Table 2.
Trial | Year | Drug | WHF Definition | Outcome | Hazard Ratio (95% Confidence Interval) |
---|---|---|---|---|---|
PROTECT pilot37 | 2010 | Tezosentan | Physician Determined WHF: Worsening signs and symptoms of HF AND initiation or uptitration of IV treatment or MCS for HF |
LOS 60 day CV/RF readmission and death |
Mean (SD): WHF vs No WHF 13.8 (6.8) vs 9.3 (5.9) 49.7% vs 19.5% in patients without WHF |
PROTECT27 | 2011 | Rolofylline | Worsening signs and symptoms of HF with resulting intensification of IV therapy for HF or MCS or ventilator support | 14 day all-cause mortality 30 day all-cause mortality |
6.84 (4.12, 11.35) 4.78 (3.10, 7.37) |
PROTECT30 | 2015 | Rolofylline | Worsening signs and symptoms of HF with resulting intensification of therapy: high intensity therapy: initiation of inotropes, vasopressors and inodilators; MCS, ventilator support, and ultrafiltration low intensity therapy: restarting/increasing diuretics or initiating vasodilators without high intensity interventions |
60 day CV/RF rehospitalization and death 60 day all-cause rehospitalization or death 180 day all-cause mortality 60 day CV/RF rehospitalization and death 60 day all-cause rehospitalization or death 180 day all-cause mortality |
1.54(1.22, 1.95), p<0.001 1.55(1.25, 1.93) , p<0.001 2.46 (1.87, 3.25) , p<0.001 High vs Low intensity 1.41 (0.88, 2.26), p=0.15 1.32 (0.85, 2.05), p=0.22 1.55 (0.93, 2.60), p=0.096 |
Pre RELAX-AHF28 | 2010 | Serelaxin | Worsening signs or symptoms of HF requiring the increase or re-institution of IV therapy or MCS for HF | 60 day HF/RF readmission or death 30 day all-cause mortality 60 day CV mortality 60 day all-cause mortality 180 day CV death |
3.93 (1.72-8.98), p=0.001 7.70 (1.72-34.41), p=0.008 4.56 (1.02-20.20), p=0.05 3.76 ( 1.23-11.50), p=0.02 6.04 (1.75-20.87), p=0.004 |
RELAX-AHF38 | 2013 | Serelaxin | Worsening signs or symptoms of HF requiring reinstitution or intensification of IV therapy or MCS for HF | 180 day all-cause mortality | 1.90 (1.11-3.22), p=0.016 |
PROTECT and RELAX-AHF29 | 2015 | Physician assessment of worsening signs or symptoms of HF requiring intensification of IV therapy or MCS The treatment required was categorized as IV loop diuretic alone, IV inotrope (e.g., dobutamine, norepinephrine, levosimendan, phenylephrine) or mechanical therapy (e.g., mechanical ventilation, MCS, ultrafiltration), or other treatment (e.g., IV nitrates, nesiritide, nonloop diuretic) |
60 day HF/RF rehospitalization or CV death 180 day all-cause mortality |
2.19 (1.80-2.67), p=0.58 2.61 (2.20-3.10, p = 0.45 |
|
VERITAS26 | 2014 | Tezosentan | WHF could occur during the index admission or after discharge. In-hospital: either: (i) the development of pulmonary edema, cardiogenic shock, or other evidence of WHF; or (ii) failure of the patient's HF condition to improve with treatment (treatment failure) Required at least one of the following: (i) initiation of new IV therapy; (ii) re-institution of prior IV therapy; (iii) increase in current IV therapy for HF; (iv) implementation of MCS or ventilatory support; or (v) use of ultrafiltration, hemofiltration, or hemodialysis. |
LOS 30 day HF rehospitalization or death 90 day mortality |
4.33 (3.54-5.13), p<0.001 2.45 (1.75-3.40), p<0.001 2.57 (1.81-3.65), p<0.001 |
ADHERE31 | 2014 | Registry | Any of the following criteria: initiated inotropic medications or an IV vasodilator more than 12 hours after hospital presentation, were transferred to the ICU, or received advanced medical therapy after the first inpatient day. | 30 day mortality 1 year mortality 30 day all-cause readmission 1 year all-cause readmission 30 day HF readmission 1 year HF readmission 30 day Medicare payments 1 year Medicare payments |
Hazard Ratio (99% CI) 2.78 (2.55-3.04), p<0.001 1.84 (1.75-1.93), p<0.001 1.47 (1.35-1.59), p<0.001 1.27 (1.21-1.34), p<0.001 1.62 (1.43-1.84), p<0.001 1.36 (1.26-1.47), p<0.001 Cost Ratio (99% CI) 1.70 (1.57-1.84), p<0.001 1.43 (1.37-1.49), p<0.001 |
ASCEND7 | 2015 | Nesiritide | At least 1 sign, symptom, or radiologic evidence of new, persistent, or worsening acute HF requiring addition of a new IV therapy (inotrope or vasodilator) or mechanical support during index hospitalization targeted specifically at HF symptoms. | 30 day all-cause mortality or HF hospitalization 30 day all-cause mortality 180 day all-cause mortality |
8.43 (6.70-10.60), p<0.001 16.56 (12.58-21.79), p<0.001 5.05 (4.23-6.03), p<0.001 |
ADHERE6 | 2015 | Registry | Any of the following criteria: use of IV inotropes or vasodilators; mechanical support including ventilator, dialysis, IABP or LVAD; or an ICU stay during the index hospitalization Early WHF: occurred during day 1 of hospitalization Late WHF: occurred after day 1 of hospitalization |
Early WHF vs Late WHF 30 day mortality 1 year mortality 30 day all-cause readmission 1 year all-cause readmission 30 day HF readmission 1 year HF readmission 30 day Medicare payments 1 year Medicare payments |
Hazard Ratio (99% CI) 0.69 (0.57-0.83), p<0.001 0.84 (0.75-0.94), p<0.001 1.04 (0.91-1.20), p=0.44 1.08(1.01-1.16), p=0.003 0.95 (0.75-1.19), p=0.54 0.99 (0.86-1.13), p=0.81 Cost Ratio (99% CI) 1.09(0.94-1.28), p=0.14 1.26 (1.16-1.37), p<0.001 |
Abbreviations: CPAP continuous positive airway pressure, HF heart failure, IABP intra-aortic balloon pump, ICU intensive care unit, IV intravenous, LVAD left ventricular assist device, MCS mechanical circulatory support, RF renal failure, WHF worsening heart failure