification of Diseases, Ninth Revision ( ICD -9) code-defined hyperlipidemia was categorized into FH and non- FH groups using an EHR algorithm designed using the modified Dutch Lipid Clinic Network criteria. Major adverse cardiovascular events, mortality, and cost of medical care were analyzed. A priori associated variables/confounders were used for multivariate analyses using binary logistic regression and linear regression with propensity score-based weighted methods as appropriate. EHR FH was identified in 32 613 individuals, which was 2.7% of the 1.18 million EHR cohort and 13.7% of 237 903 patients with hyperlipidemia. FH had higher rates of myocardial infarction (14.77% versus 8.33%; P<0.0001), heart failure (11.82% versus 10.50%; P<0.0001), and, after adjusting for traditional risk factors, significantly correlated to a composite major adverse cardiovascular events variable (odds ratio, 4.02; 95% CI, 3.88-4.16; P<0.0001), mortality (odds ratio, 1.20; CI, 1.15-1.26; P<0.0001), and higher total revenue per-year (incidence rate ratio, 1.30; 95% CI, 1.28-1.33; P<0.0001). Conclusions EHR -based algorithms discovered a disproportionately high prevalence of FH in our medical cohort, which was associated with worse outcomes and higher costs of medical care. This data-driven approach allows for a more precise method to identify traditionally high-risk groups within large populations allowing for targeted prevention and therapeutic strategies.

How Low to Go With Lipid-Lowering Therapies in a Cost-effective and Prudent Manner.

The 2013 American College of Cardiology/American Heart Association guideline on the treatment of blood cholesterol was a landmark document guiding health care professionals around the globe on how to administer lipid-lowering therapies. Those guidelines were primarily focused on statin therapy benefit groups. The writing committee found insufficient evidence for specific low-density lipoprotein cholesterol (LDL-C) treatment targets. There have been many important updates in the lipid literature since the publication of that document. Most importantly, clinical trials have provided definitive evidence for the pivotal role of LDL-C in atherogenesis and the improvement in clinical outcomes by means of aggressive LDL-C reduction. Ezetimibe, evolocumab, and alirocumab treatment resulted in substantial reductions in major adverse cardiovascular outcomes. These data encourage a discussion on whether LDL-C targets are warranted in primary and/or secondary prevention, and if so, how low should those targets be. In order to answer such questions, the costs and safety of such therapies, as well as the safety of very low levels of LDL-C need to be addressed. This review discusses the relationship between LDL-C lowering and cardiovascular risk reduction, the efficacy, safety, and cost-effectiveness of high-intensity lipid-lowering therapies, and the recommendations from the most recent lipid guidelines.

Application of PCSK9 Inhibitors in Practice.

PCSK9i (protein convertase subtilisin/kexin type 9 inhibitors) are set to revolutionize the treatment of hypercholesterolemia in the management of atherosclerotic risk, but numerous reports have detailed unprecedented barriers to access for these drugs. To overcome these challenges, our group created a model to facilitate provision of this new therapy for patients who qualify according to Food and Drug Administration criteria. This report details the real-world follow-up experience of PCSK9i use in a large patient cohort structured to ensure rigor in data collection, analysis, and interpretation. The 271 patients approved and actively followed in our PCSK9i clinic between July 2015 and August 2018 represent a 97% approval rate from insurance, with 28% of prescriptions requiring at least one appeal. Over 50% of patients were statin intolerant. On average, there was a median lapse of 15 days between initial visit and insurance approval. PCSK9i therapy was affordable for most patients, with an average monthly out-of-pocket expense of $58.05 (median $0). Only 2.3% of patients were unable to initiate or continue therapy because of cost. Reductions from baseline in LDL (low-density lipoprotein) cholesterol and Lp(a) (lipoprotein [a])were comparable to published reports with median reductions of 60% and 23% at 1 year, respectively. PCSK9i therapy was well-tolerated overall, though 9% of patients reported adverse events, and 5% of patients discontinued due mostly to musculoskeletal and flu-like symptoms. Our practice model demonstrates that PCSK9i therapy can be accessed easily and affordably for the majority of eligible patients, resulting in dramatic improvement in lipid profile results. Moreover, our registry data suggest that results from the prospective clinical trials of PCSK9i on LDL and Lp(a) reduction and on tolerability are applicable to a real-world cohort.

Profile of evolocumab and its cost-effectiveness in patients with high cardiovascular risk: literature review.

