Prescription-based cost analysis of medicines for cardiovascular risk factors at Indian Council of Medical Research-Rational Use of Medicine Centre Hospitals of India.

OBJECTIVES: India has taken several initiatives to provide health care to its population while keeping the related expenditure minimum. Since cardiovascular diseases are the most prevalent chronic conditions, in the present study, we aimed to analyze the difference in prices of medicines prescribed for three cardiovascular risk factors, based on (a) listed and not listed in the National List of Essential Medicines (NLEM) and (b) generic and branded drugs. MATERIALS AND METHODS: Outpatient prescriptions for diabetes mellitus, hypertension, and dyslipidemia were retrospectively analyzed from 12 tertiary centers. The prices of medicines prescribed were compared based on presence or absence in NLEM India-2015 and prescribing by generic versus brand name. The price was standardized and presented as average price per medicine per year for a given medicine. The results are presented in Indian rupee (INR) and as median (range). RESULTS: Of the 4,736 prescriptions collected, 843 contained oral antidiabetic, antihypertensive, and/or hypolipidemic medicines. The price per medicine per year for NLEM oral antidiabetics was INR 2849 (2593-3104) and for non-NLEM was INR 5343 (2964-14364). It was INR 806 (243-2132) for generic and INR 3809 (1968-14364) for branded antidiabetics. Antihypertensives and hypolipidemics followed the trend. The price of branded non-NLEM medicines was 5-22 times higher compared to generic NLEM which, for a population of 1.37 billion, would translate to a potential saving of 346.8 billion INR for statins. The variability was significant for sulfonylureas, angiotensin receptor blockers, beta-blockers, diuretics, and statins (P < 0.0001). CONCLUSION: The study highlights an urgent need for intervention to actualize the maximum benefit of government policies and minimize the out-of-pocket expenditure on medicines.

Prescription drug coverage and effective coverage of three chronic conditions of high prevalence in Chile: Hypertension, diabetes and dyslipidemia.

BACKGROUND: Access to medicines is a serious problem globally and in Chile. Despite the creation of coverage policies, part of the population with chronic conditions of high prevalence, still does not have access to the medicines it requires and disease control continues to be low. The objective of the study was to estimate the medication use and effective coverage for diabetes, dyslipidemia and hypertension in Chile, analyzing them according to sociodemographic variables and social determinants of health. METHODS: Cross-sectional analytical study with information from the 2016-2017 National Health Survey (sample = 6,233 people aged 15 years or older, expanded = 14,518,969). Descriptive analyses of medication use and effective coverage for hypertension, diabetes and dyslipidemia were carried out, and multivariate logistic regression models were developed to analyze possible associations with variables of interest. RESULTS: 60% of people with hypertension or diabetes use medications and only 27.7% in dyslipidemia. While 54.2% of those with diabetes have their glycemia controlled, in hypertension and dyslipidemia the effective coverage drops to 33.3% and 6.6%, respectively. There are no differences in use by health system, but there are differences in the control of hypertension and diabetes, favoring beneficiaries of the private subsystem. Effective coverage of dyslipidemia and hypertension also increases in those using medications. The drugs coincide with the established protocols, although beneficiaries of the private sector report greater use of innovative drugs. CONCLUSION: A significant proportion of Chileans with hypertension, diabetes or dyslipidemia still do not use the required medications and do not control their conditions.

The Potential Benefits and Costs of an Intensified Approach to Low Density Lipoprotein Cholesterol Lowering in People with Abdominal Aortic Aneurysm.

