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March 30, 2015

Percutaneous left atrial appendage closure in patients with left atrial appendage thrombus

Felix Meincke, MD; Felix Kreidel, MD; Jasper von Wedel, MD; Ulrich Schäfer, MD; Karl-Heinz Kuck, MD; Martin W. Bergmann*, MD

Department of Cardiology, Asklepios Klinik St. Georg, Hamburg, Germany

This paper also includes accompanying supplementary data published online at: http://www.pcronline.com/eurointervention/81st_issue/199

Occlusion of the left atrial appendage (LAA) using the WATCHMAN™ device (Boston Scientific, Natick, MA, USA) proved its safety and efficacy in the PROTECT-AF trial and has found its way into daily clinical routine since then. However, patients with known thrombus formation within the LAA have been excluded from this technique so far because of the high risk of embolisation during the procedure in these patients. We report the first two cases of successful LAA occlusion using the WATCHMAN™ device and cerebral protection systems in patients with known thrombus within the LAA. Both patients were successfully treated with a WATCHMAN™ device without procedural complications. As cerebral protection devices, a SpiderFX™ system (ev3 Endovascular, Inc., Plymouth, MN, USA) was used in the first case and a Claret Medical Montage™ (Claret Medical, Inc., Santa Rosa, CA, USA) for the second patient. We conclude that LAA occlusion with cerebral protection devices is feasible in selected patients with LAA thrombus at high risk for embolic complications.

01_Meincke.tif

Figure 1. Patient 1. A) Transoesophageal echocardiographic (TEE) view of the left atrial appendage (LAA) thrombus prior to implantation. B) WATCHMAN™ device after implantation with remaining thrombus in the distal LAA. C) 3D-TEE view of the LAA ostium with thrombus visible within the LAA. D) 3D-TEE after implantation of the WATCHMAN™ device.

Conflict of interest statement

The authors have no conflicts of interest to declare.

Online data supplement

Moving image 1. Angiographic view of the atypical approach for unfolding of the device used in the first patient. The delivery sheath is placed at the ostium of the left atrial appendage (LAA) and the device is unfolded by pushing the device forward into the LAA.

Moving image 2. Transoesophageal echocardiography after implantation of the WATCHMAN™ device in the first patient showing the device position and the thrombus further distal within the left atrial appendage.

Online data supplement

02_Meincke.tif

Online Figure 1. Patient 2. A) Transoesophageal echocardiography (TEE) prior to implantation with thrombus and “smoke” within the left atrial appendage. B) Angiographic view of the Claret™ system placed in the left carotid artery and the brachiocephalic trunk. C) TEE view of the WATCHMAN™ device after implantation.

Media

Moving image 1. Angiographic view of the atypical approach for unfolding of the device used in the first patient. The delivery sheath is placed at the ostium of the left atrial appendage (LAA) and the device is unfolded by pushing the device forward into the LAA.

Moving image 2. Transoesophageal echocardiography after implantation of the WATCHMAN™ device in the first patient showing the device position and the thrombus further distal within the left atrial appendage.

Source: EuroIntervention

One-year outcomes in 1,010 unselected patients treated with the PROMUS Element everolimus-eluting stent: the multicentre PROMUS Element European Post-Approval Surveillance Study

Martyn R. Thomas1*, MD, PhD; Ralf Birkemeyer2, MD; Peter Schwimmbeck3, MD, PhD; Victor Legrand4, MD, PhD; Raul Moreno5, MD; Carlo Briguori6, MD; Nikos Werner7, MD; Ezio Bramucci8, MD; Imre Ungi9, MD; Gert Richardt10, MD, PhD; Paul L. Underwood11, MD; Keith D. Dawkins11, MD

1. Guy’s and St. Thomas’ National Health Service Foundation Trust, London, United Kingdom; 2. Universitätsklinikum Rostock, Rostock, Germany; 3. Klinikum Leverkusen, Leverkusen, Germany; 4. Centre Hospitalier Universitaire Sart Tilman, Liege, Belgium; 5. Hospital La Paz, Madrid, Spain; 6. Clinica Mediterranea, Naples, Italy; 7. Universitätsklinikum Bonn, Bonn, Germany; 8. IRCCS Policlinico S. Matteo, Pavia, Italy; 9. University of Szeged, Szeged, Hungary; 10. Herzzentrum, Segeberger Kliniken GmbH, Bad Segeberg, Germany; 11. Boston Scientific Corporation, Marlborough, MA, USA

Abstract

Aims: The PROMUS™ Element™ European Post-Approval Surveillance Study (PE-Prove) is a prospective, open-label, multicentre observational study designed to assess outcomes following PROMUS Element everolimus-eluting stent implantation in an unselected patient population.

Methods and results: A total of 1,010 patients were enrolled at 40 clinical sites in Europe, including 24.9% with medically treated diabetes, 50.0% with Type B2/C lesions, 6.1% with chronic total occlusion, 17.8% with acute myocardial infarction (MI ≤24 hours pre-procedure), and 20.1% with unstable angina. The target lesion was the culprit for ST-segment elevation MI in 7.3% of patients. The one-year, per patient target vessel failure rate was 6.2% (60/975), 3.4% (33) being related to the PROMUS Element stent. Rates of cardiac death, MI, and Academic Research Consortium (ARC) definite/probable stent thrombosis were 1.7%, 3.5%, and 0.6%, respectively. The target vessel revascularisation rate was 3.2% (31/975), 2.1% (20) being related to the PROMUS Element stent.

Conclusions: In a large and relatively complex group of “real-world” patients, coronary artery revascularisation with the PROMUS Element everolimus-eluting stent provides favourable results with low event rates consistent with those reported for other contemporary drug-eluting stents.

Introduction

As new coronary stent designs become approved and more widely available for use in large, unselected populations outside of controlled clinical trials, it is important to evaluate their safety and effectiveness in broader “real-world” application. The PROMUS Element™ coronary stent (Boston Scientific Corporation, Marlborough, MA, USA) is a thin-strut, platinum chromium alloy stent coated with a durable, biocompatible, inert fluorocopolymer and everolimus as the antiproliferative agent. In the randomised controlled PLATINUM trial, the PROMUS Element stent was shown to be non-inferior to the predicate XIENCE V/PROMUS stent (Boston Scientific) for the primary endpoint of one-year target lesion failure1. Rates of all-cause death, cardiac death, myocardial infarction, stent thrombosis, and revascularisation were comparable between the two treatment groups at three-year follow-up2.

The PROMUS™ Element™ European Post-Approval Surveillance Study (PE-Prove) is an observational study designed to collect data on long-term outcomes in a large and relatively complex group of “real-world” patients treated with the PROMUS stent. We report here the one-year primary endpoint clinical outcomes, evaluating the safety and efficacy of this stent in a large, unselected patient population.

Methods

This prospective, open-label, multicentre study with an all-comers approach was designed to enrol approximately 1,000 patients at 40 sites in Europe.

PATIENT SELECTION, PROCEDURE, AND FOLLOW-UP

All patients who were candidates for coronary artery stenting and eligible to receive a PROMUS Element stent were evaluated for enrolment in this study. All enrolled patients signed a written informed consent form that had been approved by the independent ethics committee at each study site. Enrolment was considered complete upon signing the informed consent form. This study was conducted in accordance with the ethical principles originating in the Declaration of Helsinki and consistent with good clinical practice and applicable local regulatory requirements (ClinicalTrials.gov NCT01148329).

Follow-up assessments, including medications, NYHA/CCS classification, adverse events, and coronary angiograms performed according to standard of care at each study site, were carried out by clinic visit or phone call at 30 days, six months, and 12 months post index stent implantation, and will continue annually to five years.

STUDY ENDPOINTS

The primary endpoint of this study was the overall and PROMUS Element stent-related target vessel failure (TVF) rate, defined as cardiac death, myocardial infarction (MI) related to the target vessel, or target vessel reintervention (TVR), at 12 months post stent implantation. Secondary endpoints are detailed in the Online Appendix. An independent clinical events committee adjudicated all deaths, MI, TVR, and stent thrombosis, including the relationship of the event to the study stent.

