Background: While multiple studies characterize healthcare resource utilization (HCRU) and costs of pulmonary arterial hypertension (PAH) overall, HCRU specific to end-of-life (EOL) is not well described. Aim: To explore EOL-related HCRU and costs among patients with PAH. Methods: This retrospective cohort study analyzed data of adult patients with PAH from the IQVIA PharMetrics® Plus (P+) database (OCT2014-MAR2022). P+ does not include mortality data; therefore, evidence of fatality was determined by both a claims-based algorithm previously used in cardiovascular disease (Wade et al., 2020) and modified to PAH, and expert opinion. All-cause EOL-related HCRU and costs were explored within 30 days (30D) and 6 months (6M) of the assumed death date. Results: Of 500 PAH patients identified, only 28 patients had evidence of EOL. The mean (SD) EOL-related costs were $48,846 (±$61,031; 30D) and $167,524 (±$150,223; 6M) per patient prior to their assumed death. Most patients had ≥1 hospitalization during the EOL periods (17 [30D] and 23 [6M]), and hospitalizations contributed 58.8% (6M) to 70.8% (30D) of the EOL-related costs. Total pharmacy costs were the second leading driver of total costs, with a mean (SD) of $10,931 (±$15,903) and $52,466 (±$74,194) per patient during the 30D the 6M period, respectively (Figure). Conclusion: PAH is associated with substantial EOL HCRU and costs, largely driven by hospitalizations.

Rationale There is a lack of real-world characterization of healthcare costs and associated cost drivers in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (PH-COPD). Objectives To examine (1) excess healthcare resource utilization (HCRU) and associated costs in patients with PH-COPD compared to COPD patients without PH; and (2) patient characteristics that are associated with higher healthcare costs in patients with PH-COPD. Methods This study analyzed data from the IQVIA PharMetrics ® Plus database (OCT2014-MAY2020). Patients with PH-COPD were identified by a claims-based algorithm based on PH diagnosis (ICD-10-CM: I27.0, I27.2, I27.20, I27.21, I27.23) after COPD diagnosis. Patients aged ≥40 years and with data available ≥12 months before (baseline) and ≥6 months after (follow-up) the first observed PH diagnosis were included. Patients with other non-asthma chronic pulmonary diseases, PH associated with other causes, cancer, left-sided heart failure (HF), PH before the first observed COPD diagnosis, or right-sided/unspecified HF during baseline were excluded. Patients in the PH-COPD cohort were matched 1:1 to COPD patients without PH based on propensity scores derived from baseline patient characteristics. Annualized all-cause and COPD/PH-related (indicated by a primary diagnosis of COPD or PH) HCRU and costs during follow-up were compared between the matched cohorts. Baseline patient characteristics associated with higher total costs were examined in a generalized linear model in the PH-COPD cohort. Results A total of 2,224 patients with PH-COPD were identified and matched to COPD patients without PH. Patients with PH-COPD had higher all-cause HCRU and annual healthcare costs ($51,435 vs. $18,412, p <0.001) than matched COPD patients without PH. Among patients with PH-COPD, costs were primarily driven by hospitalizations (57%), while COPD/PH-related costs accounted for 13% of all-cause costs. Having a higher comorbidity burden and a prior history of COPD exacerbation were major risk factors for higher total all-cause costs among patients with PH-COPD. Conclusions Treatment strategies focusing on preventing hospitalizations and managing comorbidities may help reduce the burden of PH-COPD.

