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.

Medication use by US patients with pulmonary hypertension associated with chronic obstructive pulmonary disease: a retrospective study of administrative data.

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.

Changes in skin score in early diffuse cutaneous systemic sclerosis are associated with changes in global disease severity.

OBJECTIVE: To determine whether skin score changes are associated with changes in overall disease severity, function and quality of life in early dcSSc patients. METHODS: A total of 154 and 128 dcSSc patients from the Canadian Scleroderma Research Group database with 1 and 2 year follow-up and a disease duration ⩽5 years without end-stage organ damage and/or significant comorbidity at the initial visit were included. Skin was assessed using the modified Rodnan skin score (mRSS) and disease severity by the summed Medsger disease severity score (DSS) (without skin domain), physician and patient global assessments, function [HAQ disability index (HAQ-DI)] and quality of life [36-item Short Form Health Survey (SF-36) physical component summary (PCS)]. Analyses were repeated in patients with a disease duration ⩽3 years. RESULTS: At 2 years, 64 (50%) patients had improved skin (mRSS decrease of ⩾5 points and/or ⩾25%). Skin improvers had improved summed DSS (P = 0.002); better physician global assessments of disease activity, severity and damage (all P ⩽ 0.003); better HAQ-DI (P = 0.001) and SF-36 PCS (P = 0.005). Changes in the mRSS were positively correlated with changes in summed DSS (P = 0.006) and other disease outcomes. In the 26 (20.3%) patients with worsened skin (mRSS increase of ⩾5 points and/or ⩾25%), the summed DSS and physician global assessments were worse (P = 0.01 and P ⩽ 0.009, respectively). In the subgroup with a disease duration ⩽3 years, similar associations were found. CONCLUSION: At 1 and 2 years, overall disease improvement parallels skin improvement in early dcSSc. This is important for prognosis and reflects the value of mRSS as an outcome measure in trials with these patients.

Skin improvement is a surrogate for favourable changes in other organ systems in early diffuse cutaneous systemic sclerosis.

OBJECTIVES: Skin improvement in diffuse cutaneous SSc (dcSSc), measured with modified Rodnan skin score (mRSS), is frequently used as a primary outcome in clinical trials, but it is uncertain whether mRSS changes reflect changes in other organ systems. This aim of this study was to explore if skin changes in early dcSSc over 1 and 2 years are associated with changes in severity of other organ involvement. METHODS: Canadian Scleroderma Research Group database patients with dcSSc, disease duration of ≤5 years, no evidence of initial end-stage organ damage and/or significant comorbidity who had 1 year (n = 154) and 2 years (n = 128) of follow-up data were included. mRSS changes of 25% and/or ≥5 points were considered significant. Organ involvement was assessed by Medsger Disease Severity Score and Canadian Scleroderma Research Group definitions using bivariate, chi-square, ANOVA, adjusted regression and longitudinal mixed effect model analyses. RESULTS: Improvement in mRSS was found in 41% of patients at 1 year and in 50% at 2 years. Improved patients showed less forced vital capacity decline (P = 0.012) and less frequent new cardiac involvement (P = 0.02) over 1 year, as well as better lung (by both Disease Severity Score, P = 0.006, and Δforced vital capacity%, P = 0.026), peripheral vascular (P = 0.006) and joint/tendon (P = 0.002) involvement over 2 years. mRSS worsening was consistently linked to less favourable lung outcomes at both 1- and 2-year follow-up visits, and more severe gastrointestinal disease at 2 years. CONCLUSION: Changes in lung function in early dcSSc closely parallel skin changes. mRSS improvement reflects better prognosis for visceral disease and may be a reliable outcome measure in clinical trials.

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.

Excess healthcare resource utilization and costs for commercially insured patients with pulmonary arterial hypertension: A real-world data analysis.

