Treatment withdrawal not recommended after dilated cardiomyopathy recovery
Individuals previously diagnosed with dilated cardiomyopathy (DCM) who are considered recovered from their condition may still need to continue treatment, with a higher rate of relapse observed among patients who discontinued versus continued therapy, according to the TRED-HF* trial findings presented at AHA 2018.
“Withdrawal of therapy from patients deemed to have recovered DCM resulted in relapse in around 40 percent of cases. If therapy withdrawal had been continued for a medium to longer term, [relapse incidence] is likely to have been even greater,” said study author Dr Brian Halliday from the Royal Brompton Hospital, London, UK.
In this open-label, pilot trial, 51 patients (median age 55 years, 67 percent male) previously diagnosed with DCM (dilated LVEF** ≤40 percent at diagnosis; median LVEF, 25 percent) who had since recovered (LVEF ≥50 percent [median LVEF, 60 percent], normal LVEDV***, NT-pro-BNP# <250 ng/L [median, 72 ng/L], and NYHA## class I) were randomized to either continue treatment (n=26) or phased withdrawal of treatment (over 16 weeks) in the order of loop diuretics, mineralocorticoid receptor antagonists (MRAs), beta-blockers, and/or angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs; n=25). All patients were followed up for 6 months. After 6 months, patients initially assigned to withdraw therapy completed the study while those assigned to continue therapy had their therapies withdrawn (crossover period).
In the first 6-month period, more patients who withdrew therapy experienced a relapse (defined as >10 percent reduction in LVEF to <50 percent, >10 percent increase in LVEDV to higher than normal range, twofold increase in NT-pro-BNP concentration to >400 ng/L, or clinical evidence of heart failure) compared with patients who continued their treatment (44 percent vs 0 percent, estimated event rate, 45.7 percent, 95 percent confidence interval [CI], 28.5–67.2; p=0.0001). [AHA 2018, LBS.05, abstract 18621; Lancet 2018;doi:10.1016/S0140-6736(18)32484-X]
During the 6 months following the crossover period, nine patients experienced relapse (estimated event rate, 36.0 percent, 95 percent CI, 20.6–57.8). Overall, 40 percent of patients (n=20) experienced a DCM relapse.
There were three serious adverse events that occurred among patients who withdrew therapy (one incident each of urinary sepsis, non-cardiac chest pain, and an elective procedure for a pre-existing condition, all of which required hospitalization). Three patients who withdrew therapy developed atrial fibrillation (AF).
There were no deaths, or incidences of major adverse cardiovascular events or unplanned hospitalizations for heart failure.
All patients who relapsed restarted treatment. At follow up, none demonstrated symptoms of heart failure (NYHA class I) and 85 percent had LVEF >50 percent. Four patients restarted treatment despite not experiencing relapse, two due to hypertension, one after an episode of AF, and one after an episode of non-sustained ventricular tachycardia.
Older age (p=0.0309), MRA prescription pre-withdrawal (p=0.0042), prescription of >2 heart failure medications (p=0.0040), elevated NT-pro-BNP (p=0.0161), and reduced peak global radial strain (p=0.0177) at baseline were predictors of relapse risk.
Thirty-two percent of patients remained asymptomatic after treatment withdrawal.
“With advances in heart failure therapy, we now see an increase in number of patients diagnosed with DCM demonstrate evidence of recovery after a period of pharmacological therapy,” said Halliday. However, the results of this study suggest that the improvement in function represents remission rather than permanent recovery for many patients, he said.
“For now … we recommend [that our patients] stay on medications … until we have further research to say otherwise,” said Halliday. For patients who insist on withdrawing therapy, “a robust monitoring plan” is required with frequent imaging and biomarker follow-up, he added.
The timing of relapse – mostly within 8 weeks of treatment withdrawal – can also help with monitoring patients who withdraw treatment, said Halliday and co-authors.
Halliday pointed out that this advice may change should predictors of relapse be identified, as well as if studies demonstrate which DCM treatments are more crucial, thus identifying which therapies can be reduced or withdrawn.