Kidney failure affects more than 725,000 individuals in the United States with an estimated 63% of patients receiving hemodialysis and 7% of patients receiving peritoneal dialysis in 2016.1Saran R. Robinson B. Abbott K.C. et al.US Renal Data System 2018 Annual Data Report: epidemiology of kidney disease in the United States.Am J Kidney Dis. 2019; 73: A7-A8https://doi.org/10.1053/j.ajkd.2019.01.001Abstract Full Text Full Text PDF PubMed Scopus (582) Google Scholar Patients with kidney failure receiving hemodialysis have an increased risk of bleeding, thrombosis, and cardiovascular events vs patients without kidney failure.2Parker K. Mitra S. Thachil J. Is anticoagulating haemodialysis patients with non-valvular atrial fibrillation too risky?.Br J Haematol. 2018; 181: 725-736Crossref PubMed Scopus (7) Google Scholar Despite clear thrombotic risk in patients with kidney failure, especially those with atrial fibrillation,1Saran R. Robinson B. Abbott K.C. et al.US Renal Data System 2018 Annual Data Report: epidemiology of kidney disease in the United States.Am J Kidney Dis. 2019; 73: A7-A8https://doi.org/10.1053/j.ajkd.2019.01.001Abstract Full Text Full Text PDF PubMed Scopus (582) Google Scholar anticoagulant and antiplatelet use is tempered by limited evidence of efficacy, lack of randomized clinical trials, and concern for serious bleeding in patients with atrial fibrillation undergoing long-term dialysis.3Kuno T. Takagi H. Ando T. et al.Oral anticoagulation for patients with atrial fibrillation on long-term hemodialysis.J Am Coll Cardiol. 2020; 75: 273-285Crossref PubMed Scopus (93) Google Scholar, 4Devabhaktuni S.R. Mounsey J.P. Should Oral oral anticoagulation be used in ESKD patients on hemodialysis with atrial fibrillation?: PRO.Kidney360. 2021; 2: 1405-1408Crossref PubMed Scopus (2) Google Scholar, 5Lidgard B. Bansal N. Should oral anticoagulation be used in ESKD patients on hemodialysis with atrial fibrillation?: CON.Kidney360. 2021; 2: 1409-1411Crossref PubMed Google Scholar, 6Mavrakanas T.A. Charytan D.M. Winkelmayer W.C. Direct oral anticoagulants in chronic kidney disease: an update.Curr Opin Nephrol Hypertens. 2020; 29: 489-496Crossref PubMed Scopus (5) Google Scholar Although some studies indicate that anticoagulants reduce stroke, mortality, and thromboembolism without an increase in bleeding,4Devabhaktuni S.R. Mounsey J.P. Should Oral oral anticoagulation be used in ESKD patients on hemodialysis with atrial fibrillation?: PRO.Kidney360. 2021; 2: 1405-1408Crossref PubMed Scopus (2) Google Scholar others indicate that anticoagulants do not decrease mortality rates or risk of stroke in these patients and may increase bleeding.5Lidgard B. Bansal N. Should oral anticoagulation be used in ESKD patients on hemodialysis with atrial fibrillation?: CON.Kidney360. 2021; 2: 1409-1411Crossref PubMed Google Scholar This opposing evidence may be due to anticoagulant dosage, patient bias, stage of kidney disease, and study methodology.4Devabhaktuni S.R. Mounsey J.P. Should Oral oral anticoagulation be used in ESKD patients on hemodialysis with atrial fibrillation?: PRO.Kidney360. 2021; 2: 1405-1408Crossref PubMed Scopus (2) Google Scholar, 5Lidgard B. Bansal N. Should oral anticoagulation be used in ESKD patients on hemodialysis with atrial fibrillation?: CON.Kidney360. 2021; 2: 1409-1411Crossref PubMed Google Scholar, 6Mavrakanas T.A. Charytan D.M. Winkelmayer W.C. Direct oral anticoagulants in chronic kidney disease: an update.Curr Opin Nephrol Hypertens. 2020; 29: 489-496Crossref PubMed Scopus (5) Google Scholar Faced with contradictory findings, the current cardiovascular treatment guidelines provide vague recommendations on anticoagulant and antiplatelet use in patients with kidney failure.7January C.T. Wann L.S. Calkins H. et al.2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.J Am Coll Cardiol. 