Beta-blocker dosing in community-based treatment of heart failure.

BACKGROUND: Community patients with heart failure (HF) are older, less often treated by HF specialists, and have more comorbidity than those in randomized clinical trials. These differences might affect beta-blocker prescribing in HF. METHODS: To explore patterns of beta-blocker prescribing for HF in the community and their association with outcomes, we determined carvedilol doses at end titration in 4113 patients from a community-based beta-blocker HF registry according to physician and patient characteristics, HF severity, and rates of hospitalization and death. RESULTS: Female sex, age > or = 65 years, and left ventricular ejection fraction > or = 35% were associated with lower beta-blocker doses. Average daily dose of beta-blocker was lower with worse baseline New York Heart Association class. More patients of cardiologists achieved carvedilol doses > or = 25 mg twice daily, whereas in those of noncardiologists lower doses were more common. Relative risk of HF hospitalizations or all-cause death was significantly lower with higher doses of beta-blocker. CONCLUSIONS: Beta-blocker dosing in community HF appears lower than in randomized clinical trials, especially when prescribed by noncardiologists. At all doses, patients taking the beta-blocker carvedilol have a lower incidence of death and HF hospitalization than those discontinuing it, regardless of physician type in the community setting.

Comparison of outcomes and usefulness of carvedilol across a spectrum of left ventricular ejection fractions in patients with heart failure in clinical practice.

Heart failure (HF) in the community differs meaningfully from that in clinical trials, particularly the higher prevalence of patients with preserved left ventricular (LV) ejection fraction (EF) typically excluded from clinical trials, thus limiting knowledge of their responsiveness to beta-blocker therapy. From a community-based registry of 4,280 patients with HF starting treatment with the beta blocker carvedilol, we compared characteristics, carvedilol titration, and outcomes of patients according to LVEF >40% or <40% (as in clinical trials) and across the spectrum of LVEF <21%, 21% to 30%, 31% to 40%, and >40%. Patients with preserved EF (LVEF >40%) were older and more often women and hypertensive. Lower LVEF was associated with worse functional class and more HF hospitalizations in the previous year. Carvedilol dose decreased with increasing LVEF. Hospitalization rates for HF related inversely to LVEF before starting carvedilol therapy and decreased from the previous year in all LVEF groups during follow-up. Although 1-year mortality rate decreased from 8% with LVEF < or =20% to 6% with LVEF >40%, adjusted hazard ratios were not significantly different across LVEF groups. Thus, characteristics of community patients with HF vary across the spectrum of LVEF. Patients with HF and preserved EF treated with carvedilol in the community improve symptomatically and experience fewer HF hospitalizations after initiating carvedilol. In conclusion, without a control group, the effect of carvedilol on outcomes is not conclusive and trials of carvedilol in patients with HF and preserved EF should be undertaken.

Tolerability, safety, and efficacy of beta-blockade in black patients with heart failure in the community setting: insights from a large prospective beta-blocker registry.

Heart failure (HF) clinical trials suggest different responses of blacks and whites to beta-blockers. Differences between clinical trial and community settings may also have an impact. The Carvedilol Heart Failure Registry (COHERE) observed experience with carvedilol in 4280 patients with HF in a community setting. This analysis compares characteristics, outcomes, and carvedilol dosing of blacks and whites in COHERE. Compared with whites (n=3433), blacks (n=523) had more severe HF symptoms despite similar systolic function. At similar carvedilol maintenance doses, symptoms improved in 33% of blacks vs 28% of whites, while worsening in 10% and 11%, respectively (both nonsignificant), and HF hospitalization rates were reduced comparably in both groups (-58% vs -56%, respectively; both P<.001). Incidence and hazard ratios of death were similar in blacks and whites (6.9% vs 7.5%, hazard ratio 1.2 vs 1.0, P=.276). Thus carvedilol was similarly effective in blacks and whites with HF in the community setting, consistent with carvedilol clinical trials.

Predictors of clinical outcomes in patients given carvedilol for heart failure.

