Study Name Population Intervention Comparison Outcomes Follow-up Results Bottomline
MA of ACEi in HF 54,621 All-cause Proportional
16 trials randomized HF mortality: reduced effects
participants, RAAS by 11% (RR 0.89, decreased with
inhibition risks for 95% CI 0.85-0.92) increasing mean
Cardiovascular
HF LVEF for all
Mortality: reduced
by 14% (RR 0.86, outcomes. There
95% CI 0.83-0.90) was still a
Hospitalization for decrease in the
HF: reduced by risk for HF
20% (RR 0.80, 95% hospitalization in
CI 0.77-0.83) patients with
preserved LVEF
SAVE 2231 patients with Captopril (initial Placebo All-cause ~42 months All-cause Established the
LVD (LVEF 40%) 6.25-12.5mg; mortality, CV mortality: RRR benefit of ACEi
beginning 3-16 target 25mg) death, 19%; P=0.0019 in post-MI
days post-MI hospitalization for CV Death: RRR. patients who
12%, P=0.014
HF, rMI, have EF 40%
Hospitalization for
symptomatic HF HF: RRR22%;
P=0.019
Recurrent MI: RRR
25%; P=0.0015
Symptomatic HF:
RRR 37%; P<0.001
SOLVED- 2569 patients with Enalapril (2.5 to Placebo All-cause 41.4 months All-cause Established the
treatment NYHA (regardless 20mg /day) mortality, mortality: absolute benefits of ACEi
of MI) Class II and hospitalization or risk reduced by in all sx HF
III HF death from HF 4.5% (NNT=23; patients
P=0.0036)
regardless of MI
Hospitalization or
death from HF: status
absolute risk
reduced by 9.6%
(NNT=11;
P<0.0001)
SOLVED- 4226 patients with Enalapril (2.5- Placebo All-cause 37.4 months No reduction in Even if the
prevention asymptomatic LV 20mg/day) mortality, CV total/CV death patient is
dysfx (LVEF <0.35) death, asymptomatic
hospitalizations Hospitalization for there are still
HF/death: ARR benefits of using
3.9%; NNT=26 ACEi if they have
, low EF
ATLAS (low v. 3164 patients with 32.5-35mg 2.5-5mg All-cause 46 months High dose reduced Want to get
high dose ACEi) NYHA Class II-IV Lisinopril Lisinopril mortality/hospital the combined patient to high
CHF (LVEF <30%) admissions endpoints of all- dose (safely) so
cause mortality that they can
Composite endpoints: and hospital benefit i.e., high
all-cause mortality + admission (RRR dose was better
hospitalization for HF; 12%; P=0.002)
CV death + Other endpoints
hospitalization for CV;
were also
fata/non-fatal MI +
hospitalization for UA reduced.
MERIT-HF 3991 patients with Metoprolol Cr/XL Placebo All-cause 1 year (stopped Endpoints were
NYHA Class II-IV. start 12.5-25mg, mortality early) lower in
(LVEF <40%) target to 200mg intervention group
daily compared to
placebo (RR 0.66
[95% CI 0.52-
0.81]; P=0.0009)
COPERNICUS 2289 patients who Carvedilol 3.125mg Placebo Mortality, 10.4 months 35% reduction in
had symptoms of BID (target 25mg mortality, or death
HF at rest or on PO BID) hospitalization 24% reduction in
minimal exertion death or
(LVEF <25%) hospitalization
(p<0.05)
COMET 1511 patients with Carvedilol (target Metoprolol All-cause 58 months All-cause Carvedilol better
NYHA Class II-IV 25mg BID) tartrate (short mortality, CV mortality: ARR 6% than metoprolol
CHF (mean LVEF acting) (target mortality/hospital for Carvedilol
0.26) 50mg BID) admission (NNT=17; Issues: metoprolol
P=0.0017) tartrate is not
comparable to 24h B1-
receptor blockade;
difference in HR
reduction may explain
difference in outcome
COMES 4016 patients with Carvedilol or metoprolol succinate 17,672 patient- After multivariable No conclusive
observational study stable systolic CHF (Individually matched on both dose- years adjustments (HR association
equivalents and the respective 0.93; 95% CI 0.57-
propensity score for BB treatment) 1.50; P=0.75)
CHARM- 2028 patients with Candesartan Placebo CV death/HF 33.7 months ARR 7%
symptomatic HF and LVEF
Alternative <40% not taking ACEi bc of (target dose 32mg) hospital NNT 14
prior intolerance admission
VAL-HeFT 5010 patients with Valsartan Placebo Primary outcome: 27 months Mortality was the Sub-analysis:
MA of ACEi in HF 54,621 All-cause Proportional
16 trials randomized HF mortality: reduced effects
participants, RAAS by 11% (RR 0.89, decreased with
inhibition risks for 95% CI 0.85-0.92) increasing mean
Cardiovascular
HF LVEF for all
Mortality: reduced
by 14% (RR 0.86, outcomes. There
95% CI 0.83-0.90) was still a
Hospitalization for decrease in the
HF: reduced by risk for HF
20% (RR 0.80, 95% hospitalization in
CI 0.77-0.83) patients with
preserved LVEF
SAVE 2231 patients with Captopril (initial Placebo All-cause ~42 months All-cause Established the
LVD (LVEF 40%) 6.25-12.5mg; mortality, CV mortality: RRR benefit of ACEi
beginning 3-16 target 25mg) death, 19%; P=0.0019 in post-MI
days post-MI hospitalization for CV Death: RRR. patients who
12%, P=0.014
HF, rMI, have EF 40%
Hospitalization for
symptomatic HF HF: RRR22%;
P=0.019
Recurrent MI: RRR
25%; P=0.0015
Symptomatic HF:
RRR 37%; P<0.001
SOLVED- 2569 patients with Enalapril (2.5 to Placebo All-cause 41.4 months All-cause Established the
treatment NYHA (regardless 20mg /day) mortality, mortality: absolute benefits of ACEi
of MI) Class II and hospitalization or risk reduced by in all sx HF
III HF death from HF 4.5% (NNT=23; patients
P=0.0036)
regardless of MI
Hospitalization or
death from HF: status
absolute risk
reduced by 9.6%
(NNT=11;
P<0.0001)
SOLVED- 4226 patients with Enalapril (2.5- Placebo All-cause 37.4 months No reduction in Even if the
prevention asymptomatic LV 20mg/day) mortality, CV total/CV death patient is
dysfx (LVEF <0.35) death, asymptomatic
hospitalizations Hospitalization for there are still
HF/death: ARR benefits of using
3.9%; NNT=26 ACEi if they have
, low EF
ATLAS (low v. 3164 patients with 32.5-35mg 2.5-5mg All-cause 46 months High dose reduced Want to get
high dose ACEi) NYHA Class II-IV Lisinopril Lisinopril mortality/hospital the combined patient to high
CHF (LVEF <30%) admissions endpoints of all- dose (safely) so
cause mortality that they can
Composite endpoints: and hospital benefit i.e., high
all-cause mortality + admission (RRR dose was better
hospitalization for HF; 12%; P=0.002)
CV death + Other endpoints
hospitalization for CV;
were also
fata/non-fatal MI +
hospitalization for UA reduced.
MERIT-HF 3991 patients with Metoprolol Cr/XL Placebo All-cause 1 year (stopped Endpoints were
NYHA Class II-IV. start 12.5-25mg, mortality early) lower in
(LVEF <40%) target to 200mg intervention group
daily compared to
placebo (RR 0.66
[95% CI 0.52-
0.81]; P=0.0009)
COPERNICUS 2289 patients who Carvedilol 3.125mg Placebo Mortality, 10.4 months 35% reduction in
had symptoms of BID (target 25mg mortality, or death
HF at rest or on PO BID) hospitalization 24% reduction in
minimal exertion death or
(LVEF <25%) hospitalization
(p<0.05)
COMET 1511 patients with Carvedilol (target Metoprolol All-cause 58 months All-cause Carvedilol better
NYHA Class II-IV 25mg BID) tartrate (short mortality, CV mortality: ARR 6% than metoprolol
CHF (mean LVEF acting) (target mortality/hospital for Carvedilol
0.26) 50mg BID) admission (NNT=17; Issues: metoprolol
P=0.0017) tartrate is not
comparable to 24h B1-
receptor blockade;
difference in HR
reduction may explain
difference in outcome
COMES 4016 patients with Carvedilol or metoprolol succinate 17,672 patient- After multivariable No conclusive
observational study stable systolic CHF (Individually matched on both dose- years adjustments (HR association
equivalents and the respective 0.93; 95% CI 0.57-
propensity score for BB treatment) 1.50; P=0.75)
CHARM- 2028 patients with Candesartan Placebo CV death/HF 33.7 months ARR 7%
symptomatic HF and LVEF
Alternative <40% not taking ACEi bc of (target dose 32mg) hospital NNT 14
prior intolerance admission
VAL-HeFT 5010 patients with Valsartan Placebo Primary outcome: 27 months Mortality was the Sub-analysis:
