STOP-CRT: Maybe Withdraw Some Heart Failure Meds if CRT Restores LVEF

September 23, 2019

PHILADELPHIA — Some patients with heart failure (HF) whose cardiac function has improved into the normal range on optimal meds plus cardiac resynchronization therapy (CRT) can potentially stop taking neurohormonal-blocking agents without a relapse, a small randomized study suggests.

Two-year echocardiographic and clinical outcomes were similar for such patients who either continued or were carefully taken off beta blockers, renin-angiotensin-aldosterone (RAAS) inhibitors, or both drug classes in the STOP-CRT trial.

The study showed no significant differences in rates of left-ventricular (LV) volume change or clinical outcomes like death, HF hospitalization, or change in need for loop diuretics between the two patient groups, Petra Nijst, MD, Oost-Limburg Hospital, Belgium, reported here at the Heart Failure Society of America 23rd Annual Scientific Meeting.

Less than 8% of the study's 80 patients who started the trial with LV ejection fractions normalized on CRT showed adverse LV remodeling changes over 2 years, regardless of whether their neurohormonal-blocking meds had been withdrawn, said Nijst, primary investigator of STOP-CRT. Their echo changes occurred mostly between year 1 and 2 of follow-up.

Importantly, some patients taken off the drugs went back on them during the follow-up period for "safety reasons," which consisted of only transient atrial tachycardia in all but one case, Nijst told theheart.org | Medscape Cardiology.

Still, the primary echocardiographic and secondary clinical outcomes were similar for patients who stayed on or went off neurohormonal-blocking therapy in both intention-to-treat and "as-treated" analyses, she said.

Similar drug withdrawal was attempted in the randomized, single-center TRED-HF trial, which assessed 51 patients with dilated cardiomyopathy who became asymptomatic with a left ventricular ejection fraction (LVEF) that had gone from less than 40% to at least 50% on medical therapy.

About 44% of TRED-HF patients in whom the meds were withdrawn experienced relapses within 6 months. But only one patient in the study had achieved their initial recovery on CRT, an important difference from STOP-CRT, in which the device therapy was an entry prerequisite and had likely driven most of their myocardial recovery.

Patient Selection Seen as Key

"Certainly one study is not enough" to recommend that even highly selected patients like those in STOP-CRT stop taking their beta blockers or RAAS inhibitors, Nijst said. Comorbidities are common in older patients, and in this trial, with an average patient age of about 69 years, hypertension and development of supraventricular arrhythmias "hampered the withdrawal of pharmacologic therapy."

In future studies of the strategy, "we'll have to be more restrictive. We'll have to choose young patients without comorbidities." It's possible, Nijst said, that such studies will "show that neurohormonal blockers in this specific group of patients might not be indicated."

Those future studies should also look at whether the drug withdrawal deprives some patients of therapy that is helpful for other reasons, proposed Bertram Pitt, MD, University of Michigan, Ann Arbor, as a panelist after the STOP-CRT presentation.

For example, he noted, many of the trial's patients had hypertension, which is often treated with some of the same neurohormonal-blocking agents.

"Long term, we know that vascular stiffening in these people with hypertension goes on to dementia and renal disease. I'd like to be reassured that taking this away doesn't have long-term consequences," Pitt said.

Nijst proposed that the withdrawal strategy might be appropriate now for patients who don't tolerate neurohormonal-blocking therapy well. "I think that if you have a patient without comorbidities, who has myocardial recovery after CRT but is having side effects due to medication, it's probably safe to try it," she said in an interview.

Of note, the trial's patients who reached the primary end point of a greater than 15% rise in LV end-systolic volume index (LVESVI) at 2 years "became normal within 6 months if we reinitiated their drugs, without any negative effects," Nijst said.

Supervised Drug Withdrawals

STOP-CRT entered 80 patients who had achieved an LVEF of at least 50% on CRT that had been initiated at least 6 months before on a class 1 indication.

To help ensure they were at low risk, patients had to be euvolemic, in NYHA class 1 or 2, and without severe adverse ventricular remodeling. For example, their LV diastolic diameters and volumes were required not to exceed 3.2 cm/m² and 75 mL/m², respectively, indexed to body surface area and adjusted for sex.

They were randomly assigned on an open-label basis to one of four groups, each with 20 patients: no withdrawal of RAAS inhibitors or beta blockers; withdrawal of RAAS inhibitors only; withdrawal of beta blockers only; or withdrawal of both drug classes.

Drug withdrawals were supervised, Nijst said, with dosages de-escalated in an order opposite to what guidelines recommend for their uptitration.

Over the 2 years, 17 patients who had gone off neurohormonal-blocking meds started on them again: one patient who resumed RAAS inhibitors because of uncontrolled hypertension, one who went back on beta blockers because of a nonsustained ventricular arrhythmia, and 15 who returned to beta blockers because of atrial tachycardia that was mostly transient.

Six patients met the primary end point of a rise of at least 15% in LV end systolic volume (LVESV) index — one in the beta blocker withdrawal group, three in the group that withdrew both drug types, and two in the no-withdrawal group — with no significant differences among groups.

A total of four patients met the secondary end point of all-cause mortality, HF hospitalization, sustained VT, or appropriate implantable defibrillator therapy, with no between-group differences.

Although the patients who went off the meds didn't show any improvements in exercise capacity or symptoms — they were already mostly asymptomatic — they "felt better mentally" from the prospect of not having to take the drugs for the rest of their lives, Nijst said.

Many believed the drugs had been dampening their activity levels or making them dizzy and were glad to go off them, she noted. "So the people were happier, and they stayed happy during the 2-year course. I think that's important to the patients' well being."

Neither Nijst nor Pitt had disclosures.

Heart Failure Society of America 23rd Annual Scientific Meeting: Late Breaking Clinical Trials. Presented September 16, 2019.

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

 

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