Patterns of Teriparatide and Sequential Antiresorptive Agent Treatment Among Elderly Female Medicare Beneficiaries.

The 2020 American Association of Clinical Endocrinologists guidelines for assessing osteoporosis among postmenopausal women stratified postmenopausal women with osteoporosis to "high" and "very-high" fracture risk categories and recommended anabolic agents as initial therapy followed by an antiresorptive agent. Switching the order can blunt the effect of anabolic agents, and failing to follow with an antiresorptive can lead to loss of bone generated by the anabolic agent. It would be helpful to understand the real-world prescribing patterns of anabolic agents. Using the 2010-2015 Medicare 100% osteoporosis database, we assessed patient profiles, teriparatide prescribers, persistence of teriparatide therapy, and antiresorptive agent use after teriparatide discontinuation among elderly women who initiated teriparatide from 2011 to 2013. This study included 14,786 patients. In the year before teriparatide initiation, 30.0% of them had a fracture, 67.6% had a dual energy x-ray absorptiometry scan, 74.4% had a diagnosis of osteoporosis, and 47.9% used antiresorptive agents (non-naïve teriparatide users). Among those who had fractures, 49.4% initiated teriparatide within 3 months postfracture. Teriparatide was prescribed for 37% of users by primary care doctors, 19% by rheumatologists, 13% by endocrinologists, and 7.0% by orthopedists. Median time of teriparatide use was 7.2 months. After teriparatide discontinuation, 40.8% switched to antiresorptive agents (31.9% among naïve teriparatide users, 50.5% among non-naïve users). Among switchers, 42.5% switched within 60 days, 50.5% switched to denosumab, and 31.6% switched to oral bisphosphonates. This study of real-world prescribing data found that about half of teriparatide users switched from an antiresorptive agent, and less than half switched to antiresorptive agents after teriparatide discontinuation. Persistence of teriparatide use was suboptimal. In the management of postmenopausal osteoporosis, increasing the persistence of teriparatide use and improving the appropriate treatment sequence of anabolic and antiresorptive drugs are critical to maximizing gains in bone mass, providing the greatest protection against fractures. © 2021 American Society for Bone and Mineral Research (ASBMR).

Differences in utility elicitation methods in cardiovascular disease: a systematic review.

AIMS: Utility values inform estimates of the cost-effectiveness of treatment for cardiovascular disease (CVD), but values can vary depending on the method used. The aim of this systematic literature review (SLR) was to explore how methods of elicitation impact utility values for CVD. MATERIALS AND METHODS: This review identified English-language articles in Embase, MEDLINE, and the gray literature published between September 1992 and August 2015 using keywords for "utilities" and "stroke", "heart failure", "myocardial infarction", or "angina". Variability in utility values based on the method of elicitation, tariff, or type of respondent was then reported. RESULTS: This review screened 4,341 citations; 290 of these articles qualified for inclusion in the SLR because they reported utility values for one or more of the cardiovascular conditions of interest listed above. Of these 290, the 41 articles that provided head-to-head comparisons of utility methods for CVD were reviewed. In this sub-set, it was found that methodological differences contributed to variation in utility values. Direct methods often yielded higher scores than did indirect methods. Within direct methods, there were no clear trends in head-to-head studies (standard gamble [SG] vs time trade-off); but general population respondents often provided lower scores than did patients with the disease when evaluating the same health states with SG methods. When comparing indirect methods, the EQ-5D typically yielded higher values than the SF-6D, but also showed more sensitivity to differences in health states. CONCLUSIONS: When selecting CVD utility values for an economic model, consideration of the utility elicitation method is important, as this review demonstrates that methodology of choice impacts utility values in CVD.

Systematic Review and Network Meta-Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia.

BACKGROUND: The 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 RESULTS: We 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.

Identification and Management of Statin-Associated Symptoms in Clinical Practice: Extension of a Clinician Survey to 12 Further Countries.

PURPOSE: Statins 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. METHODS: A 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. RESULTS: Muscle-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%). CONCLUSIONS: The specialists and GPs surveyed use stringent criteria to establish causality between statin use and signs or symptoms, and persevere with statin treatment where possible.

Cost-effectiveness of Evolocumab in Patients With High Cardiovascular Risk in Spain.