2019; 74: 104-132Crossref PubMed Scopus (1228) Google Scholar Medicare generally covers the cost of hemodialysis and associated treatment services as defined by the Centers for Medicare & Medicaid Services.8Centers for Medicare & Medicaid Services. Medicare coverage of kidney dialysis & kidney transplant services. Published 2020. Accessed November 17, 2020. https://www.medicare.gov/Pubs/pdf/10128-medicare-coverage-esrd.pdfGoogle Scholar However, approximately 10% of US patients with kidney failure receiving hemodialysis are not insured through Medicare because of a mandated waiting period.9National Kidney Foundation. Medicare. Published 2020. Accessed November 23, 2020. https://www.kidney.org/patients/medicareGoogle Scholar The use of anticoagulants and antiplatelets among these patients is particularly poorly understood. Therefore, the objective of this retrospective observational cohort study was to assess the use of anticoagulants and antiplatelets among US patients with kidney failure receiving hemodialysis who do not have primary insurance coverage through Medicare. Administrative claims data from the Optum Clinformatics Data Mart commercial database (Optum) were analyzed. Detailed methods are found in Item S1 and Table S1. A total of 77,936 patients initiating hemodialysis between 2014 and 2018 were identified. The study population included 7,400 (9%) patients who met the inclusion criteria. One-fifth of patients in the study (n = 1,495, 20%) were on an anticoagulant and/or antiplatelet while receiving hemodialysis (Fig 1). Among these patients, more used antiplatelets (n = 854, 12%) than warfarin (n = 570, 8%) or direct oral anticoagulants (n = 242, 3%). About 1% of patients were prescribed more than one antiplatelet (n = 50) or an antiplatelet plus a direct oral anticoagulant (n = 37). Patients on anticoagulants and/or antiplatelets were slightly older than patients not on these medications (55 vs 50 years), but roughly the same percentage were male (n = 960, 64% vs n = 3,730, 63%) (Table 1). A larger proportion of patients on anticoagulants or antiplatelets vs those patients not on these medications had a history of cerebrovascular disease (n = 251, 17% vs n = 342, 6%) and myocardial infarction (n = 557, 37% vs n = 720, 12%). Patients who received an anticoagulant and/or antiplatelet used them for about one-third of the time after starting hemodialysis, assuming use at standard doses. Approximately 14% (n = 1,025) of patients had evidence of atrial fibrillation at some point during the full observation period, and more than half (n = 550, 54%) of those used an anticoagulant and/or antiplatelet after hemodialysis initiation. Following a claim including a myocardial infarction diagnosis, 105 (79.5%) patients not on an anticoagulant or antiplatelet started one, while following a claim including an ischemic stroke diagnosis, 42 (73.7%) patients started one (Table S2). Following a claim mentioning a major bleeding event, 137 (67.2%) patients on anticoagulants or antiplatelets at the time of the event stopped their therapy (Table S3).Table 1Demographics for Patients Using vs Not Using Antiplatelets/Anticoagulants After Initiating HemodialysisTime periodOn Any A/A (N=1,495)Not on any A/A (N=5,905)PostindexaIndex date is the first date of hemodialysis. date period Age (y), mean (SD)54.5 (8.0)49.4 (11.3) Sex (male), n (%)960 (64.2%)3,730 (63.2%)Preindex date time observed (d), mean (SD)1,125.4 (943.7)980.1 (867.5)Postindex date time observed (d), mean (SD)884.8 (132.3)842.0 (211.0)Charlson Comorbidity Index, mean (SD)6.1 (2.7)4.7 (2.7)Medical history, n (%) Abdominal aortic aneurysm23 (1.5%)42 (0.7%) Atherosclerosis813 (54.4%)1,201 (20.3%) Cerebrovascular-related diseases251 (16.8%)342 (5.8%) Peripheral artery disease393 (26.3%)651 (11.0%) Myocardial infarction history557 (37.3%)720 (12.2%)Abbreviations: A/A, anticoagulant/antiplatelet; SD, standard deviation.a Index date is the first date of hemodialysis. Open table in a new tab Abbreviations: A/A, anticoagulant/antiplatelet; SD, standard deviation. While 20.2% of patients were administered anticoagulants/antiplatelets following hemodialysis initiation, 23.2% filled at least 1 prescription during the full study period—including before hemodialysis. This suggests a small