Summary of contemporary therapeutic directions in heart failure
| Therapeutic direction | Clinical trial* | Key findings | Practice implications |
| Sodium-glucose cotransporter-2 inhibition with dapagliflozin in patients with type 2 diabetes mellitus with or at risk for atherosclerotic cardiovascular disease. | DECLARE-TIMI 58 | The composite of cardiovascular death or hospitalisation for heart failure was significantly reduced with dapagliflozin and was driven by a lower risk of hospitalisation for heart failure. | Incorporated into the most recent international consensus statement as second-line therapy (after metformin) in patients with type 2 diabetes mellitus with cardiovascular disease. |
| Angiotensin-neprilysin inhibition with sacubitril/valsartan in patients hospitalised for acute decompensated heart failure. | PIONEER-HF | The time-averaged reduction in NT-proBNP was significantly more reduced with sacubitril/valsartan compared with enalapril. | Sacubitril-valsartan may be considered for inpatients as this will simplify the algorithm for inpatient and subsequently outpatient heart failure management. |
| Withdrawal of heart failure medications in patients with presumed recovery of dilated cardiomyopathy. | TRED-HF | Relapse (study-specific criteria that included clinical symptoms of heart failure) was significantly greater in the medication withdrawal group compared with the medication continuation group. | Most patients thought to be in recovery are probably in remission and clinicians should be cautious in withdrawing guideline-directed medical therapy in patients with improved left ventricular function. |
| Anticoagulation with very low-dose rivaroxaban in patients with chronic heart failure with reduced ejection fraction, coronary artery disease and sinus rhythm. | COMMANDER-HF | The composite of death from any cause, myocardial infarction or stroke was not significantly different between patients taking rivaroxaban and those receiving standard of care. | There does not appear to be a role for low-dose anticoagulation among patients with heart failure who are in sinus rhythm. |
| Use of the small molecule transthyretin tetramer stabiliser, tafamidis, in patients with transthyretin amyloid cardiomyopathy and New York Heart Association class I–III symptoms. | ATTR-ACT | The composite of all-cause mortality or cardiovascular-related hospitalisations was significantly reduced with tafamidis, although not in patients with New York Heart Association class III symptoms at baseline. | Tafamidis is a safe and effective therapeutic option in patients with early-stage transthyretin amyloid cardiomyopathy. |
| Percutaneous, transcatheter repair using the MitraClip device in patients with heart failure and secondary mitral valve regurgitation. | MITRA-FR | The composite of death from any cause or hospitalisation for heart failure did not significantly differ between patients randomised to the MitraClip device as compared with controls. | A proposed cardiomyopathy-dominant form of mitral regurgitation does not appear to benefit from percutaneous transcatheter repair. |
| COAPT | Hospitalisation for heart failure was significantly reduced in patients randomised to the MitraClip device. | A proposed mitral regurgitation-dominant form of myocardial disease on fully supported medical therapy may benefit from percutaneous transcatheter repair. | |
| The fully magnetically levitated centrifugal continuous-flow circulatory pump, HeartMate 3, in patients with advanced heart failure refractory to standard medical therapy. | MOMENTUM 3 | The composite of survival free from disabling stroke or survival free from reoperation to replace or remove a malfunctioning device was significantly increased in patients randomised to HeartMate 3 compared with the axial-flow pump HeartMate II. | The HeartMate 3 device is superior in terms of reducing complications associated with left ventricular assist systems. |
| Catheter ablation for patients with heart failure and symptomatic paroxysmal or persistent atrial fibrillation. | CASTLE-AF | The composite of death from any cause or hospitalisation for heart failure was significantly reduced with ablation vs standard medical therapy. | Catheter ablation is an effective therapeutic option in carefully selected patients with atrial fibrillation and left ventricular dysfunction. |
| Wearable cardioverter-defibrillators in patients with acute myocardial infarction and severe left ventricular dysfunction. | VEST | The composite of sudden death or death from ventricular tachyarrhythmia was not significantly reduced with wearable cardioverter-defibrillators. | A clear role for wearable cardioverter-defibrillators in this patient population is not yet established. |
*Note that we have included only trials published following peer review.
ATTR-ACT, Transthyretin Amyloidosis Cardiomyopathy Clinical Trial; CASTLE-AF, Catheter Ablation vs Standard Conventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation; COAPT, Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation ; COMMANDER-HF, Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure; DECLARE-TIMI 58, Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58; MITRA-FR, Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation ; MOMENTUM 3, Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 ; NT-proBNP, N-terminal pro–B-type natriuretic peptide; PIONEER-HF, the comParIson Of sacubitril/valsartaN vs Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode; TRED-HF, withdrawal of pharmacological therapy for heart failure in recovered dilated cardiomyopathy; VEST, Vest Prevention of Early Sudden Death Trial.