Table 1.
Baseline characteristics of study patients initiating carvedilol and metoprolol
| Characteristic | Unweighted | Weighted | ||||
|---|---|---|---|---|---|---|
| Carvedilol n = 9,558 | Metoprolol n = 17,506 | Std diffa | Carvedilol n = 9,533 | Metoprolol n = 17,521 | Std diffa | |
| Age (y) | 59.8 ±14.4 | 59.5 ±14.9 | 0.026 | 59.8 ± 14.4 | 59.5 ± 14.9 | 0.026 |
| Female sex | 4,314 (45.1%) | 8,316 (47.5%) | 0.048 | 4,444 (46.6%) | 8,183 (46.7%) | 0.002 |
| Race | ||||||
| White | 4,848 (50.7%) | 9,054 (51.7%) | 0.020 | 4,881 (51.2%) | 8,991 (51.3) | 0.002 |
| Black | 4,186 (43.8%) | 7,419 (42.4%) | 0.029 | 4,103 (43.0%) | 7,524 (42.9%) | 0.002 |
| Other | 524 (5.5%) | 1,033 (5.9%) | 0.018 | 549 (5.8%) | 1,006 (5.7%) | 0.001 |
| Hispanic ethnicity | 1,925 (20.1%) | 3,351 (19.1%) | 0.025 | 1,874 (19.7%) | 3,428 (19.6%) | 0.002 |
| Low-income subsidy | 7,259 (75.9%) | 13,524 (77.3%) | 0.031 | 7,328 (76.9%) | 13,463 (76.8%) | 0.001 |
| Year index beta-blocker was prescribed | ||||||
| 2007 | 1,339 (14.0%) | 3,364 (19.2%) | 0.140 | 1,631 (17.1%) | 3,034 (17.3%) | 0.005 |
| 2008 | 1,385 (14.5%) | 3,011 (17.2%) | 0.074 | 1,534 (16.1%) | 2,833 (16.2%) | 0.002 |
| 2009 | 1,440 (15.1%) | 2,561 (14.6%) | 0.012 | 1,406 (14.8%) | 2,588 (14.8%) | 0.000 |
| 2010 | 1,524 (15.9%) | 2,696 (15.4%) | 0.015 | 1,497 (15.7%) | 2,736 (15.6%) | 0.002 |
| 2011 | 1,804 (18.9%) | 2,852 (16.3%) | 0.068 | 1,665 (17.5%) | 3,029 (17.3%) | 0.005 |
| 2012 | 2,066 (21.6%) | 3,022 (17.3%) | 0.110 | 1,801 (18.9%) | 3,302 (18.8%) | 0.001 |
| Cause of ESRD | ||||||
| Diabetes | 5,027 (52.6%) | 8,227 (47.0%) | 0.112 | 4,703 (49.3%) | 8,606 (49.1%) | 0.004 |
| Hypertension | 2,563 (26.8%) | 5,051 (28.9%) | 0.045 | 2,686 (28.2%) | 4,927 (28.1%) | 0.001 |
| Glomerular disease | 909 (9.5%) | 1,936 (11.1%) | 0.051 | 982 (10.3%) | 1,828 (10.4%) | 0.004 |
| Other | 1,059 (11.1%) | 2,292 (13.1%) | 0.062 | 1,163 (12.2%) | 2,160 (12.3%) | 0.004 |
| Body mass index | ||||||
| < 18.5 kg/m2 | 474 (5.0%) | 844 (4.8%) | 0.006 | 464 (4.9%) | 854 (4.9%) | 0.000 |
| 18.5 – 24.9 kg/m2 | 3,555 (37.2%) | 6,285 (35.9%) | 0.027 | 3,475 (36.5%) | 6,371 (36.4%) | 0.002 |
| 25.0 – 29.9 kg/m2 | 2,761 (28.9%) | 4,978 (28.4%) | 0.010 | 2,719 (28.5%) | 5,005 (28.6%) | 0.001 |
| ≥ 30.0 kg/m2 | 2,768 (29.0%) | 5,399 (30.8%) | 0.041 | 2,875 (30.2%) | 5,292 (30.2%) | 0.001 |
| History of prior kidney transplantation | 502 (5.3%) | 1,204 (6.9%) | 0.068 | 594 (6.2%) | 1,103 (6.3%) | 0.003 |
| Dialysis vintage | ||||||
| 0.7 – 0.9 years | 595 (6.2%) | 935 (5.3%) | 0.038 | 536 (5.6%) | 988 (5.6%) | 0.001 |
| 1.0 – 1.9 years | 2,118 (22.2%) | 3,705 (21.2%) | 0.024 | 2,053 (21.5%) | 3,778 (21.6%) | 0.001 |
