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Effect of beta‐1 adrenergic receptor polymorphisms on the tolerability of metoprolol CR/XL in heart failure
Author(s) -
Terra S. G.,
Pauly D. F.,
Lee C. R.,
Patterson J.,
Adams K. F.,
Schofield R. S.,
Hamilton K. K.,
Hill J. A.,
Aranda J. M.,
Johnson J. A.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.059
Subject(s) - tolerability , metoprolol , medicine , heart failure , heart rate , beta blocker , clinical pharmacology , blood pressure , pharmacology , anesthesia , cardiology , adverse effect
β 1 ‐adrenergic receptor (β 1 AR) polymorphisms at codons (c) 49 (Ser49Gly) and 389 (Arg389Gly) have functional effects and have been associated with the blood pressure lowering effect of β‐blockers. We hypothesized that these polymorphisms would be associated with differences in initial tolerability of β‐blocker therapy in heart failure (HF) patients. We prospectively enrolled 60 β‐blocker naïve patients with NYHA II‐III systolic HF. Patients were initiated on metoprolol CR/XL (MXL) 12.5‐25 mg and titrated q 2 weeks (as tolerated) to 200 mg/day or maximum tolerated dose over 8 weeks. Tolerability to MXL was assessed by the Minnesota Living with HF questionnaire (MLWHF), 6‐minute walk distance (6‐min WD), and final MXL dose. Decompensation was defined as death, HF hospitalization, increase in other HF meds, or need to discontinue MXL over a 6‐month period. Response data by c389 revealed no significant differences across genotype in any measure (Table). At baseline, Gly49 carriers demonstrated lower 6–min WD compared to Ser49Ser (346 meters vs. 296 meters, p=0.06). There were no significant differences in end of study response by c49 genotype; decompensated HF occurred in 35% of Ser49Ser patients and 29% of Gly49 carriers. In conclusion, the c49 and 389 polymorphisms of the β 1 AR do not appear to be associated with the initial tolerability of β‐blockers in HF patients. Table Clinical Pharmacology & Therapeutics (2004) 75 , P16–P16; doi: 10.1016/j.clpt.2003.11.059 Response Stratified by c389 Genotype (mean ± SE, unless noted)Arg389Arg; n = 28 Gly 389 Carriers; n = 32 P *Baseline Final Baseline FinalDecompensation, n(%) 7 (25%) 13 (40%) 0.27 6‐min WD (meters) 330 ± 21 357 ± 27 298 ± 13 302 ± 18 0.09 MLWHF 28 ± 4 21 ± 4 37 ± 4 31 ± 3 0.10 HR (bpm) 80 ± 2 >64 ± 2 79 ± 1 70 ± 2 0.10 SBP (mm Hg) 120 ± 3 110 ± 4 119 ± 3 110 ± 3 0.97 MXL Dose (mg/day) 119 ± 13 100 ± 13 0.34* Final comparison.