Health Status after Invasive or Conservative Care in Coronary and Advanced Kidney Disease.

BACKGROUND: In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of <30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS: We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS: Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, -0.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, -2.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, -1.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, -2.2 to 3.4). CONCLUSIONS: Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy. (Funded by the National Heart, Lung, and Blood Institute; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

Health-Status Outcomes with Invasive or Conservative Care in Coronary Disease.

BACKGROUND: In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS: We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS: At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS: In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Variability in 30-day major amputation rates following endovascular peripheral vascular intervention for critical limb ischemia.

Introduction: Patients with critical limb ischemia (CLI) can undergo endovascular peripheral vascular intervention (PVI) to restore blood flow and decrease risk of amputation. As a potential indicator of quality for CLI care, we sought to describe 30-day major amputation rates following PVI. We also examined rate variability, and patient-level and site-level factors predicting amputations, using a national electronic health record (EHR) database. Methods: Using the Cerner Health Facts de-identified EHR database, patients with CLI diagnosis codes undergoing PVI were identified. The rate of amputation within 30 days of PVI was calculated. Risk ratios predicting amputation were derived using a mixed effects Poisson regression model adjusting for 16 patient and clinical factors. Median risk ratios (MRRs) were calculated to quantify site-level variability in amputations. Results: A total of 20,204 PVI procedures for CLI from 179 healthcare sites were identified. Mean age at procedure was 69.0 ± 12.6 years, 58.0% were male, and 29.6% were persons of color. Amputation within 30 days of PVI occurred after 570 (2.8%) procedures. Malnutrition, previous amputation, diabetes, and being of Black race were predictors of amputation. Amputation rates across sites ranged from 0.0% to 10.0%. The unadjusted MRR was 1.40 (95% CI 1.35-1.46), which was attenuated after adjusting for patient-level factors (MRR 1.30, 95% CI 1.26-1.34) and site characteristics (MRR 1.11, 95% CI 1.09-1.13). Conclusions: Among PVI procedures for CLI treatment, 30-day amputation rates varied across institutions. Although patient-level factors explained some variability, site-level factors explained most variation in the rates of these outcomes.

Heart failure documentation in outpatients with diabetes and volume overload: an observational cohort study from the Diabetes Collaborative Registry.

BACKGROUND: Heart failure is a common and devastating complication of type 2 diabetes (T2D). Prompt recognition of heart failure may avert hospitalization, facilitate use of guideline-directed therapies, and impact choice of T2D medications. We sought to determine the rate and factors associated with heart failure documentation in T2D patients with evidence of volume overload requiring loop diuretics. METHODS: DCR is an on-going, prospective US registry of outpatient T2D patients from > 5000 cardiology, endocrinology, and primary care clinicians (current analysis used data from 2013-2019). Among T2D patients receiving loop diuretics, we examined the rate of chart documentation of heart failure. We used a 3-level hierarchical logistic regression model (patients nested within physician within practice) to examine factors associated with heart failure diagnosis. RESULTS: Among 1,322,640 adults with T2D, 225,125 (17.0%) were receiving a loop diuretic, of whom 91,969 (40.9%) had documentation of heart failure. Male sex, lower body mass index, atrial fibrillation, chronic kidney disease, and coronary artery disease were associated with greater odds of heart failure diagnosis. After accounting for patient factors, patients seen by cardiologists were the most likely to have HF documented followed by PCPs and then endocrinologists. CONCLUSIONS: Among US outpatients with T2D, 17% of patients had evidence of volume overload-defined by loop diuretic prescription-of whom fewer than half had a clinical diagnosis of heart failure. While there may be non-heart failure indications for loop diuretics, our data suggest that a substantial proportion of T2D patients may have unrecognized heart failure and therefore could be missing opportunities for targeted therapies that could alter the clinical course of heart failure.

Association of Pediatric Medical Emergency Teams With Hospital Mortality.