| 2.0 – 2.9 years | 1,668 (17.5%) | 2,778 (15.9%) | 0.042 | 1,556 (16.3%) | 2,875 (16.4%) | 0.002 |
| ≥ 3.0 years | 5,177 (54.2%) | 10,088 (57.6%) | 0.070 | 5,388 (56.5%) | 9,881 (56.4%) | 0.003 |
| CV admission during the last 30 d of baseline | 1,801 (18.8%) | 2,815 (16.1%) | 0.073 | 1,618 (17.0%) | 2,989 (17.1%) | 0.002 |
| Atrial fibrillation | 1,236 (12.9%) | 2,525 (14.4%) | 0.043 | 1,300 (13.6%) | 2,426 (13.8%) | 0.006 |
| Other arrhythmia | 930 (9.7%) | 1,630 (9.3%) | 0.014 | 906 (9.5%) | 1,657 (9.5%) | 0.002 |
| Angina | 210 (2.2%) | 302 (1.7%) | 0.034 | 182 (1.9%) | 334 (1.9%) | 0.000 |
| Cancer | 312 (3.3%) | 661 (3.8%) | 0.028 | 335 (3.5%) | 627 (3.6%) | 0.003 |
| Conduction disorder | 367 (3.8%) | 496 (2.8%) | 0.056 | 304 (3.2%) | 559 (3.2%) | 0.000 |
| COPD/asthma | 1,704 (17.8%) | 2,795 (16.0%) | 0.050 | 1,601 (16.8%) | 2,922 (16.7%) | 0.003 |
| Coronary atherosclerosis | 3,126 (32.7%) | 4,960 (28.3%) | 0.095 | 2,867 (30.1%) | 5,251 (30.0%) | 0.002 |
| Diabetes | 5,473 (57.3%) | 9,286 (53.0%) | 0.085 | 5,236 (54.9%) | 9,586 (54.7%) | 0.004 |
| GI bleed | 471 (4.9%) | 932 (5.3%) | 0.018 | 503 (5.3%) | 911 (5.2%) | 0.004 |
| Heart failure | 4,107 (43.0%) | 5,251 (30.0%) | 0.272 | 3,332 (34.9%) | 6,087 (34.7%) | 0.004 |
| Hypertension | 7,021 (73.5%) | 12,652 (72.3%) | 0.027 | 6,960 (73.0%) | 12,763 (72.8%) | 0.004 |
| Liver disease | 421 (4.4%) | 783 (4.5%) | 0.003 | 434 (4.6%) | 784 (4.5%) | 0.004 |
| Myocardial infarction | 642 (6.7%) | 1,151 (6.6%) | 0.006 | 644 (6.8%) | 1,171 (6.7%) | 0.003 |
| Peripheral artery disease | 2,149 (22.5%) | 3,729 (21.3%) | 0.029 | 2,095 (22.0%) | 3,820 (21.8%) | 0.004 |
| Stroke | 975 (10.2%) | 1,876 (10.7%) | 0.017 | 1,030 (10.8%) | 1,861 (10.6%) | 0.006 |
| Valvular disease | 904 (9.5%) | 1,337 (7.6%) | 0.065 | 795 (8.3%) | 1,457 (8.3%) | 0.001 |
| History of treatment nonadherenceb | 594 (6.2%) | 1,021 (5.8%) | 0.016 | 581 (6.1%) | 1,051 (6.0%) | 0.004 |
| Vascular access | ||||||
| Fistula | 5,645 (59.1%) | 10,054 (57.4%) | 0.033 | 5,516 (57.9%) | 10,150 (57.9%) | 0.001 |
| Graft | 2,428 (25.4%) | 4,451 (25.4%) | 0.001 | 2,448 (25.7%) | 4,470 (25.5%) | 0.004 |
| Catheter | 1,485 (15.5%) | 3,001 (17.1%) | 0.043 | 1,570 (16.5%) | 2,902 (16.6%) | 0.003 |
| Interdialytic weight gain ≥ 3 kg | 2,377 (24.9%) | 4,196 (24.0%) | 0.021 | 2,310 (24.2%) | 4,253 (24.3%) | 0.001 |
| Delivered dialysis treatment time < 240 min | 7,657 (80.1%) | 13,940 (79.6%) | 0.012 | 7,628 (80.0%) | 13,989 (79.8%) | 0.004 |
| Pre-dialysis systolic BP | ||||||
| < 130 mmHg | 1,384 (14.5%) | 2,159 (12.3%) | 0.063 | 1,241 (13.0%) | 2,289 (13.1%) | 0.001 |
| 130 – 149 mmHg | 2,696 (28.2%) | 4,744 (27.1%) | 0.025 | 2,621 (27.5%) | 4,808 (27.4%) | 0.001 |
