Summary: evaluation of the evidence on the HeartMate II® and HeartWare® ventricular assist devices for the treatment of chronic end-stage heart failure

Ano de publicação: 2012

CONTEXT:

Heart failure is a complex syndrome that arises when the heart is incapable of pumping enough blood to respond to the metabolic needs of the body. Heart failure is often caused by defective contraction and relaxation of the myocardium, accompanied by elevated cardiac filling pressure. It represents the final stage of a number of cardiovascular diseases. Characterized by limitation in activities of daily living and progressive exhaustion at rest, heart failure is a disabling and life-threatening condition. Severe heart failure, defined as class IV using the functional classification scheme of the New York Heart Association (NYHA), is associated with a 1-year mortality of about 50%. Heart failure is a major public health problem, associated with high rates of morbidity and mortality. It is estimated that more than 80,000 people are affected in Quebec, and the incidence of heart failure is expected to increase as a result of ageing of the population. More than 75% of patients suffering from heart failure in Quebec use hospital-based services. Approximately 8,500 people are hospitalized each year; about 85% of these patients are 66 years or older. More than 900 people die from heart failure annually in Quebec. End-stage chronic heart failure is characterized by advanced modifications of the cardiac system, marked symptoms at rest, and is refractory to medical and surgical treatment. Cardiac transplantation is the treatment of choice for most cases of end-stage chronic heart failure. However, access to cardiac transplantation remains relatively limited due to strict eligibility criteria and a lack of donor organs. An implantable ventricular assist device (VAD) is a technology that has been offered in Canada since 1986 and for which demand continues to grow. A VAD increases cardiac output by reducing the work of the failing heart. It is thus used to improve the chances that a patient survives until receipt of a donor heart (or, occasionally, until recuperation of cardiac function) or for long-term treatment in the case of temporary or permanent ineligibility for heart transplantation. In the past decade, VAD technology has evolved, in order to reduce the number of moving parts and device size and to increase durability; thus, newer “continuous-flow” devices have taken the place of pulsatile-flow VADs. In 2010, the Quebec Tertiary Cardiology Network (the Réseau québécois de cardiologie tertiaire, RQCT) produced a narrative review on VADs and an analysis of the situation in Quebec from 2000 to 2008. Currently, three hospitals in Quebec carry out cardiac transplantation and use implantable VADs for adult patients. In 2011, the Ministry of Health and Social Services (MSSS) gave the Institut national d’excellence en santé et en services sociaux (INESSS) the mandate to perform an evaluation of implantable VADs. Our analysis focusses on the two continuous-flow VADs that are the most relevant to the Quebec context: HeartMate II®, the device that is the most often used in Quebec, and HeartWare®, an emerging technology in Europe.

OBJECTIVES OF THIS EVALUATION:

1. synthesize, by means of a systematic review, the recent evidence (2008-2011) on HeartMate II® (HM II) and HeartWare® (HW), with regard to effectiveness, safety and economic considerations, according to initial indication (bridge to transplantation or permanent “destination” therapy) for patients with end-stage chronic heart failure; and 2. provide an overview, by means of a narrative review, of organizational and ethical issues in VAD use, including the process of patient selection.

METHODS:

A systematic search of the scientific literature published between January 2008 and April 2011 was carried out in bibliographic databases. We performed a final update of the search in January 2012 in order to identify any new articles published on economic issues, end-organ function and on HW, since limited information was found on these aspects. We also looked for follow-up publications for studies identified during our initial search. In order to summarize pertinent material on organizational aspects and eligibility of patients, we extracted information from the following sources: 1) the most recent clinical practice guidelines on management of heart failure from North America and Europe; 2) health technology assessment (HTA) reports published between 2008 and 2010; and 3) expert consensus documents found during our literature search. Document selection, extraction of data, and critical analysis of studies was carried out independently by two members of the INESSS team. Data on the number of VADs implanted were obtained from the three transplantation centres in Quebec, from publications, and through communication with key contacts in other regions. We created a scientific committee of expert clinicians, consisting of a cardiologist and cardiac surgeons representing each transplantation centre in Quebec and the RQCT. This committee played an advisory role with regards to validating our methods and assuring both the rigour of our evaluation and the appreciation of elements relevant to the clinical perspective in Quebec.