Risk factors for outcomes in heart failure (HF) were derived from populations in clinical trials, at hospital discharge, or in localized geographic or socioeconomic strata before the widespread use of beta blockers. This study observed 4,280 patients in a community-based HF registry for 1 year after completing carvedilol titration. Independent risk factors for death, hospitalization for HF, or hospitalization for cardiovascular reasons other than HF were first identified by age-, gender-, and race-adjusted analyses, then by multivariate analysis adjusted simultaneously for all factors. Over this period, 7% of patients died, 11% were hospitalized for HF, 12% were hospitalized for other cardiovascular reasons, and 27% had > or =1 of these events. The most significant outcome predictors were New York Heart Association class III or IV, history of hospitalization for HF or other cardiovascular reasons, and angina pectoris, all associated with increased odds of having an adverse outcome (all p < or =0.001). The left ventricular ejection fraction was not a significant outcome predictor by multivariate analysis. The odds ratio for an adverse outcome was significantly reduced for patients with hypertensive or idiopathic causes of HF and for those whose physicians had graduated from medical school > or =24 years earlier compared with <14 years earlier (all p <0.005). In conclusion, easily obtained historical information predicts clinical outcomes in patients with HF in the year after initiating carvedilol. In this unselected community population, these historical factors were better predictors of risk than the left ventricular ejection fraction.

Heart failure in community practice: relationship to age and sex in a beta-blocker registry.

Women and the elderly are underrepresented in clinical trials of heart failure (HF). The authors analyzed, by sex and age groups, a registry of 4280 community patients initiating carvedilol for HF. Women (n=1485) were older than men (n=2793) and had worse functional class with higher left ventricular ejection fraction and blood pressure. Women also had more HF hospitalizations, less use of angiotensin-converting enzyme inhibitors, and lower doses of carvedilol. Nevertheless, during 1-year follow-up, both groups experienced greater than 40% reductions in HF hospitalizations (P<.001), with mortality of 7.3% in women vs 9.1% in men (P=.085). With increasing age, left ventricular ejection fraction, blood pressure, and functional class increased, whereas angiotensin-converting enzyme inhibitor use and carvedilol doses decreased. HF hospitalizations fell at least 40% in all age groups after starting carvedilol (P<.001). Characteristics of women and the elderly with HF in the community suggest increased risk, but both populations respond well after initiating carvedilol.

Beta-blocker therapy for heart failure outside the clinical trial setting: findings of a community-based registry.

BACKGROUND: beta-Blockers reduce morbidity and mortality rates in heart failure (HF) clinical trials, but it is unknown whether these findings persist in the community setting. METHODS: A registry was created to survey tolerability and outcomes during initiation and 1-year follow-up of beta-blocker treatment with carvedilol in patients with HF treated by cardiologists (CARD) and primary care physicians (PCP) in the community. RESULTS: A total 4280 patients were enrolled (3121 by 259 CARD, 1159 by 129 PCP). Patient age averaged 67 +/- 13 years; 35% were women and 12% were black. The left ventricular ejection fraction averaged 31 +/- 12; New York Heart Association class was II-III in 86% and IV in 3%. Patients of PCP had higher left ventricular ejection fraction, were older, and more frequently were female, black, diabetic, hypertensive, and in New York Heart Association class III/IV. Minimal difficulty titrating carvedilol was noted by >80% of CARD and PCP. Significantly more CARD-treated patients reached carvedilol doses of 25 mg twice daily (49% vs 27%). Kaplan-Meier all-cause mortality rate was 8.5% at 1 year and did not differ between CARD-treated and PCP-treated patients (8.2% vs 9.3%, P =.254). At least one HF hospitalization occurred in 11% of patients during follow-up, compared with 28% in the preceding year. CONCLUSIONS: Community-based physicians use carvedilol with success approaching that of clinical trials. Overall mortality rates and HF hospitalizations were in the same low range as in clinical trials. Thus, it appears that results of clinical trials with carvedilol for HF can be translated to the community setting.

