B-CONVINCED

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Jondeau G, et al. "B-CONVINCED: Beta-blocker CONtinuation Vs. INterruption in patients with Congestive heart failure hospitalizED for a decompensation episode". Eur Heart J. 2009. 30(18):2186-2192.
PubMedFull textClinicalTrials.gov

Clinical Question

Among patients with HFrEF (LVEF <40% in prior year) on a stable dose of a beta-blocker as an outpatient admitted for acutely decompensated heart failure (ADHF), does cessation of that beta-blocker change feelings of wellbeing or dyspnea at 3 days?

Bottom Line

Among patients with HFrEF (LVEF <40%) on a stable dose of a beta-blocker as an outpatient admitted for acutely decompensated heart failure (ADHF), beta-blocker cessation does not improve feelings of wellbeing or dyspnea at 3 days.

Major Points

There has been much clinical uncertainty in the continuation of beta-blocker therapy during ADHF hospitalizations in HFrEF.[1] Beta-blockers have a negative inotropic effect and decreases cardiac output and increases left ventricular filling pressures, potentially acutely worsening the physiology leading to ADHF. In chronic HFrEF, there is a clear benefit for the use of beta-blockers, as has been shown in trials like MERIT-HF (1999) and COPERNICUS (2002). Observational studies have suggested a benefit for continuing beta-blockers during hospitalizations for ADHF in HFrEF, however there was no RCT evidence supporting this practice.[2][3]

Published in 2009, the Beta-blocker CONtinuation Vs. INterruption in patients with Congestive heart failure hospitalizED for a decompensation episode (B-CONVINCED) trial randomized 147 patients on chronic (>1 mo) beta-blocker use with HFrEF and ADHF hospitalization characterized by elevated RR in addition to clinical determination of an ADHF admission to a "keeping beta-blockade" or "stopping beta-blockade" strategies in an open-label fashion. At 3 days, the level of dyspnea and feeling of wellbeing was assessed by clinical staff (primary outcome) and self-reported by the patient (secondary outcome). There was no difference in these symptoms between groups. It's unclear if the outcome was assessed using validated tools. Of note, the trial was too small to detect "hard" clinical outcomes like mortality.

Despite its limitations, B-CONVINCED provides at least initial support to the practice of continuation of beta-blockers during admissions for ADHF in HFrEF for patients who were on chronic stable doses.

Guidelines

As of August 2020, no guidelines have been published that reflect the results of this trial.

Design

  • Multicenter, open label, parallel-group, randomized, controlled trial
  • N=147
    • Keeping Beta-blockade (n=69)
    • Stopping Beta-blockade (n=78)
  • Setting: 36 French centers, but only 28 enrolled patients
  • Enrollment: 2004-2008
  • Follow-up: Primary outcome was assessed at 3 days, but follow-up continued through 3 months following hospital discharge
  • Analysis: Non-inferiority
  • Primary outcome: Percentage of patients whose both general well-being and dyspnea had improved at 3 days according to the blinded physician.

Population

Inclusion Criteria

  • Aged ≥18 years
  • On a stable dosing of a beta-blocker for >1 month
  • ADHF admission
  • RR had to be >24/min at some point during the ADHF episode or at time of inclusion
  • LVEF in the preceding 12 months <40%

Exclusion Criteria

  • Need for an inotrope
  • Other reason to withdraw beta-blocker use during this hospitalization

Baseline Characteristics

From the 'keeping beta-blockade' group

  • Demographics: Aged 73 years, 59% males
  • PMH: DM 43%, hypertension 65%, former smoker 46%, active smoker 12%, prior MI 28%
  • HF details: Ischemic CM 56%, AF-related 30%
    • LVEF: 32%
  • Medications: ACE-inhibitor 65%, diuretics 81%
  • Beta-blocker details: Maximum dose 20%, less than 50% dose 54%
  • Physiological measurements: BP 127/71 mm Hg, HR 83 bpm, RR 25, O2 saturation 94%
  • Symptoms: Dyspnea 93%, fatigue 94%, rales 96%, edema 48%, JVD 48%
  • Labs: BNP 1,387 pg/mL

