The Influence of Renal Function on Clinical Outcome and Response to beta-Blockade in Systolic Heart Failure: Insights From Metoprolol CR/XL Randomized Intervention Trial in Chronic HF (MERIT-HF)

Jalal K. Ghali*, John Wikstrand, Dirk J. Van Veldhuisen, Bjorn Fagerberg, Sidney Goldstein, Ake Hjalmarson, Peter Johansson, John Kjekshus, Lis Ohlsson, Ola Samuelsson, Finn Waagstein, Hans Wedel, MERIT-HF Study Grp

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

64 Citations (Scopus)

Abstract

Background: Limited information is available on the risk and impact of renal dysfunction on the response to beta-blockade and mode of death in systolic heart failure (HF).

Methods and Results: Renal function was estimated with glomerular filtration rate (eGFR) using the simplified Modification of Diet in Renal Disease (MDRD) equation. Patients from the Metoprolol CR/XL Controlled Randomized Intervention Trial in Chronic HF (MERIT-HF) were divided into 3 renal function subgroups (MDRD formula): eGFR(MDRD) > 60 (n = 2496), eGFR(MDRD) 45 to 60 (n = 976), and eGFR(MDRD) <45 mL/min per 1.73m(2) body surface area (n = 493). Hazard ratio (HR) was estimated with Cox proportional hazards models adjusted for prespecified risk factors. Placebo patients with eGFR <45 had significantly higher risk than those with eGFR > 60: HR for all-cause mortality, 1.90 (95% confidence interval [CI], 1.28 to 2.81) comparing placebo patients with eGFR <45 and eGFR > 60, and for the combined end point of all-cause mortality/hospitalization for worsening HF (time to first event): HR, 1.91 (95% CI, 1.44 to 2.53). No significant increase in risk with deceased renal function was observed for those randomized to metoprolol controlled release (CR)/extended release (XL) due to a highly significant decrease in risk on metoprolol CR/XL in those with eGFR <45. For total mortality, metoprolol CR/XL vs placebo: HR, 0.41 (95% CI. 0.25 to 0.68; P <.001) in those with eGFR <45 compared with HR, 0.71 (95% CI, 0.54 to 0.95; P <.021) for those with eGFR > 60; corresponding data for the combined end point was HR. 0.44 (95% CI, 0.31 to 0.63; P <.0001) and HR, 0.75 (0.62 to 0.92; P = .005, respectively; P = .095 for interaction by treatment for total mortality; P = .011 for combined end point). Metoprolol CR/XL was well tolerated in all 3 renal function subgroups.

Conclusions: Renal function as estimated by eGFR was a powerful predictor of death and hospitalizations from worsening HF. Metoprolol CR/XL was at least as effective in reducing death and hospitalizations for worsening HF in patients with eGFR <45 as in those with eGFR > 60. (J Cardiac Fail 2009;15:310-318)

Original languageEnglish
Pages (from-to)310-318
Number of pages9
JournalJOURNAL OF CARDIAC FAILURE
Volume15
Issue number4
DOIs
Publication statusPublished - May-2009

Keywords

  • Heart failure
  • renal dysfunction
  • beta-blockade
  • PLACEBO-CONTROLLED TRIAL
  • CHRONIC KIDNEY-DISEASE
  • DIALYSIS PATIENTS
  • SYMPATHETIC HYPERACTIVITY
  • DILATED CARDIOMYOPATHY
  • MYOCARDIAL-INFARCTION
  • RELEASE METOPROLOL
  • ASSOCIATION
  • DYSFUNCTION
  • INSUFFICIENCY

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