Author + information
- Published online May 8, 2017.
- aRobert Wood Johnson Foundation Clinical Scholars Program, Yale School of Medicine, New Haven, Connecticut
- bSection of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- cSection of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
- dCenter for Outcomes Research and Evaluation, Yale New Haven Health, New Haven, Connecticut
- eVeterans Affairs Connecticut Healthcare System, West Haven, Connecticut
- ↵∗Address for correspondence:
Dr. Harlan M. Krumholz, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, 1 Church Street, Suite 200, New Haven, Connecticut 06510.
Heart failure hospitalizations (HFHs) are a significant burden to people experiencing HF and to society because of the significant associated cost. Nearly one-fourth of Medicare beneficiaries admitted with heart failure (HF) are rehospitalized within 30 days, and 67% within 1 year (1,2). There is a great need to develop and implement strategies to reduce the risk of hospitalization in this population.
CardioMEMS (Abbott, Sylmar, California), a permanently implanted device, is 1 such strategy. CardioMEMS received Food and Drug Administration (FDA) approval in 2014 for HFH reduction in New York Heart Association functional class III patients (3). The CardioMEMS sensor measures pulmonary artery (PA) pressures, which can be monitored by a clinical HF team that adjusts a patient’s medical therapy with the goal of preventing HFH.
In this issue of the Journal, Desai et al. (4) study CardioMEMS using Medicare claims data. The authors report a significant 45% absolute lower HFH rate and a 31% lower all-cause hospitalization rate for Medicare beneficiaries in the 6 months after receiving the device compared with the 6 months before device placement. Results were similar when restricting the analysis to patients who survived the entire 6 months and did not receive a ventricular assist device or heart transplant. Both HF and all-cause hospitalizations were also lower at 12 months after device placement compared with 12 months before. These lower hospitalization rates were associated with lower costs (excluding costs of the device and personnel monitoring). Moreover, the authors employ causal language in their conclusion by stating that the device “reduces HFH and comprehensive HF costs” (4).
Real-world evidence about CardioMEMS is particularly needed because the device was approved amid considerable controversy over the conduct of the approval trial, which was sponsored by the company that developed it (5). Physicians caring for treatment patients in the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association [NYHA] Functional Class III Heart Failure Patients) trial received communication and advice from nurses trained and employed by the device sponsor (6). This communication, beyond the scope of FDA expectations (6), contaminated the trial and led to initial FDA rejection. Although the device ultimately received approval after the company followed the initially enrolled patients for a longer duration and presented additional analyses (7), substantial uncertainty persists about the device’s effectiveness in reducing HFH (5). No additional trials have tested CardioMEMS, despite the clear need for high-quality post-market data.
Do the results from Desai et al. (4) contribute to our understanding of the effectiveness of CardioMEMS? Although the study may be promoted as an endorsement of this device, several reasons prompt caution in such an interpretation.
First, the study is observational, and the population that received the device is highly selected. During a period in which hundreds of thousands of Medicare patients were hospitalized with HF, only 1,114 received the device. Real-world evidence most often will be observational, but in this case the percentage of advanced HF patients who received the device is quite small. The particular details of each implanted patient are likely to be very specific. Therefore, causal inferences about the device and generalizability to the larger group of New York Heart Association functional class III HF patients may be particularly difficult. To this point, it is quite interesting that three-quarters of these devices were placed in ambulatory patients an average of 2 months after their last HFH. This timing raises the question about the trigger for device placement, because these patients may have already been stabilized on therapy to manage their HF.
Second, to address the challenge in finding a suitable control group, the investigators adopt a quasi-experimental pre/post design. The strength is the convenience and simplicity of following the same patients over time with data that are readily available. However, the weakness is that cointerventions—unaccounted for in the analysis—may have been taking place with the goal of keeping implanted patients outside of the hospital. Indeed, it is likely that the device was part of a multipronged strategy to reduce HFH. Without an external comparison group of patients receiving all other care except for the device, such a possibility cannot be excluded. The authors, in fact, state that they are “unable to definitively ascertain whether reduced HF hospitalizations are related to undertreatment in the pre-implant period or improved treatment in the post-implant period” (4).
This issue relates to the third limitation of this study: the investigators’ use of a national longitudinal database of Medicare beneficiaries’ health care utilization based on claims data. Claims data are good for information about health events such as HFH, but they do not provide sufficient information about patient characteristics and cannot tell us about the circumstances that preceded device implantation and how those circumstances may have changed over time.
Fourth, the device is associated with greater attention to implanted patients because it is based on daily monitoring of PA pressures. This additional attention certainly led to greater involvement of the health care team in the post-implantation period, which may be considered an effect. This involvement, motivated by the goal of reducing recurrent HFH in implanted patients, may have produced a decreased HFH rate independent of the device-generated PA pressure data. It is not possible to disentangle the effect of the device’s data from the additional disease management, which is a very particular type of cointervention. The net effect of these important limitations is that the study by Desai et al. (4) lacks the strength to move prior assumptions about CardioMEMS’ benefits in any direction.