OBJECTIVE: The aims of this study were to assess the incidence of major vascular events (MVE) and peripheral vascular events (PVE) in people with a small asymptomatic abdominal aortic aneurysm (AAA) and model the theoretical benefits and costs of an intensified low density lipoprotein cholesterol (LDL-C) lowering programme. METHODS: A total of 583 participants with AAAs measuring 30 - 54 mm were included in this study. The control of LDL-C and prescription of lipid lowering drugs were assessed by dividing participants into approximately equal tertiles depending on their year of recruitment into the study. The occurrence of MVE (myocardial infarction, stroke, cardiovascular death, and coronary or non-coronary revascularisation) and PVE (non-coronary revascularisation, AAA repair, and major amputation) were recorded prospectively, and the incidence of these events was calculated using Kaplan-Meier analysis. The relative risk reduction reported for these events in a previous randomised control trial (RCT) was then applied to these figures to model the absolute risk reduction and numbers needed to treat (NTT) that could theoretically be achieved with a mean LDL-C lowering of 1 mmol/L. The maximum allowable expense for a cost effective intensive LDL-C lowering programme was estimated using a cost utility analysis. RESULTS: At entry, only 28.5% of participants had an LDL-C of < 1.8 mmol/L and only 18.5% were prescribed a high potency statin (atorvastatin 80 mg or rosuvastatin 40 mg). The five year incidences of MVE and PVE were 38.1% and 44.7%, respectively. It was estimated that if the mean LDL-C of the cohort had been reduced by 1 mmol/L, this could have reduced the absolute risk of MVE and PVE by 6.5% (95% CI 4.4 - 8.7; NNT 15) and 5.3% (95% CI 1.4 - 7.5; NNT 19), respectively. It was estimated that the maximum allowable expense for a cost effective LDL-C lowering programme would be between $1 239 AUD (€768) and $1 582 AUD (€981) per person per annum over a five year period. CONCLUSION: People with a small asymptomatic AAA are at high risk of MVE and PVE. This study provides evidence of the possible benefits and allowable expense for a cost effective intensive LDL-C lowering programme in this population.

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.

The cost-effectiveness of intensive low-density lipoprotein cholesterol lowering in people with peripheral artery disease.

BACKGROUND: People with peripheral artery disease are at a high risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Randomized controlled trials suggest that intensive lowering of low-density lipoprotein cholesterol (LDL-C) with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors is an effective strategy to prevent these events. This study estimated the potential benefit and cost-effectiveness of administrating PCSK9 inhibitors to a cohort of participants with peripheral artery disease. METHODS: A total of 783 participants with intermittent claudication (IC; n = 582) or chronic limb-threatening ischemia (CLTI; n = 201) were prospectively recruited from three hospitals in Australia. Serum LDL-C was measured at recruitment, and the occurrence of MACE and MALE was recorded over a median (interquartile range) follow-up of 2.2 years (0.3-5.7 years). The potential benefit of administering a PCSK9 inhibitor was estimated by calculating the absolute risk reduction and numbers needed to treat (NNT) based on relative risk reductions reported in published randomized trials. The incremental cost-effectiveness ratio per quality-adjusted life year gained was estimated. RESULTS: Intensive LDL-C lowering was estimated to lead to an absolute risk reduction in MACE of 6.1% (95% confidence interval [CI], 2.0-9.3; NNT, 16) and MALE of 13.7% (95% CI, 4.3-21.5; NNT, 7) in people with CLTI compared with 3.2% (95% CI, 1.1-4.8; NNT, 32) and 5.3% (95% CI, 1.7-8.3; NNT, 19) in people with IC. The estimated incremental cost-effectiveness ratios over a 10-year period were $55,270 USD and $32,800 USD for participants with IC and CLTI, respectively. CONCLUSIONS: This analysis suggests that treatment with a PCSK9 inhibitor is likely to be cost-effective in people with CLTI.

Cost-Effectiveness of Using LDL-Direct Versus Lipid-Panel as Part of the Inpatient Stroke Workup.

