Neurohormonal Blockade, Left Ventricular Assist Devices Equal Improved Survival Outcomes in Patients With Heart Failure

Class D, or advanced, heart failure (HF) means that patients are in the final stages of severe cardiovascular disease, and therapies and symptom management strategies no longer work. To prolong life expectancy in these patients, left ventricular assist devices (LVADs) are often used to help the heart pump blood, and anticoagulation therapy is given to prevent blood clots after device implantation.

There are limited data on drug treatment beyond anticoagulation for patients with HF who have an LVAD, especially neurohormonal blockade (NHB). Measurable improvements have been seen in patients with HF with reduced ejection fraction (HFrEF) from NHB use and certain patients with LVADs on aggressive NHB treatment. The authors of a recent study in JAMA Cardiology investigated the probability of similar results in the general population of patients with LVADs.

Using 2008 to 2016 data from the Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) on patients with LVADs who remained alive 6 months after receiving their device, they ended up with a study population of 12,144 patients from 170 centers throughout the United States and Canada; of these, 10,419 (85.8%) were on NHB. The primary outcome was survival from 6 months after LVAD implantation (the baseline) to 4 years; secondary outcomes were quality of life (QOL), as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), and 6-minute walk test (6MWT), both from from baseline to 2 years. Three medication classes were considered NHB: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists.

The results did not disappoint. Overall, for patients on NHB at the 6-month mark versus those not, the Kaplan-Meier analysis showed a survival rate at 4 years of 56.0% versus 43.9%, respectively. This jumped even higher to 66.4% for patients on NHB that consisted of the 3 medication classes. Additional survival analyses were carried out to account for confounders. The Cox proportional hazard analysis confirmed the utility of triplet therapy and a propensity score-matched analysis, any NHB (59.3% vs 50.4% without NHB).

For QOL and 6MWT, follow-up measurements were taken every 6 months for 2 years, beginning at baseline. At the 2-year mark, the median KCCQ score for QOL was 68.8 versus 64.9, respectively (on a scale of 0-100), for patients with LVADs also on NHB versus those not on the therapy. The average scores were 66.6 and 63.0. For the 6MWT, for both groups, there was an overall 11.8% improvement, from 987 to 1103 feet.

There were several limitations of the study results, chief among them being that Intermacs lacks data on medication dosing, compliance, and reason for initiation or discontinuation. Therefore, the authors reason, it is difficult to tell if patients on NHB tolerated the therapy because they were healthier to start or if those not on NHB were intolerant because they were sicker.

However, there is no denying the positive outcomes for patients with advanced HF on NHB, and the results seemingly point to NHB’s place in the armamentarium of care for patients with LVADs due to HF. “The survival benefit seen in these groups was not surprising based on evidence that the combination of these therapies reduces mortality in patients with HFrEF without an LVAD,” the study authors said.

Reference

McCullough M, Caraballo C, Ravindra NG, et al [published online November 18, 2019]. Neurohormonal Blockade and Clinical Outcomes in Patients With Heart Failure Supported by Left Ventricular Assist Devices. JAMA Cardiol. doi: 10.1001/jamacardio.2019.4965.