At the same time, we believe that CMS should support evidence development for certain innovative technologies that are likely to show benefit for the Medicare population, but where the available evidence base does not provide a sufficiently persuasive basis for coverage outside the context of a clinical study, which may be the case for new technologies, or for existing technologies for which the evidence is incomplete. J Thorac Cardiovasc Surg. The randomized trial reports are as follows: Holmes et al. Ferro JM. Arch Intern Med. A transesophageal echocardiogram-capable machine should be utilized during the case. TTR – Time in therapeutic range. Al-Saady NM, Obel OA, Camm AJ. No mitigating circumstances were found to address concerns of device effectiveness. Reddy VK et al. 2014;82:716-724. The second primary endpoint had two noninferiority criteria, if either was met the endpoint would be satisfied. This circumstance is problematic in interpretation of clinical studies and can lead to erroneous conclusions. Percutaneous procedures and devices have been developed. Definitions of AF: A simplified scheme. Three approaches for excluding the LAA include: (1) surgical approaches directed at amputation or ligation of the LAA; (2) percutaneous endovascular strategies that place a device to attempt occlusion of the structure; and (3) percutaneous epicardial ligation aimed at external LAA occlusion (Sakellaridis et al. Comment:  Nine commenters do not agree with the registry requirement and contend that enough clinical data already exists. Exclusion of the left atrial appendage with a novel device: Early results of a multicenter trial. 2012;110:453-460. P080022. 2007). The stroke and bleeding risk after percutaneous LAA closure is lower than predicted by conventional risk scores.”. Accounting for the 20 events in the device arm at 900 pt-yr: Accounting for the 16 events in the control arm at 900 pt-yr: The Kaplan-Meier estimates for freedom from primary effectiveness endpoint events is found in Table 8 in the FDA document. Table 22: Number of patients with multiple safety events. A variety of other risk factors and biomarkers that are associated with AF including diabetes, obesity, genetic factors, smoking, and inflammation (January et al. The advisory panel voted for approval; however in February 2014 the FDA received updated follow-up data from the PREVAIL trial that showed additional ischemic strokes in WATCHMAN device subjects, calling into question the mechanism of the device. 2009; Blackshear and Odell 1996). Culebras A, Messe SR, Chaturvedi S, Kase C, and Gronseth G.  Summary of evidence-based guideline update: prevention of stroke in Non-valvular atrial fibrillation. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation. Only one control subject experienced an ischemic stroke during this additional follow-up time, and it occurred when the INR was sub-therapeutic due to interruption for knee surgery. Kleeman T, Becker T, Strauss M, Schneider S, Seidl K. Prevalence and clinical impact of left atrial thrombus and dense spontaneous echo contrast in patients with atrial fibrillation and low CHADS2 score. They further stated that several trials are planned and the proposed decision as written would be harmful to the success of those trials. FDA Executive Summary Memorandum. These comments are noted: Clinical narratives were reviewed to investigate the increasing number of events observed in the device group. Arch Intern Med. The rate ratio noninferiority margin was not met. A systematic review and metaregression. Comment: One commenter noted that restrictions present a significant hurdle and another hoped restrictions are not merely to minimize coverage. While bleeding is still a risk, a reduction in ICH has been demonstrated, which would affect any current perceived net clinical benefit with LAAC. Fountain RB, Holmes DR, Chandrasekaran K, et al. The PREVAIL trial. Clinical Therapeutics. Lip GYH. The true incidence of subclinical cerebral infarcts is not known. The registry must be designed to permit identification and analysis of patient, practitioner and facility level factors that predict patient risk for these outcomes. A CHADS2 score ≥ 2 (Congestive heart failure, Hypertension, Age >75, Diabetes, Stroke/transient ischemia attack/thromboembolism) or CHA2DS2-VASc score ≥ 3 (Congestive heart failure, Hypertension, Age ≥ 65, Diabetes, Stroke/transient ischemia attack/thromboembolism, Vascular disease, Sex category). 2015;128: 260-7. Lane DA, Lip GYH. Connolly SJ, Pogue J, Eikelboom J, Flaker G, et al. The advantages of these agents are fixed dosing, lack of required blood monitoring, fewer drug interactions, and most importantly an apparent lower risk of ICH as compared to adjusted dose warfarin. Boston Scientific WATCHMAN® Left Atrial Appendage Closure Therapy. Post-procedure medical therapy included life-long aspirin and 3 months of clopidogrel. Significance of the learning curve in left atrial appendage occlusion with two different devices. The upper bounds of the 95% credible interval (CI) was less than the noninferiority margin of 2.0 (1.41 for 900 pt-yr). 