STATISTICAL METHODS

Enrolled patients who received at least one PROMUS Element stent in the target lesion were included in the analysis. Statistical analyses were performed using SAS, Version 9 or later (SAS Institute Inc., Cary, NC, USA). Further details are provided in the Online Appendix.

Results

PATIENT, LESION, AND PROCEDURAL CHARACTERISTICS

Of 1,010 patients enrolled at 40 clinical sites in Europe between 28 June 2010 and 20 April 2011, one-year clinical follow-up was available for 975 (96.5%) patients (Figure 1). Baseline patient and lesion characteristics are shown in Table 1.

01_Thomas.eps

Figure 1. PE-Prove registry enrolment and follow-up.

01tab_Thomas.pdf

Procedural characteristics are shown in Online Table 1. Successful deployment of the PROMUS Element stent to the target lesion without device malfunction (i.e., technical success) was achieved in 99.8% (1,008/1,010) of patients. Two cases of longitudinal stent deformation were detected by angiography during the index procedure, both of which involved <5% proximal stent compression. Details of these cases are provided in the Online Appendix.

ONE-YEAR CLINICAL OUTCOMES

As shown in Table 2, the overall one-year TVF rate was 6.2% and TVF related to the PROMUS Element stent was 3.4%. The rates of cardiac death, MI, and TVR related to the PROMUS Element stent were 0.4%, 2.1%, and 2.1%, respectively. ARC-defined definite/probable stent thrombosis related to the PROMUS Element stent was reported in six patients (0.6%). In Figure 2, showing Kaplan-Meier time-to-event analyses for overall TVF and definite/probable stent thrombosis at one-year follow-up, there were no stent thromboses reported beyond eight months post procedure. One-year clinical outcomes for selected high-risk patient subgroups are also shown in Table 2. Relative to the study population as a whole, rates of overall and PROMUS Element-related TVF and ARC-defined definite/probable stent thrombosis were only modestly higher in patients with medically treated diabetes or long lesions (>28 mm single lesion), whereas rates among patients with small vessels (≤2.5 mm) were similar to the overall study population rates.

02tab_Thomas.pdf

02_Thomas.eps

Figure 2. Kaplan-Meier time-to-event analyses baseline to one year. A) Target vessel failure. B) ARC-defined definite/probable stent thrombosis.

At the time of the one-year follow-up visit, 79.6% (756/950) of patients were taking dual antiplatelet therapy, including 96.8% (920/950) on aspirin, 76.1% (723/950) on clopidogrel, 6.2% (59/950) on prasugrel, and 0.1% (1/950) on ticagrelor.

PREDICTORS OF TARGET VESSEL FAILURE AT ONE YEAR

Multivariate predictors of TVF within one year of stent implantation are shown in Online Figure 1. Diabetes, post-procedure dilation, and prior PCI were identified as predictors of both overall TVF and PROMUS Element stent-related TVF. The strongest predictor of overall TVF was the use of thienopyridines for six months or less, and the strongest predictor of TVF associated with the PROMUS Element stent was implantation in a vein graft.

Discussion

In this large, “real-world” population, one-year rates of cardiac death, MI, TVR, and stent thrombosis related to the PROMUS Element stent were low and consistent with rates in the randomised controlled PLATINUM trial of this stent1. Overall, clinical event rates for patients with small calibre vessels (≤2.5 mm) were similar to the rates in the study population as a whole.

As might be expected, medically treated diabetes and single lesion length >28 mm were each associated with modestly increased rates of cardiac events. The technical success rate of 99.8% reflects good deliverability of this stent, which is perhaps a reflection of the conformability and flexibility of this stent platform.

DES IN ROUTINE PRACTICE

This study contributes to a vast and growing body of “real-world” data on contemporary DES outcomes. Studies of DES that have used broad inclusion criteria or an all-comers approach include the PEXIP study of the XIENCE Prime and PROMUS Element everolimus-eluting stents3, the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) analysis of the PROMUS Element stent relative to other contemporary DES4, the XIENCE V USA study of the XIENCE V stent5, the PROENCY registry of the PROMUS everolimus-eluting stent, CYPHER sirolimus-eluting stent, and ENDEAVOR zotarolimus-eluting stent6, the COMPARE study of the PROMUS everolimus-eluting stent and the TAXUS Liberté stent7, and three studies of the Resolute zotarolimus-eluting stent, including the RESOLUTE International Registry8, the Resolute All Comers trial9, and the TWENTE trial10, the latter two both evaluating the Resolute stent versus the XIENCE V stent.

One-year clinical event rates with the PROMUS Element stent in this study are well within the one-year ranges reported from these other all-comers DES studies. The PROMUS Element all-cause mortality rate was 2.7% (other studies 1.6% to 2.8%), the rate of MI related to the PROMUS Element was 2.1% (other studies 0.7% to 7.9%), and the rate of TVR related to the PROMUS Element was 2.1% (other studies 1.3% to 8.2%)3,4,5,6,7,8,9,10. The 0.6% rate of ARC-defined definite/probable stent thrombosis is in the lower range among the all-comers DES studies (other studies 0.0% to 1.6%)3,4,5,6,8,9,10,11.

STENT DEFORMATION

The occurrence of two cases of longitudinal stent deformation (change in axial length) out of 1,679 stents placed in this study highlights the low frequency of this procedural complication. These two cases of stent deformation, which were detected by angiography during the index procedure, represent classic examples of stent deformation resulting from interaction between an ancillary device and a stent that were easily treated without severe adverse consequences.

Limitations

As a single-arm registry, this study has inherent limitations. Without a control group, the performance of the PROMUS Element stent cannot be directly compared with other contemporary DES. In addition, the broad inclusion criteria and observational design present challenges for evaluating outcomes across studies in which the “all-comers” design results in diverse patient and lesion characteristics. Finally, clinical follow-up at one year was not available for 3.5% of these unselected patients, mostly due to missed visits. Although this represents an acceptable rate of follow-up for a post-market, all-comers registry, given the very low rate of events at one year with this contemporary stent, the potential effect of these missing data should be taken into account when considering the one-year clinical event rates.

Conclusions

In this large and relatively complex group of “real-world” patients, coronary artery revascularisation with the PROMUS Element everolimus-eluting stent resulted in low clinical event rates consistent with those reported for other contemporary DES.

Impact on daily practiceAlthough randomised controlled trials remain the gold standard for proving the safety and efficacy of new devices in clinical practice, the strict inclusion and exclusion criteria typically used in these trials mean that the results may not be generalisable to an unselected, “real-world” clinical population. This large, multicentre registry presents valuable information on outcomes from everyday clinical practice with the use of the PROMUS Element stent in more than 1,000 patients in Europe. The consistency of the results from this more complex clinical population with those of the randomised controlled trial provide reassurance to the treating physician of good clinical outcomes with the PROMUS Element stent, regardless of patient comorbidities and anatomic complexity.

Acknowledgements

The authors would like to thank all of the sites that enrolled patients in the PE-Prove study, as well as the clinical events committee members and the associated research organisations (Online Table 2, Online Table 3). In addition, the authors gratefully acknowledge Laurie LaRusso (Chestnut Medical Communications) and Kristin L. Hood (Boston Scientific Corporation) for assistance with manuscript preparation, Shannon Song (Boston Scientific) and Srikanth Garre (Quintiles) for statistical assistance, and Thomas Naeschen (Boston Scientific) for project management.

Funding

This study was sponsored and funded by Boston Scientific Corporation, Marlborough, MA, USA.

Conflict of interest statement

R. Moreno reports lecture and consulting fees from Boston Scientific, Abbott, Cordis, Medtronic, Terumo, and Biotronik. G. Richardt reports serving on an advisory board and receiving speakers’ honoraria from Boston Scientific. M. Thomas reports serving on an advisory board for Boston Scientific. P. Underwood and K. Dawkins are full-time employees with equity interest in Boston Scientific. The other authors have no conflicts of interest to declare.

Online data supplement

Online Appendix

METHODS

PATIENT SELECTION, PROCEDURE, AND FOLLOW-UP

The following procedural data were collected: lesion characteristics, total procedure time, antithrombotic and antiplatelet medications administered, and serious adverse events (SAEs), including serious bleeding according to GUSTO classification12. Patients with unsuccessful implant of a study device were followed only up to hospital discharge following the initial attempted index procedure. Enrolment at 14 centres was eventually capped at approximately 40 patients to prevent skewing the results with overrepresentation from high-volume centres.