Interventions

  • Randomized to a group:
    • Keeping beta-blockade
    • Stopping beta-blockade for ≥3 days
  • After both 3 days and 8 days, two identical questionnaires were filled in, one by a physician unaware of the therapy of the patient (blinded physician) and one by the patient.
    • Dyspnea and general well-being were quoted as worsened or improved compared with entry using a 5-point Likert scale
  • After 3 months, patients were contacted to determine their vital and clinical status

Outcomes

Comparisons are keeping beta-blockade vs. stopping beta blockade.

Primary Outcomes

Improvements in both dyspnea and general well-being after 3 days
From the blinded investigator's assessment, not the patient self-assessment.
92.8% vs. 92.3% (95% CI -7.6 to 6.6%, unilateral upper limit of 6.6% indicating equivalence)

Secondary Outcomes

Improvements in both dyspnea and general well-being after 3 days
According to the patient's self-assessment.'
88.4% vs. 82.7% (Upper limit of unilateral 95% CI 3.8%, indicating equivalence)
Improvements in both dyspnea and general well-being after 8 days
According to the physician: 95.2% vs. 95.4% (Upper limit of unilateral 95% CI 6.3%)
According to the patient: 94.8% vs. 95.2% (Upper limit of unilateral 95% CI 6.9%)
BNP plasma levels at baseline and day 3
1314 +/- 1214 pg/mL to 882+/- 950 pg/mL vs. 1387 +/- 1124 pg/mL to 876 +/-1382 pg/mL
There was no significant difference in the changes between these times.
Hospitalization length
11.5 +/- 8.3 days vs. 10.4 +/- 9.7 days (P=0.2)
Re-hospitalization rate at 3 months
40% vs. 47% (p-value 0.43)
All-cause mortality
During hospitalization: 1 vs. 2 (no P-value given)
At 3 months: 9% vs. 8% (P=0.83)
Proportion of patients receiving a beta-blocker at 3 months
90% vs. 76% (P=0.04)

Criticisms

  • Open label design
  • There was no reported validation of the 5-point Likert scale used to measure the variables of dyspnea and general well-being which the trial is based on
  • The primary outcome was change in symptoms as assessed by clinical staff, not as reported by the patient. As symptoms are subjective, this was an odd choice. However, the patient's self-reported symptoms were also reported.
  • Far too underpowered to assess for changes in hard clinical outcomes.
  • Patients were less likely to be on a beta blocker at 3 months, so unclear how handoff with outpatient physicians was handled. If the primary care doctor or ambulatory cardiologist didn't realize that the beta blocker was stopped for this trial, they might have thought that it was stopped for intolerances or other medical contraindications.
  • Low use of ACE-inhibitors
  • Patients included in the trial were hospitalized with pulmonary edema, which by prior literature tends to represent approximately 25% of ADHF and patients also failed to show high severity clinical features (Low oxygen saturation, high respiratory rate and low blood pressure at baseline) which may explain the low three month mortality rate of 6% versus 15% in similarly studied populations.

Funding

Funding was supported by the French Ministry of Health (Programme Hospitalier de Recherche Clinique).

Further Reading

  1. Swedberg K & Beta-blockers in worsening heart failure: good or bad?. Eur. Heart J. 2009. 30:2177-9.
  2. Butler J et al. Beta-blocker use and outcomes among hospitalized heart failure patients. J. Am. Coll. Cardiol. 2006. 47:2462-9.
  3. Pascual-Figal DA et al. Comparison of late mortality in hospitalized patients >70 years of age with systolic heart failure receiving beta blockers versus those not receiving beta blockers. Am. J. Cardiol. 2008. 102:1711-7.