The Assessment of Partial Guideline-Directed Medical Therapy Down Titration in Heart Failure in Remission.

Condition(s) studied

Investigational drug(s) / intervention(s)

Down-titration: The intervention involves a 3-month therapy down-titration period, during which the SGLT2 inhibitor and minerolocorticoid receptor antagonist are withdrawn, and the angiotensin receptor-neprilysin inhibitor is replaced by an ACE inhibitor or angiotensin receptor blocker. The drug formulations used per drug class correspond with the ESC guideline recommendations: * ACE inhibitor: enalapril, lisinopril, ramipril, captopril or trandolapril (at the maximally tolerated dose, according to the respective drug SmPC). * ARB (second line alternative to ACEi): valsartan, losartan or candesartan (at the maximally tolerated dose, according to the respective drug SmPC). * Beta blocker: carvedilol, metroprolol, bisoprolol or nebivolol (at the maximally tolerated dose, according to the respective drug SmPC).

Continuation of guideline-directed heart failure therapy: The comparator involves the continuation of the maximally tolerated dose of guideline-recommended medical therapy (e.g., ACEi/ARB/ARNI, MRA, SGLT2i, and/or beta blocker) the patient is using at the time of screening. The formulations per drug class may differ according to treatment regimen at randomization, but may include: * ARNI: sacubitril/valsartan (at the maximally tolerated dose, according to the respective drug SmPC) * ACE inhibitor: enalapril, lisinopril, ramipril, captopril or trandolapril (at the maximally tolerated dose, according to the respective drug SmPC). * ARB: valsartan, losartan or candesartan (at the maximally tolerated dose, according to the respective drug SmPC). * Beta blocker: carvedilol, metroprolol, bisoprolol or nebivolol (at the maximally tolerated dose, according to the respective drug SmPC). * SGLT2 inhibitor: dapagliflozin or empagliflozin at 10 mg per day. * MRA: spironolactone or eplerenone (at the maximally tolerated dose, according to the SmPC).

Study summary

Heart failure (HF) is a chronic condition that is characterized by a weakened and enlarged heart. It typically causes symptoms such as breathlessness and swelling of the legs, and it is a serious illness that shortens life expectancy. In recent years, new medicines have been developed that can improve heart function and help patients with HF live longer. HF patients with reduced heart function typically are recommended to take four different medicines for the rest of their lives. Some patients respond so well to treatment that their heart function and symptoms appear to recover; this is called HF in remission. While the four standard medicines have proven to increase lifespan in patients with heart failure with reduced heart function, it is not known whether they all need to be continued lifelong after recovery of the heart. Current guidelines recommend treating patients lifelong, yet this is based on limited scientific evidence. Lifelong therapy comes with disadvantages: it carries considerable costs for patients and health care systems, causes potential side effects, and makes it harder for patients to keep up with all their other medications. This study will test whether carefully reducing certain HF medicines is safe compared to continuing them. Patients with heart failure in remission will be randomly assigned to either: (1) continue all standard therapies, or (2) gradually reduce medicines to just two per day under close medical supervision. Patients will followed for two years to see whether their heart function remains stable. This will be measured by looking at echograms of the heart (echocardiograms), blood tests, and whether patients experience serious events such as hospitalizations or death. This study will investigate whether partial therapy discontinuation is safe and feasible.

Eligibility

Primary outcome measure(s)

• Time to first occurrence of recurrent adverse remodeling, significant NT-proBNP increase or all-cause mortality. — From enrollment to 2 year follow-up
  The primary outcome is a composite of (1) adverse remodeling, defined as an LVESVi increase of more than 20% from baseline using echocardiography, (2) a significant biomarker increase, defined as an NT-proBNP increase to more than 500 pg/mL, or (3) all-cause mortality.

Trial sites (1)

More Ziekenhuis Oost-Limburg trials in Belgium

Other trials for the same condition