This retrospective study was conducted to evaluate all-cause healthcare resource utilization (HCRU) and costs in commercially insured patients living with pulmonary arterial hypertension (PAH) and explore end-of-life (EOL)-related HCRU and costs. Data from the IQVIA PharMetrics® Plus database (October 2014 to May 2020) were analyzed to identify adults (≥18 years) with PAH (PAH cohort) and those without PH (non-PH cohort). Patients were required to have data for ≥12 months before (baseline) and ≥6 months after (follow-up) the first observed PH diagnosis (index date) for PAH cohort or pseudo index date for non-PH cohort. A PAH EOL cohort was similarly constructed using a broader data window (October 2014 to March 2022) and ≥1 month of follow-up. Annualized all-cause HCRU and costs during follow-up were compared between PAH and non-PH cohorts after 1:1 matching on propensity scores derived from patient characteristics. EOL-related HCRU and costs were explored within 30 days and 6 months before the death date and estimated by a claims-based algorithm in PAH EOL cohort. The annual all-cause total ($183,616 vs. $20,212) and pharmacy ($115,926 vs. $7862; both p < 0.001) costs were 8 and 14 times higher, respectively, in the PAH cohort versus matched non-PH cohort (N = 386 for each). In PAH EOL cohort (N = 28), the mean EOL-related costs were $48,846 and $167,524 per patient within 30 days and 6 months before the estimated death, respectively. Hospitalizations contributed 58.8%-70.8% of the EOL-related costs. The study findings indicate substantial HCRU and costs for PAH. While pharmacy costs were one of the major sources, hospitalization was the primary driver for EOL-related costs.

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.

Post-switch Effectiveness of Etanercept Biosimilar Versus Continued Etanercept in Rheumatoid Arthritis Patients with Stable Disease: A Prospective Multinational Observational Study.

INTRODUCTION: To better inform clinicians about the use of etanercept biosimilar (SB4) in patients with rheumatoid arthritis (RA), COMPANION-B, a prospective real-world observational study, evaluated the effectiveness of the voluntary switch from originator (etanercept, ETN) to SB4 in patients with stable RA (low-disease activity/remission). METHODS: The study recruited adult patients (18 years or older) with RA (2010 American College of Rheumatology criteria) prescribed ETN as their first or second biologic for at least 6 months across 14 sites in Canada and five in Australia. Patients had stable disease (Disease Activity Score-28 using erythrocyte sedimentation rate [DAS28-ESR] less than 3.2) at enrollment with no evidence of flare within the previous 3 months. Concomitant disease-modifying antirheumatic drugs (DMARDs) were permitted. Patients could elect to continue ETN or voluntarily switch to SB4 in consultation with their doctors. The primary effectiveness measure was the proportion of patients with disease worsening (defined as a DAS28-ESR increase of at least 1.2 from baseline and minimum score of at least 3.2 or a defined modification in RA treatment) during 12 months of follow-up. The secondary effectiveness measure was the proportion of patients with disease worsening at month 6. Serious adverse events (SAEs) and non-serious adverse reactions (NSARs) were recorded. RESULTS: Of 163 patients enrolled, 109 elected to continue on ETN and 54 switched to SB4; 65.8% of patients received non-biologic DMARD(s), 52.6% methotrexate, and 10.5% oral corticosteroid(s). At month 12, the proportion of patients with disease worsening was comparable in the ETN group (22.8% [95% CI 15.0-32.2]) and SB4 group (17.6% [95% CI 8.4-30.9]). Similarly, the proportions of patients with disease worsening were also comparable at month 6 (ETN: 7.9% [95% CI 3.5-15.0]; SB4: 7.8% [95% CI 2.2-18.9]). SAEs were low and similar across both groups (ETN: 8.7%; SB4: 5.7%). NSARs were slightly higher in the SB4 vs. ETN group (13.2% vs. 2.9%). CONCLUSIONS: SB4 demonstrated comparable effectiveness to ETN over 12 months in patients with stable RA who voluntarily switched to the biosimilar in a real-world setting.

Results from a cross-sectional, observational study to assess inadequate pain relief in patients with knee and/or hip osteoarthritis in Mexico.