STUDY ENDPOINTS

Secondary endpoints included stent thrombosis using Academic Research Consortium (ARC) definitions (i.e., definite or probable), major adverse cardiac events (i.e., cardiac death, MI, TVR), cardiac death, MI, TVR, all deaths, and non-cardiac deaths. Technical success was defined as successful deployment of the PROMUS Element stent to the target lesion without device malfunction.

STATISTICAL METHODS

Patient demographics, clinical history, risk factors, pre- and post-procedure lesion characteristics, procedure characteristics, and outcome variables were summarised using descriptive statistics for continuous variables (mean, standard deviation, number of observations, minimum, and maximum) and frequency tables for discrete variables. Kaplan-Meier plots of time-to-event variables were constructed with 95% confidence intervals. Cox models were performed to identify risk predictors with respect to TVF rates. Backward selection was used to identify significant predictors with the threshold to stay in the model set at 0.10.

RESULTS

LONGITUDINAL STENT DEFORMATION

One case was attributed to a deep-seated guide catheter interacting with the proximal end of a deployed PROMUS Element stent, causing slight longitudinal compression, which was resolved with post-dilation and additional stent deployment, without associated patient injury. In the second case, an LAD/diagonal branch bifurcation intervention, the guidewire was jailed by the proximal end of the stent, leading to subsequent unravelling of the guidewire into a filament proximal to the diagonal. During manoeuvres for successful retrieval of the wire with a snare, the proximal end of the implanted stent was minimally damaged. Post-dilation balloon inflations were performed along the entire stented segment and a stent was placed in the proximal LAD/left main. A small non-Q-wave MI (peak CK-MB 43 U/L, troponin 2.4 ng/mL) occurred post procedure and the patient was discharged two days later. Of these two patients with longitudinal stent deformation, only one experienced a small periprocedural enzyme leak. Neither patient has had any other clinical events reported up to the time this manuscript was published.

Reference

OL1_Thomas.eps

Online Figure 1. Multivariate predictors of target vessel failure within 1 year of stent implantation.

OL01tab_Thomas.pdf

OL02tab_Thomas.pdf

OL03tab_Thomas.pdf

Source: EuroIntervention

Renal denervation with a percutaneous bipolar radiofrequency balloon catheter in patients with resistant hypertension: 6-month results from the REDUCE-HTN clinical study

Horst Sievert1*, MD; Joachim Schofer2, MD; John Ormiston3, MBChB; Uta C. Hoppe4, MD; Ian T. Meredith5, MD; Darren L. Walters6, MD; Michel Azizi7,8, MD; Juan Diaz-Cartelle9, MD; Meital Cohen-Mazor9,10, PhD; on behalf of the REDUCE-HTN investigators

1. CardioVascular Center Frankfurt CVC, Frankfurt, Germany; 2. Universitäres Herz- und Gefäßzentrum, Hamburg, Germany; 3. Mercy Angiography, Auckland, New Zealand; 4. Paracelsus Medical University, Salzburg, Austria; 5. MonashHEART, Monash Health, Melbourne, Australia; 6. The Prince Charles Hospital, Brisbane, Australia; 7. APHP, Hôpital Européen Georges Pompidou, Hypertension Unit, Paris, France; 8. Paris Descartes University, Paris, France; 9. Boston Scientific Corporation, Marlborough, MA, USA; 10. Vessix Vascular, Laguna Hills, CA, USA

Abstract

Aims: To evaluate the safety and efficacy of the balloon-based bipolar Vessix Renal Denervation System in treating patients with resistant hypertension.

Methods and results: In this prospective, multicentre, single-arm study, 146 patients (age 58.6±10.5 years; 61% men) with office systolic blood pressure (BP) ≥160 mmHg despite ≥3 antihypertensive medications at maximally tolerated doses were treated with the Vessix System. Efficacy endpoints were reductions in office and 24-hour ambulatory systolic and diastolic BPs at six months. Acute and long-term safety, with a focus on the renal artery and estimated glomerular filtration rate (eGFR), were assessed. Baseline office and ambulatory BPs were 182.4±18.4/100.2±14.0 mmHg and 153.0±15.1/87.5±13.2 mmHg, respectively. No acute renal artery injury requiring intervention or serious periprocedural cardiovascular events occurred. At six months, office BP was reduced by 24.7±22.1/10.3±12.7 mmHg (p<0.0001) and ambulatory BP was reduced by 8.4±14.4/5.9±9.1 mmHg (N=69; p<0.0001). Twenty-six patients (18%) achieved an office systolic BP <140 mmHg. One patient had renal artery stenosis which required stenting. Mean eGFR remained stable.

Conclusions: Renal artery denervation with the Vessix System reduced both office and ambulatory BP at six months in patients with resistant hypertension. Renal artery safety and renal function results are favourable.

Introduction

The relationships between elevated BP and increased cardiovascular and renal-related morbidity and mortality risks are well known1,2. Conversely, lowering BP in patients with hypertension yields benefits such as decreased incidence of stroke, major cardiovascular events, end-stage renal disease, and death1,3,4.

Renal denervation provides a novel adjunctive option for treating patients with hypertension despite lifestyle modifications and multiple antihypertensive medications5,6. Clinical studies of percutaneous renal denervation with radiofrequency energy have shown significant and sustained BP reductions for patients with resistant hypertension following treatment with either single-electrode7,8,9,10 or multielectrode11 monopolar systems. The Vessix™ Renal Denervation System (Boston Scientific, Marlborough, MA, USA), by contrast, is a balloon-based bipolar multielectrode system.

We report here the six-month results of the REDUCE-HTN study, which was designed to evaluate safety and efficacy of renal denervation with the Vessix System for the treatment of resistant hypertension.

Methods

STUDY DESIGN

The REDUCE-HTN clinical study is an international, prospective, non-randomised, single-arm study. This report describes the study results obtained up to six months (i.e., the primary endpoint) for patients enrolled in the initial first-in-man cohort and those enrolled under an amended post-market protocol. The REDUCE-HTN study is registered at ClinicalTrials.gov (NCT01541865).

The study was conducted in accordance with ethical principles which have their origins in the Declaration of Helsinki. Institutional committees on research or appropriate ethics committees at study sites approved the study protocol. Patients were required to provide written informed consent prior to receiving any study-specific tests or procedures.

PATIENTS

Inclusion and exclusion criteria for the first-in-man and post-market protocols are summarised in Table 1. Eligible patients had office-based systolic BP ≥160 mmHg and were on a stable medication regimen with at least three antihypertensive drugs (including a diuretic, unless intolerant) at maximally tolerated doses.

01tab_Sievert.pdf

BP, renal function, and renal artery anatomy were assessed at the screening visit. Seated office BP measurements2 were taken with a validated electronic device (Omron model HEM-705 CP; Omron Healthcare, Lake Forest, IL, USA). Eligible patients had an estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m2. Patients underwent renal duplex ultrasound, computed tomography angiography, or magnetic resonance angiography to screen for anatomic abnormalities. Antihypertensive medication regimen stability over the previous two weeks was confirmed by reviewing the patients’ medical records and patient-reported compliance.

VESSIX RENAL DENERVATION SYSTEM

The Vessix Renal Denervation System comprises the Vessix catheter and generator. The catheter is an over-the-wire low-pressure (3 atm) balloon catheter designed to transmit radiofrequency energy via multiple bipolar electrodes mounted on its surface in a helical pattern. The catheters used in this study were compatible with 0.36 mm (0.014 inch) and 0.46 mm (0.018 inch) guidewires and 8 Fr guide sheaths; the balloons had 4, 5, 6, or 7 mm diameters and four to eight bipolar electrodes (depending on their size).

The Vessix balloon enables electrode apposition to the artery wall while eliminating variable cooling from blood flow. The generator delivers radiofrequency energy simultaneously to all apposed electrodes and adjusts to maintain a 68°C temperature, while thermistors on the balloon surface monitor temperature throughout the 30-second treatment period. The temporary no-flow environment, bipolar electrodes, and temperature control enable a therapeutic temperature to be reached with <1 W12.

