| Authors |
| CIBIS-II Investigators and Committees |
| Title |
| The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial |
| References |
| Lancet 1999;353:9-13 |
| Background |
| This is a landmark trial that was conducted at the time when previous smaller trials had demonstrated the beneficial effects of beta-blockade in heart failure and myocardial infarction patients. |
| Purpose |
| To determine if bisoprolol, when added to evidence-based therapy, reduces mortality rates in chronic and stable heart failure patients with advanced symptoms (NYHA Class III-IV) |
| Design |
- Randomized, double-blind, placebo-controlled trial
- 2647 patients between 18-80 years with NYHA class III or IV symptoms, LVEF ≤35% (in the last 6 weeks)
- >3 months of chronic and clinically stable HF for >6 weeks or MI/UA >3 months
- receiving a diuretic and ACE inhibitor (other vasodilators permitted if intolerant to ACE inhibitor), could be receiving digoxin
|
| Exclusion Criteria |
- MI or UA within 3 months, PTCA or CABG within 6 months, previous or planned cardiac transplant
- > 1° AV block without PPM, resting HR <60 bpm
- SBP <100 mmHg or uncontrolled hypertension
- serum creatinine ≥300 µmol/L, reversible obstructive lung disease
- pre-existing or planned β-blocker use (including eye drops), calcium antagonists, inotropic agents (except digoxin) and other antiarrhythmic drugs (except amiodarone)
|
| Follow-Up |
| Mean 1.3 years (stopped prematurely, mortality significantly less with bisoprolol group) |
| Treatment Regimen |
- Bisoprolol 1.25 mg daily, titrated to target dose of 10 mg daily (as tolerated) vs. placebo
- Titration schedule: Bisoprolol 1.25 mg daily x 1 week, 2.5 mg daily x 1 week, 3.75 mg daily x 1 week, 5 mg daily x 4 weeks, 7.5 mg daily x 4 weeks, 10 mg daily
|
| Results |
Primary Endpoints Death from all causes: 12% (bisoprolol) vs. 17% (placebo); HR 0.66 (0.54-0.81), p<0.0001.
Secondary Endpoints (see study for complete list) Biso-
prolol
n=1327 | Placebo
n=1320 | Hazard Ratio | p |
|---|
| All cause hospitalization |
|---|
| 33% | 39% | 0.80 (0.71-0.91) | 0.0006 | | CV death |
|---|
| 9% | 12% | 0.71 (0.56-0.9) | 0.0049 | | Combined CV death & all cause hospitalization |
|---|
| 29% | 35% | 0.79 (0.69-0.9) | 0.0004 | - Subgroup analysis: hospitalization for worsening HF (p<0.0001), ventricular tachycardia & ventricular fibrillation (p=0.006), hypotension (p=0.03) was significantly lower in the bisoprolol group
|
| Summary |
| The addition of bisoprolol to ACE inhibitor and diuretic therapy, in patients with advanced symptoms (NYHA class III or IV) but in stable HF, significantly reduces all-cause mortality as compared to placebo. |