RESULTS:

In our systematic review of clinical outcomes, 13 studies on HM II met our selection criteria, with 8 examining VAD support in patients waiting for a heart transplant (719 “bridge to transplant” patients) and 5 examining VAD support as destination therapy (414 patients). Almost all the studies were carried out in USA. Two arose from INTERMACS (the Interagency Registry for Mechanically Assisted Circulatory Support). One international multicentre study was found on HW (50 “bridge to transplant” patients). In the studies we analyzed, destination therapy patients were, on average, 10 years older than bridge-to-transplant patients; the average age of the latter was about 50 years. The mean duration of VAD support varied from 8 to 10 months for patients awaiting transplantation and from 19 to 21 months for destination therapy patients. According to the most recent INTERMACS report, eligibility for heart transplantation is uncertain for the largest proportion of patients receiving a VAD (about 40% of recipients in 2010). Also, patients originally receiving a VAD as destination therapy may eventually receive a heart transplant, and those receiving a VAD as a bridge to transplant may keep the device indefinitely. Some patients in both of these groups can experience enough improvement of cardiac function to be able to have their VAD removed (explanted). Thus, the various classes of VAD users can overlap. According to our systematic review of effectiveness, safety and economic considerations: 1. The use of a continuous-flow implantable VAD (HM II or HW) can be considered a clinically-effective therapeutic option, compared to optimal medical treatment, if offered to appropriate patients. For both bridge to transplant and destination therapy patients, results are promising for survival, as well as for impact on function and on quality of life. Of 100 patients receiving a HM II device, more than 70 will be alive on support at 1 year and more than 80 will be able to carry out activities of daily living in the absence of heart failure symptoms, or with only minor symptoms. 2. In general, severe bleeding (affecting ≥50% of HM II patients), localized infection not related to the VAD (≥30% of patients), and septicemia (≥20%) are the principal complications in the first 30 days following implantation of a HM II device. During this period, there is also a risk of cardiovascular and cerebral complications such as serious arrhythmia (>20 %), right heart failure (≥10%) and stroke (≥10%). Beyond 1 month of VAD implantation, the incidence of infection related to the percutaneous driveline increases although this complication is a risk throughout the period of VAD support (≥20%). 3. Important gaps are present in the current scientific literature. Despite the rapid evolution of continuous-flow VADs, the use of this relatively new technology is still generally limited. As a result, we consider the level of evidence regarding the effectiveness and safety of HM II based on the scientific literature published since 2008 to be moderate, since data arise from 1) a single randomized controlled trial (RCT) of relatively small size addressing one indication in comparison with a pulsatile-flow VAD; 2) a limited number of non-randomized controlled studies; and 3) several overlapping case series. We consider the level of evidence concerning HW to be very weak due to the extremely limited number of publications. There is a relative lack of information regarding long-term survival on support (>18 months after implantation for patients awaiting transplantation and >2 years for patients initially ineligible for transplantation), rates of readmission to hospital, costs related to complications, long-term end-organ function and quality of life of VAD patients. 4. The economic literature available on the cost-effectiveness of HM II (3 studies employing models) is unfavourable, regardless of the initial indication, according to a generally-accepted indicator (i.e., an incremental cost-effective ratio of <$50,000 US per quality-adjusted life year gained). This is particularly the case for the use of a VAD as a bridge to transplant since this represents the addition of two expensive procedures, VAD implantation and cardiac transplantation; as well, the superior effectiveness of VADs compared to medical treatment implies that a greater proportion of VAD patients survive until transplantation and thus incur greater costs. However, these data should be interpreted in the context of an increasing lack of organ donors, poor effectiveness of the comparison medical treatment, the clinical reality of a choice between likely imminent death and survival, and the expected reduction in costs of VADs and technological improvement in the future as well as improved management of complications and increasing experience of expert VAD centres. It should be noted that the same cost-effectiveness threshold (using an incremental cost-effectiveness ratio, for example) does not necessarily have to be applied to all health interventions and decision contexts.

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