Effect of phosphodiesterase type 5 inhibitors on major adverse cardiovascular events and overall mortality in a large nationwide cohort of men with erectile dysfunction and cardiovascular risk factors: A retrospective, observational study based on healthcare claims and national death index data.

BACKGROUND: Treatment with phosphodiesterase type 5 inhibitors (PDE-5is) is effective in treating erectile dysfunction (ED). AIM: The objective of this study was to determine the effect of PDE-5is on the incidence of major adverse cardiovascular (CV) events (MACE; composite outcome of CV death, hospitalization for myocardial infarction, coronary revascularization, stroke, heart failure, and unstable angina pectoris) and overall mortality. METHODS: A retrospective observational cohort study was conducted in a large US claims database in men with ≥1 diagnosis of ED without prior MACE within 1 year, from January 1, 2006, to October 31, 2020. The exposed group had ≥1 claim for PDE-5i and the unexposed group had no claims for PDE-5i, and the groups were matched up to 1:4 on baseline risk variables. OUTCOME: The primary outcome was MACE and the secondary outcomes were overall mortality and individual components of MACE, determined by multivariable Cox proportional hazard modeling. RESULTS: Matched plus multivariable analyses showed that MACE was lower by 13% in men exposed (n = 23 816) to PDE-5is (hazard ratio [HR] 0.87; 95% CI 0.79-0.95; P = .001) vs nonexposure (n = 48 682) over mean follow-up periods of 37 and 29 months, respectively, with lower incidence of coronary revascularization (HR 0.85; 95% CI 0.73-0.98; P = .029), heart failure (HR 0.83; 95% CI 0.72-0.97; P = .016), unstable angina (HR 0.78; 95% CI 0.64-0.96; P = .021), and CV death (HR 0.61; 95% CI 0.41-0.90; P = .014) with PDE-5i exposure. Phosphodiesterase type 5 inhibitor-exposed men had a 25% lower incidence of overall mortality (HR 0.75; 95% CI 0.65-0.87; P < .001). Men without coronary artery disease (CAD) but with CV risk factors at baseline showed a similar pattern. In the main study cohort, men in the highest quartile of PDE-5i exposure had the lowest incidence of MACE (HR 0.45; 95% CI 0.37-0.54; P < .001) and overall mortality (HR 0.51; 95% CI 0.37-0.71; P < .001) vs the lowest exposure quartile. In a subgroup with baseline type 2 diabetes (n = 6503), PDE-5i exposure was associated with a lower MACE risk (HR 0.79; 95% CI 0.64-0.97; P = .022). CLINICAL IMPLICATIONS: PDE-5is may have cardioprotective effects. STRENGTHS AND LIMITATIONS: Strengths are the large numbers of participants and consistency of the data; limitations include the retrospective nature of the study and unknown confounders. CONCLUSIONS: In a large population of US men with ED, PDE-5i exposure was associated with lower incidence of MACE, CV death, and overall mortality risk compared to non-exposure. Risk reduction correlated with PDE-5i exposure level.

Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis.

BACKGROUND: Advanced systemic mastocytosis comprises rare hematologic neoplasms that are associated with a poor prognosis and lack effective treatment options. The multikinase inhibitor midostaurin inhibits KIT D816V, a primary driver of disease pathogenesis. METHODS: We conducted an open-label study of oral midostaurin at a dose of 100 mg twice daily in 116 patients, of whom 89 with mastocytosis-related organ damage were eligible for inclusion in the primary efficacy population; 16 had aggressive systemic mastocytosis, 57 had systemic mastocytosis with an associated hematologic neoplasm, and 16 had mast-cell leukemia. The primary outcome was the best overall response. RESULTS: The overall response rate was 60% (95% confidence interval [CI], 49 to 70); 45% of the patients had a major response, which was defined as complete resolution of at least one type of mastocytosis-related organ damage. Response rates were similar regardless of the subtype of advanced systemic mastocytosis, KIT mutation status, or exposure to previous therapy. The median best percentage changes in bone marrow mast-cell burden and serum tryptase level were -59% and -58%, respectively. The median overall survival was 28.7 months, and the median progression-free survival was 14.1 months. Among the 16 patients with mast-cell leukemia, the median overall survival was 9.4 months (95% CI, 7.5 to not estimated). Dose reduction owing to toxic effects occurred in 56% of the patients; re-escalation to the starting dose was feasible in 32% of those patients. The most frequent adverse events were low-grade nausea, vomiting, and diarrhea. New or worsening grade 3 or 4 neutropenia, anemia, and thrombocytopenia occurred in 24%, 41%, and 29% of the patients, respectively, mostly in those with preexisting cytopenias. CONCLUSIONS: In this open-label study, midostaurin showed efficacy in patients with advanced systemic mastocytosis, including the highly fatal variant mast-cell leukemia. (Funded by Novartis Pharmaceuticals and others; ClinicalTrials.gov number, NCT00782067.).