BACKGROUND: Implementation of medical emergency teams has been identified as a potential strategy to reduce hospital deaths, because these teams respond to patients with acute physiological decline in an effort to prevent in-hospital cardiac arrest. However, prior studies of the association between medical emergency teams and hospital mortality have been limited and typically have not accounted for preimplementation mortality trends. METHODS: Within the Pediatric Health Information System for freestanding pediatric hospitals, annual risk-adjusted mortality rates were calculated for sites between 2000 and 2015. A random slopes interrupted time series analysis then examined whether implementation of a medical emergency team was associated with lower-than-expected mortality rates based on preimplementation trends. RESULTS: Across 38 pediatric hospitals, mean annual hospital admission volume was 15 854 (range, 6684-33 024), and there were a total of 1 659 059 hospitalizations preimplementation and 4 392 392 hospitalizations postimplementation. Before medical emergency team implementation, hospital mortality decreased by 6.0% annually (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.92-0.96) across all hospitals. After medical emergency team implementation, hospital mortality continued to decrease by 6% annually (OR, 0.94; 95% CI, 0.93-0.95), with no deepening of the mortality slope (ie, not lower OR) in comparison with the preimplementation trend, for the overall cohort (P=0.98) or when analyzed separately within each of the 38 study hospitals. Five years after medical emergency team implementation across study sites, there was no difference between predicted (hospital mean of 6.18 deaths per 1000 admissions based on preimplementation trends) and actual mortality rates (hospital mean of 6.48 deaths per 1000 admissions; P=0.57). CONCLUSIONS: Implementation of medical emergency teams in a large sample of pediatric hospitals in the United States was not associated with a reduction in hospital mortality beyond existing preimplementation trends.

SEP-363856, a Novel Psychotropic Agent with a Unique, Non-D2 Receptor Mechanism of Action.

For the past 50 years, the clinical efficacy of antipsychotic medications has relied on blockade of dopamine D2 receptors. Drug development of non-D2 compounds, seeking to avoid the limiting side effects of dopamine receptor blockade, has failed to date to yield new medicines for patients. In this work, we report the discovery of SEP-363856 (SEP-856), a novel psychotropic agent with a unique mechanism of action. SEP-856 was discovered in a medicinal chemistry effort utilizing a high throughput, high content, mouse-behavior phenotyping platform, in combination with in vitro screening, aimed at developing non-D2 (anti-target) compounds that could nevertheless retain efficacy across multiple animal models sensitive to D2-based pharmacological mechanisms. SEP-856 demonstrated broad efficacy in putative rodent models relating to aspects of schizophrenia, including phencyclidine (PCP)-induced hyperactivity, prepulse inhibition, and PCP-induced deficits in social interaction. In addition to its favorable pharmacokinetic properties, lack of D2 receptor occupancy, and the absence of catalepsy, SEP-856's broad profile was further highlighted by its robust suppression of rapid eye movement sleep in rats. Although the mechanism of action has not been fully elucidated, in vitro and in vivo pharmacology data as well as slice and in vivo electrophysiology recordings suggest that agonism at both trace amine-associated receptor 1 and 5-HT1A receptors is integral to its efficacy. Based on the preclinical data and its unique mechanism of action, SEP-856 is a promising new agent for the treatment of schizophrenia and represents a new pharmacological class expected to lack the side effects stemming from blockade of D2 signaling. SIGNIFICANCE STATEMENT: Since the discovery of chlorpromazine in the 1950s, the clinical efficacy of antipsychotic medications has relied on blockade of dopamine D2 receptors, which is associated with substantial side effects and little to no efficacy in treating the negative and cognitive symptoms of schizophrenia. In this study, we describe the discovery and pharmacology of SEP-363856, a novel psychotropic agent that does not exert its antipsychotic-like effects through direct interaction with D2 receptors. Although the mechanism of action has not been fully elucidated, our data suggest that agonism at both trace amine-associated receptor 1 and 5-HT1A receptors is integral to its efficacy. Based on its unique profile in preclinical species, SEP-363856 represents a promising candidate for the treatment of schizophrenia and potentially other neuropsychiatric disorders.

