Darapladib for preventing ischemic events in stable coronary heart disease.

BACKGROUND: Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2. METHODS: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). RESULTS: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). CONCLUSIONS: In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

Physical activity in patients with stable coronary heart disease: an international perspective.

AIMS: Despite the known benefits of regular exercise, the reasons why many coronary heart disease (CHD) patients engage in little physical activity are not well understood. This study identifies factors associated with low activity levels in individuals with chronic CHD participating in the STABILITY study, a global clinical outcomes trial evaluating the lipoprotein phospholipaseA2 inhibitor darapladib. METHODS AND RESULTS: Prior to randomization, 15 486 (97.8%) participants from 39 countries completed a lifestyle questionnaire. Total physical activity was estimated from individual subject self-reports of hours spend each week on mild, moderate, and vigorous exercise, corresponding approximately to 2, 4, and 8 METS, respectively. Multivariate logistic regression evaluated clinical and demographic variables for the lowest compared with higher overall exercise levels, and for individuals who decreased rather than maintained or increased activity since diagnosis of CHD. The least active 5280 subjects (34%) reported exercise of ≤ 24 MET.h/week. A total of 7191 subjects (46%) reported less exercise compared with before diagnosis of CHD. The majority of participants were either 'not limited' or 'limited a little' walking 100 m (84%), climbing one flight of stairs (82%), or walking 1 km/1/2; mile (68%), and <10% were limited 'a lot' by dyspnoea or angina. Variables independently associated with both low physical activity and decreasing exercise after diagnosis of CHD included more co-morbid conditions, poorer general health, fewer years of education, race, and country (P < 0.001 for all). CONCLUSION: In this international study, low physical activity was only partly explained by cardiovascular symptoms. Potentially modifiable societal and health system factors are important determinants of physical inactivity in patients with chronic CHD.

Exact likelihood ratio and score confidence intervals for the binomial proportion.

Many methods are available for computing a confidence interval for the binomial parameter, and these methods differ in their operating characteristics. It has been suggested in the literature that the use of the exact likelihood ratio (LR) confidence interval for the binomial proportion should be considered. This paper provides an evaluation of the operating characteristics of the two-sided exact LR and exact score confidence intervals for the binomial proportion and compares these results to those for three other methods that also strictly maintain nominal coverage: Clopper-Pearson, Blaker, and Casella. In addition, the operating characteristics of the two-sided exact LR method and exact score method are compared with those of the corresponding asymptotic methods to investigate the adequacy of the asymptotic approximation.

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.

Evaluation of the Menopause-Specific Quality of Life Questionnaire: a factor-analytic approach.

OBJECTIVE: Despite being used in multiple studies, the Menopause-Specific Quality of Life Questionnaire (MENQOL) has not been assessed with factor analysis, a common method of item reduction in quality of life tools. METHODS: The Menopause Epidemiology Study is a cross-sectional population-based study of women 40 to 65 years old in the United States chosen from a source population selected by random digit dialing and probability sampling. We focused on 2,703 postmenopausal women for our analyses. Before analysis and to prevent model overfitting, we split our sample into two equal groups using a uniform random sample. Using parallel analysis for factor extraction, we performed confirmatory factor analysis on the MENQOL to examine the current factor structure and to evaluate the efficiency of the items in the existing tool. Reliability coefficients (Cronbach α) were calculated for each of the domains. RESULTS: With few exceptions, the items from the original MENQOL factored into the domains under which they were originally placed. Using this method, five items did not add significant statistical value to the scoring of the domains: difficulty sleeping; poor memory; accomplishing less than I used to; changes in appearance, texture, or tone of my skin; and feeling tired. Reliability coefficients for the four original domains were acceptable: vasomotor, 0.87; psychosocial, 0.85; physical, 0.88; and sexual, 0.77. CONCLUSIONS: Results from factor analysis indicate that although the MENQOL was developed more than 15 years ago, the strength of the items is still highly valuable today in the assessment of women's menopause-related quality of life.

Longitudinal association of vasomotor symptoms and psychosocial outcomes among postmenopausal women in the United States: a population-based study.

OBJECTIVE: Vasomotor and psychosocial symptoms persist as common manifestations of menopause; their explicit association is unclear. We investigated this association among postmenopausal women over a 2-year period. METHODS: The Menopause Epidemiology Study is a cross-sectional population-based study of women 40 to 65 years old in the United States. We followed participants who were postmenopausal at baseline and at 2-year follow-up (n = 1,506) in the analyses. The vasomotor and psychosocial domains of the Menopause-Specific Quality of Life Questionnaire were used to assess exposure and outcome. Change in symptoms was defined as the difference in the Menopause-Specific Quality of Life Questionnaire domain score from baseline to follow-up 2 years later. Demographic information, behavioral activities, reproductive history, and medication use were evaluated for effect modification and confounding. Covariate-adjusted linear regression was used to assess the relationship between the change in vasomotor symptoms and change in psychosocial symptoms. RESULTS: One quarter (n = 375) of the women reported an increase in vasomotor symptoms over the 2-year study period. Twenty-two percent of the women reported an increase in both vasomotor and psychosocial symptoms. Current smoking status was found to be an effect modifier: a one-unit increase in the vasomotor domain was associated with a 0.21-unit (95% CI, 0.12-0.29) increase in the psychosocial domain among smokers; this was stronger (0.29, 95% CI, 0.20-0.39) among past or never smokers. CONCLUSIONS: This study provides further evidence of an association between vasomotor symptoms and psychosocial symptoms using a validated instrument in a population-based study. There is a small increase in psychosocial symptoms with increasing vasomotor symptoms. Clinicians may want to note this association when treating postmenopausal women with either condition.