Prasugrel but not high dose clopidogrel overcomes the lansoprazole neutralizing effect of P2Y12 inhibition: Results of the randomized DOSAPI study.

AIMS: The potential negative metabolic interaction between proton pump inhibitors and clopidogrel is an unsolved issue. We hypothesized that doubling the clopidogrel maintenance dose (150 mg) would be less effective than switching to prasugrel 10 mg maintenance dose (MD) to overcome this negative interaction. METHOD AND RESULTS: In a randomized study with a factorial design, 82 stable coronary artery disease patients treated with 75 mg clopidogrel MD and aspirin were assigned to receive in a double blind fashion lansoprazole (30 mg/day) or placebo and to receive in an open fashion 150 mg clopidogrel MD or 10 mg prasugrel MD. The primary endpoint was the relative change in residual platelet reactivity over the 14-day study period [(RPA14day-RPAbaseline)/RPAbaseline]. The effect of doubling the clopidogrel MD on relative change in RPA was neutralized by lansoprazole (-53.6±48.4% versus +0.8±53.7% without and with lansoprazole, respectively, p = 0.02) whereas 10 mg of prasugrel MD dramatically reduced RPA irrespective of lansoprazole co-administration (-81.8 %±24.8% vs. -72.9%±32.9% without and with lansoprazole, respectively, p = NS). Lansoprazole exposure was the only parameter with a significant interaction with RPA among subgroups. CONCLUSION: The higher platelet inhibitory effect obtained by doubling the clopidogrel MD was totally neutralized by the co-administration of lansoprazole. This drug interaction was not observed with prasugrel 10 mg.

The association of tadalafil exposure with lower rates of major adverse cardiovascular events and mortality in a general population of men with erectile dysfunction.

BACKGROUND: Tadalafil is a long-acting phosphodiesterase-5 inhibitor (PDE-5i) indicated for erectile dysfunction (ED). HYPOTHESIS: Our hypothesis was that tadalafil will reduce the risk of major adverse cardiovascular events (MACE: composite of cardiovascular death, myocardial infarction, coronary revascularization, unstable angina, heart failure, stroke) and all-cause death in men with ED. METHODS: A retrospective observational cohort study was conducted in a large US commercial insurance claims database in men with a diagnosis of ED without prior MACE within 1 year. The exposed group (n = 8156) had ≥1 claim for tadalafil; the unexposed group (n = 21 012) had no claims for any PDE-5i. RESULTS: Primary outcome was MACE; secondary outcome was all-cause death. Groups were matched for cardiovascular risk factors, including preventive therapy. Over a mean follow-up of 37 months for the exposed group and 29 months for the unexposed group, adjusted rates of MACE were 19% lower in men exposed to tadalafil versus those unexposed to any PDE-5i (hazard ratio [HR] = 0.81; 95% confidence intervals [CI] = 0.70-0.94; p = .007). Tadalafil exposure was associated with lower adjusted rates of coronary revascularization (HR = 0.69; 95% CI = 0.52-0.90; p = .006); unstable angina (HR = 0.55; 95% CI = 0.37-0.81; p = .003); and cardiovascular-related mortality (HR = 0.45; CI = 0.22-0.93; p = .032). Overall mortality rate was 44% lower in men exposed to tadalafil (HR = 0.56; CI = 0.43-0.74; p < .001). Men in the highest quartile of tadalafil exposure had the lowest rates of MACE (HR: 0.40; 95% CI: 0.28-0.58; p < .001) compared to lowest exposure quartile. CONCLUSION: In men with ED, exposure to tadalafil was associated with significant and clinically meaningful lower rates of MACE and overall mortality.

Paradoxical progression of atherosclerosis related to low-density lipoprotein reduction and exposure to ezetimibe.

