AHA.18: TRED-HF exposes danger of stopping drug treatment for dilated cardiomyopathy

According to Brian P. Halliday, PhD, patients with recovered dilated cardiomyopathy often ask, “Do I need to continue to take these medications forever?”

They’re frequently young, so the prospect of using drugs for decades—exposing them to high healthcare costs, polypharmacy and potential side effects—can be daunting.

But based on the results of the randomized TRED-HF study Halliday presented Nov. 11 at the AHA Scientific Sessions in Chicago, those individuals are better off remaining on heart failure drugs indefinitely even if their ventricular function has improved.

Of 25 patients randomized to a stepwise withdrawal of therapy, 11 of them—or 44 percent—relapsed within eight weeks of being taken off the medications. None of the 26 patients assigned to continue treatment relapsed, defined as a worsening of left ventricular ejection fraction (LVEF) of at least 10 percent to below 50 percent, an increase in LV end-diastolic volumes (LVEDV) or a doubling of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP).

Halliday noted the relapse rate likely would have been even greater if these patients were followed for a longer period, further solidifying that medication should be continued in most cases. Patients in the therapy withdrawal group were reviewed every two weeks, first being those taken off of loop diuretics, followed by mineralocorticoid receptor antagonists, beta-blockers and lastly angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

“Withdrawal of therapy should not usually be advised to our patients at least until we … have a better understanding of specific therapies that may be able to be reduced and the importance of the different components of therapy,” said Halliday, with Imperial College London. “Improvement in function therefore represents remission rather than permanent recovery for many patients.”

The pilot trial included patients whose LVEFs had improved from below 40 percent to at least 50 percent, whose LVEDVs had normalized and who had NT-pro-BNP concentrations of less than 250 ng/L. Participants were in their mid-50s on average and about two-thirds were men.

Jane E. Wilcox, MD, MSc, who coauthored an editorial on the study published in The Lancet, said the trial demonstrates that indicators of true recovery remain absent in the heart failure population. But that doesn’t mean researchers should give up on identifying them.

“I don’t think this squelches the future of myocardial recovery,” said Wilcox, with the Northwestern University Feinberg School of Medicine. “I think this, in fact, should invigorate the field for a broader assessment of genomics, proteomics, metabolomics (and) looking for that true signature of cardiac recovery. I also think this highlights the importance of a rigorous standardization in how we measure cardiac mechanics.”

Halliday noted global radial strain and NT-pro-BNP concentration were associated with the risk of relapse, but said those analyses were exploratory and should be interpreted with caution due to the small sample size. Importantly, patients in the study were closely monitored and were quickly put back on medications at early signs of relapse. LVEF was typically restored soon after and there were no patient deaths or unplanned hospital admissions for heart failure.

Donald Lloyd-Jones, MD, the vice chair of programming for the AHA Scientific Sessions, credited Halliday and colleagues for taking on an ethically challenging study and attempting to answer an important clinical question.

“It does push us down the path of trying to understand better which patients we might in the future want to select for withdrawing therapy, because no patient wants to be on more medications than they need to be,” Lloyd-Jones said. “But I think for the time being this class of patients is going to have to maintain on medications until we understand a little bit more.”