Sex Differences in Quality of Life and Clinical Outcomes in Patients With Advanced Heart Failure: Insights From the PAL-HF Trial.

BACKGROUND: Palliative care improves quality of life in patients with heart failure. Whether men and women with heart failure derive similar benefit from palliative care interventions remains unknown. METHODS: In a secondary analysis of the PAL-HF trial (Palliative Care in Heart Failure), we analyzed differences in quality of life among men and women with heart failure and assessed for differential effects of the palliative care intervention by sex. Differences in clinical characteristics and quality-of-life metrics were compared between men and women at serial time points. The primary outcome was change in Kansas City Cardiomyopathy Questionnaire score between baseline and 24 weeks. RESULTS: Among the 71 women and 79 men, there was a significant difference in baseline Kansas City Cardiomyopathy Questionnaire (24.5 versus 36.2, respectively; P=0.04) but not Functional Assessment of Chronic Illness Therapy-Palliative Care scale (115.7 versus 120.3; P=0.27) scores. Among those who received the palliative care intervention (33 women and 42 men), women's quality-of-life score remained lower than that of men after enrollment. Treated men's scores were significantly higher than those untreated (6-month Kansas City Cardiomyopathy Questionnaire, 68.0 [interquartile range, 52.6-85.7] versus 41.1[interquartile range, 32.0-78.3]; P=0.047), whereas the difference between treated and untreated women was not significantly different (P=0.39). Rates of death and rehospitalization, as well as the composite end point, were similar between treated and untreated women and men. CONCLUSIONS: In the PAL-HF trial, women with heart failure experienced a greater symptom burden and poorer quality of life as compared with men. The change in treated men's Kansas City Cardiomyopathy Questionnaire score between baseline and 24 weeks was significantly higher than those untreated; this trend was not observed in women. Thus, there may be a sex disparity in response to palliative care intervention, suggesting that sex-specific approaches to palliative care may be needed to improve outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0158960.

Relationship Between Enrolling Country Income Level and Patient Profile, Protocol Completion, and Trial End Points.

BACKGROUND: Globalization of clinical trials fosters inclusion of higher and lower income countries, but the influence of enrolling country income level on heart failure trial performance is unclear. This study sought to evaluate associations between enrolling country income level, acute heart failure patient profile, protocol completion, and trial end points. METHODS AND RESULTS: The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial included 7141 patients with acute heart failure from 30 countries. Country income data in gross national income per capita in current US dollars from the year 2007 (ie, the year trial enrollment began) were abstracted from the World Bank. Patients were grouped by enrolling country income level (ie, high [>$11 455], upper middle [$3706-$11 455], lower middle [$936-$3705], and low [<$936]). Income data were available for 29 (97%) countries (N=7064). There were 3996 (57%), 1518 (21%), and 1550 (22%) patients from high-income, upper-middle-income, and lower-middle-income countries, respectively. There were no patients from low-income countries. Patients from lower-middle-income countries tended to be younger with fewer comorbidities and lower utilization of guideline-directed therapies. Rates of adverse events (13.8%) and protocol noncompletion (4.9%) during 180-day follow-up were highest among high-income countries (all P <0.01). After adjustment for race, geographic region, and clinical characteristics, compared with lower-middle-income countries, enrollment from higher income countries was associated with increased 30-day mortality or rehospitalization (high income: odds ratio, 1.70; 95% CI, 1.02-2.85; upper-middle-income: odds ratio, 2.16; 95% CI, 1.23-3.81), driven by higher rates of rehospitalization. Mortality was similar at 30 and 180 days. The association between higher country income and the 30-day composite end point was similar across geographic regions, with exception of Latin America ( P for interaction, 0.03). CONCLUSIONS: In this global acute heart failure trial, patients from higher income countries had lower rates of protocol completion, higher rates of adverse events, and similar mortality rates. After adjustment for race, geographic region, and clinical factors, enrollment from a higher income country was associated with worse clinical outcomes, driven by higher rates of rehospitalization. Variation in enrolling country income level may influence study end points and trial performance independent of geographic region. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00475852.

Comparison of International Guidelines for Assessment of Suspected Stable Angina: Insights From the PROMISE and SCOT-HEART.

OBJECTIVES: This study sought to compare the performance of major guidelines for the assessment of stable chest pain including risk-based (American College of Cardiology/American Heart Association and European Society of Cardiology) and symptom-focused (National Institute for Health and Care Excellence) strategies. BACKGROUND: Although noninvasive testing is not recommended in low-risk individuals with stable chest pain, guidelines recommend differing approaches to defining low-risk patients. METHODS: Patient-level data were obtained from the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) and SCOT-HEART (Scottish Computed Tomography of the Heart) trials. Pre-test probability was determined and patients dichotomized into low-risk and intermediate-high-risk groups according to each guideline's definitions. The primary endpoint was obstructive coronary artery disease on coronary computed tomography angiography. Secondary endpoints were coronary revascularization at 90 days and cardiovascular death or nonfatal myocardial infarction up to 3 years. RESULTS: In total, 13,773 patients were included of whom 6,160 had coronary computed tomography angiography. The proportions of patients identified as low risk by the American College of Cardiology/American Heart Association, European Society of Cardiology, and National Institute for Health and Care Excellence guidelines, respectively, were 2.5%, 2.5%, and 10.0% within PROMISE, and 14.0%, 19.8%, and 38.4% within SCOT-HEART. All guidelines identified lower rates of obstructive coronary artery disease in low- versus intermediate-high-risk patients with a negative predictive value of ≥0.90. Compared with low-risk groups, all intermediate-high-risk groups had greater risks of coronary revascularization (odds ratio [OR]: 2.2 to 24.1) and clinical outcomes (OR: 1.84 to 5.8). CONCLUSIONS: Compared with risk-based guidelines, symptom-focused assessment identifies a larger group of low-risk chest pain patients potentially deriving limited benefit from noninvasive testing. (Scottish Computed Tomography of the Heart Trial [SCOT-HEART]; NCT01149590; Prospective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550).

