Self-Reported Health and Outcomes in Patients With Stable Coronary Heart Disease.

BACKGROUND: The major determinants and prognostic importance of self-reported health in patients with stable coronary heart disease are uncertain. METHODS AND RESULTS: The STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial randomized 15 828 patients with stable coronary heart disease to treatment with darapladib or placebo. At baseline, 98% of participants completed a questionnaire that included the question, "Overall, how do you feel your general health is now?" Possible responses were excellent, very good, good, average, and poor. Adjudicated major adverse cardiac events, which included cardiovascular death, myocardial infarction, and stroke, were evaluated by Cox regression during 3.7 years of follow-up for participants who reported excellent or very good health (n=2304), good health (n=6863), and average or poor health (n=6361), before and after adjusting for 38 covariates. Self-reported health was most strongly associated with geographic region, depressive symptoms, and low physical activity (P<0.0001 for all). Poor/average compared with very good/excellent self-reported health was independently associated with major adverse cardiac events (hazard ratio [HR]: 2.30 [95% confidence interval (CI), 1.92-2.76]; adjusted HR: 1.83 [95% CI, 1.51-2.22]), cardiovascular mortality (HR: 4.36 [95% CI, 3.09-6.16]; adjusted HR: 2.15 [95% CI, 1.45-3.19]), and myocardial infarction (HR: 1.87 [95% CI, 1.46-2.39]; adjusted HR: 1.68 [95% CI, 1.25-2.27]; P<0.0002 for all). CONCLUSIONS: Self-reported health is strongly associated with geographical region, mood, and physical activity. In a global coronary heart disease population, self-reported health was independently associated with major cardiovascular events and mortality beyond what is measurable by established risk indicators. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00799903.

Sex Differences in Clinical Characteristics, Psychosocial Factors, and Outcomes Among Patients With Stable Coronary Heart Disease: Insights from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial.

BACKGROUND: Greater understanding of differences between men and women with coronary heart disease is needed. METHODS AND RESULTS: In this post hoc analysis of the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, we described psychosocial factors, treatments, and outcomes of men versus women with stable coronary heart disease and explored the association of sex with psychosocial characteristics and cardiovascular risk. Cox proportional hazards models were used to assess the relationship between sex and outcomes. Interactions among sex, psychosocial factors, and the composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were tested. Of 15 828 patients, 2967 (19%) were women. Among women, 21.2% felt often or always stressed at home (versus 9.8% of men), and 19.2% felt often or always sad or depressed (versus 10.1% of men; all P<0.0001). The median duration of follow-up was 3.7 years (25th-75th percentiles: 3.5-3.8 years). Use of evidence-based medications for coronary heart disease at baseline and 24 months was similar between sexes, as were event rates for all outcomes analyzed. In the multivariable model including psychosocial measures, female sex was associated with lower cardiovascular risk. There was a statistically significant interaction (P=0.03) such that the lower risk in women varied by depressive symptom frequency, whereby women who were more depressed had a risk similar to men. CONCLUSIONS: Female sex was independently associated with better long-term clinical outcomes, although this was modified by frequency of depressive symptoms. This suggests that emotional state may be an important target for improving outcomes in patients with coronary heart disease, specifically in women. CLINICAL TRIAL REGISTRATION: STABILITY ClinicalTrials.gov number (NCT00799903).

Secondary prevention and risk factor target achievement in a global, high-risk population with established coronary heart disease: baseline results from the STABILITY study.

AIM: There is limited contemporary data on achievement of risk factor goals for secondary prevention of cardiovascular (CV) disease from countries in many regions of the world. This report describes the global and regional prevalence of CV risk factors and use of preventive medications at baseline in participants in the ongoing STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial. METHODS AND RESULTS: Detailed individual data on CV risk factors were obtained before randomization in 15,828 patients with chronic coronary heart disease (CHD) from 39 countries on five continents. Subjects had a history of myocardial infarction, prior coronary revascularization, or multi-vessel CHD without revascularization and at least one additional CV risk factor. The majority were taking a statin (97%), antiplatelet therapy (96%), beta-blocker (79%), or angiotensin converting enzyme inhibitor/angiotensin receptor blocker (77%). However, a large proportion of patients did not achieve guideline-recommended targets. For instance, in 29% low-density lipoprotein (LDL) cholesterol was >2.5 mmol/l and in 46% blood pressure was ≥140/90 mmHg or ≥130/80 mmHg in those with diabetes or renal impairment. The body mass index was >30 kg/m(2) in 36%, waist circumference ≥102 cm for men or ≥88 cm for women in 54%, and 18% were smoking. Regional differences in risk factor prevalence and target achievement were observed and were more marked for LDL cholesterol and obesity. CONCLUSION: The prevalence of modifiable CV risk factors was generally high in the STABILITY population. Although, most patients were receiving evidence-based secondary preventive therapy many subjects from all regions did not reach recommended secondary prevention goals.

Study design and rationale for the clinical outcomes of the STABILITY Trial (STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY) comparing darapladib versus placebo in patients with coronary heart disease.

BACKGROUND: Elevated plasma levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with increased risk of cardiovascular (CV) events. Direct inhibition of this proinflammatory enzyme with darapladib may benefit CV patients when given as an adjunct to standard of care, including lipid-lowering and antiplatelet therapies. METHODS: STABILITY is a randomized, placebo-controlled, double-blind, international, multicenter, event-driven trial. The study has randomized 15,828 patients with chronic coronary heart disease (CHD) receiving standard of care to darapladib enteric-coated (EC) tablets, 160 mg or placebo. RESULTS: The primary end point is the composite of major adverse cardiovascular events (MACE): CV death, nonfatal myocardial infarction, and nonfatal stroke. The key secondary end points will include major coronary events, total coronary events, individual components of MACE, and all-cause mortality. Prespecified substudies include 24-hour ambulatory blood pressure monitoring, albuminuria progression, changes in cognitive function, and pharmacokinetic and biomarker analyses. Health economic outcomes and characterization of baseline lifestyle risk factors also will be assessed. The study will continue until 1,500 primary end points have occurred to achieve 90% power to detect a 15.5% reduction in the primary end point. The median treatment duration is anticipated to be 2.75 years. CONCLUSIONS: STABILITY will assess whether direct inhibition of Lp-PLA(2) with darapladib added to the standard of care confers clinical benefit to patients with CHD.