RENAL DENERVATION PROCEDURE

Patients who met general and anatomic criteria underwent standard angiography to confirm renal artery anatomy suitability immediately prior to the denervation procedure. Anxiolytic and analgesic medications were administered and systemic anticoagulation (e.g., activated clotting time ≥200 seconds) was attained. The Vessix catheter was delivered to the renal artery via femoral access and inflated using standard angioplasty techniques. After acceptable apposition was confirmed, the generator was activated to deliver radiofrequency energy. The balloon could be deflated, moved proximally, and re-inflated in order to treat along the full artery length. No more than two treatments per artery were recommended. The balloon was then positioned in the opposite renal artery and the radiofrequency treatment procedure was repeated. Manual compression or commercialised closure devices were used to achieve haemostasis at the puncture site.

FOLLOW-UP PROCEDURES

Patients were instructed to remain compliant with their baseline antihypertensive medication regimen throughout the study unless changes were clinically indicated. Seated BP measurements2 were repeated during office visits at one, three, and six months following the renal denervation procedure. Ambulatory BP over 24 hours was monitored with Spacelabs ABP monitors (Spacelabs Healthcare, Snoqualmie, WA, USA) and validated by a core laboratory (Biomedical Systems Corporation, St. Louis, MO, USA) at baseline and six months. A 70% success rate (e.g., excluding movement artefacts) from hourly recordings over 24 hours was required. Monitoring results that did not meet the required validation criteria were excluded from analysis.

Renal function was monitored with eGFR and creatinine levels. A renal artery duplex ultrasound was required at six months and reviewed by an independent core laboratory (VasCore, Boston, MA, USA). Angiographic images were also evaluated by a core laboratory (SynvaCor, Springfield, IL, USA).

EFFICACY AND SAFETY ENDPOINT DEFINITIONS

Efficacy was assessed as the magnitude of the changes in office-based and 24-hour ambulatory BPs from baseline to six months following treatment with the Vessix System.

The primary first-in-man study objective was to assess acute safety, defined as freedom from each of five periprocedural events: renal artery dissection/perforation that required stenting or surgery, renal artery infarction/embolus, cerebrovascular accident, myocardial infarction, and sudden cardiac death. These acute events continued to be monitored for the expanded cohort.

Long-term safety endpoint events were: chronic symptomatic orthostatic hypotension, hypertensive emergency necessitating hospital admission (unrelated to antihypertensive medication non-compliance), eGFR reduction >25%, angiographically documented renal stenosis requiring an intervention, and flow-limiting stenosis (≥60%) in the renal artery.

A data safety monitoring board adjudicated all adverse events for seriousness and relatedness to the procedure and device.

STATISTICAL METHODS

All treated patients were included in the analyses. The study sample size was not powered for efficacy or safety endpoints. Descriptive statistics are presented and confidence intervals (95%) were constructed for BP results. A paired t-test was used to assess the BP change from baseline to six months; the data normality assumption was verified with the Shapiro-Wilk test. A p-value <0.05 was considered statistically significant.

Post hoc office BP reduction comparisons in patient subgroups were made with two-sample t-tests. Logistic regression was used to analyse the relationships between baseline/treatment characteristics and a six-month office systolic BP reduction >10 mmHg or ambulatory systolic BP reduction >5 mmHg. All analyses were conducted with SAS version 9.2 or later (SAS Institute Inc., Cary, NC, USA).

Results

PATIENT CHARACTERISTICS

A total of 146 patients were treated with the Vessix System at 23 sites in Europe, Australia, and New Zealand from February 2012 to April 2013 (Figure 1, Online Appendix 1). Baseline patient characteristics are shown in Table 2. The mean (±SD) diameter of treated renal arteries was 5.3±0.7 mm and length was 34.7±8.4 mm. Twenty-four patients enrolled under the post-market protocol had accessory renal arteries treated.

01_SievertAOP11.eps

Figure 1. REDUCE-HTN patient flow. ABPM: ambulatory blood pressure monitoring; CTA: computed tomography angiography; DUS: duplex ultrasound; FIM: first-in-man; MRA: magnetic resonance angiography; PMS: post-market study. 103 patients had valid 24-hour ABPM at baseline. 89 patients had valid 24-hour ABPM at 6 months; 69 of these patients also had valid baseline ABPM.

02tab_Sievert.pdf

Nine patients who received radiofrequency treatment met exclusion criteria: one had baseline systolic BP of 157 mmHg, two had eGFRs below the eligibility threshold, two were on hormonal therapy, one had a pacemaker, one had renal artery length <15 mm, one had a previous renal denervation and renal artery stenosis >30%, and one had been placed on an antihypertensive drip within two weeks prior to the procedure. None of these patients experienced procedure-related adverse events associated with these baseline conditions during six months of follow-up.

PROCEDURE CHARACTERISTICS

Catheters with 7 mm (35%) or 6 mm (34%) balloon diameters were selected most often; the remainder were 5 mm (22%) and 4 mm (9%). Patients underwent a mean of 3.5±1.1 treatments (i.e., 30-second generator activations) with 21.2±6.4 electrode activations. All patients had at least one complete treatment cycle. To treat the full artery length, investigators administered two treatments in 54% of main renal arteries (158/292) and 41% (11/27) of treated accessory arteries. Treatments required 0.7±0.2 W per electrode to achieve temperature control. Mean procedure time (i.e., first balloon inserted to last balloon removed) was 24.9±15.8 min.

CHANGES TO ANTIHYPERTENSIVE MEDICATION REGIMENS

At six months, the mean number of antihypertensive medications per patient remained stable at 5.2±1.9, and 85.6% remained on the same number of medications as at baseline. Fifteen (10.3%) reduced their antihypertensive regimen by one drug, two patients reduced their regimen by two medications, three reduced their regimen by three medications, and one was on four fewer antihypertensive drugs at the six-month follow-up visit than at baseline; no patient had an increased number of antihypertensive drugs.

Efficacy endpoints

OFFICE BLOOD PRESSURE

Significant office-based BP reductions were observed at all follow-up time points (Figure 2). At six months, systolic/diastolic BP was reduced by 24.7±22.1/10.3±12.7 mmHg. Systolic BP reductions ≥5 mmHg or ≥10 mmHg were observed in 85% (121/142) and 76% (108/142), respectively. Six patients (4%) had a reduction in systolic BP of <5 mmHg, and 15 (11%) had an increase at six months. Systolic BP <140 mmHg was achieved by 18% (26/142) of patients at six months (Figure 3).

02_SievertAOP11.eps

Figure 2. Change in office-based blood pressure (95% confidence intervals). p<0.0001 for each time point vs. baseline.

03_SievertAOP11.eps

Figure 3. Distribution of office systolic blood pressures at baseline and follow-up up to six months.

No significant differences in the changes in office systolic BP at six months were observed between subgroups based on age, diabetic status, or sex (p>0.05 for each comparison) (Online Table 1). The mean (±SD) BP reduction observed among patients without any changes in the number of antihypertensive medications was –23.8±21.2/–9.8±12.2 mmHg, and for the 21 patients who decreased their number of medications it was –29.5±26.8/–13.7±15.2 mmHg. No significant relationships were identified between baseline characteristics and systolic BP reduction >10 mmHg at six months in logistic regression analysis (Online Table 2).

24-HOUR AMBULATORY BLOOD PRESSURE

Baseline mean (±SD) 24-hour ambulatory BP was 153.0±15.1/ 87.5±13.2 mmHg (N=103). At six months, mean ambulatory BP decreased to 147.0±16.1/83.1±12.7 mmHg (N=89) and 17% of patients (15/89) had systolic pressure <130 mmHg (vs. 4% [4/103] at baseline). The mean reduction among the 69 individuals with valid 24-hour ambulatory measurements at baseline and six months was 8.4±14.4/5.9±9.1 mmHg (p<0.0001) (Figure 4). In logistic regression analysis, greater baseline systolic BP (office or ambulatory) and greater ambulatory diastolic BP were associated with greater odds of a six-month reduction in ambulatory systolic BP >5 mmHg (Online Table 3). The mean changes in daytime and night-time ambulatory BP were similar (Online Table 4).

04_SievertAOP11.eps

Figure 4. Change in 24-hour ambulatory blood pressure (95% confidence intervals). p<0.0001 for both systolic and diastolic vs. baseline.