Quantifying sociodemographic and income disparities in medical therapy and lifestyle among symptomatic patients with suspected coronary artery disease: a cross-sectional study in North America.

OBJECTIVES: To evaluate potential gaps in preventive medical therapy and healthy lifestyle practices among symptomatic patients with suspected coronary artery disease (CAD) seeing primary care physicians and cardiologists and how gaps vary by sociodemographic characteristics and baseline cardiovascular risk. DESIGN: Cross-sectional study assessing potential preventive gaps. PARTICIPANTS: 10 003 symptomatic outpatients evaluated by primary care physicians, cardiologists or other specialists for suspected CAD. SETTING: PROspective Multicenter Imaging Study for Evaluation of Chest Painfrom 2010 to 2014. MEASURES: Primary measures were absence of an antihypertensive, statin or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker for renal protection in patients with hypertension, dyslipidaemia or diabetes, respectively, and being sedentary, smoking or being obese. RESULTS: Preventive treatment gaps affected 14% of patients with hypertension, 36% of patients with dyslipidaemia and 32% of patients with diabetes. Overall, 49% of patients were sedentary, 18% currently smoked and 48% were obese. Women were significantly more likely to not take a statin for dyslipidaemia and to be sedentary. Patients with lower socioeconomic status were also significantly more likely to not take a statin. Compared with Whites, Blacks were significantly more likely to be obese, while Asians were less likely to smoke or be obese. High-risk patients sometimes experienced larger preventive care gaps than low-risk patients. For patients with dyslipidaemia, the presence of a treatment gap was associated with a higher risk of an adverse event (HR 1.35, 95% CI 1.02 to 1.82). CONCLUSIONS: Among contemporary, symptomatic patients with suspected CAD, significant gaps exist in preventive care and lifestyle practices, and high-risk patients sometimes had larger gaps. Differences by sex, age, race/ethnicity, socioeconomic status and geography are modest but contribute to disparities and have implications for improving opulation health. For patients with dyslipidaemia, the presence of a treatment gap was associated with a higher risk of an adverse event. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov identifier NCT01174550.

Sex Differences in Demographics, Risk Factors, Presentation, and Noninvasive Testing in Stable Outpatients With Suspected Coronary Artery Disease: Insights From the PROMISE Trial.

OBJECTIVES: The aim of this study was to determine whether presentation, risk assessment, testing choices, and results differ by sex in stable symptomatic outpatients with suspected coronary artery disease (CAD). BACKGROUND: Although established CAD presentations differ by sex, little is known about stable, suspected CAD. METHODS: The characteristics of 10,003 men and women in the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial were compared using chi-square and Wilcoxon rank-sum tests. Sex differences in test selection and predictors of test positivity were examined using logistic regression. RESULTS: Women were older (62.4 years of age vs. 59.0 years of age) and were more likely to be hypertensive (66.6% vs. 63.2%), dyslipidemic (68.9% vs. 66.3%), and to have a family history of premature CAD (34.6% vs. 29.3) (all p values <0.005). Women were less likely to smoke (45.6% vs. 57.0%; p < 0.001), although their prevalence of diabetes was similar to that in men (21.8% vs. 21.0%; p = 0.30). Chest pain was the primary symptom in 73.2% of women versus 72.3% of men (p = 0.30), and was characterized as "crushing/pressure/squeezing/tightness" in 52.5% of women versus 46.2% of men (p < 0.001). Compared with men, all risk scores characterized women as being at lower risk, and providers were more likely to characterize women as having a low (<30%) pre-test probability of CAD (40.7% vs. 34.1%; p < 0.001). Compared with men, women were more often referred to imaging tests (adjusted odds ratio: 1.21; 95% confidence interval: 1.01 to 1.44) than nonimaging tests. Women were less likely to have a positive test (9.7% vs. 15.1%; p < 0.001). Although univariate predictors of test positivity were similar, in multivariable models, age, body mass index, and Framingham risk score were predictive of a positive test in women, whereas Framingham and Diamond and Forrester risk scores were predictive in men. CONCLUSIONS: Patient sex influences the entire diagnostic pathway for possible CAD, from baseline risk factors and presentation to noninvasive test outcomes. These differences highlight the need for sex-specific approaches for the evaluation of CAD.