Table 1.
Baseline characteristics of included RCTs
| Study | Year/country | Study | Intervention group | Control group | Design | Age, y | NYHA III-IV, % | All-cause mortality | Cardiovascular mortality | Heart failure hospitalization | Worsening heart failure events | Follow-up |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Aronow WS | 1997 USA | Open-label | Propranolol (n = 79) | Placebo (n = 79) | LVEF ≥ 40%, > 62 years age | 81 ± 8 vs. 81 ± 7 | 47 vs. 49 | 44/79 vs. 60/797 | / | / | / | 35 months |
| Yusuf, S | 2003 Canada | Double-blind | Candesartan (n = 1514) | Placebo (n = 1509) | CHARM preserved trial, LVEF ≥ 40% |
67.2 ± 11.1 vs 67.1 ± 11.1 |
38.5 vs. 40 | / | 170/1514 vs. 170/1509 | 241/1514vs.276/1509 | / | 36.6 months |
| Zi M | 2003 UK | Double-blind | Quinapril (n = 36) | Placebo (n = 38) | LVEF ≥ 40%, > 62 years age | 77 ± 7 vs. 78 ± 7 | 16.7 vs. 26.3 | 1/36 vs. 1/38 | 1/36 vs. 1/38 | 2/36 vs. 5/38 | 0/36 vs. 4/38 | 6 months |
| Cleland, JG | 2006 UK | Double-blind | perindopril (n = 424) | Placebo (n = 426) | PEP-CHF, LVEF ≥ 40%, > 70 years age | 75 (72,79) vs. 75 (72,79) | 23 vs. 26 | 17/424 vs. 19 /4267 | 10/424 vs. 17/426 | 34/424 vs. 53 /426 | 59/424 vs. 71/426 | 12 months |
| Ahmed, A | 2006 USA | Open-label | Digoxin (n = 492) | Placebo (n = 496) | LVEF ≥ 45%, > 45 years age | 66.7 ± 10.7 vs. 66.9 ± 9.9 | 21.5 vs. 22.6 | 115/492 vs. 116/496 | 81/492 vs. 81/496 | 61/492 vs. 73/496 | 89/492 vs. 108/496 | 37 months |
| Massie,BM | 2008 USA | Single-blind | Irbesartan (n = 2067) | Placebo (n = 2061) | PRESERVE, LVEF ≥ 45%, > 60 years age | 72 ± 7 vs. 72 ± 7 | 80 vs. 79 | 445/2067 vs. 436 /2061 | 311/2067 vs. 302 /2061 | 325/2067 vs. 336 /2061 | 291/2067 vs. 314 /2061 | 49.5 months |
| Yip, GW | 2008 Hong Kong | Open-label | Irbesartan (n = 53) vs. Ramipril (n = 39) | Placebo (n = 47) | HK-PROBE, LVEF ≥ 45%, > 18 years age | 75 ± 8.5 vs. 74 ± 6.1 vs. 73 ± 8.4 | 30.4 vs. 33.3 vs. 28.0 | 1/53 vs. 0/39 vs. 3/47 | 1/53 vs. 0/39 vs. 1/47 | 6/53 vs. 5/39 vs. 6/47 | / | 12 months |
| Solomon,SD | 2012 USA | Double-blind | Sacubitril–valsartan (n = 149) | Valsartan (n = 152) | PARAMOUNT, LVEF ≥ 45%, > 18 years age | 70.9 ± 9.4 vs. 71.2 ± 8.9 | 19 vs. 21 | 1/149 vs. 2/152 | 1/149 vs. 2/152 | / | 9/149 vs. 12/152 | 36 weeks |
| Edelmann, F | 2013 Austria | Double-blind | Spironolactone (n = 213) | Placebo (n = 209) | Aldo-DHF, LVEF ≥ 50%, > 18 years age | 67 ± 8 vs. 67 ± 8 | 15 vs. 12 | 1/213 vs. 0/209 | 1/213 vs. 0/2091 | 21/213 vs. 15/209 | / | 12 months |
| Yamamoto,K | 2013 Japan | Open-label | Carvedilol (n = 120) | Placebo (n = 125) | DHF, LVEF > 40%, > 20 years age | 73 ± 10 vs. 71 ± 11 | 15 vs. 8 | 18/120 vs. 21/1257 | 8/120 vs. 7/1255 | 21/120 vs. 27/125 | 25/120 vs. 31/125 | 24 months |
| Pitt, B | 2014 USA | Double-blind | Spironolactone (n = 1722) | Placebo (n = 1723) | TOPCAT, LVEF ≥ 45%, > 18 years age | 68.7 (61,76.4) vs. 68.7 (60.7,75.5) | 33.4 vs. 32.6 | 252/1722 vs. 274/1723 | 160/1722 vs. 176/1723 | 206/1722 vs. 245/1723 | / | 3.3 years |
| Solomon, SD | 2019 USA | Single-blind | Sacubitril–valsartan (n = 2407) | Valsartan (n = 2389) | PARAGON-HF, LVEF ≥ 45%, > 18 years age | 72.7 ± 8.3 vs. 72.5 ± 8.5 | 19.3 vs. 20.3 | 342/2407 vs. 349/2389 | 204/2407 vs. 212/2389 | 690/2407 vs. 797/2389 | 202/2407 vs. 221/2389 | 4 years |
| Armstrong, PW | 2020 Canada | Open-label | Vericiguat 15 mg (n = 264) vs. Vericiguat 10 mg (n = 262) | Placebo (n = 262) | VITALITY-HFpEF, LVEF ≥ 45%, > 45 years age | 73.1 ± 9.1 vs. 72.2 ± 9.7 vs. 72.8 ± 9.4 | 42.4 vs. 41.4 vs. 40.5 | 10/264 vs. 15/262 vs. 7/262 | 8/264 vs. 12/262 vs. 4/262 | / | / | 24 weeks |
| Anker SD | 2021 Germany | Double-blind | Empagliflozin (n = 2997) | Placebo (n = 2991) | EMPEROR-Presersed LVEF ≥ 50% | 71.8 ± 9.3 vs. 71.9 ± 9.6 | 422 vs. 427 | 219 vs.244 | 259 vs 352 | 362 vs 485 | 36 months | |
| Solomon, SD | 2022 USA | Double-blind | Dapagliflflozin (n = 3131) | Placebo (n = 3132) | DELIVER LVEF > 40% | 71.8 ± 9.6 vs. 71.5 ± 9.5 | 26.1 vs. 23.4 | 497 vs 526 | 231 vs. 261 | 329 vs 418 | 368 vs. 455 | 2.95 years |
HF heart failure, HFpEF heart failure with preserved ejection fraction, LVEF left ventricular ejection fraction; “/” = no data available