INTRODUCTION AND OBJECTIVES: There is limited data that characterizes osteoarthritis (OA) patients who experience moderate to severe pain despite analgesic treatment in Mexico. In this study, we estimate the real-world prevalence of inadequate pain relief (IPR) among individuals with knee and/or hip OA who have been prescribed analgesic therapy and characterize this patient population for each country separately. MATERIALS AND METHODS: This is a multinational, multi-site, cross-sectional, observational study. Participating physicians enrolled patients over 50 years of age with diagnosed knee and/or hip OA who had been prescribed topical and/or oral pain medication for at least 30 days prior to study visit, extracted data from their medical charts, and collected patient data using established questionnaires. RESULTS: 301 patients treated by 35 physicians in Mexico were enrolled in the study. More than half of the patients (53%) met the definition of IPR. Patients with IPR were significantly older (66.8 vs. 63.5 years, p=0.002) and were more likely to be obese (24.2% vs. 11.9%, p=0.006). Patients in the IPR group were more likely to report moderate/severe problems across all 5 dimensions of the EQ-5D and reported higher scores, indicating worse outcomes, on all three WOMAC subscales. Patients in the IPR group also reported reduced work productivity and greater treatment dissatisfaction compared to patients without IPR. DISCUSSION AND CONCLUSIONS: IPR is highly prevalent among individuals with knee and/or hip OA in Mexico. Patients with IPR experience decreased health-related quality of life HRQoL and work productivity, impaired function, and poor treatment satisfaction. Health care professionals need to be aware of the high prevalence of IPR, work toward improving OA patient management, and facilitate early intervention or changes in drug and other treatment modalities.

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.

Real-world data to assess changes in low-density lipoprotein cholesterol and predicted cardiovascular risk after ezetimibe discontinuation post reporting of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial.

BACKGROUND: The 2008 Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) study demonstrated ezetimibe + simvastatin vs simvastatin alone had a neutral effect on the surrogate endpoint of carotid intima-media thickness. Subsequent media portrayal of the study prompted ezetimibe discontinuation in many patients. OBJECTIVE: The objective of the study was to assess the impact of ENHANCE reporting on ezetimibe discontinuation, low-density lipoprotein cholesterol (LDL-C) changes, and potential cardiovascular disease (CVD) risk. METHODS: This analysis used claims data in a retrospective, observational study of patients receiving ezetimibe + statin and compared LDL-C for patients who discontinued ezetimibe (n = 970) vs those who continued ezetimibe + statins (n = 3706) after ENHANCE results disclosure. Change in relative CVD risk was estimated from the absolute LDL-C difference between groups per the Cholesterol Treatment Trialists' meta-analysis of statin trials. RESULTS: The rate of ezetimibe discontinuation was 2% in the 6 months before and 21% in the 6 months after reporting of ENHANCE results. Among patients who ultimately discontinued vs continued ezetimibe, respective mean LDL-C levels were 79.8 and 78.3 mg/dL 6 months before reporting of the ENHANCE results and 93.5 and 78.1 mg/dL 6 months after reporting of ENHANCE. Predictive application of the Cholesterol Treatment Trialists' meta-analysis suggested the 13.9 mg/dL increase in mean LDL-C translated to a 9.4% increase in relative CVD risk for those who discontinued ezetimibe. CONCLUSION: After reporting of the neutral ENHANCE results, ezetimibe discontinuation rate increased, LDL-C levels increased, and predicted CVD risk increased among those who discontinued ezetimibe. Characterization of clinical outcomes regarding lipid-altering agents based on surrogate biomarker studies not designed to assess CVD outcomes may be misleading, potentially placing patients at increased CVD risk.

Gender Disparities in Lipid-Lowering Therapy in Cardiovascular Disease: Insights from a Managed Care Population.

