IntroductionStudies have shown sex-specific differences regarding CAD and heart failure with left ventricular (LV) dysfunction. Whether these differences impact the benefit of CABG in patients with ...ischemic LV dysfunction has not been studied prospectively. Female sex is conventionally considered a risk factor for open-heart surgery, and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We investigated the impact of sex on the long-term benefit of CABG in patients enrolled in the prospective Surgical Treatment for Ischemic Heart Failure Study (STICH) trial.MethodThe STICH trial randomized 1212 patients 148 (12%) women and 1064 (88%) men with CAD and EF≤ 35% to medical therapy alone (MED) versus MED plus CABG. Long-term (10-year) outcomes with each treatment were compared according to sex.ResultsAt baseline, women were older with higher BMI and more CAD risk factors (e.g. diabetes) except for smoking, and had lower rates of prior CABG than men (all p<0.05). Moreover, women had higher NYHA class, lower 6-min walk capacity and lower Kansas City Cardiomyopathy Questionnaire scores (all p<0.05). At 10-year follow up, the all-cause mortality rate (HR 0.70, CI 0.55-0.89, adjusted p=0.002) and CV mortality rate (HR 0.64, CI 0.48-0.86, adjusted p=0.006) were significantly lower in women than men. Furthermore, with randomization to CABG vs. MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, CV mortality, mortality or CV hospitalization (all p>0.05, Figure 1). In addition, surgical deaths were similar for both sexes among patients randomized to CABG.ConclusionSex does not impact the effect of CABG on all-cause mortality, CV mortality, CV hospitalization or surgical deaths in patients with ischemic LV dysfunction. Thus, sex should not influence treatment decisions regarding CABG in these patients.
Rationale Using inhaled corticosteroids (ICS) concomitantly with rescue inhalers (Patient-Activated Reliever-Triggered ICS; ‘PARTICS’) reduces asthma exacerbations in efficacy trials, but has not ...been tested in pragmatic trials with highly-impacted asthma populations. Barriers to completing study procedures included having difficulty with log-in access to electronic questionnaires (30%, 38% at 6, 12 weeks, respectively), remembering to use ICS and rescue inhalers together (20%), and obtaining refills (19%).
Abstract only
Introduction:
Whether echocardiographic (echo) markers of left ventricular (LV) remodeling and diastolic dysfunction contribute incremental and independent prognostic information to ...clinical risk markers in patients (Pts) with coronary artery disease and severe LV systolic dysfunction is unclear. We sought to determine which echo variables provide the greatest prognostic value in the Surgical Treatment for Ischemic Heart Failure (STICH) population.
Methods:
Pts enrolled in STICH for whom transmitral Doppler (E/A ratio) was available on a baseline echo interpreted by an echo core laboratory blinded to treatment and outcomes formed the analysis cohort. Comprehensive datasets to account for missing echo data were created by multiple imputation and the impact on all-cause mortality was determined with the Cox’s regression model.
Results:
E/A ratio could be measured in 1511 of the 2136 Pts enrolled in STICH. Amongst markers of diastolic dysfunction, E/A ratio was the most significant predictor of mortality (χ
2
41.05, p <0.001) with a non-linear, u-shaped, relationship. Mortality was lowest with E/A ratio = 1.0, and increased for E/A ratio <0.6 and >1.0 up to 2.3, beyond which there was no further increase in risk. The combination of larger LV end-systolic volume index (LVESVI), low or high E/A ratio, and mitral regurgitation severity grade, had highly significant incremental negative effects on mortality (χ
2
69.65, p<0.001) when added to a multivariable model with clinical risk markers. Overall, creatinine (χ
2
30.00, p <0.001), followed by LVESVI (χ
2
27.26, p<0.001), age, and E/A ratio (χ
2
12.46, p<0.001) were among the most significant predictors of mortality and accounted for 74% of the total prognostic information. LVESVI and E/A ratio were stronger predictors of poor prognosis than New York Heart Association (NYHA) functional class, hemoglobin, diabetes, stroke, or atrial fibrillation.
