STRONG-HF: the biomarker-led post-acute heart failure treatment strategy you might have been waiting for¹

Inclusion criteria:

• Hospital admission within the 72 hours prior to screening for acute heart failure with dyspnoea at rest and pulmonary congestion on chest X-ray, and other signs and/or symptoms of heart failure such as oedema and/or positive rales on auscultation
• All measures within 24 hours prior to randomisation of systolic blood pressure ≥100 mmHg and of heart rate ≥60 bpm
• All measures within 24 hours prior to randomisation of serum potassium ≤5.0 mEq/L (mmol/L)
• Biomarker criteria for persistent congestion:
  • At screening, NT-proBNP >2,500 pg/mL
  • At the time of randomisation (within 2 days prior to discharge), NT-proBNP >1,500 pg/mL (to ensure the persistence of congestion) that has decreased by more than 10% compared to screening (to ensure the acuity of the index episode)
• At 1 week prior to admission, at screening and at Visit 2 (just prior to randomisation) either
  • ≤ ½ the optimal dose of ACEi/ARB/ARNi prescribed, no beta blocker prescribed and ≤½ the optimal dose of MRA prescribed or
  • No ACEi/ARB/ARNi prescribed, ≤½ the optimal dose of beta blocker prescribed and ≤ ½ the optimal dose of MRA prescribed
• Written informed consent to participate in the study

Exclusion criteria:

• Age <18 or >85 years
• Clearly documented intolerance to high doses of beta blockers
• Clearly documented intolerance to high doses of RAS blockers (both ACEi and ARB)
• Mechanical ventilation (not including CPAP/BiPAP) in the 24 hours prior to screening
• Significant pulmonary disease contributing substantially to the patient’s dyspnoea such as FEV1 <1 L or need for chronic systemic or non-systemic steroid therapy, or any kind of primary right heart failure such as primary pulmonary hypertension or recurrent pulmonary embolism
• Myocardial infarction, unstable angina or cardiac surgery within 3 months, or CRT device implantation within 3 months, or PTCI within 1 month prior to screening
• Index event (admission for AHF) triggered primarily by a correctable aetiology such as significant arrhythmia (e.g. sustained ventricular tachycardia, or atrial fibrillation/flutter with sustained ventricular response >130 bpm, or bradycardia with sustained ventricular arrhythmia <45 bpm), infection, severe anaemia, acute coronary syndrome, pulmonary embolism, exacerbation of COPD, planned admission for device implantation or severe non-adherence leading to very significant fluid accumulation prior to admission and brisk diuresis after admission. Troponin elevations without other evidence of an acute coronary syndrome are not an exclusion
• Uncorrected thyroid disease, active myocarditis, or known amyloid or hypertrophic obstructive cardiomyopathy
• History of heart transplant or on a transplant list, or using or plan to be implanted with a ventricular assist device
• Sustained ventricular arrhythmia with syncopal episodes within the 3 months prior to screening that is untreated
• Presence at screening of any haemodynamically significant valvular stenosis or regurgitation, except mitral or tricuspid regurgitation secondary to left ventricular dilatation, or the presence of any haemodynamically significant obstructive lesion of the left ventricular outflow tract
• Active infection at any time during the AHF hospitalisation prior to randomisation based on abnormal temperature and elevated WBC count need for intravenous antibiotics
• Stroke or TIA within the 3 months prior to screening 
• Primary liver disease considered to be life threatening
• Renal disease or eGFR <30 mL/min/1.73 m2 (as estimated by the simplified MDRD formula) at screening or history of dialysis
• Psychiatric or neurological disorder, cirrhosis, or active malignancy leading to a life expectancy <6 months
• Prior (defined as <30 days from screening) or current enrolment in a CHF trial or participation in an investigational drug or device study within the 30 days prior to screening
• Discharge for the AHF hospitalisation anticipated to be >14 days from admission, or to a long-term care facility. Randomisation must occur within 12 days following admission and within 2 days prior to anticipated discharge
• Inability to comply with all study requirements due to major comorbidities, social or financial issues, or a history of non-compliance with medical regimens, that might compromise the patient’s ability to understand and/or comply with the protocol instructions or follow-up procedures
• Pregnant or nursing (lactating) women