BACKGROUND: Numerous studies have documented the strong inverse relationship between low-density lipoprotein cholesterol (LDL-C) levels and atherosclerotic cardiovascular disease (ASCVD). However, women are less likely to be screened for hypercholesterolemia, receive lipid-lowering therapy (LLT), and achieve optimal LDL-C levels. MATERIALS AND METHODS: Data were extracted from a U.S. administrative claims database between January 2008 and December 2012 for patients with established ASCVD. The earliest date of valid LDL-C value was defined as the index date. Patients were followed for ±12 months from the index date and were stratified by gender, by baseline LDL-C level, and whether they were initially treated with a LLT then propensity score matched by gender using demographic and clinical characteristics. Both descriptive statistics and logistic regression models were used to explore the association of gender with the frequency of LDL-C monitoring, LLT treatment initiation in initially untreated patients, and prescribing patterns in initially treated patients. RESULTS: A total of 76,414 subjects with established ASCVD were identified; 42% of the sample was women. In the unmatched cohort, 50.3% of men and 32.0% of women were prescribed a preindex statin (p < 0.0001). Among matched patients (n = 51,764), women initially treated with LLT were significantly less likely to receive a prescription for a higher potency LLT. Even among those with LDL-C levels above 160 mg/dL, women were more likely to discontinue LLT, odds ratio (95% confidence interval) 1.8 (1.2-2.3). Female gender and older age were significant predictors of discontinuation, and the potency of the index medication was the strongest predictor of dose titration. Initially untreated women were less likely to initiate LLT treatment than men, irrespective of index LDL-C levels (p < 0.0001). CONCLUSIONS: The observed disparities further reinforce the need for targeted efforts to reduce the gender gap for secondary prevention in women at high risk of cardiovascular disease.

The incidence of upper gastrointestinal adverse events in clinical trials of etoricoxib vs. non-selective NSAIDs: an updated combined analysis.

OBJECTIVE: In spite of numerous studies demonstrating the serious gastrointestinal (GI) toxicity associated with non-selective non-steroidal anti-inflammatory drugs (NSAIDs), many patients at high GI risk continue to receive prescriptions for these drugs, often without gastroprotective agents. Etoricoxib, a COX-2 specific inhibitor, was developed to provide similar efficacy and less GI toxicity than non-selective NSAIDs. We compared the incidence of upper GI Perforations, symptomatic gastroduodenal Ulcers, and upper GI Bleeding (PUBs) in a combined analysis of all randomized, double-blind, clinical trials of chronic treatment with etoricoxib versus NSAIDs completed by June 2003. RESEARCH DESIGN AND METHODS: Data for 5441 individual subjects with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis were pooled from all 10 multinational etoricoxib trials completed by June 2003. Information on suspected PUBs was prospectively collected in all protocols, and all investigator-reported PUBs were judged by a blinded, external adjudication committee using pre-specified criteria. PUBs were analyzed using COX proportional hazards models using terms for treatment and known PUB risk factors. MAIN OUTCOME MEASURE: The incidence of confirmed PUBs among patients treated with etoricoxib 60 mg, 90 mg, or 120 mg (combined N=3226) was compared to that among patients treated with ibuprofen, diclofenac, or naproxen (combined N=2215). RESULTS: The incidence of PUBs over 44.3 months was significantly lower with etoricoxib vs. NSAIDs [cumulative incidence 1.24% vs. 2.48%, p < 0.001; rate/100 patient-years 1.00 vs. 2.47; relative risk 0.48, 95% Confidence Interval (CI) 0.32, 0.73]. Results of analysis of events occurring during the first year of treatment and subgroup analyses were consistent with the primary result. CONCLUSIONS: Treatment with etoricoxib was associated with a significantly lower incidence of PUBs than was treatment with non-selective NSAIDs. The difference was consistent in subgroups of patients defined by a variety of known risk factors.

Postponed development of disability in elderly runners: a 13-year longitudinal study.

BACKGROUND: The magnitude and duration of the benefit of running and other aerobic exercise on disability and mortality in elderly persons are not well understood. We sought to quantify the benefits of aerobic exercise, including running, on disability and mortality in elderly persons and to examine whether morbidity can be compressed into later years of life by regular exercise. METHODS: A 13-year prospective cohort study of 370 members of a runners' club for persons aged 50 and older and 249 control subjects initially aged 50 to 72 years (mean, 59 years), with annual ascertainment of the Health Assessment Questionnaire disability score, noting any deaths and their causes. Linear mixed models were used to compute postponement in disability, and survival analysis was conducted to determine the time to and causes of death. RESULTS: Significantly (P<.001) lower disability levels in runners' club members vs controls and in ever runners vs never runners were sustained for at least 13 years. Reaching a Health Assessment Questionnaire disability level of 0.075 was postponed by 8.7 (95% confidence interval [CI], 5.5-13.7) years in runners' club members vs controls. Running club membership and participation in other aerobic exercise protected against mortality (rate ratio, 0.36 [95% CI, 0.20-0.65] and 0.88 [95% CI, 0.77-0.99], respectively), while male sex and smoking were detrimental (rate ratio, 2.4 [95% CI, 1.4-4.2] and 2.2 [95% CI, 1.1-4.6], respectively). Controls had a 3.3 times higher rate of death than runners' club members, with higher death rates in every disease category. Accelerated rates of disability and mortality were still not seen in the runners' club members; true compression of morbidity was not yet observable through an average age of 72 years. CONCLUSION: Running and other aerobic exercise in elderly persons protect against disability and early mortality, and are associated with prolongation of a disability-free life.

Impact of Switching From High-Efficacy Lipid-Lowering Therapies to Generic Simvastatin on LDL-C Levels and LDL-C Goal Attainment Among High-Risk Primary and Secondary Prevention Populations in the United Kingdom.

PURPOSE: High cholesterol, especially high low-density lipoprotein cholesterol (LDL-C), is an important risk factor for cardiovascular disease (CVD) morbidity/mortality. Switching from high-efficacy lipid-lowering therapies (HETs) to simvastatin might lead to sub-optimal control of LDL-C. Our objective was to evaluate the impact of switching from HETs to generic simvastatin on LDL-C levels and LDL-C goal attainment among the high-risk primary and secondary prevention populations in the United Kingdom. METHODS: This retrospective cohort study was conducted using Clinical Practice Research Datalink database. Included were individuals with more than 2 months of prescriptions of the following HETs between August 1, 2004 and December 31, 2008: simvastatin/ezetimibe fixed dose (S/E), simvastatin and ezetimibe co-administration (S+E), atorvastatin and ezetimibe co-administration (A+E), rosuvastatin and ezetimibe co-administration (R+E), rosuvastatin monotherapy, and atorvastatin monotherapy. For each baseline HET, we used analysis of covariance (ANCOVA) to estimate the least squares mean (LSM) difference in the percentage change from baseline in LDL-C between switchers and non-switchers, and logistic regression to estimate the odds ratio of attaining the LDL-C goal (<3 mmol/L for primary prevention and <2 mmol/L for secondary prevention, by JBS2) at follow-up. Propensity score adjusted analyses were conducted to reduce selection bias. FINDINGS: 30,148 patients met the eligibility criteria with 83.8% received atorvastatin, 9.5% rosuvastatin and 2.6% S/E and S+E combined. 89.1% of patients switching from atorvastatin switched to an equivalent or higher dose of simvastatin (dose equivalency was determined by relative efficacy of one statin to other statins), while 100% of those switching from simvastatin/ezetimibe and 96.8% of those switching from rosuvastatin switched to lower than equivalent dose of simvastatin. Compared to non-switchers, the adjusted least squares mean differences in the percentage change in LDL-C levels from baseline were 18.74% (p = 0.0003), 16.73% (p < 0.0001), and -0.11% (p = 0.9044) when switching from simvastatin/ezetimibe, rosuvastatin, and atorvastatin, respectively. The odds of LDL-C goal attainment at follow-up among switchers from simvastatin/ezetimibe, rosuvastatin, and atorvastatin were 0.40 (95% CI: 0.23-0.70), 0.36 (95% CI: 0.26-0.51) and 1.03 (95% CI: 0.92-1.15) relative to non-switchers respectively. IMPLICATIONS: Among the high risk CVD population in UK, switching to simvastatin from HET, especially rosuvastatin and simvastatin/ezetimibe, resulted in an increase in LDL-C levels and lower goal attainment. These historical data reinforce the appropriateness of the changes in the new Joint British Guideline (JBS3) which no longer recommends starting simvastatin 40 mg.