Does outpatient cardiac rehabilitation help patients with acute myocardial infarction quit smoking?

Outpatient cardiac rehabilitation (OCR) reinforces patients' efforts to quit smoking, but the association between participation in OCR and long-term smoking status after acute myocardial infarction (AMI) is unknown. We studied hospitalized smokers with confirmed AMI from two multicenter prospective registries (PREMIER, from January 1, 2003, to June 28, 2004, and TRIUMPH, from April 11, 2005, to December 31, 2008) to describe the association of OCR participation with smoking cessation. Eligible patients smoked at least 1 cigarette per day on average in the 30 days prior to enrollment and completed 12-month follow-up (N = 1307). Structured interviews were completed on subjects at baseline and during follow-up. OCR participation and abstinence from smoking within the prior 30-days (30-day point prevalence abstinence, PPA) were self-reported. We constructed a propensity model of OCR participation based on 22 baseline sociodemographic and clinical characteristics, and constructed hierarchical modified Poisson regression models of 30-day PPA at 12 months after matching on the propensity for OCR participation (with clinical site treated as a random effect). Seventy-four percent of subjects were referred to OCR at hospital discharge, but only 36% participated during follow-up. At 12-month follow-up, 30-day PPA was 57% in OCR participants, compared to 41% in matched OCR non-participants. Participation in OCR was a significant predictor of 30-day PPA at 12 months (adjusted RR 1.38, 95% CI 1.20-1.57). In conclusion, smokers who participated in OCR were significantly more likely to abstain from smoking 12 months after AMI hospitalization.

Associations of exercise ankle-brachial index, pain-free walking distance and maximum walking distance with the Peripheral Artery Questionnaire: Finding from the PORTRAIT PAD Registry.

An exercise ankle-brachial index (ABI) test can provide further insight into the functional significance of peripheral artery disease (PAD). The variability in its use, associated patient factors and its relation to patients' symptoms are unknown. From the international PORTRAIT registry, we identified 1131 patients with PAD. We fit a hierarchical logistic regression model, adjusting for patient factors, country and site, to examine predictors of and variation in ordering exercise ABI testing. We also examined the associations between test components and health status as quantified by the Peripheral Artery Questionnaire (PAQ) using semi-parametric regression methods. Testing was ordered in 22% in the United States versus 80% in the Netherlands and 90% in Australia. Testing was likely to be performed if the patient was male, younger, had typical symptoms and a higher resting ABI, with substantial variability across sites (median odds ratio=5.9, 95% CI: 3.2-19.5). Adjusting for country and site, the resting ABI and all exercise ABI metrics were associated with the PAQ Physical Limitation score. In addition, important components of the test, namely time to onset of claudication, pain-free walking distance (PFWD), and maximum walking distance (MWD), were also associated with PAQ Symptoms and Summary scores. More importantly, even after adjusting for resting ABI, a patient with a post-exercise ABI of 0.29 (25th percentile), compared to 0.61 (75th percentile), achieved 4.4 (95% CI: 0.4-8.4, p=0.031) points less on the PAQ Physical Limitation score. Exercise ABI test use is remarkably variable, and less used in the United States. Its data, specifically PFWD and MWD, might help in objectively assessing the impact of PAD on patients' functioning and quality of life.

Sex Differences in 1-Year All-Cause Rehospitalization in Patients After Acute Myocardial Infarction: A Prospective Observational Study.