PURPOSE: Our objective was to assess the cost-effectiveness of evolocumab in patients at high risk of cardiovascular (CV) events from the Spanish National Health System perspective. METHODS: A Markov model was used to assess the cost-effectiveness (incremental [∆] cost per ∆ quality-adjusted life-year [QALY]; or cost utility) of evolocumab plus standard of care (SoC; statins) versus SoC, assuming lifetime treatment. Cohorts with baseline LDL-C >100 mg/dL and familial hypercholesterolemia (FH) or CV event history (secondary prevention [SP]) were considered. Lifetime CV event rates were predicted either (1) using risk equations considering local risk factors (Spanish Familial Hypercholesterolemia Cohort Study) adjusted to reflect the increased risk of FH patients or (2) using CV event rates from local registries (Information System for the Development of Research in Primary Care) for SP patients. LDL-C relative reductions from evolocumab trials (Evolocumab 140 mg Q2W (bi-weekly) and 420 mg QM (monthly)) were converted into CV event reductions using rate ratios per millimole per liter (mmol/L; 38.67 mg/dL) from a meta-analysis of statin trials (Cholesterol Treatment Trialists' Collaboration). FINDINGS: Predicted 10-year/lifetime CV risks were 50%/95% (FH) and 62%/82% (SP) for SoC and 27%/83% (FH) and 44%/69% (SP) for evolocumab plus SoC. Predicted 10-year/lifetime major CV event risks were 42%/86% (FH) and 47%/67% (SP) for SoC and 21%/68% (FH) and 31%/52% (SP) for evolocumab plus SoC. Predicted per patient-year rates of non-fatal/fatal CV events were 2.2/0.8 (FH) and 1.1/0.6 (SP) for SoC and 1.2/0.6 (FH) and 0.7/0.5 (SP) for evolocumab plus SoC. Predicted CV event reductions per mmol/L were 17% (FH) and 15% (SP). Evolocumab treatment was associated with increased QALYs and costs compared with SoC (FH: ∆cost, €65,369; ∆QALY, 2.12; incremental cost-effectiveness ratio [ICER], €30,893; SP: ∆cost, €42,266; ∆QALY, 0.93; ICER, €45,340). IMPLICATIONS: Evolocumab plus to SoC may provide a cost-effective option for LDL-C lowering in FH and SP patients in Spain.

Lipid-lowering treatment modifications among patients with hyperlipidemia and a prior cardiovascular event: a US retrospective cohort study.

BACKGROUND: Numerous studies demonstrate that, even with use of statins, many patients are unable to meet their LDL-C goals. This study examined modifications to statin and/or ezetimibe therapy among patients with hyperlipidemia and prior history of cardiovascular (CV) events in a US commercially insured population. METHODS: Adults (age ≥18 years) initiating statins and/or ezetimibe between 1 January 2007 and 31 December 2008 were identified from HealthCore Integrated Research Database. The index date was the initiation date of statins and/or ezetimibe. All patients had ≥1 medical claims related to myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, coronary artery bypass graft, or percutaneous coronary intervention within 12 months prior to the index date. Treatment modifications to statins and/or ezetimibe initiated on the index date (index therapy) included permanent discontinuation of any lipid lowering therapy (LLT), rechallenge, switching, subtraction, augmentation, and dose changes. RESULTS: Among 17,902 patients, around 90% initiated with statin monotherapy, followed by statin and ezetimibe combination (3.0%: 18-64 years; 3.8%: ≥65 years). Ten percent or less initiated on high intensity statins. Most common treatment modifications were rechallenging index therapy (25.2%: 18-64 years, 27.0%: ≥65 years), switching (27.5%: 18-64 years, 24.6%: ≥65 years), and permanent discontinuation of any LLT (18.6%: 18-64 years, 21.0%: ≥65 years). Only 10% of patients in both groups underwent dose escalation. CONCLUSIONS: Real-world evidence indicates that few high-risk patients initiate therapy with high-intensity statins. More than 50% of patients underwent a rechallenge or switching. Despite high CVD risk profile, approximately 20% of patients permanently discontinued any LLT. Key limitations: Pharmacy claims do not provide information on whether patients who had a pharmacy fill actually took the medication as prescribed. It is unknown whether rechallenge was a simple delay in filling a prescription or an actual rechallenge of their index therapy. Reasons for treatment discontinuations or modifications were unavailable in claims data.