A randomized, multicenter study comparing the safety and efficacy of sodium phosphate tablets with 2L polyethylene glycol solution plus bisacodyl tablets for colon cleansing.

OBJECTIVE: The safety and efficacy of NaP tablets have not been compared with 2L PEG lavage solution. A multicenter, investigator-blinded study was conducted to compare the colon-cleansing efficacy of a new NaP tablet formulation with that of 2L PEG solution plus bisacodyl tablets in adults undergoing colonoscopy. METHODS: A total of 481 patients were randomized to receive either 32 tablets (48 g) of NaP or 2L PEG solution plus 4 (20 mg) bisacodyl tablets. Quality of colon cleansing was assessed using a 4-point scale (1 = excellent, 2 = good, 3 = fair, and 4 = inadequate), and the primary efficacy end point was mean overall colon-cleansing score. Safety assessments included recording of adverse events and changes in biochemical tests and vital signs. RESULTS: A total of 411 patients were included in the efficacy analysis. The mean overall and ascending colon-cleansing scores for NaP tablets were significantly better than PEG plus bisacodyl (overall 1.5 vs 1.8, ascending 1.4 vs 1.8, P < 0.0001 for both). Patients treated with NaP tablets experienced significantly fewer adverse events (66%vs 82%, P= 0.0003) and gastrointestinal symptoms (64%vs 79%, P= 0.0001) compared with patients receiving PEG plus bisacodyl. Patients receiving NaP tablets were significantly less likely to experience abdominal distention, abdominal pain, and vomiting than patients receiving PEG plus bisacodyl (P < 0.0012). Transient fluctuations in laboratory parameters were observed in both treatment groups; however, the fluctuations were more common and of greater magnitude in the NaP group particularly in phosphorous, sodium, and potassium. CONCLUSION: The colon-cleansing efficacy of the new 32-tablet NaP dosing regimen in this study was found to be significantly better than the 2L PEG solution plus bisacodyl tablets regimen. The 32-tablet NaP dosing regimen was associated with fewer adverse events. As expected electrolyte shifts were more common and of greater magnitude in the NaP group compared with the PEG plus bisacodyl group; however, both treatment groups demonstrated significant changes in electrolytes and creatinine.

Safety and colon-cleansing efficacy of a new residue-free formulation of sodium phosphate tablets.

OBJECTIVE: A residue-free sodium phosphate tablet (RF-NaP) was formulated that lacks microcrystalline cellulose, which can appear as a whitish residue in the colon. A multicenter, randomized, investigator-blinded study was conducted to compare the colon-cleansing efficacy of 40 or 32 tablets of RF-NaP with the marketed 40-tablet NaP treatment regimen. METHODS: Eight hundred sixteen patients were randomized prior to colonoscopy to receive either 40 tablets (60 g) of NaP or RF-NaP or 32 tablets (48 g) of RF-NaP. Colon cleansing was assessed using a 4-point scale based on retained "colonic contents." The primary end point was overall colon-cleansing response rate to treatment (score of excellent/good) versus nonresponse (fair/inadequate). RESULTS: Seven hundred four patients were included in the efficacy analysis. The overall colon-cleansing response rates were comparable among treatment arms (94.5%, 97.0%, and 95.3% for NaP, RF-NaP 40, and RF-NaP 32 tablets, respectively). Ascending colon-cleansing response rates for RF-NaP 40 (95.7%) and 32 tablets (93.6%) were significantly better than for NaP tablets (88.5%, p < 0.03 for both). Patients treated with RF-NaP 32 tablets experienced less pronounced changes in electrolyte levels and fewer adverse events (138/239, 58%) compared with patients receiving NaP (161/238, 68%, p= 0.07) and RF-NaP 40 tablets (156/236, 66%, p= 0.03). The most common adverse events reported were abdominal distention, nausea, abdominal pain, and vomiting. CONCLUSIONS: Based on the safety, efficacy, and patient preferences, the 32-tablet RF-NaP regimen was superior to the 40-tablet RF-NaP and NaP regimen for colon cleansing prior to colonoscopy.