BACKGROUND: Compared with men, women are at higher risk of rehospitalization in the first month after discharge for acute myocardial infarction (AMI). However, it is unknown whether this risk extends to the full year and varies by age. Explanatory factors potentially mediating the relationship between sex and rehospitalization remain unexplored and are needed to reduce readmissions. The aim of this study was to assess sex differences and factors associated with 1-year rehospitalization rates after AMI. METHODS: We recruited 3536 patients (33% women) ≥18 years of age hospitalized with AMI from 24 US centers into the TRIUMPH study (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status). Data were obtained by medical record abstraction and patient interviews, and a physician panel adjudicated hospitalizations within the first year after AMI. We compared sex differences in rehospitalization using a Cox proportional hazards model, following sequential adjustment for covariates and testing for an age-sex interaction. RESULTS: One-year crude all-cause rehospitalization rates for women were significantly higher than men after AMI (hazard ratio, 1.29 for women; 95% confidence interval, 1.12-1.48). After adjustment for demographics and clinical factors, women had a persistent 26% higher risk of rehospitalization (hazard ratio, 1.26; 95% confidence interval, 1.08-1.47). However, after adjustment for health status and psychosocial factors (hazard ratio, 1.14; 95% confidence interval, 0.96-1.35), the association was attenuated. No significant age-sex interaction was found for 1-year rehospitalization, suggesting that the increased risk applied to both older and younger women. CONCLUSIONS: Regardless of age, women have a higher risk of rehospitalization compared with men over the first year after AMI. Although the increased risk persisted after adjustment for clinical factors, the poorer health and psychosocial state of women attenuated the difference.

Validation of the Seattle angina questionnaire in women with ischemic heart disease.

BACKGROUND: Although the Seattle Angina Questionnaire (SAQ) has been widely used to assess disease-specific health status in patients with ischemic heart disease, it was originally developed in a predominantly male population and its validity in women has been questioned. METHODS: Using data from 8892 men and 4013 women across 2 multicenter trials and 5 registries, we assessed the construct validity, test-retest reliability, responsiveness to clinical change, and predictive validity of the SAQ Summary Score (SS) and its 5 subdomains (Physical Limitation (PL), Anginal Stability (AS), Angina Frequency (AF), Treatment Satisfaction (TS), and Quality of Life (QoL)) separately in men and women. RESULTS: Comparable correlations of the SAQ SS with Canadian Cardiovascular Society class was demonstrated in both men and women (-0.48 for men, -0.46 for women). Similar correlations between the SAQ PL scale with treadmill exercise duration and Short Form-12 (SF-12) Physical Component Summary were observed in women and men (0.34-0.63 and 0.40-0.63, respectively). SAQ AS scores were significantly lower for both men and women with acute syndromes compared with 1 month later. The SAQ AF scale was strongly correlated with daily angina diaries (0.62 for men and 0.66 for women). The SAQ QoL scores were moderately correlated with the EQ5D visual analog scale and SF-12 general health question in men (0.43-0.50) and women (0.33-0.39). All SAQ scales demonstrated excellent reliability (intraclass correlation ≥0.78) in both men and women with stable CAD and were very sensitive to change after percutaneous coronary intervention (≥15-point difference in scores, standardized response mean ≥ 0.67). The SAQ SS was similarly predictive of 1-year mortality and cardiac re-hospitalizations for both men and women. CONCLUSION: The SAQ demonstrates similar psychometric properties in men and women with CAD. These findings provide evidence for validity of the SAQ in assessing women with IHD.

Association between the EPHX2 p.Lys55Arg polymorphism and prognosis following an acute coronary syndrome.

Inhibition of soluble epoxide hydrolase (sEH, EPHX2) elicits potent cardiovascular protective effects in preclinical models of ischemic cardiovascular disease (CVD), and genetic polymorphisms in EPHX2 have been associated with developing ischemic CVD in humans. However, it remains unknown whether EPHX2 variants are associated with prognosis following an ischemic CVD event. We evaluated the association between EPHX2 p.Lys55Arg and p.Arg287Gln genotype with survival in 667 acute coronary syndrome (ACS) patients. No association with p.Arg287Gln genotype was observed (P = 0.598). Caucasian EPHX2 Arg55 carriers (Lys/Arg or Arg/Arg) had a significantly higher risk of 5-year mortality (adjusted hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.01-2.55, P = 0.045). In an independent population of 2712 ACS patients, this association was not replicated (adjusted HR 0.92, 95% CI 0.70-1.21, P = 0.559). In a secondary analysis, Caucasian homozygous Arg55 allele carriers (Arg/Arg) appeared to exhibit a higher risk of cardiovascular mortality (adjusted HR 2.60, 95% CI 1.09-6.17). These results demonstrate that EPHX2 p.Lys55Arg and p.Arg287Gln polymorphisms do not significantly modify survival after an ACS event. Investigation of other sEH metabolism biomarkers in ischemic CVD appears warranted.