OBJECTIVE: To investigate whether utilizing a LDL-direct laboratory test rather than a lipid panel to determine LDL-C as part of the inpatient stroke and TIA workup is more cost-effective to the patient and hospital system. A retrospective analysis was conducted on all patients admitted to UCSD La Jolla and Hillcrest Hospital and discharged with a final diagnosis of ischemic stroke or transient ischemic attack between 7/2016 and 6/2019. A cost-analysis was extrapolated based on the current cost of each test as provided by the UCSD hospital billing department as of June 2020. Patients started on a statin, who were not on one prior to admission, were also analyzed to highlight the importance of an accurate LDL-C on management of dyslipidemia. RESULTS: A total of 1245 patients were included in the study with 87% representing Ischemic strokes and 13% transient ischemic attacks. Over the three-year period, a total savings of $77,545 would be achieved if LDL-direct were used in place of a lipid-panel, representing an overall cost savings of 33%. Over the same time-frame, 536 (43%) patients were started on a statin that were not previously on one. CONCLUSIONS: Ordering a LDL-direct test should be considered over a lipid panel to evaluate LDL-C as it may prove to be the most cost effective approach to both the patient and Healthcare system.

Comparison of Comorbidity Treatment and Costs Associated With Bariatric Surgery Among Adults With Obesity in Canada.

Importance: Information on the associations between barriers to delivery of bariatric surgery and poor weight trajectory afterward is lacking. Estimates are needed to inform decisions by administrators and clinicians to improve care. Objective: To estimate the difference in patient-years of treatment for diabetes, hypertension, and dyslipidemia and public-payer cost between the Canadian standard and an improved bariatric surgery care pathway. Design, Setting, and Participants: Economic evaluation of a decision analytic model comparing the outcomes of the standard care in Canada with an improved bariatric care pathway with earlier sleeve gastrectomy delivery and better postsurgical weight trajectory. The model was informed by published clinical data (101 studies) and meta-analyses (11 studies) between January and May 2019. Participants were a hypothetical 100-patient cohort with demographic characteristics derived from a Canadian study. Interventions: Reduction of Canadian mean bariatric surgery wait time by 2.5 years following referral and improvement of patient postsurgery weight trajectory to levels observed in other countries. Main Outcomes and Measures: Modeling weight trajectory after sleeve gastrectomy and resolution rates for comorbidities in Canada in comparison with an improved care pathway to estimate differences in patient-years of comorbidity treatment over 10 years following referral and the associated costs. Results: For the 100-patient cohort (mean [SD] 88.2% [1.4%] female; mean [SD] age, 43.6 [9.2] years; mean [SD] body mass index, 49.4 [8.2]; and mean [SD] comorbidity prevalence of 50.0% [4.1%], 66.0% [3.9%], and 59.3% [4.0%] for diabetes, hypertension, and dyslipidemia, respectively) over 10 years following referral, the improved vs standard care pathway was associated with median reduction in patient-years of treatment of 324 (95% credibility interval [CrI], 249-396) for diabetes, 245 (95% CrI, 163-356) for hypertension, and 255 (95% CrI, 169-352) for dyslipidemia, corresponding to total savings of $900 000 (95% CrI, $630 000 to $1.2 million) for public payers in the base case. Relative to standard of care, the associated reduction in costs was approximately 29% (95% CrI, 20%-42%) in the improved pathway. Sensitivity analyses demonstrated independent associations of earlier surgical delivery and various levels of postsurgical weight trajectory improvements with overall savings. Conclusions and Relevance: This study suggests that health care burden may be decreased through improvements to delivery and management of patients undergoing sleeve gastrectomy. More data are needed on long-term patient experience with bariatric surgery in Canada to inform better estimates.

Care continuity impacts medicare expenditures of older adults: Fact or fiction?