proportion of patients discontinued anticoagulants/antiplatelets after starting hemodialysis. Some limitations to the analysis should be considered. Insurance claims data do not reflect patients’ full medical histories, coverage continuity, or whether prescribed medication was taken. Additionally, the algorithms for identifying myocardial infarctions, ischemic strokes and major bleeding events from International Classification of Diseases, Tenth Revision codes have not been validated. Although the published algorithm identifying major bleeding events from International Classification of Diseases, Ninth Revision codes distinguishes between first and subsequent diagnoses in the patient record, the Optum commercial database does not. The lack of distinction between first and subsequent diagnoses also means that records for events such as myocardial infarction or stroke may refer to a history of such events rather than an event at the time the claim was recorded. Additionally, patients receiving hemodialysis on anticoagulants/antiplatelets used them only about a third of the time after initiating hemodialysis, assuming use at standard doses. If instructed to take at reduced doses, they may have been on these therapies longer. Beyond standard claims data limitations, the study depended on non-Medicare medical coverage data, which presented challenges because of the nature of insurance coverage surrounding hemodialysis. The analysis was limited to 30 months of follow-up because of the typical 30-month Medicare transition period. Results may not be generalized to a Medicare population. In this retrospective claims-based study, we found that one-fifth of non-Medicare patients with kidney failure were being treated with an antiplatelet and/or anticoagulant while receiving hemodialysis. Our results are similar to those found in an analysis of a Medicare hemodialysis population using US Renal Data System data.1Saran R. Robinson B. Abbott K.C. et al.US Renal Data System 2018 Annual Data Report: epidemiology of kidney disease in the United States.Am J Kidney Dis. 2019; 73: A7-A8https://doi.org/10.1053/j.ajkd.2019.01.001Abstract Full Text Full Text PDF PubMed Scopus (582) Google Scholar In that study, an estimated 20% of the Medicare hemodialysis population with a history of cardiovascular disease received an antiplatelet and 3% received a direct oral anticoagulant. Our study also found that more than half of patients with atrial fibrillation used an antiplatelet and/or anticoagulant after initiating hemodialysis. More research is warranted to understand the risk–benefit profile of anticoagulants and antiplatelets in treating patients with kidney failure receiving hemodialysis. Our findings can provide context for quantifying the use of these medications among this patient population. Research idea and study design: DL, DRR, BA, RB; data acquisition: LY, SL; data analysis/interpretation: LY, RB, DL, DRR, BA, CJM; statistical analysis: LY, DRR, RB; supervision or mentorship: DRR, BA, CJM. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, New Jersey, USA. Medical writing assistance in the preparation of this article was provided by Julia Zolotarjova, MSc, MWC, Shannon Gardell, PhD, Holly Richendrfer PhD, and Philip Leventhal, PhD of Evidera. Support for this assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Kenilworth, New Jersey, USA. Data analysis was performed by TigerMed Consulting Co, Ltd (Hangzhou, China). Drs Boggs, Liu, and Lautsch and Authors Rosen Ramsey and McMullan are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, New Jersey, who may own stock and/or stock options in Merck & Co, Inc, Rahway, New Jersey, USA. Dr Yang was an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, New Jersey, USA, at the time this work was performed. Received March 16, 2022. Evaluated by 1 external peer reviewer, with direct editorial input from the Statistical Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form October 2, 2022. Download .pdf (.19 MB) Help with pdf files Supplementary File (PDF)Item S1, Table S1-S3.