Practitioner Gender and Quality of Care in Ambulatory Cardiology Practices: A Report From the National Cardiovascular Data Practice Innovation and Clinical Excellence (PINNACLE) Registry.

BACKGROUND: Some studies suggest that female practitioners are more likely to provide guideline-concordant care than male practitioners; however, little is known about the role of practitioner gender in cardiology. OBJECTIVE: The aim of the study was to measure the association between practitioner gender and adherence to the cardiovascular performance measures in the American College of Cardiology's ambulatory Practice Innovation and Clinical Excellence Registry. METHODS: Patients with at least 1 outpatient visit with a unique practitioner were included. Among eligible patients, adherence to 7 guideline-supported performance measures for coronary artery disease, heart failure, and atrial fibrillation over 12 months after registry entry was compared by practitioner gender using hierarchical models adjusting for practitioner type (physicians vs advance practice practitioners) and number of visits. RESULTS: The study cohort included 1493 individual practitioners who saw 769 139 patients; 80% of practitioners were men. Male practitioners were more often physicians compared with female practitioners (98.2% vs 43.7%, P < .01). Accounting for practitioner category and visit frequency, guideline adherence rates were similar by practitioner gender for all measures with the exception of marginally higher rates for coronary artery disease performance measures for male practitioners compared with female practitioners (antiplatelet: rate ratio [RR] = 1.06; 95% confidence interval [CI], 1.03-1.09; ß-blockers: RR = 1.06; 95% CI, 1.01-1.10; and lipid-lowering drug: RR = 1.07; 95% CI, 1.04-1.10) and atrial fibrillation (oral anticoagulants: RR = 1.05; 95% CI, 1.01-1.09). CONCLUSION: Male practitioners marginally outperformed their female counterparts in ambulatory practices enrolled in a voluntary cardiovascular performance improvement registry program. Overall low adherence to some performance measures suggests room for improvement among all practitioners.

A general framework for constraint approaches to adjusted risk differences.

The risk difference is an intelligible measure for comparing disease incidence in two exposure or treatment groups. Despite its convenience in interpretation, it is less prevalent in epidemiological and clinical areas where regression models are required in order to adjust for confounding. One major barrier to its popularity is that standard linear binomial or Poisson regression models can provide estimated probabilities out of the range of (0,1), resulting in possible convergence issues. For estimating adjusted risk differences, we propose a general framework covering various constraint approaches based on binomial and Poisson regression models. The proposed methods span the areas of ordinary least squares, maximum likelihood estimation, and Bayesian inference. Compared to existing approaches, our methods prevent estimates and confidence intervals of predicted probabilities from falling out of the valid range. Through extensive simulation studies, we demonstrate that the proposed methods solve the issue of having estimates or confidence limits of predicted probabilities out of (0,1), while offering performance comparable to its alternative in terms of the bias, variability, and coverage rates in point and interval estimation of the risk difference. An application study is performed using data from the Prospective Registry Evaluating Myocardial Infarction: Event and Recovery (PREMIER) study.

Patient and physician discordance in reporting symptoms of angina among stable coronary artery disease patients: Insights from the Angina Prevalence and Provider Evaluation of Angina Relief (APPEAR) study.

