Trials Flashcards
1
Q
CONSENSUS
A
NEJM 1987
RCT, enalapril (vs placebo) improved survival
-in >250 pts w/ NYHA IV HFrEF 6mo and 12 mo
2
Q
SOLVD
A
NEJM 1992
- RCT, enalapril (vs placebo) reduced HF hospitalizations, HF incidence and mortality
- in > 4200 asymptomatic HF patient w/ EF < 35% taking diuretics/digoxin after 4 years
3
Q
CHARM-added
A
Lancet 2003
-Addition of candesartan (vs placebo) to ACEi in HFrEF, EF < 40%, reduced CV mortality and HF hospitalization
4
Q
CHARM-alternative
A
Lancet 2003
- Candesartan (vs placebo) reduced CV mortality (by 20%) and HF hospitalizations (by 40%)
- in >2000 pts with HFrEF, who were intolerant to ACEi
5
Q
I-PRESERVE
A
NEJM 2008
-irbesartan did NOT reduced death or hospitalization, in pts w/ HFrEF, EF<45%
6
Q
PARADIGM-HF
A
NEJM 2014
- ARNI (vs enalapril 10 mg BID) reduced CV mortality, all-cause mortality, and HF hospitalization
- in > 8000 chronic HFrEF pts, EF < 40% and < 35%, NYHA II-IV.
- ARNI was well tolerated except for hypotension.
7
Q
PIONEER-HF
A
NEJM 2019
- ARNI (vs enalapril 10 mg BID) reduced NT-proBNP concentration
- in > 800 pts w/ acute decompensated HF, at 4 and 8 weeks.
8
Q
EVALUATE-HF
A
JAMA 2019
- ARNI at target dose 97/103 mg BID (vs enalapril 10 mg QD) did not show differences in change of aortic stiffness (measured with characteristic impedance via echo)
- neither of them lowered aortic stiffness
- in HFrEF < 40%, after 12 weeks
9
Q
PARAGON-HF
A
NEJM 2019
- ARNI 97/103 mg BID (vs valsartan 160 mg BID) did NOT reduce HF hospitalizations/CVD death (rate ratio 0.87, 95%CI 0.75-1.01)
- in > 4800 pts w HFpEF > 45%, NYHA II,III,IV, structural heart disease
- However, ARNI was a/w less renal dysfunction (1.4% vs 2.7%, HR 0.5)
- PARAGON was performed given positive results of PARAMOUNT (phase 2 trial in HFpEF).
- FDA approved ARNI in HFpEF in Dec 2020 after analyzing PARAGON-HF
10
Q
OVERTURE
A
- omapatrilat (a previous neprilysin inhibitor) is a/w higher freq of angioedema (OVERTURE trial).
- Omapatrilat was a/w lower mortality and hospitalization as compared to enalapril, but produced too much angioedema!
11
Q
MERIT-HF
A
Lancet 1999
- metoprolol succinate 12.5-25 mg daily (vs placebo) reduced all-cause mortality (by 34%), all-cause hospitalizations, and CV events
- in ~4000 pts w/HFrEF <40%, NYHA II-III
12
Q
CIBIS-II
A
Lancet 1999
- bisoprolol (start dose 1.2510 mg daily (vs placebo) reduced all-cause mortality
- in HFrEF < 35%, NYHA III-IV
13
Q
COPERNICUS
A
Circulation 2002
- carvedilol (3.125 – 25 mg BID, uptitrated q2w) vs placebo reduced risk of death and HF hospitalizations (by 31%)
- in > 2000 euvolemic pts w/HFrEF < 25%, NYHA III-IV
14
Q
COMET
A
Lancet 2003
- carvedilol 3.125-25 mg BID (vs metoprolol tartrate 5-50 mg BID) reduced all-cause mortality
- in >3000 pts w/ HFrEF < 35%, NYHA II-IV
- after 4.8 years
- Largest and most well-known head-to-head trial of Beta blockers
- Criticism: it used metoprolol Tartrate (instead of succinate).
15
Q
RALES
A
NEJM 1999
- spironolactone 25-50 mg daily (vs placebo) reduced all-cause mortality (by 30%), SCD, and HF hospitalization
- > 1600 in pts w/ HFrEF < 35%, NYHA III-IV
- Aldactone a/w gynecomastia/mastalgia (10% vs 1%).
- Only 10% of pts were on beta blockers
16
Q
EPHESUS
A
NEJM 2003
- eplerenone 25-50 mg daily (vs placebo) reduced mortality in patients with acute MI (3-14 d) complicated by LV dysfunction (EF < 40%) and HF.
- A lot more patients (than in RALES) were on beta blockers.
17
Q
EMPHASIS-HF
A
NEJM 2011
- eplerenone (vs placebo) reduced risk of death (by 15%) and hospitalization
- in > 2700 pts with HFrEF <30%, NYHA II.
- 85% were on beta blockers (only 10% in RALES).
18
Q
TOPCAT
A
NEJM 2014
- spironolactone 15-45 mg daily (vs placebo) did not reduce CV mortality, HF hospitalizations, of aborted cardiac arrests
- in ~ 3400 pts w/ s/s HF with LVEF > 45%, as compared to placebo.
- There was a small reduction of HF hospitalizations: lead to subanalysis in 2017: Eastern European (Russian/Georgian) vs North/South American subjects Eastern European subjects likely were not taking medication (metabolites were undetectable, potassium did not vary).
- Criticism: used broad ACC/AHA HfpEF definitions, so maybe included pts who had no HF and did not need med.