AIMS: Ezetimibe reduces low-density lipoprotein cholesterol (LDL-C) but has complex actions on cholesterol transport and metabolism, and thus, LDL-C reduction may not solely define its overall effects. We explored the relationship between treatment effects and cumulative exposure to ezetimibe, with its effects on carotid intima-media thickness (CIMT) in ARBITER 6-HALTS. METHODS AND RESULTS: This analysis includes the 159 patients randomized to ezetimibe within ARBITER 6-HALTS that completed the final imaging endpoint assessment. Eligibility criteria for ARBITER 6-HALTS included known coronary artery disease (CAD) or high risk for coronary heart disease, and treatment with a statin with LDL-C <100 mg/dL and high-density lipoprotein cholesterol <50 or 55 mg/dL for men and women, respectively. The mean CIMT was measured in the far wall of the distal common carotid artery. We analysed the univariate and multivariate relationships of the change in CIMT with baseline characteristics, on-treatment effects, and cumulative ezetimibe exposure (treatment duration × dose × adherence). Ezetimibe reduced LDL-C from 84 ± 23 to 66 ± 20 mg/dL. No net effect on CIMT was observed (baseline CIMT 0.898 ± 0.151 mm; net change -0.002 mm; P = 0.52). There was an inverse relationship between LDL-C and change in CIMT such that greater reductions in LDL-C were associated with greater CIMT progression (r = -0.266; P < 0.001). Change in CIMT also had univariate associations with baseline LDL-C, triglycerides (TG), high-sensitive C-reactive protein, and systolic blood pressure and was directly associated with the change in TG and inversely associated with the change in high-sensitive C-reactive protein. Multivariable models controlling for change in LDL-C, cumulative ezetimibe exposure, and baseline and on-treatment variables showed that both increased LDL-C reduction (P = 0.005) and cumulative drug exposure (P = 0.02) were associated with ezetimibe-associated CIMT progression. CONCLUSION: Among CAD and high-risk patients on statin therapy in the ARBITER-6 trial, ezetimibe leads to paradoxical progression of CIMT in association with both greater LDL-C reduction and cumulative drug exposure. These findings may suggest the presence of off-target actions of ezetimibe. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00397657.

A new wearable diagnostic home sleep testing platform: comparison with available systems and benefits of multinight assessments.

STUDY OBJECTIVES: We assessed the real-world performance of the ANNE Sleep system against 2 Food and Drug Administration-cleared home sleep testing platforms and the intraindividual night-to-night variability of respiratory event index measured by ANNE Sleep. METHODS: We evaluated the home performance of the ANNE Sleep system compared with 2 Food and Drug Administration-cleared home sleep testing platforms (WatchPAT: n = 29 and Alice NightOne: n = 46) during a synchronous night with unsupervised patient application. Additionally, we evaluated night-to-night variability of respiratory event index and total sleep time using the ANNE Sleep system (n = 30). RESULTS: For the diagnosis of moderate and severe obstructive sleep apnea, the ANNE Sleep system had a positive percent agreement of 58% (95% confidence interval, 28-85%) and a negative percent agreement of 100% (95% confidence interval, 80-100%) compared to WatchPAT. The positive and negative percent agreement for ANNE Sleep vs Alice NightOne was 85% (95% confidence interval, 66-96%) and 95% (95% confidence interval, 74-100%). There were no differences in mean total sleep time or respiratory event index across multiple nights of monitoring with ANNE. There were no differences consistent with a first-night effect but testing multiple nights reclassified obstructive sleep apnea severity in 5 (17%) individuals and detected 3 additional cases of moderate disease, with only a 12% (standard deviation, 28%) mean fluctuation in respiratory event index from the first night of testing compared to a mean of multiple nights. Overall, 80% of users found ANNE comfortable and easy to use. CONCLUSIONS: ANNE Sleep exhibited stronger concordance with Alice NightOne compared to WatchPAT. While we illustrated low night-to-night variability for ANNE Sleep, the results suggest multiple nights increased detection of moderate or severe obstructive sleep apnea. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: ANNE Diagnostic Agreement With Home Sleep Testing; URL: https://clinicaltrials.gov/ct2/show/NCT05421754; Identifier: NCT05421754. CITATION: Walter J, Lee JY, Blake S, et al. A new wearable diagnostic home sleep testing platform: comparison with available systems and benefits of multinight assessments. J Clin Sleep Med. 2023;19(5):865-872.

Extended-release niacin or ezetimibe and carotid intima-media thickness.

BACKGROUND: Treatment added to statin monotherapy to further modify the lipid profile may include combination therapy to either raise the high-density lipoprotein (HDL) cholesterol level or further lower the low-density lipoprotein (LDL) cholesterol level. METHODS: We enrolled patients who had coronary heart disease or a coronary heart disease risk equivalent, who were receiving long-term statin therapy, and in whom an LDL cholesterol level under 100 mg per deciliter (2.6 mmol per liter) and an HDL cholesterol level under 50 mg per deciliter for men or 55 mg per deciliter for women (1.3 or 1.4 mmol per liter, respectively) had been achieved. The patients were randomly assigned to receive extended-release niacin (target dose, 2000 mg per day) or ezetimibe (10 mg per day). The primary end point was the between-group difference in the change from baseline in the mean common carotid intima-media thickness after 14 months. The trial was terminated early, on the basis of efficacy, according to a prespecified analysis conducted after 208 patients had completed the trial. RESULTS: The mean HDL cholesterol level in the niacin group increased by 18.4% over the 14-month study period, to 50 mg per deciliter (P < 0.001), and the mean LDL cholesterol level in the ezetimibe group decreased by 19.2%, to 66 mg per deciliter (1.7 mmol per liter) (P < 0.001). Niacin therapy significantly reduced LDL cholesterol and triglyceride levels; ezetimibe reduced the HDL cholesterol and triglyceride levels. As compared with ezetimibe, niacin had greater efficacy regarding the change in mean carotid intima-media thickness over 14 months (P = 0.003), leading to significant reduction of both mean (P = 0.001) and maximal carotid intima-media thickness (P < or = 0.001 for all comparisons). Paradoxically, greater reductions in the LDL cholesterol level in association with ezetimibe were significantly associated with an increase in the carotid intima-media thickness (R = -0.31, P < 0.001). The incidence of major cardiovascular events was lower in the niacin group than in the ezetimibe group (1% vs. 5%, P = 0.04 by the chi-square test). CONCLUSIONS: This comparative-effectiveness trial shows that the use of extended-release niacin causes a significant regression of carotid intima-media thickness when combined with a statin and that niacin is superior to ezetimibe. (ClinicalTrials.gov number, NCT00397657.)

Healthcare resource utilization and cost of obstructive hypertrophic cardiomyopathy in a US population.

Background: There are limited data evaluating all-cause and disease-related healthcare resource utilization (HCRU) and cost of care for patients with obstructive hypertrophic cardiomyopathy (oHCM). Methods: This was a retrospective study using US longitudinal medical and pharmacy claims data during 2012-2020. Adults with ≥2 oHCM diagnoses were identified, with the first diagnosis date used as the index date. HCRU and costs of care were reported for the year preindex (baseline) and at 1- and 2-year follow-ups. Results: We identified 1841 patients with oHCM (63 ± 15 years; 52% male). The mean number of hypertrophic cardiomyopathy (HCM)-related outpatient and cardiology visits increased from baseline to 1-year follow-up (2.3 vs. 7.8 and 0.6 vs. 2.2, respectively). At baseline, 8% of patients had ≥1 HCM-related inpatient hospitalization (mean 0.11 visits, 5.4 days length of stay), increasing to 27% postdiagnosis (mean 0.42 visits, 5.9 days length of stay). Total HCM-related costs increased from $5968 to $20,290 at 1-year follow-up, largely driven by inpatient hospitalization costs ($3889 vs. $14,369) and surgical costs ($2259 vs. $7217). The proportion with ≥1 HCM-related prescription increased from baseline (69%; mean fills 5.3) to 1-year follow-up (82%; mean fills 7.8). Pharmacy costs were generally low but also increased ($449 vs. $752). Conclusions: This benchmark economic dataset for management and evaluation of patients with oHCM shows increased HCM-related costs over a 2-year period after oHCM diagnosis, driven by inpatient hospitalizations and surgical costs. Medication use was high, but costs were low, possibly reflecting use of generic multi-indication drugs for oHCM treatment.

Characteristics of Patients With Obstructive Hypertrophic Cardiomyopathy in Real-World Community-Based Cardiovascular Practices.

The clinical profile of patients with obstructive hypertrophic cardiomyopathy (oHC) is not well characterized, with little evidence outside selected referral populations. Using longitudinal medical claims data from a United States nationwide database, we retrospectively identified adults who were newly diagnosed with oHC. Clinical characteristics were compared from 1 year before diagnosis and at the 2-year follow-up. Patients (N = 1,841) with oHC (age 63 ± 15 years; 52% were male) with geographic representation across the United States were identified. Most patients received care within community-based cardiovascular practices and 7% at referral hypertrophic cardiomyopathy (HC) centers. Baseline diagnostic procedures included electrocardiogram (66%), echocardiogram (51%), magnetic resonance imaging (4%), and HC genetic testing (0.7%). Baseline co-morbidities were hypertension (59%), coronary artery disease (30%), diabetes (19%), and atrial fibrillation (19%). For all HC-related medications, use significantly increased after diagnosis. During follow-up, 144 patients (8%) received an implantable cardioverter-defibrillator for sudden death prevention, 99 underwent septal myectomy (5%), and 24 underwent alcohol septal ablation (1%). By the 1-year follow-up, 2% of patients had sudden cardiac arrest and 26% had atrial fibrillation, and heart failure increased from 16% to 27%. In conclusion, in a community-based population of patients with oHC, patients' age at diagnosis of oHC was older than reported for referral populations and patients had a significant co-morbidity burden. Cardiovascular medication use was appropriate, but the rate of guideline-supported surgical procedures was low.

Costs and Healthcare Resource Utilization for Obstructive Hypertrophic Cardiomyopathy With Septal Reduction Therapy.

BACKGROUND: Patients with obstructive hypertrophic cardiomyopathy (oHCM) and severe refractory symptoms may require invasive septal reduction therapies (SRTs), either surgical septal myectomy (SM) or transcatheter alcohol septal ablation (ASA). The main objective of this study was to quantify all-cause and oHCM-related healthcare resource utilization (HCRU) and costs for patients receiving SM or ASA. METHODS: This retrospective study utilized medical and pharmacy claims submitted during 2012-2020. HCRU and costs for 119 adults with oHCM who had at least 1 SM (n = 95) or ASA (n = 24) were compared for baseline and follow-up periods. RESULTS: The mean inpatient hospitalization stay was longer for SM (8.3 days) than ASA (6.0 days). Postprocedure HCM-related medication usage was greater following SM (98%) than ASA (88%). The mean number of HCM-related outpatient visits increased from pre- to post procedure (12.2 vs 15.9 in the SM group; 7.2 vs 9.5 in the ASA group), with most patients having at least 1 cardiology visit post procedure (86% of the SM group; 83% of the ASA group). Total mean HCM-related costs (reported in United States currency) increased with both procedures ($27,045 vs $119,772 in the SM group; $11,278 vs $54,351 in the ASA group), driven by increased inpatient hospitalization ($10,325 vs $112,923 in the SM group; $5509 vs $47,450 in the ASA group) and surgical costs ($6665 vs $92,031 in the SM group; $52 vs $44,815 in the ASA group). CONCLUSIONS: Our results indicate increasing costs for patients undergoing SRT, driven by inpatient hospitalizations and surgical costs. Commercially insured and Medicare Advantage patients with oHCM experience high healthcare costs and economic burden attributable to SRT.

A single-arm, open-label, multicenter, and comparative study of the ANNE sleep system vs polysomnography to diagnose obstructive sleep apnea.

STUDY OBJECTIVES: Evaluate per-patient diagnostic performance of a wireless dual-sensor system (ANNE sleep) compared with reference standard polysomnography (PSG) for the diagnosis of moderate and severe obstructive sleep apnea (OSA) with a minimum prespecified threshold of 80% for both sensitivity and specificity. METHODS: A multicenter clinical trial was conducted to evaluate ANNE sleep vs PSG to diagnose moderate and severe OSA in individuals 22 years or older. For each testing approach, apnea-hypopnea index (AHI) was manually scored and averaged by 3 registered sleep technologists blinded to the other system. Average variations > 15% were adjudicated by a sleep medicine physician. RESULTS: In a total of n = 225 participants (mean age 53 years, range 22-88 years), PSG diagnosed 30% (n = 68) of participants with moderate or severe OSA (AHI ≥ 15 events/h) compared to 29% (n = 65) diagnosed by ANNE sleep (P = .55). The sensitivity and specificity for ANNE sleep were 90% (95% confidence interval: 80-96%) and 98% (95% confidence interval: 94-99%), respectively. Strong correlation was shown in terms of final AHI (r = .93), with an average AHI bias of 0.5 (95% limits of agreement: -12.8 to 11.8). The majority of users noted comfort with using the ANNE sleep in the home setting. No adverse events were noted. CONCLUSIONS: Using PSG as the gold standard, ANNE sleep demonstrated high sensitivity and specificity for the diagnosis of moderate or severe OSA. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Comparative Study of the ANNE™ One System to Diagnose Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT04643782; Identifier: NCT04643782. CITATION: Davies C, Lee JY, Walter J et al. A single-arm, open-label, multicenter, and comparative study of the ANNE sleep system vs polysomnography to diagnose obstructive sleep apnea. J Clin Sleep Med. 2022;18(12):2703-2712.

Cost-Effectiveness of a Proteomic Test for Preterm Birth Prediction.

BACKGROUND: Preterm birth (PTB) carries increased risk of short- and long-term health problems as well as higher healthcare costs. Current strategies using clinically accepted maternal risk factors (prior PTB, short cervix) can only identify a minority of singleton PTBs. OBJECTIVE: We modeled the cost-effectiveness of a risk-screening-and-treat strategy versus usual care for commercially insured pregnant US women without clinically accepted PTB risk factors. The risk-screening-and-treat strategy included use of a novel PTB prognostic blood test (PreTRM®) in the 19th-20th week of pregnancy, followed by treatment with a combined regimen of multi-component high-intensity-case-management and pharmacologic interventions for the remainder of the pregnancy for women assessed as higher-risk by the test, and usual care in women without higher risk. METHODS: We built a cost-effectiveness model using a combined decision-tree/Markov approach and a US payer perspective. We modeled 1-week cycles of pregnancy from week 19 to birth (preterm or term) and assessed costs throughout the pregnancy, and further to 12-months post-delivery in mothers and 30-months in infants. PTB rates and costs were based on >40,000 mothers and infants from the HealthCore Integrated Research Database® with birth events in 2016. Estimates of test performance, treatment effectiveness, and other model inputs were derived from published literature. RESULTS: In the base case, the risk-screening-and-treat strategy dominated usual care with an estimated 870 fewer PTBs (20% reduction) and $54 million less in total cost ($863 net savings per pregnant woman). Reductions were projected for neonatal intensive care admissions (10%), overall length-of-stay (7%), and births <32 weeks (33%). Treatment effectiveness had the strongest influence on cost-effectiveness estimates. The risk-screening-and-treat strategy remained dominant in the majority of probabilistic sensitivity analysis simulations and model scenarios. CONCLUSION: Use of a novel prognostic test during pregnancy to identify women at risk of PTB combined with evidence-based treatment is estimated to reduce total costs while preventing PTBs and their consequences.

Clinical Diagnosis of Hypertrophic Cardiomyopathy Over Time in the United States (A Population-Based Claims Analysis).

Hypertrophic cardiomyopathy (HC) is a common genetic heart disease. However, the number of gene mutation carriers who develop HC and manifest clinical symptoms is not well established. Our objective was to estimate annual prevalence and incidence rates of clinically diagnosed HC in the United States. Data from the HealthCore Integrated Research Database (HIRD) were interrogated for years 2013-2019 to identify patients with ≥1 claim of HC International Classification of Diseases, Clinical Modification Ninth and Tenth Revision diagnosis codes. In 2013, among 16,243,109 patients, 8,526 were identified with HC, yielding an estimated prevalence of clinically diagnosed HC of 0.052% (0.035% for obstructive [oHC], 0.017% for nonobstructive [nHC]). This prevalence yielded an estimated 164,403 patients with clinical diagnosis of HC. For the same year, the incidence of new HC diagnoses was 0.030% (0.020% for oHC, 0.010% for nHC). Over the following 6 years, prevalence and incidence of HC increased by 0.005%/year (p <0.01) and 0.001%/year (p <0.01), respectively, with an estimated 262,591 patients with a clinical diagnosis of HC in 2019. Over this period, incidence of nHC increased (0.012% vs 0.026%, p <0.01), whereas incidence of oHC decreased (0.020% versus 0.015%, p <0.01). In conclusion, over 6 years, the number of patients with clinically diagnosed HC in the United States increased 1.5-fold to ∼262,591, primarily because of a rise in nHC diagnoses. These prevalence data support further investigation to better understand factors accounting for increasing clinical recognition of HC.

Achievement of optimal combined lipid values in a managed care setting: is a new treatment paradigm needed?

BACKGROUND: Published guidelines suggest the management of high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) values after the low-density lipoprotein cholesterol (LDL-C) goal is achieved. OBJECTIVE: This study evaluated the attainment of optimal combined lipid values (LDL-C, HDL-C, and TGs) and associated therapy over time. METHODS: This retrospective cohort analysis was conducted among managed-care patients who had a baseline lipid panel taken between October 1, 1999, and September 30, 2000; were naive to lipid therapy; and had plan eligibility for at least 12 months before and 12 to 36 months after the baseline lipid values. Patients were categorized as elevated-risk primary prevention (ERP) or as coronary heart disease (CHD) and CHD risk equivalents (CHD-RE). The attainment of optimal combined lipid values was assessed at baseline and quarterly thereafter. Associations between lipid values and the use of lipid-altering therapy were assessed using multivariate logistic regression. RESULTS: A total of 30,348 patients were monitored for a mean (SD) duration of 27 (8) months. Mean (SD) age was 66 (12) years and 55% (16,549/30,348) were men; 43% (13,059/30,348) were categorized as ERP and 57% (17,289/30,348) as CHD-RE. Combined lipid values were optimal in 14% (4167/30,348),18% (5508/30,348), and 22% (2936/13,100) of patients at baseline, 12 months, and 36 months, respectively. After 36 months, 78% (10,164/13,100) of patients did not attain optimal combined lipid values. Lipid therapy, primarily statin monotherapy (87% [7992/ 92251), was prescribed in 30% (9225/30,348) of patients. After 36 months, 34% (4492/13,100) of patients had isolated elevated LDL-C and 20% (2588/13,100) had non-optimal HDL-C and/or TGs. Lipid therapy was associated with the attainment of optimal combined values for LDL-C and TGs (both, P < 0.05), but not for HDL-C. Because the study was retrospective, causality cannot be determined. CONCLUSIONS: Based on the results of this study, use of combination lipid therapy and targeted therapy aimed at the specific lipid abnormalities may increase the attainment of optimal lipid parameters.