A systematic review to assess adherence and persistence with statins.

OBJECTIVE: To identify and assess studies published over a 10 year period up to February 2016 which measure adherence or persistence with statins, to summarize their methods, strengths and weaknesses and to summarize evidence linking statin adherence/persistence with risk of cardiovascular events. METHODS: Electronic databases and abstracts from four major cardiovascular disease conferences were searched from January 2005 to February 2016. The study selection process was performed by two reviewers working independently. Studies were included if they reported data regarding patient adherence or persistence with statins in adults with primary hypercholesterolemia, using any type of study design or length of follow-up. One reviewer extracted the study data and assessed study quality, which was checked by a second reviewer independently. Given the heterogeneity between the included studies a narrative critique and summary is presented. RESULTS: We report on 84 real world studies which aimed to assess adherence or persistence with statins. The majority of studies concluded that good adherence/persistence was associated with reduction in cardiovascular events and mortality. In two studies high intensity statin regimens were associated with poorer patient adherence when compared to low intensity statins. Adherence and persistence with statin therapy also has an impact on hospitalization costs and other cardiovascular disease (CVD) related costs. CONCLUSIONS: Adherence and persistence are associated with a reduction in CVD events and mortality. There was limited evidence to suggest that high intensity statin regimens are associated with poorer treatment adherence when compared to lower intensity regimens. Hence, more robust studies are required to establish this association. As recommended by the 2013 ACC/AHA, 2016 ESC and several other clinical guidelines, clinicians and pharmacy managers should regularly monitor statin therapy adherence.

A Systematic Review of Cardiovascular Outcomes-Based Cost-Effectiveness Analyses of Lipid-Lowering Therapies.

BACKGROUND: Previous reviews have evaluated economic analyses of lipid-lowering therapies using lipid levels as surrogate markers for cardiovascular disease. However, drug approval and health technology assessment agencies have stressed that surrogates should only be used in the absence of clinical endpoints. OBJECTIVE: The aim of this systematic review was to identify and summarise the methodologies, weaknesses and strengths of economic models based on atherosclerotic cardiovascular disease event rates. METHODS: Cost-effectiveness evaluations of lipid-lowering therapies using cardiovascular event rates in adults with hyperlipidaemia were sought in Medline, Embase, Medline In-Process, PubMed and NHS EED and conference proceedings. Search results were independently screened, extracted and quality checked by two reviewers. RESULTS: Searches until February 2016 retrieved 3443 records, from which 26 studies (29 publications) were selected. Twenty-two studies evaluated secondary prevention (four also assessed primary prevention), two considered only primary prevention and two included mixed primary and secondary prevention populations. Most studies (18) based treatment-effect estimates on single trials, although more recent evaluations deployed meta-analyses (5/10 over the last 10 years). Markov models (14 studies) were most commonly used and only one study employed discrete event simulation. Models varied particularly in terms of health states and treatment-effect duration. No studies used a systematic review to obtain utilities. Most studies took a healthcare perspective (21/26) and sourced resource use from key trials instead of local data. Overall, reporting quality was suboptimal. CONCLUSIONS: This review reveals methodological changes over time, but reporting weaknesses remain, particularly with respect to transparency of model reporting.

Longitudinal treatment patterns among US patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia initiating lipid-lowering pharmacotherapy.

BACKGROUND: The most recent American College of Cardiology-American Heart Association guidelines recommend high-dose statin therapy for most patients with confirmed atherosclerotic cardiovascular disease (ASCVD) and patients with high cardiovascular risk. There is limited information regarding long-term treatment patterns among these patients. OBJECTIVE: To examine longitudinal treatment modifications in patients with ASCVD or familial hypercholesterolemia (FH). METHODS: This retrospective analysis of administrative claims data identified patients initiating statin or ezetimibe therapy between January 1, 2007, and December 31, 2012, who had evidence of ASCVD or FH. Patients were followed for up to 3 years and up to 4 treatment episodes. After initial treatment, subsequent treatment episodes began on the date of a treatment modification, which included discontinuation, statin dose change, switching, and augmentation. RESULTS: A total of 92,621 patients (mean age 64.7 years, 57.3% male) were identified; 91,740 had ASCVD, 937 had FH (56 had both). Most ASCVD (89.6%) and FH (85.8%) patients initiated on statin monotherapy. The most common treatment modification in the first treatment episode was discontinuation (ASCVD: 42.0%; FH: 58.4%); among patients who discontinued, most reinitiated therapy (70.5% of ASCVD, 76.8% of FH). Most ASCVD (68.2%) and FH (71.1%) patients initiated on moderate-dose statins; statin dose increase occurred in 10.3% of ASCVD and 18.5% of FH patients in the first episode. CONCLUSION: Among patients with high cardiovascular risk, most initiated on moderate-dose statins with infrequent uptitration. In light of the recent American College of Cardiology-American Heart Association guidelines, statin initiation practices will need to change to ensure appropriate therapy for high-risk patients.