BACKGROUND: Older adults with cardiometabolic conditions are typically seen by multiple providers. Management by multiple providers may compromise care continuity and increase health expenditures for older adults, which may partly explain the inverse association between continuity and Medicare expenditures found in prior studies. This study sought to examine whether all-cause admission, outpatient expenditures or total expenditures were associated with the number of prescribers of cardiometabolic medications. METHODS: Medicare fee-for-service beneficiaries with diabetes (n = 100,191), hypertension (n = 299,949) or dyslipidemia (n = 243,598) living in 10 states were identified from claims data. The probability of an all-cause hospital admission in 2011 was estimated via logistic regression and Medicare (outpatient, total) expenditures in 2011 were estimated using generalized linear models, both as a function of the number of prescribers in 2010. Regressions were adjusted for demographic characteristics, Medicaid status, number of prescriptions, and 17 chronic conditions. RESULTS: In all three cohorts, older adults with more prescribers in 2010 had modestly higher adjusted odds of all-cause inpatient admission than older adults with a single prescriber. Compared to a single prescriber, outpatient and total expenditures in 2011 were 3-10% higher for older adults with diabetes and multiple prescribers, 2-6% higher for older adults with hypertension and multiple prescribers, and 2-5% higher for older adults with dyslipidemia and multiple prescribers. CONCLUSIONS AND IMPLICATIONS: These results provide some evidence that older adults with multiple prescribers also have modestly higher Medicare utilization than those with a single prescriber; thus care continuity may impact patient utilization. LEVEL OF EVIDENCE: Level III (retrospective cohort analysis).

Implications of cost-effectiveness analyses of lipid-lowering therapies: From the policy-maker's desk to the patient's bedside.

In our increasingly cost-conscious health system, patients, clinicians, hospitals, and payers all agree about the urgent need to rein in runaway healthcare costs. High pharmaceutical costs make drugs unaffordable to many patients who may benefit from them, including some insured patients who face prohibitive out-of-pocket costs. Health systems and payers can use the systematic framework of cost-effectiveness analysis and estimated budgetary impact to prioritize the adoption of new therapies and technologies. In this review article, we discuss basic principles of cost-effectiveness research for practicing clinicians, the concept of cost-effectiveness versus affordability, other considerations relevant to resource allocation, and limitations of cost-effectiveness research. We use the example of lipid lowering therapies to discuss application of cost-effectiveness research in informing health care policy, its use for health care systems and in the development of clinical practice guidelines, and its implications for clinicians and patients. As clinicians and patients become more cognizant of the cost-implications of new therapies, professional societies can help improve the quality of decision-making by incorporating unbiased value statements into their expert guidelines.

Economic Evaluation of the 2016 Chinese Guideline and Alternative Risk Thresholds of Initiating Statin Therapy for the Management of Atherosclerotic Cardiovascular Disease.

OBJECTIVE: The 2016 Chinese guidelines for the management of dyslipidemia recommended mixed rules that centered around a 10% 10-year risk threshold to initiate statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). The present study aimed to evaluate the cost-effectiveness of the guideline statin-initiation strategy and alternative strategies. METHODS: A decision analytic model using discrete event simulation with event probabilities based on a validated ASCVD risk prediction tool for Chinese was constructed. Risk factor inputs were from the dataset of a nationally representative survey of middle-aged and elderly Chinese. Data of statin treatment effectiveness were from a published meta-analysis. Other key input data were identified from the literature or relevant databases. The strategies we evaluated were the guideline strategy, a 15% 10-year risk threshold strategy and a 20% 10-year risk threshold strategy. After excluding any extended dominance strategies, the incremental costs per quality-adjusted life year (QALY) gained of each strategy was calculated. RESULTS: The 20% 10-year risk threshold strategy was an extended dominance option. The incremental costs per QALY gained from the 15% 10-year risk threshold strategy compared with no treatment and the guideline strategy compared with the 15% 10-year risk threshold strategy were CN¥69,309 and CN¥154,944, respectively. The results were robust in most sensitivity analyses. CONCLUSIONS: The guideline strategy and the 15% 10-year risk threshold strategy are optimal when using the three times and the two times the gross domestic product per capita willingness-to-pay standards, respectively.

Longitudinal changes of lipid profile in the Lebanese pediatric population.