BACKGROUND: A principal goal of treating patients with coronary artery disease (CAD) is to minimize angina and optimize quality of life. For this, physicians must accurately assess presence and frequency of patients' angina. The accuracy with which cardiologists estimate their patients' angina in contemporary, busy outpatient clinics across the United States (US) is unknown. METHODS: We enrolled patients with CAD across 25 US cardiology outpatient practices. Patients completed the Seattle Angina Questionnaire before their visit, which assessed their angina and quality of life over the prior 4 weeks. The Seattle Angina Questionnaire angina frequency domain categorized patients' angina as none, daily/weekly, or monthly. After the visit, cardiologists estimated the frequency of their patients' angina using the same categories. Kappa statistic helped to assess agreement between patient-reported and cardiologist-estimated angina. RESULTS: Among 1,257 outpatients with CAD, 67% reported no angina, 25% reported monthly angina, and 8% reported daily/weekly angina. When patients reported no angina, cardiologists accurately estimated this 93% of the time, but when patients reported monthly or daily/weekly angina symptoms, cardiologists agreed 17% and 69% of the time, respectively. Among patients with daily/weekly angina, 26% were noted as having no angina by their physicians. Agreement between patients' and cardiologists' reports (assessed by the kappa statistic) was 0.48 (95% CI 0.44-0.53), indicating moderate agreement. CONCLUSIONS: Among outpatients with stable CAD, there is substantial discordance between patient-reported and cardiologist-estimated burden of angina. Inclusion of patient-reported health status measures in routine clinical care may support better recognition of patients' symptoms by physicians.

Bleeding risk following percutaneous coronary intervention in patients with diabetes prescribed dual anti-platelet therapy.

BACKGROUND: Patients with diabetes mellitus (DM) experience higher rates of in-stent restenosis and greater benefit from drug-eluting stents implant at the time of percutaneous coronary intervention (PCI), necessitating prolonged dual anti-platelet therapy (DAPT). While DAPT reduces risk of ischemic events post-PCI, it also increases risk of bleeding. Whether bleeding rates differ among patients with and without DM, receiving long-term DAPT is unknown. METHODS: Among patients who underwent PCI and were maintained on DAPT for 1 year in a multicenter US registry, we assessed patient-reported bleeding over one year following PCI in patients with and without DM. Multivariable, hierarchical Poisson regression was used to evaluate the association of DM with bleeding during follow-up. RESULTS: Among 2334 PCI patients from 10 US hospitals (mean age 64, 54% ACS), 32.6% had DM. In unadjusted analyses, patients with DM had fewer bleeding events over the year following PCI (DM vs no DM: BARC = 1: 78.0% vs 87.7%, P < .001; BARC ≥2: 4.3% vs 5.3%, P = .33). Following adjustment, patients with (vs without DM) had a lower risk of BARC ≥1 bleeding during follow-up (relative risk [RR] 0.89, 95% CI 0.83-0.96). This decreased bleeding risk persisted after removing bruising from the endpoint definition. CONCLUSIONS: In a real-world PCI registry, patients with DM experienced lower risk of bleeding risk on DAPT. As patients with DM also derive greater ischemic benefit from drug-eluting stents, which requires prolonged DAPT, our findings suggest that the balance between benefit and risk of this therapeutic approach may be even more favorable in patients with DM than previously considered.

Variation of Quality of Life Data Collection Across INTERMACS Sites.

