| Trial |
No.of patients |
Follow up duration (month) |
Therapeutic intervention |
Inclusion criteria |
NYHAclass |
Primary endpoint |
Outcomes |
| CHARM-Preserved [20] |
3023 |
36.6 |
Candesartan 4-32 mg PO/day |
Age ≥ 18; LVEF>40% and hospital admission for cardiac reason |
II-IV |
CV death or HF hospitalization |
Candesartan vsplacebo:CV death or HF hospitalization: 22% vs 24% ; HR 0.89 (95% CI 0.77-1.03) |
| I-Preserve [21] |
4128 |
49.5 |
Irbesartan 75-300mg PO/day |
Age ≥60; LVEF ≥45% and symptomatic HF; NYHA class II-IV and hospitalized for HF in past 6 months |
II-IV |
Death from any cause or CV hospitalization |
Irbesartanvs placebo:All-cause mortality or CV
hospitalization: 36% vs 37%; HR 0.95
(95% CI 0.86-1.05) |
| PEP-CHF [22] |
850 |
26.2 |
Perindopril 2-4 mg PO/day |
Age ≥ 70; LVEF ≥40%; hospitalized for HF in past 6 months; Diastolic dysfunction on ECHO; Receiving diuretics for CHF |
I-IV |
All-cause mortality and HF hospitalization |
Perindopril vs placebo:All-cause mortality orunplanned HF hospitalization:
23.6% vs 25.1% patients; HR 0.92 (95% CI 0.70-1.21) |
| RAAM-PEF [23] |
44 |
6.5 |
Eplerenone 25-50mg PO/day |
Age ≥18; LVEF≥50%; clinical HF; BNP ≥ 100pg/ml |
II-III |
Change in 6 minute walk distance |
Eplerenonevs placebo: Change in 6MWDEplerenone- 271.4+75.7 m to 310.7+ 89.8 versus Placebo-249.0+66.8 m to 286.3+ 66.7 (p=0.91) |
| TOPCAT [24] |
3445 |
39.6 |
Spironolactone 15-45
mg PO/day |
Age ≥50; LVEF≥45%; hospitalized for HF in past 12 months or elevated BNP in 6 months |
I-IV |
CV death; HF hospitalization or aborted cardiac arrest |
Spironolactone vs placebo:
CV death, HF hospitalization,
or aborted cardiac arrest: 18.6% vs 20.4%;
HR 0.89 (95% CI 0.77-1.04) |
| Aldo-DHF [25] |
422 |
11.6 |
Spironolactone 25mg PO/day |
Age ≥ 50; LVEF≥55%; ECHO evidence of diastolic dysfunction; peak VO2≤ 25ml/kg/min |
II-III |
Change in E/e’, change in peak VO2 |
Spironolactone vs placebo:
Spironolactone - E/e’ 12.7 (SD, 3.6) to 12.1 (SD, 3.7) versus Placebo- E/e’
12.8 (SD, 4.4) to 13.6 (SD, 4.3) (adjusted
Mean difference, -1.5; 95% CI, -2.0 to -0.9; P=0.001).
Spironolactone-Peak VO2-16.3 [SD, 3.6] mL/min/kg to 16.8 [SD, 4.6] ml/min/kg versus Placebo -16.4 [SD, 3.5]ml/min/kgto 16.9 [SD, 4.4] ml/min/kg (adjusted mean difference,-0.1 ml/min/kg;95%CI,-0.6 to-0.8 mL/min/kg; P=0.81) |
| ELANDD [26] |
116 |
6 |
Nebivolol 2.5-10
mg PO/day |
Age ≥ 40; LVEF>45%; ECHO evidence of diastolic dysfunction |
II-III |
Change in 6min walk distance |
Nebivololvs placebo: Change in 6MWD
Nebivolol- 420±143 meters to 428± 141meters versus Placebo- 412±123 metersto 446± 109 meters (p=0.004) |
| SENIORS [27] |
2128 |
21 |
Nebivolol10 mg PO/day |
Age ≥70; LVEF>35%; hospitalized for HF in past 12 months |
I-IV |
Death from any cause or CV hospitalization |
Nebivololvs placebo:All-cause mortality or CVhospitalization: 29% vs 33.6%; HR 0.81
(95% CI 0.63-1.04); |
| J-DHF [28] |
245 |
38.4 |
Carvedilol 1.25-10
mg PO twice/day |
Age ≥20; LVEF>45%; clinical HF |
I-IV |
CV death or unplanned HF hospitalization |
Carvedilolvs no carvedilol:
CV death or unplanned
HF hospitalization: 21% vs 24%; HR 0.90
(95% CI 0.55-1.49) |
| RELAX [29] |
216 |
6 |
Sildenafil 20 mg PO 3
times/day for 12 weeks,
then 60 mg PO 3
times/day for 12 weeks |
LVEF>50%; Objective evidence of HF; Reduced exercise capacity and either elevated NT-pro BNP or LV filling pressures |
II-IV |
Change in peak VO2 |
Sildenafil vs placebo:
Change in peak VO2
Sildenafil (-0.20 [IQR, -1.70 to 1.11] versus Placebo (-0.20 [IQR,
-0.70 to 1.00])
(P=.90) |
| DIG Ancillary [30] |
988 |
37.2 |
Digoxin 0.125-0.5
mg PO/day (median
dose 0.25 mg PO/day) |
LVEF>45%; Clinical HF and Normal sinus rhythm |
I-IV |
HF hospitalization or HF mortality |
Digoxin vs placebo:
HF hospitalization or HF
mortality: 23.4% versus 23.4% ; HR 0.82
(95% CI 0.63-1.07); |
| PARAMOUNT [31] |
308 |
9 |
LCZ696 titrated to 200 mg twice daily or valsartan titrated to 160 mg twice daily |
LVEF>45%
NT-proBNP >400 pg/ml |
I-III |
Change in NT- proBNP at 3 months |
Ratio of change in proBNP for
LCZ696/valsartan
0.77 (P=0.005) |
