Table 6.
Summarize results of landmark trials stratified for LVEF
| Study | Prevalence (%) | Main outcomes | Outcomes stratified for LVEF | ||||
|---|---|---|---|---|---|---|---|
| HFrEF | HFmrEF | HFpEF | HFrEF | HFmrEF | HFpEF | ||
| DIG trial60 | 75.42 | 15.34 | 9.23 | Digoxin/placebo HR for HF hospitalization | 0.71 [95% CI 0.65–0.77] | 0.80 [95% CI 0.63–1.03] | 0.85 [95% CI 0.62–1.17] |
| Digoxin/placebo HR for the composite of HF death or HF hospitalization | 0.74 [95% CI 0.68–0.81] | 0.83 [95% CI 0.66–1.05] | 0.88 [95% CI 0.65–1.19] | ||||
| CHARM programme8 | 57 | 17 | 26 | Cardiovascular death or HF hospitalization | 15.9 per 100 p‐y | 8.5 per 100 p‐y | 8.9 per 100 p‐y |
| Candesartan/placebo HF for the composite of cardiovascular death or HF hospitalization | 0.82 [95% CI 0.75–0.91; P < 0.001] | 0.76 [95% CI 0.61–0.96; P = 0.02] | 0.95 [95% CI 0.79–1.14; P = 0.57] | ||||
| Candesartan/placebo incident RR for recurrent HF hospitalization | 0.68 [95% CI 0.58–0.80; P < 0.001] | 0.48 [95% CI 0.33–0.70; P < 0.001] | 0.78 [95% CI 0.59–1.03; P = 0.08] | ||||
| TOPCAT7 | 0 | 15a | 85 | Composite of CV death, aborted cardiac arrest, or HF hospitalization | — | 1.37 [95% CI 1.09–1.72] | Referentb |
| HF hospitalization | — | 1.06 [95% CI 0.79–1.44] | Referentb | ||||
| CV death | — | 1.86 [95% CI 1.35–2.55] | Referent | ||||
| Spironolattone/placebo HR for composite of CV death, aborted cardiac arrest, or HF hospitalization | — | 0.72 [95% CI 0.50–1.05] | 0.97 [95% CI 0.76–1.23; P = 0.046]b | ||||
| Spironolattone/placebo HR for HF hospitalization | — | 0.76 [95% CI 0.46–1.27] | 0.98 [95% CI 0.74–1.30; P = 0.039]b | ||||
| PARAGON‐HF61 | 0 | 52c | 48c | ARNI/valsartan RR for HF hospitalizations and CV death | — | 0.78 [95% CI 0.64–0.95] | 1.00 [95% CI 0.81–1.23] |
| Meta‐analysis on beta‐blockers (Cleland et al.)62 | 94 | 4 | 2 | All‐cause mortality HR for each 5% lower LVEF | 1.16 [95% CI 1.26–1.19; P < 0.0001] | 1.16 [95% CI 1.26–1.19; P < 0.0001] | 1.16 [95% CI 1.26–1.19; P < 0.0001] |
| Beta‐blockers/placebo HR for all‐cause mortality in sinus rhythm | 0.67 [95% CI 0.50–0.90]; P = 0.007d | 0.59 [95% CI 0.34–1.03]; P = 0.066 | 1.79 [95% CI 0.78–4.10]; P = 0.17 | ||||
| Beta‐blockers/placebo HR for CV death in sinus rhythm | 0.72 (0.52–0.99); P = 0.041d | 0.48 [95% CI 0.24–0.97]; P = 0.040 | 1.77 [95% CI 0.61–5.14]; P = 0.29 | ||||
| Beta‐blockers/placebo mean change in LVEF from baseline to follow up in sinus rhythm (SE) | +4.9% (0.9)d | +1.9% (1.1%) | +0.1% (1.2%) | ||||
CI, confidence interval; CV, cardiovascular; HF, heart failure; HR, hazard ratio; LVEF, left ventricular ejection fraction; p‐y, patient‐years; RR, rate ratio; SE, standard error.
a
LVEF values are ≥45% and <50%.
b
For LVEF, ≥60%.
c
In the analysis of pre‐specified groups of PARAGON‐HF trial, the cut‐off value of LVEF is 57% (45–57% and >57%).
d
These results belong to the subgroups of patients with LVEF 35–39%; for the other subgroups of HFrEF (LVEF <20%, 21–25%, and 26–34%), the HR are superimposable.