Productivity losses associated with cardiovascular disease: a systematic review.

INTRODUCTION: People with cardiovascular disease (CVD) often require time off work to recover from illness or surgery; for example, following a myocardial infarction (MI) or stroke. These individuals incur income losses, work-related productivity is reduced for employers, and output is reduced for the wider economy. Productivity impacts to the economy also arise due to CVD-related mortality. Areas covered: A systematic literature review was conducted to identify and collate studies that report the magnitude of work-related productivity losses associated with CVD generally or specific cardiovascular (CV) events or conditions (coronary heart disease, MI, stroke, transient ischemic attack, angina, heart failure, peripheral artery disease, coronary revascularization). The search was conducted using Medline, Embase, the Cochrane Library, and Google to find studies published from January 2004 to January 2015. In total, 60 studies were identified, including 20 studies conducted in the USA, 25 studies conducted in Europe, and 18 studies conducted in other countries (three studies were conducted in multiple regions). The studies differed by the scope of losses assessed (absenteeism, presenteeism, early retirement, premature mortality) and CVD conditions/events included. Studies reported either average patient or population losses, and generally used a human capital rather than friction cost method. Outcomes were standardized and adjusted to 2015 US dollars where possible. Expert commentary: The review demonstrates that CVD imposes substantial morbidity- and mortality-related productivity costs. The studies identified in the review may be used to inform and populate societal economic evaluations in CVD, with the most appropriate source study being that most closely matching the context of the evaluation.

Patient-level costs of major cardiovascular conditions: a review of the international literature.

OBJECTIVE: Robust cost estimates of cardiovascular (CV) events are required for assessing health care interventions aimed at reducing the economic burden of major adverse CV events. This review synthesizes international cost estimates of CV events. METHODS: MEDLINE database was searched electronically for English language studies published during 2007-2012, with cost estimates for CV events of interest - unstable angina, myocardial infarction, heart failure, stroke, and CV revascularization. Included studies provided at least one estimate of patient-level direct costs in adults for any identified country. Information on study characteristics and cost estimates were collected. All costs were adjusted for inflation to 2013 values. RESULTS: Across the 114 studies included, the average cost was US $6,466 for unstable angina, $11,664 for acute myocardial infarction, $11,686 for acute heart failure, $11,635 for acute ischemic stroke, $37,611 for coronary artery bypass graft, and $13,501 for percutaneous coronary intervention. The ranges for cost estimates varied widely across countries with US cost estimate being at least twice as high as European Union costs for some conditions. Few studies were found on populations outside the US and European Union. CONCLUSION: This review showed wide variation in the cost of CV events within and across countries, while showcasing the continuing economic burden of CV disease. The variability in costs was primarily attributable to differences in study population, costing methodologies, and reporting differences. Reliable cost estimates for assessing economic value of interventions in CV disease are needed.

Systematic Review of Low-Density Lipoprotein Cholesterol Apheresis for the Treatment of Familial Hypercholesterolemia.