2001;285:2864-70. CMS believes that if the ACC, HRS, and SCAI consensus document and their public comment regarding operator and institutional criteria are followed this potential is minimized. Circulation. P130013. January CT, Wann S, Alpert JS, et al. Coverage in the context of ongoing clinical research protocols or with additional data collection can expedite earlier beneficiary access to innovative technology while ensuring that systematic patient safeguards, including assurance that the technology is provided to clinically appropriate patients, are in place to reduce the risks inherent to new technologies, or to new applications of older technologies. JAMA 2015;313(19):1950-1962. Age and Ageing. Noninferiority trials. A MEDCAC meeting was not convened on this issue. 2014 Apr 1;83(5):796-802. Reddy VY et al. The stated purpose of this study was to determine the outcomes of patients who had undergone LAAC with the PLAATO device, a device that is no longer marketed. P080022. Closure of the LAA might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation.”, Post-hoc analysis with data on patients from PROTECT AF trial followed up for a total of 1500 patient-years and data from patients in the Continued Access Protocol (CAP) Registry from 460 patients. Some commenters suggested that CMS use alternative language. 2009;120:1919-26. 2015;65:2614-23. 2008;72(11):1725-1729. The absolute risk is highest for those patients with a history of stroke and transient ischemic attack (TIA). Boston Scientific WATCHMAN® Left Atrial Appendage Closure Therapy. As described previously, the primary analyses were based on ITT, censoring data from patients without events at the time of the last known status. A CT laboratory with CT technologists and specialists skilled in obtaining high-quality cardiac studies of the heart for procedures where CT imaging is necessary as part of the evaluation (e.g., LARIAT). The critical appraisal of the evidence enables us to determine to what degree we are confident that: 1) the specific assessment questions can be answered conclusively; and 2) the intervention will improve health outcomes for beneficiaries. available reasonable alternative steps to protect the employees involved. Does left atrial appendage occlusion eliminate the need for warfarin? FDA Executive Summary Memorandum. This risk reduction is closely accompanied by an increased potential for bleeding as the factors for both are similar. Table 4. We believe our summary is accurate. The study protocol must explicitly discuss beneficiary subpopulations affected by the item or service under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria effect enrollment of these populations, and a plan for the retention and reporting of said populations in the trial. Public access information from the FDA website was also used. Plicht B, Konorza TFM, Kahlert P, et al. Holmes DR et al. The evidence provided by an additional case series, studying patients without contraindications to anticoagulation, and 4 case series, studying patients with contraindications to anticoagulation, is insufficient to permit conclusions about efficacy. Using the Watchman device to close the left atrial appendage reduces risk of stroke in atrial fibrillation, compared to using warfarin. Table 19: Primary safety endpoint (ITT). Such respirators are often referred to … Figure 1. This table includes a comparison of age, gender, race, height and weight between the WATCHMAN and control groups. Four subjects were on aspirin in addition to warfarin at the time of the stroke, and no antiplatelet use was available for another subject. 2009;374:534-42. Hemorrhagic stroke was less frequent in the LAA closure group (RR, 0.09; 95% CI, 0–0.45), but ischemic stroke was insignificantly more frequent (RR, 1.34; 95% CI, 0.60–4.29), in part because of procedure-related strokes (occurring in 5 of the 449 patients in whom LAA closure was attempted, including 2 with longterm residual deficits). FDA Executive Summary Memorandum. Comment:  Several commenters requested that CMS cover LAAC devices off-label under CED. Patients who requested elective LAA closure despite an absence of contraindications to anticoagulation were not enrolled in this study.”  Study population characteristics included a mean CHADS2 score 2.6 ± 1.4, and a HAS-BLED score of 3.3 ± 1.0. Some commenters believe that the indicated population should include those at high risk for falls, which could include the following: competitive athletes; the economically disadvantaged; and those having experience with previous bleeding. Therefore, we are adding the requirement of a MDT to be involved in the patient’s care. WATCHMAN LAA Closure Technology, Atritech, Inc. Total trial mortality included 17 deaths in the WATCHMAN group and 15 deaths in the control. 1785 0 obj <>stream CMS Response: CMS understands that bleeding risk estimation in AF is less well-established than stroke risk assessment. Discontinuation of OAC 45 days after implantation was also safe.”. B2. Instructions for enabling "JavaScript" can be found here. PROTECT AF/PREVAIL combined meta-analysis shows comparable primary efficacy results to warfarin. Lip and Lane. ACC – American College of Cardiology Relevant studies were added to aspirin in patients with atrial fibrillation investigators Committee on.. 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