1. Centrifugal-flow left ventricular assist devices (LVAD) were found to be noninferior to traditional axis-flow devices for the treatment of New York Heart Association (NYHA) class IIIb and IV heart failure refractory to medial therapy.
2. Though there was a significantly lower rate of device failure requiring surgical intervention, centrifugal-flow devices demonstrated a significantly higher rate of stroke, right heart failure, and sepsis.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The shortage of effective medical therapy for patients with advanced heart failure has lead to technological advances in mechanical circulatory devices. LVADs have demonstrated increased survival and improved quality of life among heart failure patients. However, the risks of infection, neurologic events, and pump failure must be balanced with the clinical benefits of LVADs. The ENDURANCE trial assessed the safety and efficacy of the centrifugal-flow LVAD (study device) compared to the traditional axial-flow device (control). At the two year mark, the LVAD demonstrated to be noninferior comparing to the traditional axial-flow device in regards to disabling stroke and device malfunction. Among secondary endpoints, the centrifugal-flow device was associated with a significantly higher incidence of stroke, right heart failure, and sepsis; however, patients in the axial-flow control group were more likely to have device malfunction requiring surgical pump exchange or transplantation. Limitations of the included the use of individualized anticoagulation and antiplatelet regimens that may have impacted adverse events, a change in study device design during the trial, and the failure to assess durability beyond 2 years.
In-Depth [randomized controlled trial]: In this trial, 466 patients were randomized to the study device (intention-to-treat group, n = 297) or control (n = 148) in a 2:1 ratio. Eligibility criteria included patients with NYHA class IIIb or IV heart failure, left ventricular ejection fraction below 25%, and who were ineligible for transplant at the time of enrollment. The primary outcome was a composite of 2-year survival free from disabling stroke and device malfunction that required surgery or urgent implantation. Secondary endpoints included prespecified major adverse events, overall survival, and changes in quality of life defined by clinically validated questionnaires. Two thirds of participants received a modified (sintered) device during the course of the trial, and a separate analysis of the primary endpoint was done in this subgroup.
The study device was found to be noninferior to the control device in the analysis of the primary endpoint (estimated success rates based on a Weibull model, 55.4% and 59.1%, respectively; upper one-sided CI, 12.56 percentage points; p = 0.01 for noninferiority). The sintered device was also found to be noninferior in the subgroup analysis. The Kaplan-Meier estimated survival without stroke or device replacement at 2 years was 55.0% with the study device and 57.4% with the control device (p = 0.67). Conpared to the study group, a higher percentage of patients in the control group reported device malfunction or failure requiring exchange, explantation, or urgent transplantation (8.8% vs. 16.2%, respectively). Furthermore, a within the first six months a significantly higher incidence of both ischemic and hemorrhagic stroke were reported in the study group compared to placebo (29.7% vs. 12.1%, p < 0.001). The study device also had significantly higher rates of right heart failure (38.5% vs. 26.8%, p = 0.02) and sepsis (23.6% vs. 15.4%, p = 0.048). No significant difference was found in all other secondary outcomes, including functional status and quality of life.
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