BACKGROUND: Apheresis is an important treatment for reducing low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). We systematically reviewed the current literature surrounding LDL-C apheresis for FH. METHODS AND RESULTS: Electronic databases were searched for publications of LDL-C apheresis in patients with FH. Inclusion criteria include articles in English published in 2000-2013 that provide descriptions of practice patterns, efficacy/effectiveness, and costs related to LDL-C apheresis in patients with FH. Data were stratified by country and FH genotype where possible. Thirty-eight studies met the inclusion criteria: 8 open-label clinical trials, 11 observational studies, 17 reviews/guidelines, and 2 health technology assessments. The prevalence of FH was not well characterized by country, and underdiagnosis was a barrier to FH treatment. Treatment guidelines varied by country, with some guidelines recommending LDL-C apheresis as first-line treatment in patients with homozygous FH and after drug therapy failure in patients with heterozygous FH. Additionally, guidelines typically recommended weekly or biweekly LDL-C apheresis treatments conducted at apheresis centers that may last 2 to >3 hours per session. Studies reported a range for mean LDL-C reduction after apheresis: 57-75% for patients with homozygous FH and 58-63% for patients with heterozygous FH. Calculated annual costs (in US$2015) may reach US$66 374 to US$228 956 per patient for weekly treatment. CONCLUSIONS: LDL-C apheresis treatment may be necessary for patients with FH when drug therapy is inadequate in reducing LDL-C to target levels. While apheresis reduces LDL-C, high per-session costs and the frequency of guideline-recommended treatment result in substantial annual costs, which are barriers to the optimal treatment of FH.

The relationship between Lp(a) and CVD outcomes: a systematic review.

Robust associations between lipoprotein(a) [Lp(a)] and CVD outcomes among general populations have been published in previous studies. However, associations in high risk primary prevention and secondary prevention populations are less well defined. In order to investigate this further, a systematic review was performed including prospective studies, which assessed the relationship between Lp(a) and CVD outcomes using multivariable analyses. Additional information was gathered on Lp(a) assays, multivariable modelling and population characteristics. Literature searches from inception up to December 2015 retrieved 2850 records. From these 60 studies were included. Across 39 primary prevention studies in the general population (hazard ratios ranged from 1.16 to 2.97) and seven high risk primary prevention studies (hazard ratios ranged from 1.01 to 3.7), there was evidence of a statistically significant relationship between increased Lp(a) and an increased risk of future CVD. Results in 14 studies of secondary prevention populations were also suggestive of a modest statistically significant relationship (hazard ratios ranged from 0.75 to 3.7).Therefore current evidence would suggest that increased Lp(a) levels are associated with modest increases in the risk of future CVD events in both general and higher risk populations. However, further studies are required to confirm these findings.

Cardiovascular Disease, Mortality Risk, and Healthcare Costs by Lipoprotein(a) Levels According to Low-density Lipoprotein Cholesterol Levels in Older High-risk Adults.

BACKGROUND: The value of lipoprotein(a) (Lp[a]) for predicting cardiovascular disease (CVD) across low-density lipoprotein cholesterol (LDL-C) is uncertain. HYPOTHESIS: In older high-risk adults, higher LDL and Lp(a) combined would be associated with higher CVD risk and more healthcare costs. METHODS: We included 3251 high-risk subjects (prior CVD, diabetes, or 10-year Framingham CVD risk >20%) age ≥65 years from the Cardiovascular Health Study and examined the relation of Lp(a) tertiles with incident CVD, coronary heart disease (CHD), and all-cause mortality within LDL-C strata (spanning <70 mg/dL to ≥160 mg/dL). We also examined 1-year all-cause and CVD healthcare costs from Medicare claims. RESULTS: Over a 22.5-year follow-up, higher Lp(a) levels predicted CVD and total mortality (both standardized hazard ratio [HR]: 1.06, P < 0.01), whereas higher LDL-C levels predicted higher CHD (standardized HR: 1.09, P < 0.01) but lower total mortality (standardized HR: 0.94, P < 0.001). Adjusted HRs in the highest (vs lowest) tertile of Lp(a) level were 1.95 (P = 0.06) for CVD events and 2.68 (P = 0.03) for CHD events when LDL-C was <70 mg/dL. One-year all-cause healthcare costs were increased for Lp(a) ($771 per SD of 56 µg/mL [P = 0.03], $1976 for Lp(a) 25-64 µg/mL vs <25 µg/mL [P = 0.02], and $1648 for Lp(a) ≥65 µg/mL vs <25 µg/mL [P = 0.054]) but not LDL-C. CONCLUSIONS: In older high-risk adults, increased Lp(a) levels were associated with higher CVD risk, especially in those with LDL-C <70 mg/dL, and with higher healthcare costs.

Cost-Effectiveness of LDL-C Lowering With Evolocumab in Patients With High Cardiovascular Risk in the United States.

