Use of B-Type Natriuretic Peptide (BNP) and N-Terminal proBNP (NT-proBNP) as Diagnostic Tests in Adults With Suspected Heart Failure: A Health Technology Assessment

Abstract

Background: Heart failure is a complex clinical syndrome that usually presents with breathlessness, leg edema, and fatigue. Clinically measurable natriuretic neurohormones such as B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are elevated in people with heart failure. We conducted a health technology assessment of BNP and NT-proBNP tests for people with suspected heart failure, which included an evaluation of diagnostic accuracy, clinical impact, cost-effectiveness, the budget impact of publicly funding BNP and NT-proBNP tests, and patient preferences and values.

Methods: We performed a literature search of previously published systematic reviews of the clinical evidence. We conducted an overview of reviews and included only reviews with a low risk of bias as assessed using the Risk of Bias in Systematic Reviews tool (ROBIS). We excluded any reviews where we found 100% overlap of included primary studies and selected systematic reviews or health technology assessments published after 2006 for inclusion.We performed an economic literature review of BNP and NT-proBNP testing in people with suspected heart failure. Medical and health economic databases were searched from database inception until July 25, 2019. Next, we assessed the cost-effectiveness of BNP and NT-proBNP based on the published economic literature. We transferred the cost-effectiveness results of two applicable, recent economic evaluations from the National Institute for Health and Care Excellence (NICE) to the Ontario setting in lieu of conducting de novo primary economic evaluations. We also estimated the budget impact of publicly funding BNP and NT-proBNP tests in people with suspected heart failure in Ontario over the next 5 years.To contextualize the potential value of BNP and NT-proBNP testing, we spoke with people with suspected heart failure.

Results: We included eight systematic reviews in the clinical evidence review. B-type natriuretic peptides and NT-proBNP had a high pooled sensitivity (80% to 94% and 86% to 96%, respectively; strength of evidence: high) and a low pooled negative likelihood ratio (0.08-0.30 and 0.09-0.23, respectively; strength of evidence: not reported) within varying thresholds or cut points and settings, as reported in seven systematic reviews. In one systematic review, when BNP or NT-proBNP was used in the diagnosis of heart failure in the emergency department (ED), there was a decrease in the mean length of hospital stay (-1.22 days; confidence interval [CI] -2.31 to -0.14; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] Working Group criteria: Moderate). B-type natriuretic peptide testing did not reduce hospital admission rates (odds ratio [OR]: 0.82; CI: 0.67-1.01; GRADE: Moderate), 30-day hospital readmission rates (OR: 0.88; CI: 0.64-1,20; GRADE: Moderate), or hospital mortality rates (OR: 0.96; CI: 0.65-1.41; GRADE: Moderate). No systematic review was identified that addressed the impact on clinical outcomes of BNP use in the community setting.Our economic literature review found a total of 12 studies evaluating the cost-effectiveness of BNP or NT-proBNP testing in patients with suspected heart failure. The studies suggested that BNP or NT-proBNP tests, when used in addition to standard clinical investigations, were either dominant (less costly and more effective) or cost-effective across different countries (including Canada) and settings.Two economic evaluations conducted by NICE were considered applicable to our research question and of high methodological quality. Based on the transferred results from the two NICE economic evaluations, we concluded that BNP and NT-proBNP were highly likely to be cost-effective in Ontario in the ED setting, and NT-proBNP was highly likely to be cost-effective in the community care setting.Our budget impact analysis estimated that over the next 5 years, publicly funding BNP and NT-proBNP tests would result in an additional cost of $38 million in the ED (at a cost of $75 per test) and a cost savings of $20 million in community care (at a cost of $28 per test).We received strong support from interview participants about BNP or NT-proBNP diagnostic testing. The main reason was the perceived potential benefit of receiving a speedier diagnosis. The overall process, from diagnosis to treatment, is a substantial emotional burden for patients and caregivers, and for those living further away from secondary or tertiary care settings. An earlier diagnosis could allow patients to receive treatment at a hospital better equipped to manage their potentially fatal symptoms and conditions.

Conclusions: B-type natriuretic peptide and NT-proBNP tests have high sensitivity and low negative likelihood ratio, suggesting that concentrations of either natriuretic peptides within the appropriate cut points can rule out the presence of heart failure with a high degree of confidence. Additionally, BNP or NT-proBNP testing along with usual care in an ED setting likely can reduce the length of hospital stay by at least 1 day but likely results in little to no difference in hospital mortality, 30-day readmission, or admission rates to hospital.Based on the published economic literature, we expected BNP or NT-proBNP tests used in addition to standard clinical investigations to be cost-effective as a rule-out test in patients with suspected heart failure in Ontario. If BNP and NT-proBNP tests are publicly funded in Ontario, we estimated that there would be additional costs in the ED setting (due to increased detection of heart failure) and savings in community care (due to reduced referrals to echocardiography and cardiologists).People we interviewed gave BNP and NT-proBNP testing strong support, citing the perceived benefits of quicker, more accurate diagnoses that could reduce misdiagnoses, stress, and the burden on patients and caregivers.

Figure 1:. PRISMA Flow Diagram—Clinical Search Strategy

Figure 2:. PRISMA Flow Diagram—Economic Search Strategy

Figure 3:. Cost-Effectiveness Acceptability Curve–Standard Clinical Investigations With BNP Versus Standard Clinical Investigations Alone in the Emergency Department Setting

Figure 4:. Cost-Effectiveness Acceptability Curve–Standard Clinical Investigations With NT-proBNP Versus Standard Clinical Investigations Alone in the Emergency Department Setting

Figure 5:. Cost-Effectiveness Acceptability Curve—NT-proBNP 125 pg/mL Versus Echocardiography for All in the Community Care Setting

Figure 6:. Budget Impact Model Schematic

Figure 7:. Flow Diagram for Estimating the Number of People With No History of Heart Failure

Figure 8:. Flow Diagram for Estimating the Number of People With History of Heart Failure

Figure 9:. Model Structures–Natriuretic Peptide Testing for Suspected Heart Failure