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

From: Individual patient data meta-analysis of beta-blockers in heart failure: rationale and design

Trial (drug) by year n Population Inclusion criteria Exclusion criteria Major endpoints Withdrawal/ Lost to follow-up Study period
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, 2nd or 3rd 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 2nd/3rd 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 2nd/3rd 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
  1. BB, beta-blocker; CAD, coronary artery disease; CCB, calcium channel blocker; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; EF, ejection fraction; HF, heart failure; HR, heart rate; IDC, idiopathic dilated cardiomyopathy; IDDM, insulin-dependent diabetes mellitus; MI, myocardial infarction; NYHA, New York Health Association; QoL, quality of life; SBP, systolic blood pressure.