Statins and Exercise Training Response in Heart Failure Patients: Insights From HF-ACTION.

OBJECTIVES: The aim of this study was to assess for a treatment interaction between statin use and exercise training (ET) response. BACKGROUND: Recent data suggest that statins may attenuate ET response, but limited data exist in patients with heart failure (HF). METHODS: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized trial of 2,331 patients with chronic HF with ejection fraction ≤35% who were randomized to usual care with or without ET. We evaluated whether there was a treatment interaction between statins and ET response for the change in quality of life and aerobic capacity (peak oxygen consumption and 6-min walk distance) from baseline to 3 months. We also assessed for a treatment interaction among atorvastatin, simvastatin, and pravastatin and change in these endpoints with ET. Multiple linear regression analyses were performed for each endpoint, adjusting for baseline covariates. RESULTS: Of 2,331 patients in the HF-ACTION trial, 1,353 (58%) were prescribed statins at baseline. Patients treated with statins were more likely to be older men with ischemic HF etiology but had similar use of renin angiotensin system blockers and beta-blockers. There was no evidence of a treatment interaction between statin use and ET on changes in quality of life or exercise capacity, nor was there evidence of differential association between statin type and ET response for these endpoints (all p values \u3e0.05). CONCLUSIONS: In a large chronic HF cohort, there was no evidence of a treatment interaction between statin use and short-term change in aerobic capacity and quality of life with ET. These findings contrast with recent reports of an attenuation in ET response with statins in a different population, highlighting the need for future prospective studies. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437)

Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ( guided therapy ) with inconsistent results. Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Interventions: Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. Main Outcomes and Measures: The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Results: The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. Conclusions and Relevance: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01685840

Uncovering the emotional aspects of working on a clinical trial: a qualitative study of the experiences and views of staff involved in a type 1 diabetes trial

Background The perspectives and experiences of trial staff are increasingly being investigated as these can be used to improve recruitment, adherence to trial protocols and support given to future staff. We interviewed staff working on a type 1 diabetes trial in order to aid interpretation of trial findings, inform recommendations for the rollout of the treatments investigated and provide recommendations for the conduct of future trials. However, our interviews uncovered aspects of trial work erstwhile unrecognised or underreported in the trials literature, and it is these which form the focus of this paper. Methods In-depth interviews were conducted with (n = 18) staff, recruited from seven centres, who were involved in recruitment and trial delivery. Data were analysed thematically. Results Alongside logistical and practical issues which made trial work challenging, staff often talked spontaneously and at length about how trial work had affected them emotionally. Staff not only described the emotional stresses arising from having to meet recruitment targets and from balancing research roles with clinical responsibilities, they also discussed having to emotionally manage patients and their colleagues. The emotional aspects of trial work particularly came to the fore when staff notified patients about their treatment allocation. On such occasions, staff described having to employ emotional strategies to pre-empt and manage potential patient disappointment and anger. Staff also described having to manage their own emotions when patients withdrew from the trial or were not randomised to the treatment arm which, in their clinical judgment, would have been in their best interests. To help address the emotional challenges they encountered, staff highlighted a need for more practical, emotional and specialist psychological support. Conclusions More attention should be paid to the emotional aspects of trial work to help ensure trial staff are adequately supported. Such support could comprise: increased training for staff to improve their own and patients’ understandings of randomization, role-play to develop techniques to manage patient anger and disappointment, sharing of good practice, formalised team support with psychological input and access to specialist psychological support to troubleshoot complex emotional and ethical issues

Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.

OBJECTIVES: The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of BACKGROUND: Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF. METHODS: GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of CONCLUSIONS: The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)

Advancing Research on the Complex Interrelations Between Atrial Fibrillation and Heart Failure A Report From a US National Heart, Lung, and Blood Institute Virtual Workshop

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF

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

Supporting self-management after attending a structured education programme: a qualitative longitudinal investigation of type 1 diabetes patients’ experiences and views

Background: Structured education programmes for patients with diabetes and other chronic conditions are being widely adopted. However, follow-up studies suggest that course graduates may struggle to sustain the self-care practices taught on their courses over time. This study explored the support needs of patients with type 1 diabetes after attending a structured education programme promoting an empowerment approach and training in use of flexible intensive insulin therapy, a regimen now widely advocated and used to manage this condition. The objective was to inform future support offered to course graduates. Methods: Repeat, in-depth interviews with 30 type 1 diabetes patients after attending Dose Adjustment for Normal Eating (DAFNE) courses in the UK, and six and 12 months later. Data were analysed using an inductive, thematic approach. Results: While the flexible intensive insulin treatment approach taught on DAFNE courses was seen as a logical and effective way of managing one’s diabetes, it was also considered more technically complex than other insulin regimens. To sustain effective disease self-management using flexible intensive insulin treatment over time, patients often expected, and needed, on-going input and support from health care professionals trained in the approach. This included: help determining insulin dose adjustments; reassurance; and, opportunities to trouble-shoot issues of concern. While some benefits were identified to receiving follow-up support in a group setting, most patients stated a preference or need for tailored and individualised support from appropriately-trained clinicians, accessible on an ‘as and when needed’ basis. Conclusions: Our findings highlight potential limitations to group-based forms of follow-up support for sustaining diabetes self-management. To maintain the clinical benefits of structured education for patients with type 1 diabetes over time, course graduates may benefit from and prefer ongoing, one-to-one support from health care professionals trained in the programme’s practices and principles. This support should be tailored and personalised to reflect patients’ specific and unique experiences of applying their education and training in the context of their everyday lives, and could be the subject of future research