| 150 – 169 mmHg | 3,175 (33.2%) | 6,084 (34.8%) | 0.032 | 3,253 (34.1%) | 5,997 (34.2%) | 0.002 |
| ≥170 mmHg | 2,303 (24.1%) | 4,519 (25.8%) | 0.040 | 2,419 (25.4%) | 4,427 (25.3%) | 0.002 |
| Recent history of frequent IDHc | 1,349 (14.1%) | 2,363 (13.5%) | 0.018 | 1,321 (13.9%) | 2,415 (13.8%) | 0.002 |
| Albumin | ||||||
| ≤ 3.0 g/dL | 468 (4.9%) | 883 (5.0%) | 0.007 | 483 (5.1%) | 877 (5.0%) | 0.003 |
| 3.1 – 4.0 g/dL | 6,221 (65.1%) | 11,057 (63.2%) | 0.040 | 6,092 (63.9%) | 11,191 (63.9%) | 0.001 |
| > 4.0 g/dL | 2,869 (30.0%) | 5,566 (31.8%) | 0.038 | 2,959 (31.0%) | 5,453 (31.1%) | 0.002 |
| Calcium | ||||||
| < 8.5 mg/dL | 1,338 (14.0%) | 2,497 (14.3%) | 0.008 | 1,352 (14.2%) | 2,488 (14.2%) | 0.001 |
| 8.5 – 10.2 mg/dL | 7,756 (81.1%) | 14,159 (80.9%) | 0.007 | 7,714 (80.9%) | 14,180 (80.9%) | 0.000 |
| > 10.2 mg/dL | 464 (4.9%) | 850 (4.9%) | 0.000 | 467 (4.9%) | 853 (4.9%) | 0.002 |
| Phosphorus | ||||||
| < 3.5 mg/dL | 1,088 (11.4%) | 1,907 (10.9%) | 0.016 | 1,050 (11.0%) | 1,936 (11.0%) | 0.001 |
| 3.5 – 5.5 mg/dL | 5,224 (54.7%) | 9,431 (53.9%) | 0.016 | 5,175 (54.3%) | 9,495 (54.2%) | 0.002 |
| > 5.5 mg/dL | 3,246 (34.0%) | 6,168 (35.2%) | 0.027 | 3,309 (34.7%) | 6,091 (34.8%) | 0.001 |
| Potassium | ||||||
| < 4.0 mEq/L | 1,064 (11.1%) | 1,918 (11.0%) | 0.006 | 1,047 (11.0%) | 1,931 (11.0%) | 0.001 |
| 4.0 – 6.0 mEq/L | 8,152 (85.3%) | 14,915 (85.2%) | 0.003 | 8,127 (85.2%) | 14,934 (85.2%) | 0.000 |
| > 6.0 mEq/L | 342 (3.6%) | 673 (3.8%) | 0.014 | 360 (3.8%) | 656 (3.7%) | 0.002 |
| Hemoglobin | ||||||
| < 9.5 g/dL | 663 (6.9%) | 1,166 (6.7%) | 0.011 | 650 (6.8%) | 1,185 (6.8%) | 0.002 |
| 9.5 – 12.0 mg/dL | 6,164 (64.5%) | 10,709 (61.2%) | 0.069 | 5,972 (62.6%) | 10,942 (62.4%) | 0.004 |
| > 12.0 mg/dL | 2,731 (28.6%) | 5,631 (32.2%) | 0.078 | 2,912 (30.5%) | 5,394 (30.8%) | 0.005 |
| Equilibrated Kt/V < 1.2 | 2,235 (23.4%) | 3,850 (22.0%) | 0.033 | 2,145 (22.5%) | 3,944 (22.5%) | 0.000 |
| Number of medications in last 30 days of baseline | 5.5 ± 3.8 | 5.5 ± 3.9 | 0.014 | 5.5 ± 3.9 | 5.5 ± 3.9 | 0.014 |
| Alpha blocker | 63 (0.7%) | 168 (1.0%) | 0.034 | 83 (0.9%) | 151 (0.9%) | 0.001 |
| ACE inhibitor | 2,232 (23.4%) | 4,040 (23.1%) | 0.006 | 2,224 (23.3%) | 4,070 (23.2%) | 0.002 |
| Angiotensin receptor blocker | 1,212 (12.7%) | 1,848 (10.6%) | 0.066 | 1,103 (11.6%) | 2,004 (11.4%) | 0.004 |
| Calcium channel blocker | 3,060 (32.0%) | 5,959 (34.0%) | 0.043 | 3,195 (33.5%) | 5,853 (33.4%) | 0.002 |
| Central alpha agonist | 1,272 (13.3%) | 2,486 (14.2%) | 0.026 | 1,339 (14.0%) | 2,446 (14.0%) | 0.003 |
| Diuretic | 1,239 (13.0%) | 1,845 (10.5%) | 0.075 | 1,095 (11.5%) | 2,010 (11.5%) | 0.000 |
