4. What is the effect of treatment with ACE-inhibitors in non-oncology populations with asymptomatic cardiomyopathy?
First Author Year	Study Design Treatment era Years of follow-up	Participants	Treatment	Main outcomes	Addt’l remarks
SOLVD investigators57 1992	Double-blind, placebo-controlled RCT Mean: 37.4 (range: 14.6 – 62) months	4228 asymptomatic patients with EF <35%, and no medication for heart failure	Enalapril: N=2111 Placebo: N=2117	All-cause mortality: Enalapril: 313 (14.8%) Placebo: 334 (15.8%) Risk reduction: 8% (95% CI −8% to +21%) Clinical heart failure or all cause mortality: Enalapril: 630 (29.8%) Placebo: 818 (38.6%) Risk reduction: 29% (95% CI 21% to 36%)	Flather 2000: 74% of all SOLVD-patients (including another RCT with symptomatic patients) had a previous MI. Exner 1999: one third of the SOLVD prevention trial was in NYHA II EF was determined by echocardiography
Pfeffer58 1992	Double-blind, Placebo controlled RCT Mean: 42 (range: 24 – 60) months	2231 asymptomatic patients with EF ≤40%, 3 – 16 days after MI	Captopril: N=1115 Placebo: N=1116	All-cause mortality: Captopril: 20% versus placebo 25% (RR 19%, 3 – 32%, P=0.014) Development of clinical heart failure: Captopril: 11% versus placebo 16%, RR 37% (20– 50%, P<0.001)	EF was determined by RNA
Jong59 2003	Cohort study after RCT 11.2 years (IQR: 10.3 – 12.1) since randomization	3581 patients of the SOLVD prevention trial (asymptomatic patients with EF <35%), treated previously with enalapril or placebo during a mean of 37.4 months, who survived the time of the trial	Enalapril group: N=1798 Placebo group: N=1783	All-cause mortality: Enalapril: 1074 (50.9%) Placebo: 1195 (56.4%) HR: 0.86 (95% CI 0.77 – 0.93) Increased life expectancy (median): 9.2 months (95% CI 0 – 19.2 months)	Patients with a lower EF had more benefit of treatment EF was determined by echocardiography
Kober60 1995	Double-blind, Placebo controlled RCT 24 – 50 months clinical follow-up	1749 patients with an MI in the previous week and EF ≤35%	Trandopril: N=876 Placebo: N=873	All-cause mortality: Trandopril versus placebo: RR 0.78 (0.67 – 0.91) Clinical heart failure: Trandopril versus placebo: RR 0.71 (0.56 – 0.89)	41% of patients was in NYHA I EF was determined by echocardiography
Hunt61,62 AHA/ACC Guideline (2005 and 2009)	Angiotensin converting enzyme inhibitors can be useful to prevent HF in patients at high risk for developing HF	Stage A * with a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors	Perindopril Ramipril	Class of recommendation IIa Level of evidence A
Hunt61,62 AHA/ACC Guideline (2005 and 2009)	Angiotensin converting enzyme inhibitors should be used in patients with a reduced EF and no symptoms of HF, even if they have not experienced MI	Stage B*	Enalapril	Class of recommendation I Level of evidence A
Dickstein63 2008 ESC Guideline	Recommendation to treat with beta-blockers based upon the patients enrolled in the RCTs	LVEF ≤40% Mild to severe symptoms (NYHA II–IV)** and patients with asymptomatic LV systolic dysfunction after MI	Bisoprolol Carvedilol Metoprolol succinate Nebivolol	Class of recommendation I Level of evidence A	CIBIS-II 1999 MERIT-HF 1999 & 2000 Packer 2001 COPERNICUS 2002 SENIORS 2005 BBEST 2001 COMET 2003