INTRODUCTION: Evolocumab is fully human monoclonal antibody which binds to proprotein convertase subtilisin/kexin type 9 (PCSK9), and prevents its blocking effect on recycling of liver low-density lipoprotein (LDL) receptors. Areas covered: The aim of this review is to assess efficacy, safety, and cost-effectiveness of evolocumab in adult patients with high cardiovascular risk. Major research databases MEDLINE, EBSCO, and CENTRAL were systematically searched for relevant study reports. Expert commentary: Even when given in full doses, statins augmented with ezetimibe and cholesterol-binding resins could not reduce cholesterol baseline level for more than 66%, while evolocumab reduces cholesterol level for 75% or even more. Up to now, evolocumab showed good safety profile, and patents tolerate it very well. The abovementioned advantages of evolocumab made it almost ideal drug for hypercholesterolemia, and probably in the future the best drug for secondary prevention of major cardiovascular events. Evolocumab is borderline cost-effective for the treatment of patients with high cardiovascular risk in European countries, while in the U.S.A. it is under debate where the underlying assumption (risk of cardiovascular disease events) determine the true value.

Cost-effectiveness and Budget Impact of Treatment with Evolocumab Versus Statins and Ezetimibe for Hypercholesterolemia in Spain.

INTRODUCTION AND OBJECTIVES: To analyze the cost-effectiveness ratio and budget impact of treatment with evolocumab (PCSK9 inhibitor) for patients in secondary prevention in the Spanish National Health System. METHODS: A budget impact analysis, decision tree and Markov models were designed under the public health system perspective, based on the only study with morbidity and mortality data (FOURIER). The alternatives compared were evolocumab vs statins, and dual therapy with ezetimibe in 5% of the population. The measure of effectiveness used was the number of cardiovascular events avoided. Univariate and probabilistic sensitivity analyses were performed. RESULTS: The average annual cost of patients receiving evolocumab was 11 134.78€ and 393.83€ for standard treatment (statins plus ezetimibe). The incremental cost-effectiveness ratio was > 600 000 € per avoided cardiovascular event for both assessed outcomes (first: cardiovascular death, myocardial infarction, stroke, and hospitalization due to unstable angina or coronary revascularization; second: includes the first 3 events). To perform the 10-year Markov model, the average cost of standard treatment was 13 948.45€ vs 471 417.37€ with evolocumab. Treatment with evolocumab for patients with familial hypercholesterolemia would cost between 3 and 6.1 million euros, assuming a difference of 2.5 and 5.1 million euros with the standard treatment (2017). This difference would be between 204.3 and 1364.7 million euros (2021) for those with nonfamiliar hypercholesterolemia (secondary prevention). CONCLUSIONS: Treatment with evolocumab is associated with a lower frequency of cardiovascular events, but is inefficient for patients suitable to receive this drug in the Spanish National Health System.

Are PCSK9 Inhibitors Cost Effective?

The objective of this study was to review available health economic evaluations of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. These drugs reduce low-density lipid cholesterol levels and cardiovascular risk, but their cost effectiveness has been questioned. We searched Medline and Embase for economic evaluations in any language at any time. Studies were included if they analysed any PCSK9 inhibitor compared with either statin alone or in combination with ezetimibe or any other therapy considered standard prior to the introduction of PCSK9 inhibitors. We found ten full health economic evaluations of PCSK9 inhibitors, two from Europe and eight from the United States (US). Six of the eight from the US were from two different consortia that analysed PCSK9 inhibitors at different stages through the development of evidence. All studies generally reported incremental cost-effectiveness ratios above suggested thresholds for cost effectiveness, except one study from Spain. The results of this review indicate that PCSK9 inhibitors in general are not cost effective at the current prices, but lower prices may change the results.

Estimated costs of hospitalization due to coronary artery disease attributable to familial hypercholesterolemia in the Brazilian public health system.

OBJECTIVE: Cardiovascular diseases are the leading cause of death in Brazil, imposing substantial economic burden on the health care system. Familial hypercholesterolemia (FH) is known to greatly increase the risk of premature coronary artery disease (CAD). This study aimed to estimate the economic impact of hospitalizations due to CAD attributable to FH in the Brazilian Unified Health Care System (SUS). SUBJECTS AND METHODS: Retrospective, cross-sectional study of data obtained from the Hospital Information System of the SUS (SIHSUS). We selected all adults (≥ 20 years of age) hospitalized from 2012--2014 with primary diagnoses related to CAD (ICD-10 I20 to I25). Attributable risk methodology estimated the contribution of FH in the outcomes of interest, using international data for prevalence (0.4% and 0.73%) and relative risk for events (RR = 8.56). RESULTS: Assuming an international prevalence of FH of 0.4% and 0.73%, of the 245,981 CAD admissions/year in Brazil, approximately 7,249 and 12,915, respectively, would be attributable to an underlying diagnosis --of FH. The total cost due to CAD per year, considering both sexes and all adults, was R$ 985,919,064, of which R$ 29,053,500 and R$ 51,764,175, respectively, were estimated to be attributable to FH. The average cost per FH-related CAD event was R$ 4,008. CONCLUSION: Based on estimated costs of hospitalization for CAD, we estimated that 2.9-5.3% are directed to FH patients. FH can require early specific therapies to lower risk in families. It is mandatory to determine the prevalence of FH and institute appropriate treatment to minimize the clinical and economic impact of this disease in Brazil.