19
Q
V-HeFT
A
NEJM 1986
- ISDN/hydralazine (vs prazosin and vs placebo) improved survival in >600 patients with HFrEF, EF<45%.
- A subgroup analysis showed statistically significant benefit among self-identified black patients.
20
Q
V-HeFT II
A
NEJM 1991
- enalapril improved survival compared to ISDN/hydralazine
- in > 800 male pts w/HFrEF, EF<45%, already taking diuretics and digoxin.
21
Q
A-HeFT
A
NEJM 2004
- ISDN/hydralazine (vs placebo) improved survival (40%) and hospitalization
- in > 1000 blacks with HFrEF on ACEi/ARB/BB/diuretics
22
Q
DAPA-HF
A
NEJM 2019
- RCT, dapagliflozin (10 mg QD) (vs placebo) +GDMT was a/w less CVD death/HF exacerbation (HR 0.7, 16.3% vs 21.2%) and all-cause mortality
- after 18.2 months, in > 4700 pts with NYHA II-VI HFrEF < 40%, regardless of diabetes status.
23
Q
EMPEROR-Reduced
A
NEJM 2020
- empagliflozin 10mg/d (vs placebo) +GDMT was a/w less CV death/ HF hospitalization (HR 0.75, 19.4 vs 24.7%), slower eGFR decline, and worse renal outcomes
- in > 3700 pts w class II-IV HFrEF < 40%, regardless of diabetes status
24
Q
SUGAR-DM-HF
A
Circulation 2021
- empagliflozin 10mg/d (vs placebo) +GDMT was a/w reduced LV end-systolic volume index by 6.0, reduced LV end-diastolic volume index by 8.2, no difference in global longitudinal strain (CMR), reduced N-terminal pro-BNP by 28%, no difference in KCCQ, 6MWT, or B-lines
- in pts w NYHA II-IV HFrEF < 40% + T2DM or prediabetes
25
Q
DIG
A
NEJM 1997
- digoxin (vs placebo) reduced hospitalizations (by 28%) but not mortality
- in > 6000 pts w/HFrEF <45%
26
Q
SHIFT
A
Lancet 2010
- ivabradine (vs placebo) reduced HF mortality and hospitalizations
- in > 6000 pts with HFrEF < 35%, NYHA II-IV, w/ HF hospitalization in the preceding year, and resting HR>70 despite being on max-tolerated GDMT
27
Q
VICTORIA
A
NEJM 2020
- vericiguat (target dose 10mg QD), as compared to placebo, was a/w lower death from CV causes (16.4% vs 17.5%) or HF hospitalization (HR 0.9, CI 0.8-1.0).
- over 10.8 mo, among pts with high-risk HF (NYHA II-IV, EF <45%),
- Vericiguat was a/w symptomatic hypotension in 9.1% (7.9% in placebo), and syncope.
28
Q
AFFIRM-HF
A
Lancet 2020
- IV iron (ferric carboxymaltose, for up to 24 weeks) vs placebo reduced risk of HF hospitalizations without difference in CV death
- in > 1100 pts w iron deficiency (ferritin < 100, transferrin sat < 20%) and LVEF > 50% stabilized after episode of ADHF
29
Q
ESCAPE
A
JAMA 2005
- pulmonary artery catheter-guided therapy did not improve survival and increased adverse events, compared to clinical assessment-guided therapy
- in >400 patients with ADHF (EF < 30%)
30
Q
PAC-MAN
A
Lancet 2005
-in critically-ill patients, pul artery catheter did not show benefit or harm, vs no catheter.
RCT.
31
Q
EVEREST
A
JAMA 2007
- tolvaptan PO (vs placebo) did not reduce all-cause mortality, CVD mortality, of HF rehospitalization
- in > 4000 patients with acute HF exacerbation, for 60 days
32
Q
DOSE
A
NEJM 2011
- high-dose (2.5 x home dose) loop diuretics (vs home dose) was a/w better symptom improvement, while diuretic infusion is not better than intermitted diuretic boluses (but were less likely to require thiazide-like diuretics)
- in 300 pts w/ ADHF
33
Q
ROPA-DOP
A
JACC 2018
- furosemide infusion (vs bolus q12h) was a/w worse renal function (because infusion does not allow adequate re-equilibration of intra/extravascular volumes in congestion)
- in 90pts w HFpEF >50% and ADHF
- This was especially true for women, African Americans, and CKD.
- Low dose-dopamine (3mcg/kg/min) had no impact on renal function.
34
Q
ROSE
A
JAMA 2013
- neither low-dose dopamine (2 mcg/kg/min) nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy
- in 360 pts w ADHF and renal dysfunction (eGFR 15-60)
35
Q
DAD-HF
A
2010
- low-dose dopamine 5 mcg/kg/min + low-dose furosemide 5 mg/h x8h (vs high-dose furosemide 20mg/h x8h w/o dopamine) was a/w better renal function profile and less hypokalemia
- in 60 pts w ADHF
36
Q
DAD-HF II
A
2014
- high-dose furosemide 20mg/h (vs low-dose furosemide 5mg/h) was not a/w differences in hospital and post-discharge outcomes.
- Addition of low-dose dopamine infusion was NOT a/w any benefits.
37
Q
OPTIME-CHF
A
JAMA 2002
-in ADHF, routine use of milrinone as adjunct to standard therapy was NOT a/w lower mortality (in hospital of at 60 days), or death/readmission.
-milrinone be harmful in ischemic HF, but neutral to beneficial in nonischemic CMP
38
Q
CHAMPION
A
2017
-PA pressure-guided HF management reduces morbidity and mortality in pts with HFrEF on GDMT