BACKGROUND: Given the importance of patients' health-related quality of life (HRQL) after mechanical circulatory support (MCS) device implantation, the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) collects the Kansas City Cardiomyopathy Questionnaire (KCCQ) before and after MCS. The success of data collection and potential implications of missing data on HRQL analyses are unknown. METHODS: We examined the frequency and reasons for not collecting baseline and 3-month KCCQ data across INTERMACS sites from May 2012 to December 2013. Hierarchical logistic regression was used to examine site variability (median odds ratios [MOR]) for not collecting KCCQ data to demonstrate the degree to which some sites can collect more complete data than others. RESULTS: Among 3960 and 3523 patients participating in INTERMACS before and 3 months after left ventricular assist device implantation, the KCCQ was not collected in 43.1% at baseline (range across sites, 0-100%) and 40.9% (range, 0-100%) at follow-up. The most common reasons for incomplete KCCQ data at baseline were that the patient was too sick (13.9%) and consent to participate in research was not obtained (12.4%). Significant variation across sites was observed for missingness because of patient (MOR, 2.8; P < .001) and administrative (MOR, 4.8; P < .001) reasons. The most variable patient reasons were that the patients were too stressed (MOR, 7.2; P < .001) and too busy (MOR, 10.6; P < .001). The most variable administrative reasons were that the coordinator was too busy/forgot (MOR, 7.1; P < .001) and miscellaneous reasons (MOR, 8.7; P < .001). At 3 months, significant variation persisted for both patient (MOR, 2.7; P < .001) and administrative (MOR, 3.5; P < .001) reasons. The most variability across sites was that the patient was too busy (MOR, 6.0, P < .001) and that the coordinator was too busy/forgot (MOR, 5.8; P < .001). CONCLUSIONS: Sites vary substantially in collecting KCCQ data, and many of these variations seem addressable. Improving the consistency of HRQL data collection can improve the value of INTERMACS in defining the patient-centered benefits of MCS treatment.

Quantifying clinical change: discrepancies between patients' and providers' perspectives.

PURPOSE: Interpreting the clinical significance of changes in patient-reported outcomes (PROs) is critically important. The most commonly used approach is to anchor mean changes on PRO scores against a global assessment of change. Whether the assessor of global change should be patients or their physicians is unknown. We compared patients' and physicians' assessments of change over time to examine which was more aligned with patients' changes in PRO measures. METHODS: A total of 459 chronic heart failure patients aged >30 years were enrolled from 13 US centers. Data were obtained by medical record abstraction, physical assessments, and patient interviews at a baseline clinic visit and 6 weeks later. Health status was measured with the disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ), and both patients and physicians completed a validated 15-level global assessment of change, ranging from large deterioration to large improvement. RESULTS: There was substantial variation between physicians/patients' global assessment of clinical change (weighted kappa = 0.36, 95 % CI 0.28, 0.43). Overall, physician assessments were more strongly correlated with change on the KCCQ summary score than were patients' assessments (physician R = 0.37, patient R = 0.29). CONCLUSION: There was substantial variation between patients' and physicians' global assessment of 6-week change in heart failure status. Physician assessments of the importance of clinical changes were more strongly associated with changes in all domains of patient-reported health status, as assessed by the KCCQ, and may provide a more consistent method for defining the clinical importance of changes in patients' health status.

Derivation and validation of a risk standardization model for benchmarking hospital performance for health-related quality of life outcomes after acute myocardial infarction.

BACKGROUND: Before outcomes-based measures of quality can be used to compare and improve care, they must be risk-standardized to account for variations in patient characteristics. Despite the importance of health-related quality of life (HRQL) outcomes among patients with acute myocardial infarction (AMI), no risk-standardized models have been developed. METHODS AND RESULTS: We assessed disease-specific HRQL using the Seattle Angina Questionnaire at baseline and 1 year later in 2693 unselected AMI patients from 24 hospitals enrolled in the Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients' Health status (TRIUMPH) registry. Using 57 candidate sociodemographic, economic, and clinical variables present on admission, we developed a parsimonious, hierarchical linear regression model to predict HRQL. Eleven variables were independently associated with poor HRQL after AMI, including younger age, previous coronary artery bypass graft surgery, depressive symptoms, and financial difficulties (R(2)=20%). The model demonstrated excellent internal calibration and reasonable calibration in an independent sample of 1890 AMI patients in a separate registry, although the model slightly overpredicted HRQL scores in the higher deciles. Among the 24 TRIUMPH hospitals, 1-year unadjusted HRQL scores ranged from 67-89. After risk-standardization, HRQL score variability narrowed substantially (range=79-83), and the group of hospital performance (bottom 20%/middle 60%/top 20%) changed in 14 of the 24 hospitals (58% reclassification with risk-standardization). CONCLUSIONS: In this predictive model for HRQL after AMI, we identified risk factors, including economic and psychological characteristics, associated with HRQL outcomes. Adjusting for these factors substantially altered the rankings of hospitals as compared with unadjusted comparisons. Using this model to compare risk-standardized HRQL outcomes across hospitals may identify processes of care that maximize this important patient-centered outcome.