Safety objectives

ACUTE SAFETY

No patient had periprocedural renal artery dissection or perforation that required intervention, or renal artery infarction or embolus. One mild procedural vessel dissection which did not require intervention was reported. No cerebrovascular accidents, myocardial infarctions, or sudden cardiac deaths occurred within 30 days. Seven serious adverse events that were determined by the data safety monitoring board to be related to the procedure occurred within the first month post procedure, including two access-site infections, one pseudoaneurysm at the access site, and one femoral artery thrombus. One haematoma, one instance of bilateral flank pain, and one case of vomiting, all of which occurred within one day of the procedure, were classified as serious because hospitalisation was prolonged for observation. All events have resolved.

LONG-TERM SAFETY ENDPOINTS

Up to six months, one patient had a hypertensive emergency necessitating hospital admission and none had symptomatic orthostatic hypotension. Fifteen patients (11%) had an eGFR reduction >25% at six months. Two of these 15 patients presented with acute renal insufficiency which was related to medication use: one occurred approximately three months post procedure and was treated by lowering the diuretic dose, and the other was treated by withholding an ACE inhibitor and statin at approximately six months post procedure. Mean eGFR and serum creatinine remained stable at 82.9±23.7 mL/min per 1.73 m2 (change: −0.9±16.4 mL/min per 1.73 m2; N=138) and 85.2±24.2 µmol/L (change: 2.4±13.4 µmol/L; N=140) at six months, respectively.

Evaluable duplex ultrasounds were obtained from 123 patients at the six-month follow-up visit. Two of these patients had stenosis ≥60% based on core laboratory analysis and underwent subsequent imaging. The first had a 26% left renal artery stenosis at baseline which progressed to 65% in the treated area according to renal angiography conducted approximately seven months post procedure (core laboratory analysis). The second patient had 14% stenosis at baseline, and computed tomography angiography at eight months confirmed moderate left renal artery narrowing. These two patients have not undergone renal angioplasty or stenting and continue to be monitored.

Two additional patients with non-interpretable or abnormal duplex ultrasounds who underwent subsequent imaging studies were found to have renal artery stenoses within six months. One of these patients had 17% stenosis at baseline, and angiography at six months showed 60% stenosis within the treated area of the right renal artery. The patient underwent angioplasty and stenting, and continues to be monitored. This event was considered by the data safety monitoring board to be serious and both procedure- and device-related. The remaining patient had progression of a pre-existing 25% stenosis of the left renal artery to 73% at six months (core laboratory angiogram analysis) which did not need angioplasty or stenting.

Discussion

The REDUCE-HTN study results show that BP was reduced significantly for patients with resistant hypertension following multielectrode balloon-based renal denervation. Significant office-based BP reductions were observed one month post treatment and sustained up to six months, while 24-hour ambulatory monitoring results at six months further support the clinical effectiveness of the Vessix System. BP reductions were similar to results from other uncontrolled and controlled studies six months after treatment13 with various monopolar radiofrequency systems7,9-11,14.

At six months, clinically relevant reductions of at least 5 mmHg15 were observed in 85% of patients (76% had a reduction of ≥10 mmHg): this response rate is within the range reported in previous renal denervation studies (58% to 84%)7,10,11,16,17,18. Baseline and treatment characteristics were not significantly associated with the office systolic BP response in post hoc analyses, although baseline BP was significantly associated with an ambulatory systolic BP reduction >5 mmHg. These analyses were limited by the subgroup sizes, and additional research is needed to identify or rule out possible predictors of the response to treatment. Achieving systolic BP <140 mmHg reduces the risk for cardiovascular morbidity2, and 18% of patients in the REDUCE-HTN study had BP below this level at the six-month visit. Two previous studies have reported BP control rates of approximately 40% at six months following renal denervation10,11; however, comparisons are limited because baseline BP for patients in REDUCE-HTN was greater on average than in the other studies (182 mmHg vs. 176-178 mmHg), necessitating a greater reduction in order to reach the target level, and because the sample sizes in previous studies were relatively small (<50 subjects assessed vs. 142 subjects in REDUCE-HTN). These findings suggest that radiofrequency treatment with the bipolar balloon-based Vessix System may provide clinically meaningful BP reductions for patients with resistant hypertension.

Like other first-in-man and post-market studies of radiofrequency renal denervation devices, the REDUCE-HTN study was designed as a single-arm, non-blinded, non-randomised study7,9,11,14. The study design is prone to observer bias, and lack of a control arm precludes definitive conclusions regarding efficacy19. However, relevant variables are difficult to control, even with a control arm. The recently published results of the sham-controlled, blinded SYMPLICITY HTN-3 study did not show a significant difference in the BP reduction at six months between patients treated with a single-electrode, monopolar renal denervation device (Symplicity™ Renal Denervation System; Medtronic, Minneapolis, MN, USA) and those in the control arm18. This lack of difference between treatment and control has raised many questions, including whether medication regimens were stable and whether denervation procedures were adequately performed with the single-point device, which may be highly influenced by the operator18,20,21,22. In contrast to the SYMPLICITY HTN-3 results, Global SYMPLICITY registry23 data showed significant BP reductions for patients who had renal denervation with the Symplicity catheter, including those whose office BP aligned with the HTN-3 criteria21. Additional research is needed to reconcile the results of this and other previous studies with those of the SYMPLICITY HTN-3 trial.

The single-arm design of the REDUCE-HTN study limits our ability to investigate possible confounding effects of antihypertensive medications. Two weeks may be an insufficient duration for pre-treatment changes to the antihypertensive regimen to have observable effects on baseline BP, and patient-reported adherence may inadequately gauge regimen stability. Notwithstanding these limitations, the sample size was relatively large compared with previous uncontrolled studies7,9,11,14, and the inclusion of 24-hour ambulatory BP measurements mitigates observer bias, which is possible with office-based BP measurements19.

Results from the REDUCE-HTN study demonstrate a favourable safety profile for the Vessix System. No acute events indicative of seriously compromised renal artery integrity or cardiovascular complications occurred, and fewer than 6% of patients had serious procedure-related adverse events during six months of follow-up. Mean eGFR remained stable over six months, similar to other studies10,11,16. Of the four patients in this study with renal artery stenosis detected up to six months, only one required angioplasty and stenting. Two were found to have progression of pre-existing stenoses, as has been reported in other studies10,11,14. The requirement for core laboratory evaluation of the six-month duplex ultrasound contributed to the stenosis detection rate, and renal artery stenosis must continue to be examined in larger trials and registries17.

Conclusion

Patients with resistant hypertension were safely treated with a percutaneous balloon-based multielectrode bipolar radiofrequency system and achieved significant, clinically meaningful15, BP reductions over six months of follow-up.

Impact on daily practiceIn addition to lifestyle modifications and antihypertensive medications, renal denervation may be a treatment option for some patients with hypertension. This study suggests that denervation with a balloon-based multielectrode bipolar radiofrequency system provides clinically meaningful blood pressure reductions and a favourable safety profile for patients with resistant hypertension.

Acknowledgements

This work was supported by Vessix Vascular, Laguna Hills, CA, USA, and Boston Scientific, Marlborough, MA, USA. The authors thank Ana Becker for clinical programme management and Elizabeth J. Davis, PhD, for medical writing assistance (Boston Scientific, Maple Grove, MN, USA) and H. Terry Liao, PhD (Boston Scientific, Marlborough, MA, USA) for statistical analysis. Preliminary analyses were presented at VIVA 2013, October 8-11, Las Vegas, NV, USA, at TCT 2013, October 27-November 1, San Francisco, CA, USA, and at CRT 2014, February 22-25, Washington, DC, USA.

Funding

This work was supported by Vessix Vascular, Laguna Hills, CA, USA, and Boston Scientific, Marlborough, MA, USA.