Opportunity for intervention to achieve American Heart Association guidelines for optimal lipid levels in high-risk women in a managed care setting.

BACKGROUND: The American Heart Association (AHA) recently established evidence-based recommendations for cardiovascular disease (CVD) prevention in women, including lipid management. This study evaluated optimal lipid-level attainment and treatment patterns on the basis of these guidelines in high-risk women in a managed care setting. METHODS AND RESULTS: We conducted a historical prospective cohort analysis of a 1.1-million-member, integrated, managed-care database. Eligible high-risk women were those with evidence of previous CVD or risk equivalent who had a full lipid panel available between October 1, 1999, and September 30, 2000; were naive to lipid therapy; and had a minimum of 12 months health plan eligibility preindex and postindex lipid panel. Optimal lipid levels were defined as LDL cholesterol (LDL-C) <100 mg/dL, HDL cholesterol (HDL-C) >50 mg/dL, non-HDL-C <130 mg/dL, and triglycerides <150 mg/dL. Laboratory values and lipid pharmacotherapy were assessed longitudinally over the postindex follow-up (up to 36 months). A total of 8353 high-risk women (mean age, 66+/-14 years) with a mean follow-up of 27+/-8 months were included. Only 7% attained optimal combined lipid levels initially, and this increased to 12% after 36 months. Lipid-modifying therapy was initiated in 32% of patients, including 35% of women with LDL-C > or =100 mg/dL and 15% with LDL-C <100 mg/dL. CONCLUSIONS: Among high-risk women, few attained the AHA's standards for all lipid fractions, and only one third received recommended drug therapy, highlighting significant opportunities to apply evidence-based recommendations to manage lipid abnormalities in high-risk women.

An Internet-based Controlled Trial Aimed to Improve Osteoporosis Prevention among Chronic Glucocorticoid Users.

OBJECTIVE: To address the low prevention and treatment rates for those at risk of glucocorticoid-induced osteoporosis (GIOP), we evaluated the influence of a direct-to-patient, Internet-based educational video intervention using "storytelling" on rates of antiosteoporosis medication use among chronic glucocorticoid users who were members of an online pharmacy refill service. METHODS: We identified members who refilled ≥ 5 mg/day of prednisone (or equivalent) for 90 contiguous days and had no GIOP therapy for ≥ 12 months. Using patient stories, we developed an online video addressing risk factors and treatment options, and delivered it to members refilling a glucocorticoid prescription. The intervention consisted of two 45-day "Video ON" periods, during which the video automatically appeared at the time of refill, and two 45-day "Video OFF" periods, during which there was no video. Members could also "self-initiate" watching the video by going to the video link. We used an interrupted time series design to evaluate the effectiveness of this intervention on GIOP prescription therapies over 6 months. RESULTS: Among 3017 members (64.8%) exposed to the intervention, 59% had measurable video viewing time, of which 3% "self-initiated" the video. The GIOP prescription rate in the "Video ON" group was 2.9% versus 2.7% for the "Video OFF" group. There was a nonsignificant trend toward greater GIOP prescription in members who self-initiated the video versus automated viewing (5.7% vs 2.9%, p = 0.1). CONCLUSION: Among adults at high risk of GIOP, prescription rates were not significantly affected by an online educational video presented at the time of glucocorticoid refill. ClinicalTrials.gov Identifier: NCT01378689.

Effectiveness of aggressive management of dyslipidemia in a collaborative-care practice model.

The Cardiovascular Risk Identification and Treatment Center was established in 1997, adopting a collaborative-care clinic model for the purpose of improving the management of high-risk patients with dyslipidemia. This was a retrospective analysis of 417 high-risk patients with > or =1 year of follow-up laboratory data. Analysis included changes in total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, triglycerides, and total cholesterol to HDL ratio; lipoprotein goal achievement; Framingham risk score; liver function; and cardiovascular events. At baseline, 66% of patients had coronary heart disease (CHD) or equivalent risk, 45% were not receiving dyslipidemia therapy, and 29% were on statin monotherapy. After 3 years in the program, 56% were receiving combination therapy, 41% were on monotherapy, and 2% were not on therapy. The 3 most common treatment regimens were statin plus niacin (36%), statin alone (22%), and niacin alone (14%). All lipoproteins improved from baseline (p <0.001). Overall, 62% to 74% of patients reached singular lipid goals and 35% achieved combined lipid goals. Patients with Framingham 10-year CHD risk of >20% were reduced from 6% to <1%. Only 29 patients (7.0%) had a cardiovascular event, including 5 (1.0%) who experienced a myocardial infarction. Aspartate aminotransferase/alanine transferase elevation >3 times normal occurred in 1% of patients. In conclusion, a collaborative-care practice model adopting individualized, aggressive pharmacologic and nonpharmacologic treatment strategies is highly effective in achieving lipid goals, is sustainable, and is safe. Furthermore, this approach yields reduced projected 10-year CHD risk. A low rate of cardiovascular events was observed.

