Heart failure: bisoprolol reduced death and hospital admissions

Clinical bottom line (level 1b)

  1. Patients with stable chronic heart failure who took bisoprolol compared with placebo were less likely to die (NNT = 18 at 1.3 years) , especially suddenly (NNT = 37 at 1.3 years) .
  2. Patients on bisoprolol were less likely to be admitted to hospital (NNT = 18 at 1.3 years) , particularly with worsening heart failure (NNT = 18 at 1.3 years) .
CIBIS-II Investigators and Committees : Lancet 1999; 353: 9-13
Expires October 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: outpatient clinics of 274 hospitals, 18 countries in Europe

2647 patients (aged range 22 to 80 years; mean 61, 81% male) with chronic symptomatic heart failure (dyspnoea on exertion, orthopnoea, or paroxysmal nocturnal dyspnoea with or without edema and fatigue - equivalent to NYHA class III or IV) and a left ventricular ejection fraction < 35% measured in the last 6 weeks.

Excluded if
  • aged < 18, > 80
  • reversible obstructive lung disease
  • pre-existing or planned therapy with beta-blockers
  • CABG or PTCA in previous 6 months, previous or scheduled heart transplant
  • 2nd or 3rd atrioventricular block without a permanent pacemaker
  • resting heart rate < 60 beats/min; systolic blood pressure at rest < 100 mmHg
  • renal failure (serum creatinine < 300 µ mol/l)
  • not taking ACE inhibitor and a diuretic
  • clinically unstable in the last 6 weeks
  • within 3 months of an acute MI or episode of unstable angina
  • no change in cardiovascular medication in the previous 2 weeks


    • Control Group: (n = 1320, 1320 analysed): placebo
    Experimental Group: (n = 1327, 1327 analysed): oral bisoprolol 1.25 mg daily increased to 2.50 mg, 3.75 mg, 5.00 mg, 7.50 mg or 10.0 mg depending on tolerance.
    All patients took ACE inhibitors and a diuretic. An alternative vasodilator was allowed in patients intolerant of ACE inhibitors. Digoxin was optional. Treatment with beta-blockers, calcium antagonists, inotropic agents except digitalis, or antiarrhythmic drugs except amiodarone was not allowed.
    99.8% followed for 1.3 years

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death 1.3 years 228
    (17.3%)    		 156
    (11.8%)    		 32%
    (18% to 44%)    		 5.52%
    (2.84% to 8.19%)    		 18
    (12 to 35)
    sudden death 1.3 years 83
    (6.29%)    		 48
    (3.62%)    		 42%
    (19% to 59%)    		 2.67%
    (1.02% to 4.32%)    		 37
    (23 to 98)
    admitted to hospital 1.3 years 513
    (38.9%)    		 440
    (33.2%)    		 15%
    (6% to 23%)    		 5.71%
    (2.05% to 9.36%)    		 18
    (11 to 49)
    admitted with worsening heart failure 1.3 years 232
    (17.6%)    		 159
    (12.0%)    		 32%
    (18% to 43%)    		 5.59%
    (2.90% to 8.29%)    		 18
    (12 to 35)

    Comments

    1. This and MERIT-HF are the basis behind the use of beta-1 selective beta-blockers in heart failure.
    2. Subgroup analysis for cause of heart failure and severity of disease showed no significant difference between the groups for death or admissions to hospital.
    3. No outcomes relating to morbidity (functional or QoL measures) were taken.

    Citation

    1. CIBIS-II Investigators and Committees , : the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999; 353: 9-13
    Contributor: Chris Ball and Clare Wotton, October 1999
    Reviewer: Christian Torp-Pedersen

    Clinical Question.
    Patient heart failure
    Intervention or Exposure bisoprolol
    Comparison placebo
    Outcome death