Rationale & Objective: Access patency outcomes for arteriovenous fistulas (AVFs) as compared with arteriovenous grafts (AVGs) in patients receiving hemodialysis (HD) who have achieved a func-tioning permanent access are not fully explored. Study Design: Observational cohort study.Setting & Population: Fee-for-service Medicare beneficiaries aged >= 18 years with kidney failure who were newly using a permanent access for maintenance HD from the United States Renal Data System (2010-2015). Patients using an oral anticoagulant were excluded. Exposure: AVG or AVF.Outcomes: Loss of primary unassisted, primary assisted, and secondary patency.Analytical Approach: Outcomes were character-ized using cumulative incidence curves, and HRs adjusted for sociodemographic and clinical factors were estimated for the comparison of AVF versus AVG.Results: The cohort included 60,329 and 17,763 patients newly using an AVF and AVG, respectively, for HD. Over 3 years of follow-up, AVG users, compared to AVF users, had a higher cumulative incidence of loss of primary unassisted patency (87% vs 69%; HR, 1.56; 95% CI, 1.52-1.6 0), loss of primary assisted patency (69% vs 25%; HR, 3.79; 95% CI, 3.67-3.92), and loss of secondary patency (22% vs 10%; HR, 2.03; 95% CI, 1.92-2.16). Stratified analyses revealed differences by subgroups; in particular, incidence of patency loss was higher among patients who underwent prior interventions to maintain prefunctional access patency and Black patients. Limitations: This analysis focused on outcomes occurring after first successful use of a permanent access and thus does not inform about risk of patency loss during access maturation. Conclusions: Among patients with kidney failure who successfully used a permanent access for HD, patency loss was consistently substantially higher in those using AVGs compared with AVFs. New interventions, such as prophylactic drugs, are needed to improve access longevity and reduce the need for invasive interventions, particularly among patients unable to receive a fistula.

The risks of major bleeding, thrombosis, and cardiovascular events are elevated in patients receiving maintenance hemodialysis (HD). Our objective was to compare the risk of these outcomes in HD according to the permanent vascular access type.Observational cohort study.Using data from the United States Renal Data System (2010-2015), we included patients with kidney failure who were greater than 18 years, had Medicare as the primary payer, were not using an oral anticoagulant, and were newly using an arteriovenous (AV) access for HD.AV graft (AVG) or AV fistula (AVF).Major bleeding, venous thromboembolism, ischemic stroke, myocardial infarction, cardiovascular death, and critical limb ischemia.Comparing 17,763 AVG and 60,329 AVF users, we estimated the 3-year incidence rates and incidence rate ratios (IRRs) of each outcome using Poisson regression. IRRs were adjusted for sociodemographic and clinical covariates.The use of an AVG, compared with that of an AVF, was associated with an increased risk of venous thromboembolism (10.8 vs 5.3 events per 100 person-years; adjusted IRR, 1.74; 95% CI, 1.63-1.85) but not with the risk of major bleeding (IRR, 1.04; 95% CI, 0.93-1.17). The use of an AVG was also potentially associated with a slightly increased risk of cardiovascular death (IRR, 1.09; 95% CI, 1.01-1.16).This analysis focused on patients with a functioning AV access; adverse events that may occur during access maturation should also be considered when selecting a vascular access.The use of an AVG, relative to an AVF, in HD is associated with an increased risk of venous thromboembolism. Given recent guidelines emphasizing selection of the "right access" for the "right patient," the results of this study should potentially be considered as one additional factor when selecting the optimal access for HD.

Abstract Background Pulmonary hypertension (PH) is a serious complication of chronic obstructive pulmonary disease (COPD). While clinical guidelines recommend specific drug therapies for pulmonary arterial hypertension (PAH), these drug therapies are not recommended for PH due to lung disease. Methods This was a retrospective cohort study using the Optum® Clinformatics® Data Mart from January 2009–September 2019. An algorithm was designed to identify adults with ≥ 2 ICD-9-CM or ICD-10-CM diagnosis codes for PH and with ≥ 2 diagnosis codes for COPD. Sensitivity analyses were conducted among subgroups of patients with evidence of a right heart catheterization (RHC) or pulmonary function test (PFT). Patient characteristics, medications used, and durations of use of PAH and COPD medications were analyzed. Results A total of 25,975 patients met the study inclusion criteria. Their mean age was 73.5 (SD 10.0) years and 63.8% were female. Medications targeting PAH were prescribed to 643 (2.5%) patients, most frequently a phosphodiesterase-5 inhibitor (2.1%) or an endothelin receptor antagonist (0.75%). Medications for COPD were prescribed to 17,765 (68.4%) patients, most frequently an inhaled corticosteroid (57.4%) or short-acting beta agonist (50.4%). The median durations of use ranged from 4.9 to 12.8 months for PAH medications, and from 0.4 to 5.9 months for COPD medications. Of the subgroup of patients with RHC (N = 2325), 257 (11.1%) were prescribed a PAH medication and 1670 (71.8%) used a COPD medication. Of the subgroup with a PFT (N = 2995), 58 (1.9%) were prescribed a PAH medication and 2100 (70.1%) a COPD medication. Conclusions Patients with PH associated with COPD were identified in a US administrative claims database. Very few of these patients received any of the medications recommended for PAH, and only about two thirds received medications for COPD.

