Placebo adherence, clinical outcomes, and mortality in the women's health initiative randomized hormone therapy trials.
ABSTRACT Medication adherence may be a proxy for healthy behaviors and other factors that affect outcomes. Prior studies of the association between placebo adherence and health outcomes have been limited primarily to men enrolled in clinical trials and cardiovascular disease outcomes. We examined associations between adherence to placebo and the risk of fracture, coronary heart disease, cancer, and all-cause mortality in the 2 Women's Health Initiative hormone therapy randomized trials.
Postmenopausal women randomized to placebo with adherence measured at least once were eligible for analysis. Time-varying adherence was assessed by dispensing history and pill counts. Outcome adjudication was based on physician review of medical records. Cox proportional hazards models evaluated the relation between high adherence (≥80%) to placebo and various outcomes, referent to low adherence (<80%).
A total of 13,444 postmenopausal women were under observation for 106,066 person-years. High placebo adherence was inversely associated with most outcomes including hip fracture [hazard ratio (HR), 0.50; 95% confidence interval (CI), 0.33-0.78], myocardial infarction (HR, 0.69; 95% CI, 0.50-0.95), cancer death (HR, 0.60; 95% CI, 0.43-0.82), and all-cause mortality (HR, 0.64; 95% CI, 0.51-0.80) after adjustment for potential confounders. Women with low adherence to placebo were 20% more likely to have low adherence to statins and osteoporosis medications.
In the Women's Health Initiative clinical trials, high adherence to placebo was associated with favorable clinical outcomes and mortality. Until the healthy behaviors and/or other factors for which high adherence is a proxy can be better elucidated, caution is warranted when interpreting the magnitude of benefit of medication adherence.
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ABSTRACT: We examined the effect of chlorthalidone-based stepped care on the competing risks of cardiovascular (CV) versus non-CV death in the Systolic Hypertension in the Elderly Program (SHEP). Participants were randomly assigned to chlorthalidone-based stepped-care therapy (n = 2,365) or placebo (n = 2,371) for 4.5 years, and all participants were advised to take active therapy thereafter. At the 22-year follow-up, the gain in life expectancy free from CV death in the active treatment group was 145 days (95% confidence interval [CI] 23 to 260, p = 0.012). The gain in overall life expectancy was smaller (105 days, 95% CI -39 to 242, p = 0.073) because of a 40-day (95% CI -87 to 161) decrease in survival from non-CV death. Compared with an age- and gender-matched cohort, participants had markedly higher overall life expectancy (Wilcoxon p = 0.00001) and greater chance of reaching the ages of 80 (81.3% vs 57.6%), 85 (58.1% vs 37.4%), 90 (30.5% vs 22.0%), 95 (11.9% vs 8.8%), and 100 years (3.7% vs 2.8%). In conclusion, Systolic Hypertension in the Elderly Program participants had higher overall life expectancy than actuarial controls and those randomized to active therapy had longer life expectancy free from CV death but had a small increase in the competing risk of non-CV death.The American journal of cardiology 11/2013; · 3.58 Impact Factor
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ABSTRACT: To provide a current perspective on nutrition and physical activity influence on breast cancer. A comprehensive literature review was conducted and selective presentation of findings follows. While some observational studies have associated higher dietary fat intake with higher breast cancer incidence, two full-scale randomized, clinical trials of dietary fat intake reduction programs were negative. However, a lifestyle intervention targeting fat intake reduction in the Women's Intervention Nutrition Study (WINS), resulted in weight loss and also reduced breast cancer recurrences in women with early stage disease. Observational studies evaluating specific nutrient intakes and dietary supplements have provided mixed results. Several observational studies find women with early stage breast cancer with lower 25-hydroxyvitamin D levels at higher recurrence risk, a finding requiring cautious interpretation. The lifestyle factor most strongly and consistently associated with both breast cancer incidence and breast cancer recurrence risk is physical activity. A meta-analyses of observational studies supports the concept that moderate recreational physical activity (about 3-4 h walking per week) may reduce breast cancer incidence and that women with early stage breast cancer who increased or maintain their physical activity may have lower recurrence risk as well. Feasibility of achieving increased physical activity and weight loss in women with early-stage breast cancer has been established. Two full-scale randomized clinical trials are evaluating weight loss/maintenance and increased physical activity in relation to recurrence risk in women with early-stage, resected breast cancer. Dietary intake may influence breast cancer but influence is difficult to separate from influence of body weight. A consistent body of observational study evidence suggests higher physical activity has favorable influence on breast cancer incidence and outcome. While awaiting definitive evidence from ongoing randomized trials, breast cancer patients can reasonably be counseled to avoid weight gain and reduce body weight if overweight or obese and increase or maintain a moderate level of physical activity.Breast (Edinburgh, Scotland) 08/2013; 22S2:S30-S37. · 2.09 Impact Factor
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ABSTRACT: Background:Non-persistence and non-compliance are common in women prescribed hormonal therapy for breast cancer, but little is known about their influence on recurrence.Methods:A nested case-control study of associations between hormonal therapy non-persistence and non-compliance and the risk of early recurrence in women with stage I-III breast cancer was undertaken. Cases, defined as women with a breast cancer recurrence within 4 years of hormonal therapy initiation, were matched to controls (1 : 5) by tumour stage and age. Conditional logistic regression was used to examine associations between early recurrence and hormonal therapy non-persistence and non-compliance.Results:Ninety-four women with breast cancer recurrence were matched to 458 controls. Women who were non-persistent (180 days without hormonal therapy) had a significantly increased adjusted recurrence odds ratio (OR) of 2.88 (95%CI 1.11, 7.46) compared with persistent women. There was no significant association between low compliance (OR 1.30; 95% CI 0.74, 2.30) and breast cancer recurrence.Conclusion:Hormonal therapy non-persistence is associated with a significantly higher risk of early recurrence in women with stage I-III oestrogen receptor (ER)-positive breast cancer. This finding is consistent with results from randomized studies of hormonal therapy treatment duration and suggests that interventions to target modifiable risk factors for non-persistence are required.British Journal of Cancer advance online publication, 3 September 2013; doi:10.1038/bjc.2013.518 www.bjcancer.com.British Journal of Cancer 09/2013; · 5.08 Impact Factor