Estimated costs of hospitalization due to coronary artery disease attributable to familial hypercholesterolemia in the Brazilian public health system

ABSTRACT Objective: Cardiovascular diseases are the leading cause of death in Brazil, imposing substantial economic burden on the health care system. Familial hypercholesterolemia (FH) is known to greatly increase the risk of premature coronary artery disease (CAD). This study aimed to estimate the economic impact of hospitalizations due to CAD attributable to FH in the Brazilian Unified Health Care System (SUS). Subjects and methods: Retrospective, cross-sectional study of data obtained from the Hospital Information System of the SUS (SIHSUS). We selected all adults (≥ 20 years of age) hospitalized from 2012­-2014 with primary diagnoses related to CAD (ICD-10 I20 to I25). Attributable risk methodology estimated the contribution of FH in the outcomes of interest, using international data for prevalence (0.4% and 0.73%) and relative risk for events (RR = 8.56). Results: Assuming an international prevalence of FH of 0.4% and 0.73%, of the 245,981 CAD admissions/year in Brazil, approximately 7,249 and 12,915, respectively, would be attributable to an underlying diagnosis ­­of FH. The total cost due to CAD per year, considering both sexes and all adults, was R$ 985,919,064, of which R$ 29,053,500 and R$ 51,764,175, respectively, were estimated to be attributable to FH. The average cost per FH-related CAD event was R$ 4,008. Conclusion: Based on estimated costs of hospitalization for CAD, we estimated that 2.9-5.3% are directed to FH patients. FH can require early specific therapies to lower risk in families. It is mandatory to determine the prevalence of FH and institute appropriate treatment to minimize the clinical and economic impact of this disease in Brazil.

Comparative effectiveness of lipid-lowering treatments to reduce cardiovascular disease.

INTRODUCTION: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is a new treatment option for patients with hypercholesterolemia. The objective of this study was to systematically review the cost-effectiveness of lipid-lowering agents. AREAS COVERED: Based on Pubmed, Embase, and Cochrane Database of Systematic Reviews, we identified 29 relevant articles. Studies found statins were cost-effective compared with placebo or no treatment in general. Atorvastatin was reported to be cost-effective against simvastatin. In most cases, rosuvastatin was more cost-effective than atorvastatin or simvastatin. Additionally, ezetimibe was considered to be cost-effective compared with no treatment for statin intolerant patients. For patients not meeting treatment goals with their statins, switching to ezetimibe plus simvastatin was consistently reported cost-effective. The cost-effectiveness of ezetimibe plus a hybrid of a statin varied by the source of clinical data and cost of ezetimibe. Finally, the cost-effectiveness of PCSK9 inhibitor plus a statin against statin monotherapy was uncertain. The PCSK9 inhibitor plus a stain was cost-ineffective compared with ezetimibe plus a statin. EXPERT COMMENTARY: Drug costs and treatment efficacy were the key drivers of the cost-effectiveness results in prior analyses. Future evaluations are warranted to reflect the decreasing drug prices and the long-term treatment effects of PCSK9 inhibitors.

Effects of Transitioning to Medicare Part D on Access to Drugs for Medical Conditions among Dual Enrollees with Cancer.

