Table 1 Details of studies proposed for inclusion in meta-analysis

MDC

383

Symptomatic IDC

EF <40%;

Treatment with BB or CCB; Significant CAD on angiography; Myocarditis; Life-threatening diseases; COPD requiring beta agonists; Drug or alcohol abuse; IDDM; Thyroid disease; SBP <90 mmHg; HR <45

All-cause mortality; Need for transplantation; exercise capacity; NYHA, QoL

12% metoprolol, 16% placebo /

18 months (12 after 1990); additional 3-year data

(metoprolol)

Age 16 to 75

one lost

1993

CIBIS

641

Symptomatic HF

EF <40%;

Hypertrophic/restrictive cardiomyopathy; Untreated valve disease; Awaiting bypass surgery; MI in previous three months; On heart transplantation list; IDDM; Asthma; Creatinine >300 μmol/L; Thyroid disease; Life threatening disease; SBP <100 or >160 mmHg; HR <65

All-cause mortality; Bisoprolol tolerability (based on NYHA and adverse events)

23% bisoprolol, 26% placebo /

Mean 1.9 years

one lost

Age 18 to 75; NYHA III or IV

(bisoprolol)

1994

US-HF

1,094

Symptomatic HF

EF ≤35%;

Major CV event/surgery within three months; Uncorrected valve disease; Myocarditis; Uncontrolled ventricular tachycardia/heart block; Clinically important hepatic or renal disease; Conditions limiting exercise or survival; Treatment with BB, CCB or class 1C antiarrhythmic agents; SBP <85 or >160 mmHg; HR <68

All-cause mortality; Hospitalization

5.7% carvedilol, 7.8% placebo /

Median 6.5 months

(carvedilol)

zero lost

1996

ANZ

415

Symptomatic HF due to CAD

EF <45%;

Coronary event/procedure within four weeks; Sick sinus, 2^nd or 3^rd degree heart block; Treadmill exercise duration <2 or >18 minutes; Myocardial or valvular disease; Treatment with BB, beta agonist or verapamil; IDDM; COPD; hepatic disease; Creatinine >250 μmol/L); Life-threatening disease; SBP <90 or >160 mmHg; HR <50

EF; Exercise duration; NYHA; Death; Hospitalization

20% carvedilol, 14%

Mean 19 months

placebo /

NYHA II or III

zero lost

(carvedilol)

1997

CIBIS II

2,647

Symptomatic HF

EF <35%;

MI/unstable angina within three months; Revascularization within six months; Prior or scheduled heart transplant; Uncontrolled 2^nd/3^rd degree heart block; Creatinine >300 μmol/L; Reversible COPD; Treatment with BB, CCB or antiarrhythmic drugs other than amiodarone; SBP <100 mmHg or uncontrolled hypertension; HR <60

All-cause mortality; All-cause hospital admissions; CV mortality

15% bisoprolol, 15% placebo /

Mean 1.3 years

(bisoprolol)

NYHA III or IV

six lost

1999

MERIT-HF

3,991

Symptomatic HF

EF ≤40%;

MI/unstable angina within 28 days; BB within six weeks, CCB or amiodarone within six months; Planned or performed transplantation or implanted defibrillator; Bypass surgery or percutaneous intervention planned or in last four months; Uncorrected 2^nd/3^rd degree heart block; Other serious diseases; SBP <100 mmHg; HR <68

All-cause mortality; All-cause mortality plus all-cause hospitalization

14% metoprolol, 15% placebo /

Mean 1 year

(metoprolol XL)

Age 40 to 80

zero lost

1999

COPERNICUS

2,289

Severe HF

EF <25%;

Uncorrected valvular disease or reversible cause; Prior or planned cardiac transplant; Primary pulmonary or hepatic disease; Creatinine >247.5 μmol/L; Potassium <3.5 or >5.2 mmol/L; Coronary revascularization, MI; stroke or ventricular arrhythmia within two months; Treatment with BB within two months or alpha-blocker, CCB or class I antiarrhythmic within four weeks; SBP <85 mmHg; HR <68

All-cause mortality; Hospitalization

15% carvedilol, 19% placebo /

Mean 10.4 months

(carvedilol)

NYHA III or IV

zero lost

2001

CAPRICORN

1,959

Left ventricular dysfunction post-MI

3 to 21 days post-MI;

Continued requirement of intravenous diuretics; Unstable angina; Unstable IDDM; BB indication other than HF; Inhaled beta agonists or steroids; SBP <90 mmHg or uncontrolled hypertension; HR <60

All-cause mortality; All-cause mortality or CV hospitalization; Sudden death; HF-hospitalization; Non-fatal events

20% carvedilol, 18% placebo /

Mean 1.3 years

(carvedilol)

endpoint-driven

EF ≤40%

2001

BEST

2,708

Symptomatic HF

EF <35%;

Reversible cause of HF or valvular disease; Untreated thyroid disease; Obstructive/hypertrophic cardiomyopathy; Pericardial disease; Amyloidosis; Myocarditis; MI within six months; Candidate for heart transplantation; Revascularization within 60 days; Unstable angina; Life expectancy <3 years; Active liver disease or excess alcohol; Creatinine >265 μmol/L; Other serious diseases; Treatment with BB within 30 days, CCB or beta-agonists within one week, class 1 antiarrhythmic within two weeks or amiodarone within eight weeks; SBP <80 mmHg; HR <50

All-cause mortality; Death from CV causes; Hospitalization; EF; Non-fatal MI; QoL

23% bucindolol, 25% placebo /

Mean 2 years

(bucindolol)

NYHA III or IV;

eight lost

2001

Digoxin in all patients pre-1997

CHRISTMAS

375

Stable HF due to CAD

EF <40%;

Women of child-bearing age; Acute CV event within three months; Hospital admission within one month; Unstable angina; Arrhythmias (for example, atrial fibrillation); Uncontrolled hypertension; COPD; Poorly controlled diabetes; Clinically relevant renal or hepatic disease; Treatment with non-dihydropiridine CCB, BB or antiarrhythmic other than amiodarone; SBP <85 mmHg; HR <60

Change in EF (hibernators vs. non-hibernators);

15% carvedilol, 7% placebo /

Mean 6.3 months

(carvedilol)

Age ≥40 years;

one lost

Regional echocardiographic contractile dysfunction;

2003

NYHA I to III

Death or worsening HF.

SENIORS

2,128

Elderly HF

Age ≥70;

Uncorrected valvular disease; Current use of BB; Significant hepatic or renal dysfunction; Stroke within three months; Pending coronary revascularization; Other serious medical conditions reducing survival; SBP <90 mmHg; HR <60

All-cause mortality or CV hospitalization; All-cause mortality; All-cause hospitalization; NYHA

27% nebivolol, 25% placebo /

Mean 21 months

(nebivolol)

HF-hospitalization within 12 months or EF ≤35% within 6 months

37 lost

2005