Sigmoidal maximal effect modeling of low-density lipoprotein cholesterol concentration and annual incidence of coronary heart disease events in secondary prevention trials.

STUDY OBJECTIVES: To evaluate the relationship between low-density lipoprotein cholesterol (LDL-C) concentration and the annual incidence of combined coronary heart disease (CHD) events­death or nonfatal myocardial infarction (NFMI)­by using sigmoidal maximal effect (sEmax) modeling of published data in various populations at risk for CHD events, and to use the best performing sEmax model generated to calculate the number needed to treat (NNT) to prevent a single CHD death or NFMI event across a range of LDL-C concentrations. DESIGN: Literature-based modeling analysis. PATIENTS: A total of 95,955 patients from 22 published cardiovascular secondary prevention trials. MEASUREMENTS AND MAIN RESULTS: Four distinct sEmax models were created based on intervention approach and CHD event risk for each trial population. Model outputs included the following: Emax (maximum CHD death/NFMI rate), E0 (minimum CHD death/NFMI rate), and fit parameters. The best-fitting sEmax model was compared with linear, log-linear, and logit models, and it was used for calculation of annualized NNT to prevent one CHD death or NFMI event with statins. The best fitting sEmax model was constructed from nine statin intervention trials in 60,483 clinically stable patients with CHD or CHD risk equivalents (Emax = 4.84%/year [95% confidence interval (CI) 4.11­5.41%/year], E0 = 1.24%/year [95% CI 0.64­1.83%/year]) and was superior to linear, log-linear, and logit models. Reduction of CHD death/NFMI incidence diminished at an LDL-C level near 90 mg/dl and became near static at an LDL-C level of 60­70 mg/dl. Annual NNT for LDL-C reduction from a baseline of 130­100 mg/dl, 90, and 70 mg/dl was 129, 104, and 83, respectively, and from a baseline of 100­70 mg/dl was 232. CONCLUSION: An sEmax model fully characterized the relationship between LDL-C concentration and incidence of CHD death or NFMI in a high-risk population receiving statins, with diminishing event reduction at an LDL-C level less than 90 mg/dl, and limited projected event reduction beyond an LDL-C level of ~60­70 mg/dl. As baseline LDL-C level declines, the NNT sharply increases.

Statin use in asthmatics on inhaled corticosteroids is associated with decreased risk of emergency department visits.

OBJECTIVE: Statins are hypothesized to have beneficial effects in asthma management through their pleiotropic anti-inflammatory effects. Several studies have examined this relationship, but have yielded conflicting results. This study investigates the effect of statin use on asthma-related hospitalizations and/or emergency department (ED) visits, and whether this relationship varies by concomitant inhaled corticosteroid (ICS) in a large cohort of asthma patients. METHODS: Subjects with asthma, a recent history of asthma exacerbation, and who were 18 years or older were selected from the population-based Medco Health Solutions administrative database over a 1 year period. Prescription claims for statins and asthma medications, and asthma-related hospitalizations and/or ED visits were ascertained over a 12 month follow-up period. Subjects were stratified into two groups based on their ICS use. RESULTS: A total of 3747 ICS users and 2905 non-ICS users were included in this study. Statin users represented 21% of ICS users and 11% of non-users. Among ICS users, statin use was significantly associated with decreased odds of asthma-related ED visits (OR = 0.77, 95% CI 0.64-0.94, p = 0.008), but not with asthma-related hospitalizations (OR = 1.09, 95% CI 0.92-1.30, p = 0.31). No significant associations were found among non-ICS users (for asthma-related ED visits: OR = 0.92, 95% CI 0.57-1.49, p = 0.73; asthma-related hospitalizations: OR = 1.10, 95% CI 0.85-1.41, p = 0.48). The statistical interactions between ICS and statin use on asthma-related hospitalizations and/or ED visits were not significant. CONCLUSION: Statin use is associated with fewer ED visits in asthma patients who are using ICS.

Physician Awareness and Utilization of Food and Drug Administration (FDA)-Approved Labeling for Pharmacogenomic Testing Information.

We surveyed 10,303 United States physicians on where they obtain pharmacogenomic testing information. Thirty-nine percent indicated that they obtained this from drug labeling. Factors positively associated with this response included older age, postgraduate instruction, using other information sources, regulatory approval/ recommendation of testing, reliance on labeling for information, and perception that patients have benefited from testing. Physicians use pharmacogenomic testing information from drug labeling, highlighting the importance of labeling information that is conducive to practice application.