OBJECTIVES: To evaluate the impact of transitioning from Medicaid to Medicare Part D drug coverage on the use of noncancer treatments among dual enrollees with cancer. METHODS: We leveraged a representative 5% national sample of all fee-for-service dual enrollees in the United States (2004-2007) to evaluate the impact of the removal of caps on the number of reimbursable prescriptions per month (drug caps) under Part D on 1) prevalence and 2) average days' supply dispensed for antidepressants, antihypertensives, and lipid-lowering agents overall and by race (white and black). RESULTS: The removal of drug caps was associated with increased use of lipid-lowering medications (days' supply 3.63; 95% confidence interval [CI] 1.57-5.70). Among blacks in capped states, we observed increased use of lipid-lowering therapy (any use 0.08 percentage points; 95% CI 0.05-0.10; and days' supply 4.01; 95% CI 2.92-5.09) and antidepressants (days' supply 2.20; 95% CI 0.61-3.78) and increasing trends in antihypertensive use (any use 0.01 percentage points; 95% CI 0.004-0.01; and days' supply 1.83; 95% CI 1.25-2.41). The white-black gap in the use of lipid-lowering medications was immediately reduced (-0.09 percentage points; 95% CI -0.15 to -0.04). We also observed a reversal in trends toward widening white-black differences in antihypertensive use (level -0.08 percentage points; 95% CI -0.12 to -0.05; and trend -0.01 percentage points; 95% CI -0.02 to -0.01) and antidepressant use (-0.004 percentage points; 95% CI -0.01 to -0.0004). CONCLUSIONS: Our findings suggest that the removal of drug caps under Part D had a modest impact on the treatment of hypercholesterolemia overall and may have reduced white-black gaps in the use of lipid-lowering and antidepressant therapies.

Cholesterol Control Among Uninsured Adults Did Not Improve From 2001-2004 to 2009-2012 as Disparities With Both Publicly and Privately Insured Adults Doubled.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) control is higher among insured than uninsured adults, but data on time trends and contributing factors are incomplete and important for improving health equity. METHODS AND RESULTS: Awareness, treatment, and control of elevated LDL-C were compared among insured versus uninsured and publicly versus privately insured adults, aged 21 to 64 years, in National Health and Nutrition Examination Surveys from 2001 to 2004, 2005 to 2008, and 2009 to 2012 using Adult Treatment Panel-3 criteria. Compared with insured adults, uninsured adults were younger; were more often minority; reported lower incomes, less education, and fewer healthcare encounters; and had lower awareness and treatment of elevated LDL-C (P<0.0001). LDL-C control was higher among insured than uninsured adults in 2001 to 2004 (mean±SEM, 21.4±1.6% versus 10.5±2.6%; P<0.01), and the gap widened by 2009 to 2012 (35.1±1.9% versus 11.3±2.2%; P<0.0001). Despite more minorities (P<0.01), greater poverty, and less education (P<0.001), publicly insured adults had more healthcare visits/year than privately insured adults (P<0.001) and similar awareness, treatment, and control of LDL-C from 2001 to 2012. In multivariable logistic regression, significant positive predictors of cholesterol awareness, treatment, and control included more frequent health care (strongest), increasing age, private healthcare insurance versus uninsured, and hypertension. Public insurance (versus uninsured) was a significant positive predictor of LDL-C control, whereas income <200% versus ≥200% of federal poverty was a significant negative predictor. CONCLUSIONS: LDL-C control improved similarly over time in publicly and privately insured adults but was stagnant among the uninsured. Healthcare insurance largely addresses socioeconomic barriers to effective LDL-C management, yet poverty retains an independent adverse effect.

Updated Cost-effectiveness Assessments of PCSK9 Inhibitors From the Perspectives of the Health System and Private Payers: Insights Derived From the FOURIER Trial.

Importance: Preliminary cost-effectiveness analyses of proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) were based on benefits estimated from reductions in low-density lipoprotein cholesterol that occurred in PCSK9i trials with variable results. The recent Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial provides better information about the effectiveness of the drug. Objective: To use the trial results to determine the cost-effectiveness of a PCSK9i and statin treatment strategy compared with a statin alone strategy. Design, Setting, and Participants: We derived observed rates of events, outcomes, cost of care, and health insurance from existing literature for a theoretical cohort of patients designed to resemble the FOURIER PCSK9i trial population and created a Markov model during the time horizon of a full lifetime. Main Outcomes and Measures: We evaluated the incremental cost-effectiveness ratio from a health system perspective, and the return on investment from a private payer perspective. For both measures, we assumed an annual PCSK9i drug price of $14 300, with a lapse in US patent protection that would reduce the price by 43% in year 12. Costs were reported in 2016 US dollars. Results: This study modeled 1000 hypothetical patients with attributes similar to those of the FOURIER trial cohort. At the current price, the incremental cost-effectiveness ratio of statin plus PCSK9i therapy was $337 729 per quality-adjusted life-year. Our probabilistic sensitivity analysis found that a statin plus PCSK9i strategy had a low probability (<1%) of being cost effective at the commonly accepted societal threshold of $100 000 per quality-adjusted life-year. Furthermore, PCSK9i produced a negative return on investment of 86% for private payers. In our threshold analysis, the price of PCSK9i would need to drop 62%, to $5459 per year, to reach $100 000 per quality-adjusted life year. Conclusions and Relevance: At current prices, the addition of PCSK9i to statin therapy is estimated to provide an additional quality-adjusted life year for $337 729 . Significant discounts are necessary to meet conventional cost-effectiveness standards.