A small number of adverse events of seizure in patients using desloratadine (DL) have been reported. The European Medicines Agency requested a post-authorization safety study to investigate whether there is an association between DL exposure and seizure. The aim was to study the association between DL exposure and incidence of first seizure. A new-user cohort study of individuals redeeming a first-ever prescription of DL in Denmark, Finland, Norway, and Sweden in 2001–2015 was conducted. DL exposure was defined as days’ supply plus a 4-week grace period. DL unexposed periods were initiated 27 weeks after DL prescription redemption. Poisson regression was used to estimate the adjusted incidence rate and adjusted incidence rate ratio (aIRR) of incident seizure. A total of 1,807,347 first-ever DL users were included in the study, with 49.3% male and a mean age of 29.5 years at inclusion; 20.3% were children aged 0–5 years. The adjusted incidence rates of seizure were 21.7 and 31.6 per 100,000 person-years during DL unexposed and exposed periods, respectively. A 46% increased incidence rate of seizure was found during DL exposed periods (aIRR = 1.46, 95% confidence interval [CI] 1.34–1.59). The aIRR ranged from 1.85 (95% CI 1.65–2.08) in children aged 0–5 years to 1.01 in adults aged 20 years or more (95% CI 0.85–1.19). This study found an increased incidence rate of seizure during DL exposed periods as compared to unexposed periods among individuals younger than 20 years. No difference in incidence rate of seizure was observed in adults between DL exposed and unexposed.

This study aimed to validate an algorithm developed to identify chronic thromboembolic pulmonary hypertension (CTEPH) among patients with a history of pulmonary embolism. Validation was halted because too few patients had gold-standard evidence of CTEPH in the administrative claims/electronic health records database, suggesting that CTEPH is underdiagnosed.

Introduction: Brenzys was developed as an etanercept biosimilar of Enbrel. The aim of this study was to assess preference and perceived ease of use for the new Brenzys autoinjector compared to the currently available marketed Enbrel MYCLIC autoinjector (Australia) and Enbrel SureClick autoinjector (Canada) for the treatment of rheumatoid arthritis (RA). Because RA affects manual dexterity, ease of use of an autoinjector is a particularly important consideration in developing effective self-delivery of long-term courses of therapy.Methods: Patients (N = 191) reporting a diagnosis of RA and nurses and rheumatologists (N = 90) with experience managing RA were shown how to use Brenzys and Enbrel autoinjectors (in counterbalanced order between participants), then they used each autoinjector by injecting into a pad simulating skin, and completed a questionnaire. Study sessions took place in Australia and Canada.Results: A binomial test showed that significantly more patients indicated that the Brenzys autoinjector was easier to use than the Enbrel autoinjector (79% reporting Brenzys easier to use; p < 0.001, two-sided, 95% CI [73%, 85%]). In addition, significantly more nurses and rheumatologists with experience managing RA also indicated that the Brenzys autoinjector was easier to use (86%; p < 0.001, two-sided, 95% CI [77%, 92%) and that they would recommend the buttonless Brenzys autoinjector over the Enbrel autoinjector to patients (83%; p < 0.001, two-sided, 95% CI [74%, 90%]). Almost all patients who reported past experience using an Enbrel autoinjector (N = 17) reported on the basis of using the two devices in the study that they would prefer to switch their device to the Brenzys autoinjector rather than continue their course of therapy using the Enbrel autoinjector (16/17, 94%, 95% CI [71%, 100%]).Conclusion: On the basis of the study results, the Brenzys autoinjector was rated statistically significantly easier to use, and was overall preferred by patients and healthcare professionals with experience managing RA patients.Funding: Merck & Co., Inc.

