BNP-Guided Heart Failure Prevention

Abstract & Commentary

By Andrew J. Boyle, MBBS, PhD

Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco

Dr. Boyle reports no financial relationships relevant to this field of study.

Source: Ledwidge M, et al. Natriuretic peptide-based screening and collaborative care for heart failure. The STOP-HF randomized trial. JAMA 2013; 310:66-74.

Financial Disclosure: Clinical Cardiology Alert's Editor, Michael H. Crawford, MD, reports no financial relationships relevant to this field of study, and peer reviewer, Ethan Weiss, MD, is a scientific advisory board member for Bionovo. Managing Editor, Neill Kimball, and Executive Editor, Leslie Coplin, report no financial relationships relevant to this field of study.

Heart failure (HF) is associated with a high mortality rate, debilitating symptoms, impaired quality of life, and major financial costs. As our society ages, the prevalence of heart failure (HF) is increasing. Current treatments for HF are imperfect and prevention of HF is the best possible option. In this study, the authors target patients at risk for developing HF and study a strategy of using serum brain-type natriuretic peptide (BNP) measurement in the primary care setting to guide referral and therapy aids in preventing left ventricular (LV) dysfunction and HF. The study recruited patients from 39 primary care practices in Ireland.

Patients were referred from primary care to the study if they were older than 40 years and had one or more risk factors for developing HF, including hypertension, hyperlipidemia, obesity (body mass index > 30), vascular disease (coronary, peripheral, or cerebral), diabetes, arrhythmia requiring treatment, or moderate/severe valvular disease. Exclusion criteria were the presence of established LV dysfunction or prior HF, or any other cause of limited life expectancy. Patients were randomized 1:1 to intervention (BNP-driven collaborative care between the primary care physician [PCP] and specialist cardiovascular center; n = 697) or control (routine PCP management; n = 677) groups. All patients had BNP testing but the results were only available to the PCP in the intervention group. The control group received advice on lifestyle modification and risk factor intervention as determined by their PCP. In the intervention group, BNP results were made available to the PCP, with protocol-driven echocardiography, referral to a cardiologist, and further lifestyle counseling and management if the BNP was > 50 ng/L. Those with BNP < 50 ng/L received usual care. Patients and treating physicians could not be blinded, but at study completion all patients underwent echocardiography and clinical evaluation by a blinded cardiologist. The primary endpoint was development of LV systolic or diastolic dysfunction with or without HF. Secondary endpoints included emergency hospitalization for arrhythmia, transient ischemic attack, stroke, myocardial infarction, peripheral or pulmonary thrombosis/embolus, or HF.

Patients were followed for 4.2 ± 1.2 years. A total of 263 patients (41.6%) in the intervention group had at least one BNP reading of 50 pg/mL or higher. The primary endpoint of LV dysfunction with or without HF occurred in 59 of 677 (8.7%) in the control group and 37 of 697 (5.3%) in the intervention group (odds ratio [OR] 0.55; P = 0.003). Asymptomatic LV dysfunction was found in 6.6% of control patients and 4.3% of intervention-group patients (OR 0.57; P = 0.01). Heart failure occurred in 2.1% of controls and 1.0% of intervention-group patients (OR 0.48; P = 0.12). The incidence rates of emergency hospitalization for major cardiovascular events were 40.4 per 1000 patient-years in the control group vs 22.3 per 1000 patient-years in the intervention group (incidence rate ratio, 0.60; P = 0.002). The intervention group underwent more cardiovascular investigations (control group, 496 per 1000 patient-years vs intervention group, 850 per 1000 patient-years; incidence rate ratio, 1.71; P < 0.001) and received more renin-angiotensin-aldosterone system (RAAS) inhibitors (control group, 49.6%; intervention group, 56.5%; P = 0.01). Blood pressure reductions were similar in the control and intervention groups. In patients with BNP < 50 ng/L, there was no change in BNP level over the 4.2-year follow-up. However, in those with BNP > 50 ng/L, the BNP level increased over the study period, but the increase was significantly attenuated in the intervention group. The authors conclude that among patients at risk of HF, BNP-based screening and collaborative care reduced the combined rates of LV systolic dysfunction, diastolic dysfunction, and HF.

Commentary

This study is an interesting and important one. First, it confirms that BNP measurement in patients at risk of HF can predict the development of future LV dysfunction. Second, this strategy also reduces emergency admissions to the hospital from a variety of cardiovascular causes. Unfortunately, though, there was no prespecified intervention in this study, so we are left to ponder what it was that resulted in the better outcomes in the intervention group. Was it the increased use of RAAS inhibition? Was it the extra patient counseling that improved compliance? Was it engagement of the patients with the specialist care and the extra diagnostic testing that facilitated a more tailored pharmacological management of these patients? These should all be tested in prospective studies.

Several limitations of this study should be noted. First, it was performed in a small area of Ireland and the results may not be generalizable to other populations. Second, because the participants could not be blinded, there is a possibility of some confounding, which would likely but not definitely create bias toward a negative result. Third, new onset HF was defined as requiring hospitalization for HF. This definition would have missed HF that was treated as an outpatient. Despite these limitations, BNP-guided therapy for patients at risk for HF seems to be a reasonable strategy. I hope we will see a formal cost-effectiveness analysis from this dataset, as the intervention group had higher rates of diagnostic testing but lower rates of hospitalization, and the overall effect on health care budgets remains unknown.