Randomized trials have shown marked reductions in low-density lipoprotein cholesterol (LDL-C), a risk factor for cardiovascular disease (CVD), when evolocumab is administered. We hypothesized that evolocumab added to standard of care (SOC) vs SOC alone is cost-effective in the treatment of patients with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic CVD (ASCVD) with or without statin intolerance and LDL-C >100 mg/dL. Using a Markov cohort state transition model, primary and recurrent CVD event rates were predicted considering population-specific trial-based mean risk factors and calibrated against observed rates in the real world. The LDL-C-lowering effect from population-specific phase 3 randomized studies for evolocumab was used together with estimated LDL-C-lowering effect on CVD event rates per 38.67-mg/dL LDL-C lowering from a statin-trial meta-analysis. Costs and utilities were included from published sources. Evolocumab treatment was associated with both increased cost and improved quality-adjusted life-years (QALY): HeFH (incremental cost: US$153 289, incremental QALY: 2.02, incremental cost-effectiveness ratio: US$75 863/QALY); ASCVD (US$158 307, 1.12, US$141 699/QALY); and ASCVD with statin intolerance (US$136 903, 1.36, US$100 309/QALY). Evolocumab met both the American College of Cardiology/American Heart Association (ACC/AHA) and World Health Organization (WHO) thresholds in each population evaluated. Sensitivity and scenario analyses confirmed that model results were robust to changes in model parameters. Among patients with HeFH and ASCVD with or without statin intolerance, evolocumab added to SOC may provide a cost-effective treatment option for lowering LDL-C using ACC/AHA intermediate/high value and WHO cost-effectiveness thresholds. More definitive information on the clinical and economic value of evolocumab will be available from the forthcoming CVD outcomes study.

Relationship between changes in coronary atherosclerotic plaque burden measured by intravascular ultrasound and cardiovascular disease outcomes: a systematic literature review.

Objective Evidence from coronary imaging studies suggests an association between increased atherosclerotic plaque burden and cardiovascular disease (CVD) outcomes. A systematic review was performed to evaluate the relationship between coronary atherosclerotic plaque burden changes measured by intravascular ultrasound (IVUS) and CVD outcomes. Research design and methods Rigorous systematic review methodology was used to identify prospective studies of any design assessing the relationship between atherosclerotic plaque volume (percentage or total atheroma volume [PAV or TAV]) changes and CVD outcomes, using multivariable analyses. Main outcome measures CVD outcomes including major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). Results Literature searches from inception to February 2015 retrieved 6958 records after de-duplication. From these four studies (14 papers) were included. One study reported a significantly lower rate of CVD outcomes associated with a greater reduction in PAV (hazard ratio [HR] 0.26, 95% confidence interval [CI] 0.07-0.83). One study reported that large plaque volume was significantly associated with a greater risk of major adverse cardiac events (MACEs) (HR 1.73, 95% CI: 1.02-2.96). Similarly, a third study reported a significant increase in MACE with an increase in baseline PAV (HR 1.51, 95% CI: 1.06-2.51). Only one potentially inadequately powered Japanese study did not find a statistically significant relationship between PAV changes and MACE. Conclusions The current evidence suggests an independent and statistically significant association between increases in coronary atherosclerotic plaque burden measured by IVUS and greater long-term risk of future CVD outcomes. However, this evidence comes from a limited number of studies which mainly focus on Japanese populations and populations after PCI. Further large prospective studies are required to confirm these findings.

Assessment of statin therapy, LDL-C levels, and cardiovascular events among high-risk patients in the United States.

