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).
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).


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.
Ghali
Jalal K
JK
Detroit Medical Center, Detroit, Michigan, USA.
Wikstrand
John
J
Van Veldhuisen
Dirk J
DJ
Fagerberg
Björn
B
Goldstein
Sidney
S
Hjalmarson
Ake
A
Johansson
Peter
P
Kjekshus
John
J
Ohlsson
Lis
L
Samuelsson
Ola
O
Waagstein
Finn
F
Wedel
Hans
H
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000368:Aged; D002908:Chronic Disease; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D054143:Heart Failure, Systolic / Q000178:diet therapy / Q000188:drug therapy* / Q000503:physiopathology*; D006760:Hospitalization / Q000639:trends; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007677:Kidney Function Tests / Q000639:trends; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies
D000319:Adrenergic beta-Antagonists; D008790:Metoprolol