Conflict of interest statement

H. Sievert has received study honoraria, travel expenses and consulting fees from Abbott, Access Closure, AGA, Angiomed, Aptus, Atrium, Avinger, Bard, Boston Scientific, BridgePoint, Cardiac Dimensions, CardioKinetix, CardioMEMS, Coherex, Contego, Covidien, CSI, CVRx, EndoCross, ev3, FlowCardia, Gardia, Gore, Guided Delivery Systems, InSeal Medical, Lumen Biomedical, HLT, Lifetech, Lutonix, Maya Medical, Medtronic, NDC, Occlutech, Osprey, Ostial, PendraCare, pfm Medical, ReCor, ResMed, Rox Medical, SentreHeart, Spectranetics, SquareOne, Svelte Medical Systems, Trireme, Trivascular, Venus Medical, Veryan, and Vessix Vascular; grant support from Cook and St. Jude Medical; and has stock options with Cardiokinetix, Access Closure, Velocimed, Lumen Biomedical, Coherex, SMT. J. Schofer has received speakers’ honoraria from Boston Scientific. U. Hoppe has received grant support and honoraria from Boston Scientific/Vessix Vascular, grant support and consultancy fees from Medtronic, and consultancy fees from St. Jude Medical. I. Meredith has received honoraria and consulting fees from Boston Scientific. M. Azizi has received honoraria for advisory board meetings from Vessix, Boston Scientific, and Cordis, and speakers’ honoraria from Cordis and CVRx. J. Diaz-Cartelle is an employee of Boston Scientific and holds stock in the company. M. Cohen-Mazor is an employee of Boston Scientific and holds stock in the company. The other authors have no conflicts of interest to declare.

Online data supplement

Appendix 1. REDUCE-HTN Investigators

Writing Committee: Horst Sievert (CardioVascular Center Frankfurt, Frankfurt, Germany), Joachim Schofer (Universitäres Herz- und Gefäßzentrum, Hamburg, Germany), John Ormiston (Mercy Angiography, Auckland, New Zealand), Uta C. Hoppe (Paracelsus Medical University, Salzburg, Austria), Ian Meredith (MonashHEART, Monash Health, Melbourne, Australia), Darren Walters (The Prince Charles Hospital, Brisbane, Australia), Michel Azizi (Hôpital Européen Georges Pompidou, Paris, France ), Juan Diaz-Cartelle (Boston Scientific, Natick, MA, USA) and Meital Cohen-Mazor (Vessix Vascular, Laguna Hills, CA, USA, and Boston Scientific, Natick, MA, USA).

Clinical Investigators: Uta C. Hoppe (Paracelsus Medical University, Salzburg, Austria), Clemens Steinwender (Allgemeines öffentliches Krankenhaus der Stadt Linz, Linz, Austria), Eric Wyffels (Onze-Lieve-Vrouwziekenhuis, Aalst, Belgium), Ian Meredith (MonashHEART Monash Health, Melbourne, Australia), Horst Sievert (CardioVascular Center Frankfurt, Frankfurt, Germany), Michel Azizi, Marc Sapoval (Hôpital Européen Georges Pompidou, Paris, France), Darren Walters (The Prince Charles Hospital, Brisbane, Australia), Georg Ehret (Cardiology Center, Geneva University Hospitals, Geneva, Switzerland), Mark Webster (Auckland City Hospital, Auckland, New Zealand), Ajay Sinhal (Flinders Medical Centre, Bedford Park, South Australia, Australia), Joost Daemen (Erasmus Medical Center, Rotterdam, The Netherlands), Ralf Langhoff (Vascular Center Berlin, Berlin, Germany), Nicolaus Reifart (Main Tanus Kliniken, Bad Soden, Germany), David Muller (St. Vincent’s, Sydney, Australia), Dierk Scheinert (Zentrum für Gefäßmedizin, Leipzig, Germany), Robbert-Jan de Winter (Academic Medical Center, Amsterdam, The Netherlands), Alexandre Persu (Cliniques Universitaires Saint Luc, Bruxelles, Belgium), Jean Fajadet (Clinique Pasteur, Toulouse, France), Ilka Ott (German Heart Centre, Munich, Germany), Joachim Schofer (Universitäres Herz- und Gefäßzentrum Hamburg, Hamburg, Germany), Ahmed Farah (Zentralklinik Bad Berka, Bad Berka, Germany), Steven Worthley (Royal Adelaide Hospital, Adelaide, Australia), John Ormiston (Mercy Angiography, Auckland, New Zealand).

Data Safety Monitoring Board: Farrell Mendelsohn (Cardiology PC, Birmingham, AL, USA), William Gray (Columbia University Medical Center, New York, NY, USA), Daniel Clair (Cleveland Clinic Foundation, Cleveland, OH, USA).

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Vessix™ – Renal Denervation System

Study Design

The REDUCE-HTN Post-Market Study (PMS), including the First in Man (FIM) cohort, is a prospective, non-randomized, single arm, multicenter study evaluating the Vessix™ Renal Denervation System in patients with resistant hypertension. Enrolled patients had office-based systolic blood pressure (SBP) ≥ 160 mm Hg while on ≥ 3 antihypertensive medications (including a diuretic unless the patient had a documented intolerance to diuretics) at maximally tolerated doses.

A total of 146 patients were enrolled and treated at 23 centers in Europe, Australia, and New Zealand.

graphic reduce

Office Blood Pressure Reduction

24-hours Ambulatory Blood Pressure Reduction

 

 

No patients experienced prespecified acute safety events
Procedure-related serious adverse events* of 5.5% among the 146 patients to date Hematoma, bilateral flank pain, vomiting, pseudoaneurysm at access site, thrombus at access site, access site infection (2), renal artery stenosis requiring treatment
6-month patency§ 99.2% (252/254 arteries**) by core lab duplex ultrasound analysis.

Scientific Commitment

Boston Scientific collaborates with researchers, physicians and hospital systems worldwide to advance the science of cardiovascular medicine. A key component of that commitment is the Vessix Global Clinical Program, which includes both the REDUCE-HTN and RELIEVE Clinical Series. The REDUCE-HTN Clinical Series plans to enroll more than 1,200 resistant hypertension patients worldwide and already includes the largest cohort of patients studied following treatment with a multi-electrode renal denervation system. The RELIEVE Clinical Series includes pre-clinical, clinical and investigator initiated research evaluating the Vessix System technology in additional disease states including end-stage renal disease, heart failure, atrial fibrillation and diabetes.

REDUCE – HTN Interim 6 Month Data

Presenter: Horst Sievert MD

Top

Blood pressure reductions are mean values.
Caution: Investigational device limited under U.S. law for investigational use only. Not for sale in the U.S.
* Serious adverse events (SAEs) defined according to International Organization for Standardization ISO14155.
† Baseline stenosis was 17% based on core lab assessment of angiogram; stenosis of 60% noted by angiography at 6 month follow-up; patient received percutaneous transluminal angioplasty/stent and continues to be monitored.
§ Patency defined as stenosis < 60%.
** Treated renal arteries with 6 month post-treatment diagnostic DUS.
Schofer J, MD. REDUCE-HTN Clinical Study interim 12- and 18-month Data. Presented at EuroPCR; May 2014.

SYNERGY Stent Investigator-Sponsored Research

The SYNERGY Stent Investigator-Sponsored Research1 Program will study the SYNERGY Stent in many different patient populations that interventional cardiologists see in their everyday practice.

Infographic

SYNERGY Stent Clinical Trials

Supporting Research of the SYNERGY Stent

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1Boston Scientific is not responsible for the collection, analysis or reporting of the investigator-sponsored research output which is the sole responsibility of the investigators. Boston Scientific’s involvement in investigator-sponsored research is limited to providing financial support for research that advances medical and scientific knowledge about our products.SYNERGY is an unregistered or registered trademark of Boston Scientific Corporation or its affiliates. All other trademarks are the property of their respective owners.

CAUTION: The law restricts these devices to sale by or on the order of a physician. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. Information contained here is for distribution outside the US, France, and Japan only.

Boston Scientific Receives FDA Approval for WATCHMAN™ Left Atrial Appendage Closure Device

First-Of-Its-Kind Alternative to Long-Term Warfarin Therapy for Stroke Risk Reduction in Patients with Non-Valvular Atrial Fibrillation

Mar 13, 2015

MARLBOROUGH, Mass., March 13, 2015 /PRNewswire/ — Boston Scientific Corporation (NYSE: BSX) has received U.S. Food and Drug Administration (FDA) approval for the WATCHMAN Left Atrial Appendage Closure Device. The WATCHMAN Device offers a new stroke risk reduction option for high-risk patients with non-valvular atrial fibrillation who are seeking an alternative to long-term warfarin therapy. The WATCHMAN Device will be made available to U.S. centers involved in our clinical studies and additional, specialized centers as physicians are trained on the implant procedure.

