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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).

AbstractBACKGROUND:
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 1.73 m(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.
AuthorsJalal K Ghali, John Wikstrand, Dirk J Van Veldhuisen, Björn Fagerberg, Sidney Goldstein, Ake Hjalmarson, Peter Johansson, John Kjekshus, Lis Ohlsson, Ola Samuelsson, Finn Waagstein, Hans Wedel, MERIT-HF Study Group
JournalJournal of cardiac failure (J Card Fail) Vol. 15 Issue 4 Pg. 310-8 (May 2009) ISSN: 1532-8414 [Electronic] United States
PMID19398079 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic beta-Antagonists
  • Metoprolol
Topics
  • Adrenergic beta-Antagonists (pharmacology, therapeutic use)
  • Aged
  • Chronic Disease
  • Feeding Behavior (physiology)
  • Female
  • Glomerular Filtration Rate (drug effects, physiology)
  • Heart Failure, Systolic (diet therapy, drug therapy, physiopathology)
  • Hospitalization (trends)
  • Humans
  • Kidney (drug effects, physiology)
  • Kidney Function Tests (trends)
  • Male
  • Metoprolol (pharmacology, therapeutic use)
  • Middle Aged
  • Prospective Studies

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