A Systematic Review: Use of Left Ventricular Assist Devices as Destination Therapy in End-Stage Congestive Heart Failure
Heart transplantation is currently the preferred treatment for end-stage heart failure, but the supply of donor hearts is insufficient to meet the need and many patients are not eligible for transplantation due to age or comorbid conditions. Implantable mechanical pumps can assist the circulation of blood by the heart. Left ventricular assist devices (LVADs) have been approved by the FDA for use in patients awaiting transplant, and as a last resort in patients with refractory heart failure who are not eligible for a heart transplant (destination therapy). In January 2010, the first newer generation, rotary continuous flow ventricular assist device (HeartMate II) was approved by the FDA for destination therapy.
Investigators with the VA Evidence-based Synthesis Program in Minneapolis, MN conducted a review of the literature from 1995 through October 2011, in order to assess the scientific evidence on the use of the current generation of left ventricular assist devices as destination therapy. After conducting in-depth reviews of 146 articles, 9 were determined to be appropriate for addressing the following key questions:
How does use of an FDA-approved, current generation LVAD as destination therapy (i.e., the HeartMate II left ventricular assist device) affect patient outcomes?
- A single study provides moderate-strength evidence that use of the HeartMate II produces better patient outcomes, including patient survival, with fewer harms and hospitalizations, compared to the older generation HeartMate XVE, which is the only other ventricular assist device approved by the FDA for destination therapy.
- After 24 months, the primary endpoint of survival free of disabling stroke or re-operation to remove the device was 46% for individuals in the HeartMate II group vs. 11% for those in the HeartMate XVE group.
- Survival for those in the HeartMate II group was significantly better (58% vs. 24% after 2 years), and subjects spent a greater percentage of their follow-up time outside of a hospital (88% vs. 74%), largely due to a lower readmission rate. During follow-up, survivors with the HeartMate II also had fewer functional limitations due to heart failure.
- The incidences of several adverse events were lower among individuals with the HeartMate II, including right heart failure, cardiac arrhythmias, device-related infections, sepsis, respiratory failure, renal failure, and device replacement. None of the adverse events rates were higher in the HeartMate II group than the HeartMate XVE group, including major bleeding and strokes.
Clinical trials of other, newer-generation continuous flow ventricular assist devices for destination therapy are ongoing; however, results are not expected for several years.
What patient or site characteristics have been associated with patient benefits or harms when the FDA-approved, current generation LVAD is used as destination therapy?
- The available evidence is insufficient to refine patient or site selection criteria for use of the HeartMate II as destination therapy.
A few studies have identified risk factors for mortality and complications -- and developed or applied mortality prediction models to this particular patient population. Further studies are needed to validate use of different criteria to improve patient outcomes. In the meantime, the approved FDA indication and CMS (Centers for Medicare and Medicaid Services) criteria for coverage are available to guide patient selection.
What is the range of cost-effectiveness estimates of using the FDA-approved, current generation LVAD as destination therapy in end-stage heart failure, and what explains variation in these estimates?
- A single industry-funded analysis has estimated that the cost-effectiveness of using the FDA-approved, current generation LVAD as destination therapy in patients with end-stage heart disease is approximately $200,000 per quality-adjusted life year.
- The strength of the evidence for this estimate is low.
Even with favorable assumptions regarding the cost and effectiveness of treatment, destination therapy using the current generation, continuous flow ventricular assist device does not appear to have a very favorable cost-effectiveness ratio compared with traditional standards and other Medicare approved interventions. However, large improvements in cost-effectiveness have occurred in the past decade. If improvements continue to be made, destination therapy in end-stage heart disease with an LVAD may become cost-effective.
Additional high-quality data are needed to inform clinical practices and policies regarding the use of ventricular assist devices to treat patients with end-stage heart failure who are not eligible for a heart transplant. Investigators suggest the following recommendations regarding future research:
- Create or participate in a registry of all Veterans that receive an LVAD as destination therapy, and support enrollment of Veterans in ongoing, randomized controlled clinical trials.
- Validate and, if necessary, update prediction models, particularly for early post-operative mortality. Solicit a consensus opinion about unacceptably high-predicted post-operative mortality, and validate prediction models to classify patient risk accordingly.
- Develop decision aids to help providers communicate information about the benefits, risks, and care needed when patients are considering an approved ventricular assist device as destination therapy, and to help providers elicit patients' values and preferences.
- Update cost-effectiveness models as better data become available.
- Conduct a budget impact analysis that specifically addresses the potential impact within VA of the use of the currently approved continuous flow ventricular assist devices as destination therapy.
This report is a product of VA/HSR&D's Quality Enhancement Research Initiative's (QUERI) Evidence-Based Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers -- and to disseminate these reports throughout VA.
Rector T, Taylor B, Greer N, Rutks I, and Wilt T. Use of Left Ventricular Assist Devices as Destination Therapy in End-Stage Congestive Heart Failure: A Systematic Review. VA-ESP Project #09-009;2012.
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