Conclusions:
Echo markers of advanced LV remodeling and diastolic dysfunction add incremental prognostic value to clinical risk markers and are more predictive of poor prognosis than advanced NYHA functional class or anemia. LVESVI and E/A ratio outperformed other echo markers and should be considered standard in assessing risk in Pts with ischemic LV dysfunction.
To assess the influence of therapy crossovers on treatment comparisons and mortality at 5 years in patients with ischemic heart disease and heart failure randomly assigned to medical therapy alone ...(MED) or to MED and coronary artery bypass graft (CABG) surgery in the Surgical Treatment for Ischemic Heart Failure (STICH) trial.
The influence of early crossover (within the first year after randomization) on 5-year mortality was assessed using time-dependent multivariable Cox models. CABG was performed in 65/602 patients (10.8%) assigned to MED, and 55/610 patients (9.0%) assigned to CABG received MED only. Common reasons for crossover from MED to CABG were progressive symptoms or acute decompensation. MED-assigned patients who underwent CABG had lower 5-year mortality than those who received MED only (25% vs 42%; hazard ratio, 0.50; 95% confidence interval, 0.30-0.85; P=0.008).The main reason for crossover from CABG to MED was patient/family decision. Five patients did not undergo their assigned CABG within a year but died before receiving surgery without status change. They were deemed crossover to MED. The CABG-to-MED crossover population had higher 5-year mortality compared with those treated with CABG per-protocol (59% vs 33%; hazard ratio, 2.01; 95% confidence interval, 1.36-2.96; P<0.001). CABG was associated with lower mortality compared with MED in per-protocol and several time-dependent analyses (all P<0.05).
CABG reduced mortality in both the per-protocol and crossover STICH patient populations. Crossover from assigned therapy, therefore, diminished the impact of CABG on survival in STICH when analyzed by intention to treat.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.
The objective of this study was to assess the prognostic significance of exercise capacity in patients with ischemic left ventricular (LV) dysfunction eligible for coronary artery bypass graft ...surgery (CABG).
Poor exercise capacity is associated with mortality, but it is not known how this influences the benefits and risks of CABG compared with medical therapy.
In an exploratory analysis, physical activity was assessed by questionnaire and 6-min walk test in 1,212 patients before randomization to CABG (n = 610) or medical management (n = 602) in the STICH (Surgical Treatment for Ischemic Heart Failure) trial. Mortality (n = 462) was compared by treatment allocation during 56 months (interquartile range: 48 to 68 months) of follow-up for subjects able (n = 682) and unable (n = 530) to walk 300 m in 6 min and with less (Physical Ability Score PAS >55, n = 749) and more (PAS ≤55, n = 433) limitation by dyspnea or fatigue.
Compared with medical therapy, mortality was lower for patients randomized to CABG who walked ≥300 m (hazard ratio HR: 0.77; 95% confidence interval CI: 0.59 to 0.99; p = 0.038) and those with a PAS >55 (HR: 0.79; 95% CI: 0.62 to 1.01; p = 0.061). Patients unable to walk 300 m or with a PAS ≤55 had higher mortality during the first 60 days with CABG (HR: 3.24; 95% CI: 1.64 to 6.83; p = 0.002) and no significant benefit from CABG during total follow-up (HR: 0.95; 95% CI: 0.75 to 1.19; p = 0.626; interaction p = 0.167).
These observations suggest that patients with ischemic left ventricular dysfunction and poor exercise capacity have increased early risk and similar 5-year mortality with CABG compared with medical therapy, whereas those with better exercise capacity have improved survival with CABG. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease STICH; NCT00023595).
Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ...ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction.
In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor-α receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: χ(2)=40.6; P<0.0001 and sTNFR-1: χ(2)=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ(2)=30.3) and sTNFR-1 (χ(2)=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ(2)=6.0; P=0.049) and sTNFR-1 (χ(2)=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ≤0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement.
Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.
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