BACKGROUND: Statins have demonstrated significant benefit in reducing cardiovascular disease (CVD) risk. OBJECTIVE: To evaluate statin treatment patterns by intensity, elevated low-density lipoprotein cholesterol (LDL-C) levels, and cardiovascular (CV) events in high-risk CVD patients. METHODS: Patients included were aged ≥ 18 years, with a coronary heart disease (CHD; Jan 1, 2007-Dec 31, 2011, index date) or CHD risk equivalent (CHD RE) diagnosis (Jan 1, 2007-Dec 31, 2010, index date), in the Truven MarketScan claims database, continuously enrolled for 2 years pre- and up to 1 (CHD) or 2 (CHD RE) years post-index. Patients with CHD, CHD RE, rhabdomyolysis, or chronic kidney disease any time pre-index were excluded. Statin therapy was assessed at baseline, 30, 90, and 365 days post-index. LDL-C values were captured in patients with available data at 30-day intervals up to 1 year. CV events were evaluated up to 1 year post-index. Descriptive statistics were used to report results. RESULTS: There were 175,103 CHD and 68,290 CHD RE patients; 3333 CHD RE patients had post-index CV events. At 1 year, 38.7% of CHD patients and 44.3% of CHD RE patients with post-index CV events were not prescribed statins. Most patients who were prescribed statins, received a moderate-intensity statin. The percentage of patients with LDL-C ≥ 100 mg/dL reduced over time, but at 1 year, 29.3% of CHD and 30.0% of CHD RE patients with post-index CV events had LDL-C ≥ 100 mg/dL. At 1 year post-index, 9.9% CHD and 7.3% CHD RE patients had at least 1 CV event. CONCLUSION: There is room for better LDL-C management among high-risk CVD patients to reduce their overall CV risk.

A US Claims-Based Analysis of Real-World Lipid-Lowering Treatment Patterns in Patients With High Cardiovascular Disease Risk or a Previous Coronary Event.

The objective was to examine real-world treatment patterns of lipid-lowering therapies and their possible associated intolerance and/or ineffectiveness in patients with high cardiovascular disease (CVD) risk initiating statins and/or ezetimibe. Patients aged ≥18 years who initiated statins and/or ezetimibe from January 01, 2007, to June 30, 2011, were retrospectively identified from the IMS LifeLink PharMetrics Plus commercial claims database. Patients were further classified into 2 cohorts: (1) history of cardiovascular event (CVE) and (2) history of coronary heart disease risk equivalent (CHD RE). Patients had continuous health plan enrollment ≥1 year pre- and post-index date (statin and/or ezetimibe initiation date). Primary outcomes were index statin intensity, treatment modifications, possible associated statin/nonstatin intolerance and/or ineffectiveness issues (based on treatment modification), and time-to-treatment modifications. Analyses for each cohort were stratified by age group (<65 and ≥65 years). A total of 41,934 (history of CVE) and 170,344 patients (history of CHD RE) were included. On the index date, 8.8% to 25.1% of patients were initiated on high-intensity statin. Among patients aged <65, 79.2% and 48.8% of those with history of CVE and 78.6% and 47.3% of those with a history of CHD RE had ≥1 and 2 treatment modifications, respectively. Among all patients, 24.6% to 25.6% had possible statin intolerance and/or ineffectiveness issues after accounting for second treatment modification (if any). In conclusion, in patients with high CVD risk, index statin treatment modifications that imply possible statin intolerance and/or ineffectiveness were frequent; low use of high-intensity statins indicates unmet need in the management of hyperlipidemia and possible remaining unaccounted CVD residual risk.

Clinical and economic burden associated with cardiovascular events among patients with hyperlipidemia: a retrospective cohort study.

BACKGROUND: Annual direct costs for cardiovascular (CV) diseases in the United States are approximately $195.6 billion, with many high-risk patients remaining at risk for major cardiovascular events (CVE). This study evaluated the direct clinical and economic burden associated with new CVE up to 3 years post-event among patients with hyperlipidemia. METHODS: Hyperlipidemic patients with a primary inpatient claim for new CVE (myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, coronary artery bypass graft, percutaneous coronary intervention and heart failure) were identified using IMS LifeLink PharMetrics Plus data from January 1, 2006 through June 30, 2012. Patients were stratified by CV risk into history of CVE, modified coronary heart disease risk equivalent, moderate- and low-risk cohorts. Of the eligible patients, propensity score matched 243,640 patients with or without new CVE were included to compare healthcare resource utilization and direct costs ranging from the acute (1-month) phase through 3 years post-CVE date (follow-up period). RESULTS: Myocardial infarction was the most common CVE in all the risk cohorts. During the acute phase, among patients with new CVE, the average incremental inpatient length of stay and incremental costs ranged from 4.4-6.2 days and $25,666-$30,321, respectively. Acute-phase incremental costs accounted for 61-75% of first-year costs, but incremental costs also remained high during years 2 and 3 post-CVE. CONCLUSIONS: Among hyperlipidemic patients with new CVE, healthcare utilization and costs incurred were significantly higher than for those without CVE during the acute phase, and remained higher up to 3 years post-event, across all risk cohorts.