Experience the interactive Multimedia News Release here: http://www.multivu.com/players/English/7223452-boston-scientific-watchman-fda-approval

The WATCHMAN Device is indicated to reduce the risk of thromboembolism from the left atrial appendage in patients with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2-VASc scores, are deemed by their physicians to be suitable for warfarin; and have an appropriate rationale to seek a non-pharmacologic alternative to warfarin, taking into account the safety and effectiveness of the device compared to warfarin.

“The WATCHMAN Device is an important step forward in stroke management for patients with AF,” said Vivek Reddy, M.D., Director of the Cardiac Arrhythmia Service at the Mount Sinai Hospital and co-principal investigator of the PROTECT AF and PREVAIL studies. “We know that up to 40 percent of patients who are eligible for oral anticoagulation do not take it for numerous reasons1, highlighting the need for additional treatment options. The WATCHMAN Device is a breakthrough treatment providing those patients who are suitable for warfarin with an implant-based alternative to long-term warfarin therapy while still reducing the risk of stroke.”

The FDA approval of the WATCHMAN Device is based on the robust WATCHMAN clinical program which consists of numerous studies, with more than 2,400 patients and nearly 6,000 patient-years of follow-up. The WATCHMAN clinical program provided strong evidence that the WATCHMAN Device can be implanted safely2 and reduces the risk of stroke in eligible patients while enabling most patients to discontinue warfarin3. Additionally, a meta-analysis of all of the randomized trial data demonstrated that while ischemic stroke reduction favored warfarin, the WATCHMAN Device provided patients with a comparable protection against all-cause stroke and statistically superior reductions in hemorrhagic stroke, disabling stroke, and cardiovascular death compared to warfarin over long-term follow-up.4

“Today marks a defining moment in the company’s journey towards establishing left atrial appendage closure therapy in the United States.  Boston Scientific is proud to offer this potentially life-changing stroke risk treatment option to high-risk patients with AF who have a reason to seek a non-drug alternative to warfarin.   This therapy could free them from the challenges of long-term warfarin therapy,” said Joe Fitzgerald, executive vice president and president, Rhythm Management, Boston Scientific.  “FDA approval of the WATCHMAN Device is another example of Boston Scientific delivering on its commitment to bring meaningful innovations to patient care.”

The WATCHMAN Device has been commercially available internationally since 2009 and is the leading device in percutaneous left atrial appendage closure globally.  It is registered in 75 countries and more than 10,000 patients have been treated with the WATCHMAN Device.

Investor Event and Webcast Information
Boston Scientific, in connection with its attendance at the 2015 American College of Cardiology 64th Annual Scientific Session in San Diego, CA, will host an investor event and live webcast to discuss the WATCHMAN Device on Sunday, March 15.  The event, which will include a question and answer session, is scheduled to begin at 1:00 p.m. PT and adjourn at approximately 2:30 p.m. PT and will be hosted by Joe Fitzgerald, executive vice president and president, Rhythm Management, and Kenneth Stein, M.D., senior vice president and chief medical officer, Rhythm Management. Vivek Reddy, M.D., Director of the Cardiac Arrhythmia Service at the Mount Sinai Medical Center will also present.

A live webcast of the event will be available via the Boston Scientific website. Webcast registration is available on the Investor Relations section of the website at www.bostonscientific.com/investors. Registration at least 15 minutes prior to the scheduled start time is encouraged to ensure a timely connection.

A replay of the webcast will be archived and accessible at www.bostonscientific.com/investors approximately one hour following the completion of the conference call.

About Atrial Fibrillation and Stroke
Non-valvular atrial fibrillation (AF) is an irregular heartbeat that can lead to blood clots, stroke, heart failure and other heart-related complications.  AF is the most common cardiac arrhythmia, currently affecting more than five million Americans.5 Patients with AF have a five-fold increased risk of stroke due to blood stagnating from the improperly beating atrium and the resulting blood clot formation.6 Twenty percent of all strokes occur in patients with AF.7 Stroke is more severe for patients with AF, as they have a 70 percent chance of death or permanent disability.8

The most common treatment for stroke risk reduction in patients with AF is blood-thinning warfarin therapy.  Despite its proven efficacy, long-term warfarin therapy is not well-tolerated by some patients due to numerous quality-of-life tradeoffs – like dietary restrictions and regular blood monitoring – and carries a significant risk for bleeding complications.

About the WATCHMAN LAAC Device
The WATCHMAN LAAC Device is a catheter-delivered heart implant designed to close the left atrial appendage (LAA) in order to prevent the migration of blood clots from the LAA, and thus, reduce the incidence of stroke and systemic embolism for higher risk patients with non-valvular AF.  The LAA is a thin, sack-like appendix arising from the heart and is believed to be the source of >90 percent of stroke-causing clots that come from the left atrium in patients with non-valvular AF.4 Images of the WATCHMAN Device are available at http://bostonscientific.mediaroom.com/image-gallery?mode=gallery&cat=1760.

About Boston Scientific
Boston Scientific transforms lives through innovative medical solutions that improve the health of patients around the world.  As a global medical technology leader for more than 35 years, we advance science for life by providing a broad range of high performance solutions that address unmet patient needs and reduce the cost of healthcare.  For more information, visit www.bostonscientific.com and connect on Twitter and Facebook.

Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934.  Forward-looking statements may be identified by words like “anticipate,” “expect,” “project,” “believe,” “plan,” “estimate,” “intend” and similar words.  These forward-looking statements are based on our beliefs, assumptions and estimates using information available to us at the time and are not intended to be guarantees of future events or performance.  These forward-looking statements include, among other things, statements regarding our products, our business plans, product launches and availability, clinical trials and data impact, competitive offerings, and product performance and impact.  If our underlying assumptions turn out to be incorrect, or if certain risks or uncertainties materialize, actual results could vary materially from the expectations and projections expressed or implied by our forward-looking statements.  These factors, in some cases, have affected and in the future (together with other factors) could affect our ability to implement our business strategy and may cause actual results to differ materially from those contemplated by the statements expressed in this press release.  As a result, readers are cautioned not to place undue reliance on any of our forward-looking statements.

Factors that may cause such differences include, among other things: future economic, competitive, reimbursement and regulatory conditions; new product introductions; demographic trends; intellectual property; litigation; financial market conditions; and future business decisions made by us and our competitors.  All of these factors are difficult or impossible to predict accurately and many of them are beyond our control.  For a further list and description of these and other important risks and uncertainties that may affect our future operations, see Part I, Item 1A – Risk Factors in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, which we may update in Part II, Item 1A – Risk Factors in Quarterly Reports on Form 10-Q we have filed or will file hereafter.  We disclaim any intention or obligation to publicly update or revise any forward-looking statements to reflect any change in our expectations or in events, conditions or circumstances on which those expectations may be based, or that may affect the likelihood that actual results will differ from those contained in the forward-looking statements.  This cautionary statement is applicable to all forward-looking statements contained in this document.

CONTACTS
Media:
Nisha Deo
508-683-5571 (office)
408-893-9243 (cell)
Media Relations
Boston Scientific Corporation
Nisha.deo@bsci.com

Investors:
Susie Lisa, CFA
508-652-5345 (office)
Investor Relations
Boston Scientific Corporation
investor_relations@bsci.com

 

1 NCDR Pinnacle Registry
2 PROTECT AF, CAP, PREVAIL and CAP2
3 PROTECT AF, CAP, PREVAIL
4 POOLED PROTECT AF and PREVAIL data
5 Colilla et al., Am J Cardiol. 2013; 112:1142-1147
6 Holmes DR, Seminars in Neurology 2010; 30:528–536
7 Hart RG, Halperin JL., Ann Intern Med. 1999; 131:688–695
8 Blackshear J. and Odell J., Annals of Thoracic Surgery. 1996; 61:755-759

 

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/boston-scientific-receives-fda-approval-for-watchman-left-atrial-appendage-closure-device-300050512.html

SOURCE Boston Scientific Corporation

Boston Scientific Announces First U.S. Commercial Procedures With The WATCHMAN™ Left Atrial Appendage Closure Device

Novel Stroke Risk Reduction Option for Indicated Patients with Atrial Fibrillation

Mar 24, 2015

MARLBOROUGH, Mass., March 24, 2015 /PRNewswire/ — This week, four patients in the United States received the first implants of the Boston Scientific Corporation (NYSE: BSX) WATCHMAN Left Atrial Appendage Closure (LAAC) Device. The WATCHMAN Device offers a novel stroke risk reduction option for high-risk patients with non-valvular atrial fibrillation (AF) who are seeking an alternative to long-term warfarin therapy. The WATCHMAN Device received U.S. Food and Drug Administration (FDA) approval on Friday, March 13, 2015.