Goal attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) is suboptimal. Little is known about how patient factors influence physicians’ treatment decision-making in hypercholesterolemia. We examined physicians’ treatment recommendations in high-risk patients whose LDL-C remained uncontrolled despite statin monotherapy.

The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) clinical trial, including 1,873 patients found an increased risk for cancer with lipid-lowering therapy with ezetimibe/simvastatin 10/40 mg/day, relative to placebo. In a registry-based follow-up study over 21 months from the conclusion of the SEAS trial, new incident cancer and total mortality were investigated in the SEAS study cohort from Denmark, Finland, Norway, Sweden, and the United Kingdom. Among 1,359 subjects eligible for follow-up (73% of the original total cohort), 1,194 had no history of cancer (primary follow-up cohort). New cancers and deaths were identified in the national cancer and mortality registries and classified by an Expert Review Committee. Data were analyzed using Cox proportional-hazards models of new cancers and mortality during follow-up according to treatment group assigned in the SEAS base study and with age, gender, smoking history, and previous cancers as covariates. The primary follow-up cohort had 12 patients with new cancers in the ezetimibe/simvastatin group and 22 in the placebo group (hazard ratio 0.55, 95% confidence interval 0.27 to 1.11), indicating no significant difference between the treatment groups. During follow-up, 43 patients assigned to ezetimibe/simvastatin and 33 assigned to placebo died (hazard ratio 1.29, 95% confidence interval 0.82 to 2.03). In conclusion, in this registry-based observational follow-up study of the original SEAS study patient population, treatment with ezetimibe/simvastatin was not associated with an increased risk for cancer or mortality in the 21-month period after the completion of the original SEAS study.

Background Statin therapy is recommended as the first-line pharmacotherapeutic approach for lowering LDL-C levels in patients at high cardiovascular risk. Objective To assess LDL-C levels among patients at high cardiovascular risk treated with rosuvastatin monotherapy. Methods This retrospective cohort study used patient records from the GE Centricity Electronic Medical Records (GE Centricity EMR) database and administrative claims data from Humana Medicare to identify patients at high cardiovascular risk with a first prescription for rosuvastatin monotherapy (index date) from January 1, 2008 through December 31, 2010. Eligible adult patients had an International Classification of Diseases, Ninth Revision (ICD-9) diagnosis or a Current Procedural Terminology (CPT) procedure code indicating coronary heart disease or atherosclerotic vascular disease, ≥1 LDL-C measurement 3 to 12 months after the index date, and continuous data during 1-year baseline and 1-year follow-up. Mean LDL-C levels and distribution of patients around <70 mg/dL and <100 mg/dL thresholds overall and by daily rosuvastatin dose were assessed. Results Among 6004 GE Centricity EMR patients (mean [SD] age, 66 [10] years; 56% men) and 11,320 Humana Medicare patients (mean [SD] age, 74 [8] years; 44% men) who met selection criteria, the most frequently prescribed rosuvastatin dose was 10 mg, and the mean (SD) follow-up LDL-C level was 89 (37) mg/dL for GE Centricity EMR patients and 92 (36) mg/dL for Humana Medicare patients. Overall, lower mean LDL-C levels were observed as rosuvastatin dose increased. However, less than one-third of GE Centricity EMR and Humana Medicare patients had an LDL-C level <70 mg/dL, and approximately two-thirds had an LDL-C level <100 mg/dL. Conclusion More effective lipid-lowering strategies, such as statin up-titration or combination therapy, may be needed to achieve therapeutic goals in a substantial proportion of high-risk patients.