BACKGROUND: Few studies looked at the prevalence of dyslipidemia in pediatric Middle-Eastern countries. In addition, worldwide longitudinal changes of lipid profile is not well documented. The purpose of this study is to look at the longitudinal changes of lipid parameters in Lebanese school-age children. MATERIALS AND METHODS: A total of 97 subjects (41 girls and 56 boys) aged between 11 and 21 years were included in this study. The subjects were selected among 339 school-age children with a previous abnormal lipid profile who were recruited from 10 schools of varying socio-economic levels (SEL). A fasting lipid profile [total cholesterol (TC), triglycerides (TG) and HDL-cholesterol (HDL-C)] was performed. Non-HDL-cholesterol (Non-HDL-C) was calculated. Weight and height were measured under the same conditions, and BMI percentiles were calculated. A multivariate covariance analysis model (MANCOVA) was used with TG, HDL-C and non-HDL-C as dependent variables with additional post-MANCOVA F tests. RESULTS: The age of the current cohort is 16.5 ± 2.9 years with no significant difference according to gender. The current lipid profile was obtained 3.1 ± 0.7 years following the initial one, with 53.6% of the subjects having it normalized. TC, TG, and non-HDL-C decreased significantly over time in girls, while only TG decreased significantly in boys. No significant changes were observed for HDL-C. Using MANCOVA, a significant time by age interaction was observed (p < 0.0001), while gender, BMI and SEL were found not to be significant. Post-hoc F tests showed that the time by age interaction was driven by TG (p = 0.03) and non-HDL-C (p < 0.001), the larger effect being observed in younger children. CONCLUSION: A high proportion of school-age children normalize their abnormal lipid profile with time. Screening for lipid disorders could be postponed until post puberty age.

Lipid-lowering therapy with PCSK9-inhibitors in the real-world setting: Two-year experience of a regional lipid clinic.

AIM: PCSK9 inhibitors (PCSK9i) effectively lower cholesterol levels in randomized trials with reduction in cardiovascular outcomes and favorable safety profile. However, the access to PCSK9i is limited due to high cost and data regarding the use of PCSK9i in real-world practice is limited. METHODS: Data on all patients submitted for approval of PCSK9i at a regional lipid clinic, outside of clinical trials. Patients' profile, approval rates, low-density lipoprotein cholesterol (LDL-C) reduction rates, and adverse events were evaluated. RESULTS: Recommendation for PCSK9i was given to 133 patients; 16 did not receive insurance approval and additional 16 were approved but did not initiate therapy. Of the 101 treated patients (47% females; mean age 61 ± 11 years), 52 had probable/definite familial hypercholesterolemia (FH) (peak LDL-C level 305 ± 87 mg/dL vs non-FH 204 ± 39 mg/dL) and 62% had an established cardiovascular disease. Statin intolerance was reported by 77%. Follow-up lipid panel was available in 66/101 patients: mean LDL-C reduction was 59% ± 19. Subjects with heterozygous FH had similar LDL-C decrease than those with non-FH (59% ± 22 vs 60% ± 14, P = .792). LDL-C < 100 mg/dL was achieved by 76%, LDL-C < 70 mg/dL by 58% and LDL-C < 40 mg/dL by 18% of those with follow-up data. Side effects were reported by 10%, mainly musculoskeletal complaints and flu-like symptoms, and 15% have discontinued treatment. CONCLUSIONS: Patient selection by a regional lipid clinic resulted in a high real-world PCSK9i insurance approval, with efficacy and safety comparable to randomized clinical trials. Cost and medication nonadherence are potential barriers to successful implementation of therapy in routine clinical care.

A Cost Analysis of Universal versus Targeted Cholesterol Screening in Pediatrics.