Rethinking composite end points in clinical trials: insights from patients and trialists.

BACKGROUND: Many clinical trials use composite end points to reduce sample size, but the relative importance of each individual end point within the composite may differ between patients and researchers. METHODS AND RESULTS: We asked 785 cardiovascular patients and 164 clinical trial authors to assign 25 "spending weights" across 5 common adverse events comprising composite end points in cardiovascular trials: death, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. We then calculated end point ratios for each participant's ratings of each nonfatal end point relative to death. Whereas patients assigned an average weight of 5 to death, equal or greater weight was assigned to myocardial infarction (mean ratio, 1.12) and stroke (ratio, 1.08). In contrast, clinical trialists were much more concerned about death (average weight, 8) than myocardial infarction (ratio, 0.63) or stroke (ratio, 0.53). Both patients and trialists considered revascularization (ratio, 0.48 and 0.20, respectively) and hospitalization (ratio, 0.28 and 0.13, respectively) as substantially less severe than death. Differences between patient and trialist end point weights persisted after adjustment for demographic and clinical characteristics (P<0.001 for all comparisons). CONCLUSIONS: Patients and clinical trialists did not weigh individual components of a composite end point equally. Whereas trialists are most concerned about avoiding death, patients place equal or greater importance on reducing myocardial infarction or stroke. Both groups considered revascularization and hospitalization as substantially less severe. These findings suggest that equal weights in a composite clinical end point do not accurately reflect the preferences of either patients or trialists.

The association of chronic kidney disease with the use of renin-angiotensin system inhibitors after acute myocardial infarction.

BACKGROUND: Renin-angiotensin system (RAS) inhibitor use after acute myocardial infarction (AMI) is a quality indicator, but there may also be reasons not to use this therapy. We sought to determine how chronic kidney disease (CKD) and acute kidney injury (AKI) affected RAS inhibitor prescription after AMI in patients with and without decreased ejection fraction (EF). METHODS: Participants from the TRIUMPH registry were categorized by admission estimated glomerular filtration rate (eGFR in mL/min per 1.73 m(2); severe [<30], moderate [30-59], mild [60-89], and no [≥90] CKD) and occurrence of AKI (an increase in creatinine ≥0.3 mg/dL or ≥50%). Renin-angiotensin system inhibitor prescriptions at discharge were compared across categories of CKD, AKI, and decreased EF (<40% vs ≥40%) using a hierarchical modified Poisson model. RESULTS: Among 4,223 AMI patients (mean age 59.0 years, 67.0% male, 67.3% white), RAS inhibitor use decreased significantly with lower eGFR (P < .001), but there was no effect of decreased EF on this relationship (interaction P = .40). Without AKI, severe and moderate CKD were associated with significantly less RAS inhibitor use: relative risks (RRs) 0.67 (95% CIs, 0.58-0.78) and 0.94 (0.90-0.99), respectively. When AKI occurred, CKD was associated with less RAS inhibitor use: RRs 0.84 (0.76-0.93) for mild CKD, 0.78 (0.68-0.88) for moderate CKD, and 0.50 (0.42-0.61) for severe CKD. Ejection fraction <40% was associated with use (RR 1.11, 1.03-1.18), independent of renal function. CONCLUSIONS: Chronic kidney disease and AKI are associated with fewer RAS inhibitor prescriptions at discharge, but in both AKI and non-AKI patients, eGFR was more strongly associated with use than EF.