Healthcare resource utilization in patients with pulmonary hypertension associated with chronic obstructive pulmonary disease (PH-COPD): a real-world data analysis.

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.

Hemodialysis Access Type and Access Patency Loss: An Observational Cohort Study.

Rationale & Objective: Access patency outcomes for arteriovenous fistulas (AVFs) as compared with arteriovenous grafts (AVGs) in patients receiving hemodialysis (HD) who have achieved a functioning 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 characterized 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, 1.52-1.60), 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.

Hemodialysis Vascular Access and Risk of Major Bleeding, Thrombosis, and Cardiovascular Events: A Cohort Study.

Rationale & Objective: 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. Study Design: Observational cohort study. Setting & Participants: 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. Exposure: AV graft (AVG) or AV fistula (AVF). Outcomes: Major bleeding, venous thromboembolism, ischemic stroke, myocardial infarction, cardiovascular death, and critical limb ischemia. Analytical Approach: 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. Results: 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). Limitations: 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. Conclusions: 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.

Desloratadine Exposure and Incidence of Seizure: A Nordic Post-authorization Safety Study Using a New-User Cohort Study Design, 2001-2015.

INTRODUCTION: 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. OBJECTIVE: The aim was to study the association between DL exposure and incidence of first seizure. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Validation of a claims-based algorithm to identify patients with chronic thromboembolic pulmonary hypertension using electronic health record data.

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.

Patient and Healthcare Professionals Preference for Brenzys vs. Enbrel Autoinjector for Rheumatoid Arthritis: A Randomized Crossover Simulated-Use Study.

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.

Patient and physician factors influence decision-making in hypercholesterolemia: a questionnaire-based survey.

BACKGROUND: 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. METHODS: Physicians completed a questionnaire prior to randomization into period I of a two-period randomized controlled trial evaluating LDL-C goal attainment in patients whose LDL-C remained ≥100 mg/dL after 5 weeks' treatment with atorvastatin 10 mg/day (NCT01154036). Physicians' treatment recommendations were surveyed for two hypothetical and one real scenario: (1) LDL-C presumed near goal (between 100-105 mg/dL), (2) LDL-C presumed far from goal (~120 mg/dL), and (3) observed baseline LDL-C of enrolled patients. Prognostic factors considered during decision-making were identified by regression analysis. Observed lipid outcomes at the end of period I (following 6 weeks' treatment with ezetimibe 10 mg plus atorvastatin 10 mg, atorvastatin 20 mg, or rosuvastatin 10 mg) were compared with estimated LDL-C outcomes for physicians' treatment recommendations after 6 weeks (based on individual patients' pre-randomization LDL-C and expected incremental change). RESULTS: Questionnaires were completed for 1,534 patients. No change in therapy, or double atorvastatin dose, were frequently recommended, even when LDL-C was far from goal (6.5% and 52.2% of patients, respectively). Double atorvastatin dose was commonly recommended in all scenarios (43-52% of patients). More intensive LDL-C-lowering regimens were recommended infrequently e.g. double atorvastatin dose and add ezetimibe only <12% in all scenarios. Overall, cardiovascular risk factors and desire to achieve a more aggressive LDL-C goal were prominent factors in decision-making for treatment. Comparison of observed and estimated LDL-C levels showed that physicians tended to overestimate the effectiveness of their recommendations. CONCLUSIONS: This study provides insight into physicians' perspectives on clinical management of hypercholesterolemia and highlights a gap in knowledge translation from guidelines to clinical practice. The need for lower LDL-C and cardiovascular risk were key drivers in clinical decision-making, but physicians' treatment choices were more conservative than guideline recommendations, potentially resulting in poorer LDL-C reduction. When compared with actual outcomes, projected LDL-C control was better if physicians used more comprehensive strategies rather than simply doubling the statin dose. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01154036.

Incidence of cancer and mortality in patients from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial.

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.

LDL-C levels in US patients at high cardiovascular risk receiving rosuvastatin monotherapy.

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.

Total and low-density lipoprotein cholesterol in high-risk patients treated with atorvastatin monotherapy in the United Kingdom: analysis of a primary-care database.

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 (CHD), 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.

Changes in prescription patterns before and after reporting of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial (ENHANCE) results and expected effects on low-density lipoprotein-cholesterol reduction.

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.

Systematic review of trials of the effect of continued use of oral non-selective NSAIDs on blood pressure and hypertension.

OBJECTIVE: To investigate the effects of continued use of non-selective NSAIDs (nsNSAIDs) on blood pressure and hypertension. RESEARCH DESIGN AND METHODS: This was a systematic review of randomized clinical trials of oral nsNSAIDs used for at least a 4-week duration. Searches were conducted of PubMed and the Cochrane Database of Systematic Reviews, using key terms for nsNSAIDs and blood pressure or hypertension, to identify articles published in the English language peer-reviewed literature through March 2007. MAIN OUTCOME MEASURES: Change from baseline to end of study in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the incidence of hypertension. Pooled statistics were computed using fixed and random-effects analyses. RESULTS: Thirty-two articles were included. The mean change (95% confidence interval [CI]) in blood pressure (in mmHg) from baseline to end of study for five trials of ibuprofen was 3.54 (2.70, 4.39) for SBP and 1.16 (0.68, 1.64) for DBP (p < 0.001 for both changes). Results of four trials of indomethacin were similar to those for ibuprofen: 2.90 (-0.28, 6.08) for SBP (p = 0.07) and 1.58 (0.29, 2.87) for DBP (p = 0.02). Mean changes from baseline for two trials of diclofenac were -0.46 (-1.48, 0.56) for SBP (p = 0.38) and -0.56 (-1.19, 0.07) for DBP (p = 0.08) and were similar to those for placebo. Changes from baseline in SBP were positive but not statistically significant for naproxen, sulindac, and nabumetone. Compared with placebo, the risk ratio (95% CI) for hypertension was 2.85 (1.44, 5.65; p = 0.003) in two ibuprofen trials. CONCLUSIONS: Continued use of ibuprofen increases blood pressure and raises the incidence of hypertension. There appears to be heterogeneity in such effects with continued use of other nsNSAIDs but, due to limitations in the data, results for naproxen, sulindac, and nabumetone are inconclusive.