PCSK9 inhibitors and managing cost in the managed care setting.

In patients with hypercholesterolemia who have atherosclerotic cardiovascular disease and/or familial hypercholesterolemia, a new class of drugs may be helpful in reducing serum levels of low-density lipoprotein cholesterol (LDL-C) beyond maximally tolerated statin therapy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower LDL-C through a different mechanism of action than standard cholesterol-lowering therapies. Currently approved PCSK9 inhibitors are the monoclonal antibodies alirocumab and evolocumab. Although the drugs produce substantial reductions in LDL-C, cost issues and efficacy in preventing cardiovascular events should be evaluated when considering the adoption of PCSK9 inhibitors in the managed care setting.

Eligibility for alirocumab or evolocumab treatment in 1090 hypercholesterolemic patients referred to a regional cholesterol treatment center with LDL cholesterol ≥70 mg/dL despite maximal-tolerated LDL-cholesterol-lowering therapy.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors, Praluent (alirocumab [ALI]) and Repatha (evolocumab [EVO]) have been approved as adjuncts to the standard-of-care maximal-tolerated dose (MTD) of low-density lipoprotein cholesterol (LDLC)-lowering therapy (LLT), statin therapy, in heterozygous (HeFH) (ALI or EVO) or homozygous (EVO) familial hypercholesterolemia, or clinical atherosclerotic cardiovascular disease (CVD) where LDLC lowering is insufficient (both). Since LDLC lowering has been revolutionized by ALI and EVO, specialty pharmaceutical pricing models will be applied to a mass market. METHODS: We applied US Food and Drug Administration (FDA) and insurance eligibility criteria for ALI and EVO to 1090 hypercholesterolemic patients serially referred over 3 years who then received ≥2 months maximal-tolerated dose of standard-of-care LDL cholesterol-lowering therapy (MTDLLT) with follow-up LDLC ≥70 mg/dL. MTDLLT did not include ALI or EVO, which had not been commercially approved before completion of this study. RESULTS: Of the 1090 patients, 140 (13%) had HeFH by clinical diagnostic criteria and/or CVD with LDLC >100 mg/dL despite ≥2 months on MTDLLT, meeting FDA insurance criteria for ALI or EVO therapy. Another 51 (5%) patients were statin intolerant, without HeFH or CVD. CONCLUSION: If 13% of patients with HeFH-CVD and LDLC >100 mg/dL despite MTDLLT are eligible for ALI or EVO, then specialty pharmaceutical pricing models (~$14,300/year) might be used in an estimated 10 million HeFH-CVD patients. Whether the health care savings arising from the anticipated reduction of CVD events by ALI or EVO justify their costs in populations with HeFH-CVD and LDLC >100 mg/dL despite MTDLLT remains to be determined.

Has cost inhibited the uptake of more potent statins in England?

BACKGROUND: The use of statins has increased substantially over the last 2 decades in England and represents a significant cost burden to the National Health Service. Therefore, it is important to understand what influences prescribers' choice. OBJECTIVES: This study examines the changes in use pattern of all statins in England (1998-2015). The study focuses on the use of simvastatin and atorvastatin before and after their patent expiry and rosuvastatin, to investigate the impact of the reduced acquisition costs on prescribing. METHODS: Interrupted time series analysis of primary care use data from the health and social care information centre database from 1998 to 2015. RESULTS: Primary care expenditure on statins increased by 125% during the period 1998 to 2004 driven by branded simvastatin and atorvastatin. Before 2003, the rate of use of more potent branded atorvastatin exceeds branded simvastatin. Between 2004 and 2011, the less potent but less expensive agent generic simvastatin has the higher utilisation rate (66%). Since 2012, the more potent agent but less expensive generic atorvastatin has the higher utilisation rate (50%). The more potent branded rosuvastatin failed to make a significant impact on the English statins market. CONCLUSIONS: The availability of generic statins has reduced overall expenditure significantly. When there is a significant price difference, acquisition cost appears to be the main influencing factor in prescribing statins, but, when costs are similar, potency is a key factor. This suggests that English prescribers are cost sensitive and appear to be prepared to trade marginal benefit for savings.