| Vasodilator | 997 (10.4%) | 1,916 (10.9%) | 0.017 | 1,030 (10.8%) | 1,893 (10.8%) | 0.000 |
| Statin | 2,578 (27.0%) | 4,509 (25.8%) | 0.028 | 2,512 (26.4%) | 4,606 (26.3%) | 0.001 |
| Other cholesterol medicationd | 394 (4.1%) | 717 (4.1%) | 0.001 | 394 (4.1%) | 720 (4.1%) | 0.001 |
| Digoxin | 258 (2.7%) | 332 (1.9%) | 0.054 | 205 (2.2%) | 382 (2.2%) | 0.002 |
| Long-acting nitrate | 845 (8.8%) | 1,216 (6.9%) | 0.070 | 733 (7.7%) | 1,344 (7.7%) | 0.001 |
| Antiplatelet medication | 1,280 (13.4%) | 2,065 (11.8%) | 0.048 | 1,202 (12.6%) | 2,187 (12.5%) | 0.004 |
| Anticoagulant medication | 711 (7.4%) | 1,458 (8.3%) | 0.033 | 754 (7.9%) | 1,401 (8.0%) | 0.003 |
| Midodrine | 192 (2.0%) | 350 (2.0%) | 0.001 | 192 (2.0%) | 352 (2.0%) | 0.000 |
| Use of ≥ 1 potent inhibitor of CYP2D6e | 2,690 (29.5%) | 5,162 (28.1%) | 0.030 | 2,767 (29.0%) | 5,090 (29.0%) | 0.001 |
Abbreviations: Std diff, standardized difference; CV, cardiovascular; IDH, intradialytic hypotension; BP, blood pressure.
All-covariates were measured during the baseline period prior to carvedilol or metoprolol initiation. Values for categorical variables are given as number (%) and as mean ± standard deviation for continuous variables. The weighted cohort is the pseudo-population that was generated by the inverse probability of treatment weighting process.
A standardized difference > 0.1 represents meaningful imbalance between groups.16
Claims-based definition of nonadherernce included ICD-9 discharge diagnosis codes V15.81 (personal history of noncompliance with medical treatment, presenting hazards to health) and V45.12 (noncompliance with renal dialysis).
Patients were considered as having a recent history of frequent IDHBP if they had an intradialytic nadir systolic BP < 90 mmHg in at least 30% of outpatient hemodialysis treatments during the last 30 days of the baseline period.25
Other cholesterol medications included the following non-statin cholesterol medications: bile acid sequestrants, cholesterol absorption inhibitors, fibrates and niacin.
Both carvedilol and metoprolol are metabolized by cytochrome P450 2D6. Concomitant use of medications that are potent inhibitors cytochrome P450 2D6 of may increase serum concentrations of both carvedilol and metoprolol, putting patients at increased risk for beta-blocker—related adverse events such as hypotension. Cytochrome P450 2D6 inhibitors included: amiodarone, bupropion, chloroquine, cinacalcet, diphenhydramine, fluoxetine, haloperidol, imatinib, paroxetine, propafenone, propoxyphene, quinidine, terbinafine and thioridazine.
Abbreviations: COPD, chronic obstructive pulmonary disease; ESRD, end-stage renal disease; GI, gastrointestinal