Therapeutics

Review: Natriuretic peptide–guided therapy reduces mortality more than clinically guided therapy in heart failure

Troughton RW, Frampton CM, Brunner-La Rocca HP, et al. Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient metaanalysis. Eur Heart J. 2014;35:1559-67.

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Commentary

In chronic heart failure (HF), how do natriuretic peptide–guided (NP-guided) therapy and clinically guided therapy compare for mortality?

The meta-analysis by Troughton and colleagues shows that NPguided therapy in chronic HF reduces all-cause mortality as well as hospitalizations due to HF or cardiovascular disease more than clinically guided therapy. The IPD-level, rather than aggregatelevel, meta-analysis is a strength of the review because it allows for analysis of subgroups and treatment effects across studies. The choice of all-cause mortality as the primary endpoint is another strength—this outcome is clinically relevant and, unlike a diseasespecific outcome such as cardiovascular death, is not subject to the potential bias of adjudication or competing risk from other outcomes related to treatment (e.g., death from hyperkalemia).

Review scope Included studies compared B-type NP-guided therapy with clinically guided therapy for HF and reported all-cause mortality or robust secondary outcome results. Outcomes included all-cause mortality and hospitalization for HF during the treatment period.

Review methods MEDLINE and EMBASE/Excerpta Medica (both 2000 to Feb 2012), Cochrane Controlled Clinical Trials Register, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs). 11 RCTs (n = 2431, mean age 72 y, 67% men), ranging in size from 60 to 499 patients, met the selection criteria. {Treatment durations ranged from 90 days to 3 years.}* Individual patient data (IPD) were available from 8 RCTs for all-cause mortality and from 9 RCTs for hospitalization for HF.

Main results IPD meta-analyses showed that NP-guided therapy reduced mortality and HF hospitalizations more than clinically guided therapy during the treatment period (Table). Subgroup analyses showed that NP-guided therapy reduced mortality in patients aged < 75 years (hazard ratio [HR] 0.62, 95% CI 0.45 to 0.85) but not in patients aged ≥ 75 years (HR 0.98, CI 0.75 to 1.3) (P = 0.028 for interaction). At study end, the mean dose of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II–receptor blockers (ARBs) was at 70% of target values in the NP-guided group and 60% in the clinically guided group.

Conclusion In chronic heart failure, natriuretic peptide–guided therapy reduces mortality more than clinically guided therapy. *Information provided by author.

Source of funding: No external funding. For correspondence: Dr. R.W. Troughton, Christchurch Hospital, Christchurch, New Zealand. E-mail [email protected]. ■ Natriuretic peptide–guided (NP-guided) vs clinically guided therapy in chronic heart failure† Outcomes

Number of trials (n)

Event During treatment period rates (90 d to 3 y) NP- Clinically RRR (95% CI) NNT (CI) guided guided

Mortality

8 (2000)

17%

21%

35% (13 to 52) 14 (10 to 39)

Hospitalization for heart failure

9 (2151)

23%

27%

18% (5 to 30)

21 (13 to 71)

†Abbreviations defined in Glossary. RRR, NNT, and CI calculated from control event rates and adjusted hazard ratios in article. Analyses include studies with individual patient data available.

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© 2014 American College of Physicians

Troughton and colleagues speculate that the reduction in all-cause mortality may be related to higher dosing of ACEIs or ARBs in the NP-guided group; however, there are 2 arguments against this being the sole mechanism of benefit. First, an RCT studying ACEIs in 3164 patients with HF showed no reduction in all-cause mortality with high-dose compared with low-dose lisinopril, and only a small reduction in hospitalization with a 7-fold higher average dose of ACEIs in the high-dose lisinopril group (1). In the analysis by Troughton and colleagues, a 1.1-fold higher ACEI/ ARB dose in the NP-guided group could not be expected to reduce the rate of all-cause mortality by 38%. Second, the variation in ACEI/ARB dosing between NP-guided and clinically guided groups does not explain why NP-guided therapy reduced mortality in younger (< 75 y) but not older patients (≥ 75 y). Whether the 2 treatment groups differed in frequency or tolerability of medication dose changes, or in the time to reach maximum tolerated dose of each class of drugs, is unclear. The beneficial effect of NP-guided therapy in patients with preserved ejection fraction needs to be interpreted with caution, as < 10% of patients had a left ventricular ejection fraction (LVEF) > 45%. NPs may be more sensitive than clinical assessment alone for determining cardiac loading conditions and for predicting risk. Mechanisms of benefit of NP-guided therapy could include more reliable risk assessment and earlier detection of decompensation— with a tailored treatment response—in patients who may otherwise be challenging to assess clinically. The meta-analysis by Troughton and colleagues provides evidence that an NP-guided treatment strategy should be considered in younger patients with chronic HF and reduced LVEF. The effect of NP-guided therapy in older patients and in those with preserved LVEF warrants further investigation. Harriette G.C. Van Spall, MD, MPH, FRCPC McMaster University and Population Health Research Institute Hamilton, Ontario, Canada Reference 1. Packer M, Poole-Wilson PA, Armstrong PW, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation. 1999;100:2312-8.

19 August 2014 | ACP Journal Club | Volume 161 • Number 4

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ACP Journal Club. Review: Natriuretic peptide-guided therapy reduces mortality more than clinically guided therapy in heart failure.

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