Beyond the limitations, are the results plausible? The reported improvement in HFH rates, which is portrayed as an effect of the device, is immense. The investigators report that the placement of the device is associated with 1 HFH averted for about every 2 devices placed. This size effect, nevertheless, represents an even larger reduction than was found in the pivotal clinical trial of the device (8), which had design flaws that likely amplified the reported benefit. It can be argued that greater reductions in PA pressures are being achieved in practice than in the trial (9), but the reduction is still quite profound and it is not clear that HFHs would be expected to so profoundly be reduced.
In the end, the study raises many questions, yet does not reduce the uncertainty about this device even as the investigators employed reasonable methods based on the data they had available. The concern is that some patients, clinicians, and policymakers may assume that the results reported here represent a meaningful estimate of what the device is achieving. CardioMEMS is not currently endorsed in the American College of Cardiology/American Heart Association guidelines, and this study should not cause that to change.
The issues raised by this study are important and particularly relevant to devices that are expensive, invasive, and uncommon—but the topic of needing post-market evidence on devices is growing in importance. The FDA is increasingly approving devices with more limited pre-market evaluation with the goal of expediting access to beneficial innovative technologies (10), and is placing greater emphasis on post-market data. One step in this direction was the creation of the Expedited Access Pathway in 2015 for medical devices that address unmet medical needs (11,12). Additionally, the 21st Century Cures Act, signed into law on December 13, 2016, created a new pathway for breakthrough devices (11). Specifically, these devices can be approved on clinical trials that are “as efficient and flexible as practicable” (13) and with a greater focus on post-market data collection.
Going forward, we need to generate more trials and high-quality observational data that can inform decision-making. Efforts are underway to create a national system of evidence generation to leverage and extend the volumes of continuously updated health care data that are increasingly becoming available (14). For medical devices, which involve the dilemma of ensuring timely access while ensuring appropriate use, a National Evaluation System for Health Technology is being created. The National Evaluation System for Health Technology will aim to leverage clinical data linked from multiple sources including claims, electronic health records, and registries while employing advanced analytic approaches to determine device safety and effectiveness (15). Such efforts are promising, but will require a united community to develop evidentiary standards and the means to generate the needed data.
In conclusion, this article responds to the great need for evidence about CardioMEMS, but does not have the evidentiary strength to inform clinical decisions. The causal language in the authors’ conclusion is not commensurate with the data available and the methods employed. The low adoption of the device may be a signal to the manufacturer that the initial industry-sponsored, and potentially biased, study is insufficient to fundamentally shift practice. There is a need for additional independent trials—and more detailed observational studies—to fill the gaps in knowledge that remain.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Krumholz is a recipient of research agreements from Medtronic and Johnson & Johnson (Janssen), through Yale, to develop methods of clinical trial data sharing; is the recipient of a grant from Medtronic and the Food and Drug Administration, through Yale, to develop methods for post-market surveillance of medical devices; works under contract with the Centers for Medicare & Medicaid Services to develop and maintain performance measures; chairs a cardiac scientific advisory board for UnitedHealth; is a participant/participant representative of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science and the Physician Advisory Board for Aetna; and is the founder of Hugo, a personal health information platform. Dr. Dhruva has reported that he has no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
- Krumholz H.M.,
- Hsieh A.,
- Dreyer R.P.,
- Welsh J.,
- Desai N.R.,
- Dharmarajan K.
- ↵US Food and Drug Administration. CardioMEMS™ HF system approval order. May 28, 2014. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf10/P100045a.pdf. 2014. Accessed March 8, 2017.
- Desai A.S.,
- Bhimaraj A.,
- Bharmi R.,
- et al.
- Dhruva S.S.,
- Krumholz H.M.
- ↵US Food and Drug Administration. FDA executive summary addendum prepared for the December 8, 2011 meeting of the Circulatory System Devices Panel, P100045, CardioMEMS Champion™ HF monitoring system, CardioMEMS, Inc. Available at:. Accessed March 8, 2017.
- Heywood J.T.,
- Jermyn R.,
- Shavelle D.,
- et al.
- Hillebrenner M.,
- Zuckerman B.,
- Fiuzat M.,
- Stockbridge N.,
- Califf R.
- ↵Food & Drug Administration. Guidance document: expedited access for premarket approval and de novo medical devices intended for unmet medical need for life threatening or irreversibly debilitating diseases or conditions. 2015. Available at: https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm393978.pdf. Accessed March 15, 2017.
- ↵H.R.34 - 21st Century Cures Act. 2016. Available at: https://www.congress.gov/bill/114th-congress/house-bill/34/text.
- Califf R.M.,
- Robb M.A.,
- Bindman A.B.,
- et al.
- Shuren J.,
- Califf R.M.