OBJECTIVE: To compare the number of children needed to screen to identify a case of childhood dyslipidemia and estimate costs under universal vs targeted screening approaches. STUDY DESIGN: We constructed a decision-analytic model comparing the health system costs of universal vs targeted screening for hyperlipidemia in US children aged 10 years over a 1-year time horizon. Targeted screening was defined by family history: dyslipidemia in a parent and/or early cardiovascular disease in a first-degree relative. Prevalence of any hyperlipidemia (low-density lipoprotein [LDL] ≥130 mg/dL) and severe hyperlipidemia (LDL ≥190 mg/dL or LDL ≥160 mg/dL with family history) were obtained from published estimates. Costs were estimated from the 2016 Maryland Medicaid fee schedule. We performed sensitivity analyses to evaluate the influence of key variables on the incremental cost per case detected. RESULTS: For universal screening, the number needed to screen to identify 1 case was 12 for any hyperlipidemia and 111 for severe hyperlipidemia. For targeted screening, the number needed to screen was 7 for any hyperlipidemia and 49 for severe hyperlipidemia. The incremental cost per case detected for universal compared with targeted screening was $1980 for any hyperlipidemia and $32 170 for severe hyperlipidemia. CONCLUSIONS: Our model suggests that universal cholesterol screening detects hyperlipidemia at a low cost per case, but may not be the most cost-efficient way to identify children with severe hyperlipidemia who are most likely to benefit from treatment.

Cardiovascular Genetic Risk Testing for Targeting Statin Therapy in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Cost-Effectiveness Analysis.

BACKGROUND: It is unclear whether testing for novel risk factors, such as a cardiovascular genetic risk score (cGRS), improves clinical decision making or health outcomes when used for targeting statin initiation in the primary prevention of atherosclerotic cardiovascular disease (ASCVD). Our objective was to estimate the cost-effectiveness of cGRS testing to inform clinical decision making about statin initiation in individuals with low-to-intermediate (2.5%-7.5%) 10-year predicted risk of ASCVD. METHODS AND RESULTS: We evaluated the cost-effectiveness of testing for a 27-single-nucleotide polymorphism cGRS comparing 4 test/treat strategies: treat all, treat none, test/treat if cGRS is high, and test/treat if cGRS is intermediate or high. We tested a set of clinical scenarios of men and women, aged 45 to 65 years, with 10-year ASCVD risks between 2.5% and 7.5%. Our primary outcome measure was cost per quality-adjusted life-year gained. Under base case assumptions for statin disutility and cost, the preferred strategy is to treat all patients with ASCVD risk >2.5% without cGRS testing. For certain clinical scenarios, such as a 57-year-old man with a 10-year ASCVD risk of 7.5%, cGRS testing can be cost-effective under a limited set of assumptions; for example, when statins cost $15 per month and statin disutility is 0.013 (ie, willing to trade 3 months of life in perfect health to avoid 20 years of statin therapy), the preferred strategy (using a willingness-to-pay threshold of $50 000 per quality-adjusted life-year gained) is to test and treat if cGRS is intermediate or high. Overall, the results were not sensitive to assumptions about statin efficacy and harms. CONCLUSIONS: Testing for a 27-single-nucleotide polymorphism cGRS is generally not a cost-effective approach for targeting statin therapy in the primary prevention of ASCVD for low- to intermediate-risk patients.

PCSK9 inhibitor valuation: A science-based review of the two recent models.

Low-density lipoprotein cholesterol (LDL-C) has been extensively evaluated. Prospective cohort studies, randomized controlled trials, biology, pathophysiology, genetics, and Mendelian randomization studies, have clearly taught us that LDL-C causes atherosclerotic cardiovascular disease. The newest class of drugs to lower LDL-C, the proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, have been found to safely reduce LDL-C approximately 60% when added to high-intensity statin therapy. Because their cost is much greater than that of the currently available agents, their value has been questioned. In late August, 2017, two groups assessed the value of this class of drugs looking at cost-effectiveness; however, the Institute for Clinical and Economic Review and Fonarow and colleagues found disparate results when assessing PCSK9 valuation. Herein, we review the evolution of LDL-C from hypothesis to fact, and then attempt to adjudicate the 2 models, shedding light on the complex modeling process. We find that models of cost-effectiveness are helpful adjuncts to decision making, but that their conclusions depend on many assumptions. Ultimately, clinician judgment regarding their clinical benefit, balanced by some estimation of cost, may be more productive to target the right patients for whom the benefits can be well-justified.

