Withdrawal of HF Meds Can Be Safe After Cardiotoxic Cancer Chemotherapy

September 19, 2014

LAS VEGAS, NV — Some cancer survivors who were put on ACE inhibitors, beta-blockers, or other heart-failure meds to fight or prevent chemotherapy cardiotoxicity don't have to stay on them forever as recommended, if they don't need them for other reasons, suggests a small feasibility study presented this week at the Heart Failure Society of America (HFSA) 2014 Scientific Meeting [1].

Following a protocol developed for the purpose, 15 such patients, in NYHA functional class 1 with normal LVEF for at least six months after having been on renin-angiotensin-inhibiting agents for heart failure with LV systolic dysfunction, were weaned off the HF meds without showing a drop in LVEF to below 50% either in the short term or, in the 12 who stayed in the study long enough, at six months, reported Dr Anecita P Fadol (MD Anderson Cancer Center, Houston, TX).

The patients were also followed with and showed no deterioration by troponin and natriuretic peptide testing and showed no changes in global longitudinal strain with speckle-tracking echocardiography. Nor did any of the 12 become symptomatic.

Of the three patients who didn't complete the six-month follow-up, two dropped out for personal reasons unrelated to their health status and one chose to withdraw because his heart rate rose after going off beta-blockers, according to Fadol.

"The first patients I enrolled in the trial have been there for a year and a half now," she told heartwire . Everyone will be followed out to two years. So far, she said, all 12 have maintained an LVEF >50%, "so I'm keeping my fingers crossed [it will show that] patients can be withdrawn from the medications."

Dr Anecita P Fadol

She emphasized that the strategy would be only for selected cancer survivors who had been on cardiotoxic chemotherapy agents. Although the study allowed patients aged <80 to enter (the oldest was 69), exclusion criteria made sure most in the group were younger than a typical heart-failure population. They could have no history of hypertension, coronary disease, diabetes, arrhythmias, or other recognized source of cardiomyopathy, or any condition besides the chemotherapy history that would make it inappropriate to withdraw beta-blockers, ACE inhibitors, or angiotensin-receptor blockers (ARB). They could have no symptoms suggestive of heart failure.

"They were 'clean' patients without [cardiovascular] risk factors, which may not be common," she said. "But there are a lot of younger cancer survivors now."

The patients' malignancies, mostly breast cancer but one case of leukemia, had been successfully treated with cyclophosphamide or trastuzumab (Herceptin, Genentech) or the anthracyclines doxorubicin or epirubicin (Ellence, Pfizer). All those referred for the study had been on beta-blockers; two also were on an ACE inhibitor and ARB, respectively.

If the patient is on a beta-blocker only, Fadol said, weaning is achieved by cutting the dosage in half, waiting a week, and then withdrawing the drug. The dosage is restored at each point if blood pressure rises to >140/90 mm Hg or heart rate to >110 beats per minute.

If the patient is on an ACE inhibitor or ARB only, the dosage is halved as long as blood pressure stays below 140/90 mm Hg, and a week later withdrawn with the same caution.

Patients on a beta-blocker and either an ACE inhibitor or ARB first follow the steps for the latter two agents; if blood pressure remains <140/90 mm Hg, the beta-blocker can then be withdrawn per protocol.

It's common for such patients to go off their heart-failure meds, but it's against guidelines, and there are yet no trial data to shed light on the safety or success of doing so, according to Fadol. She said a larger trial is planned based on the current study.

Fadol reported having no conflicts of interest.


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