The first WATCHMAN Device procedures in the U.S. were performed by Shephal K. Doshi, M.D., director of Cardiac Electrophysiology and Pacing at Saint John’s Health Center in Santa Monica, CA, and Saibal Kar, M.D., director of the Cardiovascular Intervention Center Research at Cedars-Sinai Hospital in Los Angeles, CA.

“With today’s successful implantations of the WATCHMAN Device, we are changing the way we deal with stroke risk in high-risk patients with non-valvular atrial fibrillation,” said Kar. “For indicated patients like those who received an implant this week, the WATCHMAN Device reduces the risk of stroke, without the need for long-term anticoagulation therapy and its subsequent bleeding risks.”

More than five million Americans suffer from an irregular heartbeat called non-valvular atrial fibrillation.i Many of these patients are at increased risk of stroke, but as many as 40 percent of those patients eligible for oral anticoagulant therapy do not take this medicationii and may need a treatment alternative.

“As physicians, we are always looking for new therapies to satisfy unmet patient needs,” said Doshi. “There are many patients like the ones we treated this week with the WATCHMAN Device who are suitable for warfarin, but are not ideal candidates for chronic anticoagulant use.  These patients now have a new, proven option to reduce their risk of AF-related stroke.”

The WATCHMAN Device is indicated to reduce the risk of thromboembolism from the left atrial appendage in patients with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2-VASc scores, are deemed by their physicians to be suitable for warfarin, and have an appropriate rationale to seek a non-pharmacologic alternative to warfarin, taking into account the safety and effectiveness of the device compared to warfarin.

“Boston Scientific is proud to work with physicians in making a meaningful impact on patient lives by bringing left atrial appendage closure therapy to the United States,” said Kenneth Stein, M.D., chief medical officer, Rhythm Management, Boston Scientific.

The WATCHMAN Device was approved by the FDA based on a robust clinical program, which has now included more than 3,300 patients with 6,000 patient-years of follow-up to date.  The WATCHMAN clinical program provides strong evidence that the WATCHMAN Device can be implanted safely and reduces the risk of stroke in eligible patients while enabling most patients to discontinue warfarin.iii

Additionally, a meta-analysis of all of the randomized trial data demonstrated that while ischemic stroke reduction favored warfarin, the WATCHMAN Device provided patients with a comparable protection against all-cause stroke and statistically superior reductions in hemorrhagic stroke, disabling stroke, and cardiovascular death compared to warfarin over long-term follow-up.iii

The WATCHMAN LAAC Device has been commercially available internationally since 2009. It is registered in 75 countries and more than 10,000 patients have been treated with the WATCHMAN Device.

About Atrial Fibrillation and Stroke

Non-valvular atrial fibrillation (AF) is an irregular heartbeat that can lead to blood clots, stroke, heart failure and other heart-related complications.  AF is the most common cardiac arrhythmia, currently affecting more than five million Americans.i Patients with AF have a five-fold increased risk of stroke due to blood stagnating from the improperly beating atrium and the resulting blood clot formation.iv Twenty percent of all strokes occur in patients with AF.v Stroke is more severe for patients with AF, as they have a seventy percent chance of death or permanent disability.vi

The most common treatment for stroke risk reduction in patients with AF is blood-thinning warfarin therapy.  Despite its proven efficacy, long-term warfarin is not well-tolerated by some patients due to a significant risk for bleeding complications, and numerous quality-of-life tradeoffs, including dietary restrictions and regular blood monitoring.

About the WATCHMAN LAAC Device

The WATCHMAN LAAC Device is a catheter-delivered heart implant designed to close the left atrial appendage (LAA) in order to prevent the migration of blood clots from the LAA, and thus, reduce the incidence of stroke and systemic embolism for higher risk patients with non-valvular AF.  The LAA is a thin, sack-like appendix arising from the heart and is believed to be the source of >90% of stroke-causing clots that come from the left atrium in people with non-valvular AF. Images of the WATCHMAN Device are available at http://bostonscientific.mediaroom.com/image-gallery?mode=gallery&cat=1760.

About Boston Scientific

Boston Scientific transforms lives through innovative medical solutions that improve the health of patients around the world.  As a global medical technology leader for more than 35 years, we advance science for life by providing a broad range of high performance solutions that address unmet patient needs and reduce the cost of healthcare.  For more information, visit www.bostonscientific.com and connect on Twitter and Facebook.

Cautionary Statement Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934.  Forward-looking statements may be identified by words like “anticipate,” “expect,” “project,” “believe,” “plan,” “estimate,” “intend” and similar words.  These forward-looking statements are based on our beliefs, assumptions and estimates using information available to us at the time and are not intended to be guarantees of future events or performance.  These forward-looking statements include, among other things, statements regarding our products, markets for our products, clinical trials, and product performance and impact.  If our underlying assumptions turn out to be incorrect, or if certain risks or uncertainties materialize, actual results could vary materially from the expectations and projections expressed or implied by our forward-looking statements.  These factors, in some cases, have affected and in the future (together with other factors) could affect our ability to implement our business strategy and may cause actual results to differ materially from those contemplated by the statements expressed in this press release.  As a result, readers are cautioned not to place undue reliance on any of our forward-looking statements.

Factors that may cause such differences include, among other things: future economic, competitive, reimbursement and regulatory conditions; new product introductions; demographic trends; intellectual property; litigation; financial market conditions; and future business decisions made by us and our competitors.  All of these factors are difficult or impossible to predict accurately and many of them are beyond our control.  For a further list and description of these and other important risks and uncertainties that may affect our future operations, see Part I, Item 1A – Risk Factors in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, which we may update in Part II, Item 1A – Risk Factors in Quarterly Reports on Form 10-Q we have filed or will file hereafter.  We disclaim any intention or obligation to publicly update or revise any forward-looking statements to reflect any change in our expectations or in events, conditions or circumstances on which those expectations may be based, or that may affect the likelihood that actual results will differ from those contained in the forward-looking statements.  This cautionary statement is applicable to all forward-looking statements contained in this document.

CONTACTS

Media:
Trish Backes
651-582-5887 (office)
Media Relations
Boston Scientific Corporation
trish.backes@bsci.com

Investors:
Susie Lisa
508-683-5565 (office)
Investor Relations
Boston Scientific Corporation
investor_relations@bsci.com

i Colilla S, et al. Estimates of Current and Future Incidence and Prevalence of Atrial Fibrillation in the U.S. Adult Population. Am J Cardiol 2013;112: 1142-1147.
ii Shah N, et al. Use of Novel Oral Anticoagulants for Patients with Non-valvular Atrial Fibrillation: Results from the NCDR Pinnacle Registry. J Am Coll Cardiol 2014;63(12S).
iii U.S. Food and Drug Administration. Circulatory System Devices Panel: Boston Scientific WATCHMAN® Left Atrial Appendage Closure Therapy (P130013). Sponsor Executive Summary available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm395638.htm.
iv Holmes DR, et al. Atrial Fibrillation and Stroke Management: Present and Future. Semin Neurol. 2010;30: 528–536.
v Hart R, et al. Atrial Fibrillation and Thromboembolism: A Decade of Progress in Stroke Prevention. Ann Intern Med 1999;131: 688–695.
vi Blackshear J, et al. Appendage Obliteration to Reduce Stroke in Cardiac Surgical Patients with Atrial Fibrillation. Ann Thorac Surg 1996;61: 755-759.

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SOURCE Boston Scientific Corporation