Prior Authorization Requirements for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Across US Private and Public Payers.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) are an innovative treatment option for patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require further lowering of low-density lipoprotein cholesterol. However, the high costs of these agents have spurred payers to implement utilization management policies to ensure appropriate use. We examined prior authorization (PA) requirements for PCSK9is across private and public US payers. METHODS AND RESULTS: We conducted an analysis of 2016 formulary coverage and PA data from a large, proprietary database with information on policies governing >95% of Americans with prescription drug coverage (275.3 million lives) within 3872 plans across the 4 major insurance segments (commercial, health insurance exchange, Medicare, and Medicaid). The key measures included administrative PA criteria (prescriber specialty, number of criteria in PA policy or number of fields on PA form, requirements for medical record submission, reauthorization requirements) and clinical/diagnostic PA criteria (approved conditions, required laboratories or other tests, required concomitant therapy, step therapy requirements, continuation criteria) for each of 2 Food and Drug Administration-approved PCSK9is. Select measures (eg, number of PA criteria/fields, medical record submission requirements) were obtained for 2 comparator cardiometabolic drugs (ezetimibe and liraglutide). Between 82% and 97% of individuals were enrolled in plans implementing PA for PCSK9is (depending on insurance segment), and one third to two thirds of these enrollees faced PAs restricting PCSK9i prescribing to a specialist. For patients with familial hypercholesterolemia, diagnostic confirmation via genetic testing or meeting minimum clinical scores/criteria was also required. PA requirements were more extensive for PCSK9is as compared with the other cardiometabolic drugs (ie, contained 3×-11× the number of PA criteria or fields on PA forms and more frequently involved the submission of medical records as supporting documentation). CONCLUSIONS: PA requirements for PCSK9is are greater than for selected other drugs within the cardiometabolic disease area, raising concerns about whether payer policies to discourage inappropriate use may also be restricting access to these drugs in patients who need them.

National Trends in Nonstatin Use and Expenditures Among the US Adult Population From 2002 to 2013: Insights From Medical Expenditure Panel Survey.

BACKGROUND: Evidence supporting nonstatin lipid-lowering therapy in atherosclerotic cardiovascular disease risk reduction is variable. We aim to examine nonstatin utilization and expenditures in the United States between 2002 and 2013. METHODS AND RESULTS: We used the Medical Expenditure Panel Survey database to estimate national trends in nonstatin use and cost (total and out-of-pocket, adjusted to 2013 US dollars using a gross domestic product deflator) among adults 40 years or older. Nonstatin users increased from 3 million (2.5%) in 2002-2003 (20.1 million prescriptions) to 8 million (5.6%) in 2012-2013 (45.8 million prescriptions). Among adults with atherosclerotic cardiovascular disease, nonstatin use increased from 7.5% in 2002-2003 to 13.9% in 2012-2013 after peaking at 20.3% in 2006-2007. In 2012-2013, 15.9% of high-intensity statin users also used nonstatins, versus 9.7% of low/moderate-intensity users and 3.6% of statin nonusers. Nonstatin use was significantly lower among women (odds ratio 0.80; 95% confidence interval 0.75-0.86), racial/ethnic minorities (odds ratio 0.41; 95% confidence interval 0.36-0.47), and the uninsured (odds ratio 0.47; 95% confidence interval 0.40-0.56). Total nonstatin expenditures increased from $1.7 billion (out-of-pocket cost, $0.7 billion) in 2002-2003 to $7.9 billion (out-of-pocket cost $1.6 billion) in 2012-2013, as per-user nonstatin expenditure increased from $550 to $992. Nonstatin expenditure as a proportion of all lipid-lowering therapy expenditure increased 4-fold from 8% to 32%. CONCLUSIONS: Between 2002 and 2013, nonstatin use increased by 124%, resulting in a 364% increase in nonstatin-associated expenditures.