Study Findings Presented for Medtronic's HVAD System

April 24, 2017—Medtronic recently announced the findings of two studies of the company's HeartWare Ventricular Assist device (HVAD) system that were presented as late-breaking trials at the 2017 International Society for Heart and Lung Transplantation (ISHLT) Scientific Meeting held on April 5–8 in San Diego, California.

In the first presentation, the ENDURANCE Supplemental trial showed positive results at 1 year in patients seeking long-term (destination) left ventricular assist device (LVAD) therapy, but the trial did not meet its primary endpoint of all neurologic events at 12 months.

In the second presentation, preliminary results from the HVAD LATERAL study evaluated the delivery of the HVAD system through a less-invasive thoracotomy procedure in patients with end-stage heart failure who have not responded to standard medical management and are eligible for heart transplantation.

In related news, Medtronic issued a notice on April 18 that the US Food and Drug Administration (FDA) has classified the company's recently initiated voluntary field action related to its HVAD system Controllers (serial numbers lower than CON300000) and DC Adapters (all serial numbers for product code 1435) as a class I recall. The company's full press release with specific details is available online here.

Medtronic stated that the HVAD system is a full-support, centrifugal LVAD that is approved for implantation via the thoracotomy procedure in the European Union. The HVAD pump is smaller than other commercially available devices and more easily enables implantation through a thoracotomy approach. In the United States, the HVAD system is approved for implantation via a median sternotomy in patients with end-stage heart failure who are eligible for heart transplantation.

The HVAD system is indicated for use as a bridge to cardiac transplantation in patients who are at risk of death from refractory end-stage left ventricular heart failure. The HVAD system is not approved in the United States for destination therapy.

Medtronic has submitted its premarket approval application to the FDA for a destination (long-term) therapy indication for the HVAD system based on the ENDURANCE and ENDURANCE Supplemental trial datasets, advised the company.

The HVAD became part of the Medtronic Cardiac Rhythm and Heart Failure division's portfolio in August 2016, with the company's acquisition of HeartWare International, a developer and manufacturer of less-invasive, miniaturized, mechanical circulatory support technologies for treating patients with advanced heart failure.

As presented at ISHLT, although the ENDURANCE Supplemental trial did not meet its primary endpoint in the evaluation of the HVAD system as a destination therapy for patients needing LVADs who received improved blood pressure management, the secondary results showed that 76.4% of patients receiving the HVAD system were alive on the originally implanted device and free of disabling stroke, compared to 66.9% of patients in the control arm (noninferiority P < .0001; superiority P = .0354).

This prespecified secondary endpoint analysis showed the HVAD system was superior to the control group (absolute difference 9.2%), as evaluated by the composite endpoint used in most clinical trials of LVAD therapies.

Medtronic reported that device exchange was not included in the primary endpoint, but transient ischemic attacks were (14.7% of patients who received the HVAD system experienced a neurologic event within 12 months of implantation, compared to 12.1% of patients in the control arm [P = .14]). Post hoc analysis revealed a rate of disabling stroke or death of 18.8% at 12 months among patients receiving the HVAD system, compared to 21.6% of patients receiving the control device.

Post hoc analyses comparing data from the ENDURANCE Supplemental trial to data from the original ENDURANCE Destination Therapy trial showed that the prespecified blood pressure management protocol in the ENDURANCE Supplemental trial was effective in reducing the mean arterial blood pressure by a clinically meaningful amount when compared to HVAD patients from the original ENDURANCE trial (as well as when compared to the control group in ENDURANCE Supplemental). Additionally, there was a 24.7% reduction of overall stroke and transient ischemic attack incidence—and a 50% reduction in hemorrhagic strokes—in patients receiving support from the HVAD system. 

In the second presentation at ISHLT, the HVAD LATERAL study showed implantation of the HVAD system through a thoracotomy procedure that showed 87.65% of patients remained alive on the original device and free from disabling stroke, or received a heart transplant, or were explanted because of recovery. The trial successfully met its primary endpoint with the percentage of patients exceeding the prespecified performance goal of 77.5% (P = .002). 

The LATERAL study, involving 30 centers in the United States and Canada, enrolled 145 patients with end-stage heart failure who had not responded to standard medical management and who were eligible for heart transplantation. Patients were followed for 6 months postimplantation. Adverse events observed in the study at 30 days included cardiac arrhythmia (22.1%), right heart failure (22.1%), bleeding requiring reoperation (3.4%), and stroke (4.1%). Overall survival among patients receiving an HVAD via the thoracotomy procedure was 91.8% at 6 months. FDA submission of the data is planned for later this year.

Also at ISHLT, a subset of data presented from the ENDURANCE trial showed that very sick patients—those classified as INTERMACS level 1 or 2 (95 patients)—did not have worse outcomes than those considered less sick—INTERMACS level 3 (121 patients) and levels 4-7 (80 patients). Previous studies of ventricular assist devices have shown that sicker patients have worse outcomes.

In February 2017, the primary results from the ENDURANCE study were published by Joseph G. Rogers, MD, et al in The New England Journal of Medicine (2017;376:451–460).