Objective:British clinical guidelines recommend statins as first-line lipid-modifying treatment (LMT) for patients at high risk of cardiovascular disease (CVD). We undertook an observational study to assess total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in high-risk patients who were treated with atorvastatin monotherapy by UK general practitioners.Methods:This retrospective database study included patients with a prescription for atorvastatin monotherapy between November 30, 2008, and November 30, 2011, with the index date defined as the first atorvastatin prescription during this period. Eligible high-risk patients with evidence of coronary heart disease (CND), atherosclerotic vascular disease (AVD), diabetes mellitus (DM), or familial hypercholesterolemia (FH) were required to have >= 1 TC and LDL-C measurement between 3 and 12 months after the index date, and continuous enrollment 1 year before and 1 year after the index date. Cholesterol levels were assessed using the National Institute for Health and Care Excellence (NICE) guidelines: TC <4.0 mmol/L or LDL-C <2.0 mmol/L.Results:Of 2999 high-risk patients (60.2% men; mean [SD] age = 67.9 [10.6] years) meeting selection criteria, 23.9% 28.2%, 36.2%, and 11.6% received prescriptions for atorvastatin 10, 20, 40, and 80 mg, respectively (percentages do not sum to 100 because of rounding). Across all doses, the mean (SD) follow-up TC was 4.08 (0.80) mmol/L and LDL-C 2.08 (0.65) mmol/L. A large proportion of patients (88.8%) had TC <5.0 mmol/L. However, only 45.8% had TC <4.0 mmol/L, and 46.5% had LDL-C < 2.0 mmol/L. Although a larger proportion of patients with CHD/AVD + DM reached guideline-recommended lipid levels, only 63.7% of such patients had TC <4.0 or LDL-C <2.0 mmol/L, which are the current targets for this subgroup as recommended by NICE.Conclusions:Less than half of UK high-CVD-risk patients receiving atorvastatin monotherapy achieved guideline-recommended treatment targets for TC, and less than two-thirds of patients with CHD/AVD DM had values below TC (4.0 mmol/L) or LDL-C (2.0 mmol/L) targets. More effective lipid-lowering strategies may be warranted to optimize cholesterol lowering and target attainment in high-risk patients. Limitations of this study include its retrospective, observational nature.

BACKGROUND: Recent trends suggest a decreased use of ezetimibe/simvastatin combination and coadministered ezetimibe plus statin therapies.OBJECTIVE: This analysis evaluated changes in prescription patterns for ezetimibe/simvastatin, ezetimibe plus statins, and statin therapies and expected effects on low-density lipoprotein cholesterol (LDL-C) lowering during 2007 to 2008.METHODS: Prescription pattern changes were assessed by the use of patient-level data from the IMS Health Longitudinal Rx database during two time periods, July 14, 2007 to January 13, 2008 (n = 8,813,674) and January 14, 2008 to July 13, 2008 (n = 9,131,030), 6 months before and after reporting of the results of The Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial (ENHANCE) trial on January 14, 2008. Expected LDL-C reductions were estimated using data from previous controlled clinical trials.RESULTS: During 6 months post-ENHANCE, greater proportions of patients were switched from ezetimibe/simvastatin and ezetimibe plus statins to other lipid-lowering therapies by health care providers than 6 months pre-ENHANCE (21.1% vs 6.0% and 46.9% vs 38.5%, differences: -15.06% [95% confidence interval -15.14%, -14.97%] and -8.43% [95% confidence interval -8.70%, -8.17%], respectively). Greater proportions of these patients switched to statin monotherapy in the later than earlier period. Prescription patterns were similar for statins during both time periods, although fewer patients switched to ezetimibe/simvastatin and ezetimibe plus statin therapies post-ENHANCE. In both time periods, greater proportions of patients on ezetimibe/simvastatin and ezetimibe plus statins switched to less-than-equivalent LDL-C lowering efficacy doses of statins than those on statin therapy. On the basis of previous clinical data for these therapies, smaller LDL-C reductions would be expected in patients who switched from ezetimibe/simvastatin and ezetimibe plus statins to statins, despite a trend toward switching to greater statin doses in the later time period.CONCLUSIONS: More patients switched from ezetimibe/simvastatin and ezetimibe plus statin to statin monotherapy 6 months after the reporting of the ENHANCE trial, the majority of which were prescribed less potent, LDL-C-lowering therapies. On the basis of the known LDL-C lowering efficacies for these therapies, such changes would be expected to increase LDL-C levels in these patients and may reduce the proportion of patients who achieve guideline-recommended LDL-C goals. (C) 2012 National Lipid Association. All rights reserved.