Anticoagulation and Antiplatelet Strategies After On-X Mechanical Aortic Valve Replacement.

BACKGROUND: The burden oral anticoagulation is a limitation of mechanical valve prostheses. OBJECTIVES: The aim of this study was to test whether patients could be safely managed with dual-antiplatelet therapy (DAPT) (aspirin 325 mg and clopidogrel 75 mg) or lower warfarin after On-X mechanical aortic valve replacement (mAVR). METHODS: PROACT (Prospective Randomized On-X Anticoagulation Trial) (n = 576) is a multicenter (41 sites) noninferiority trial. From June 2006 through February 2014, 201 patients ≥18 years of age without thromboembolic risk factors undergoing mAVR were randomized to receive DAPT (n = 99) or standard warfarin plus aspirin (n = 102) 3 months after mAVR (low-risk arm). From June 2006 through October 2009, 375 patients with 1 or more thromboembolic risk factors were also randomized to lower intensity warfarin plus aspirin (international normalized ratio 1.5 to 2.0; n = 185) or standard warfarin plus aspirin (international normalized ratio 2.0 to 3.0; n = 190) 3 months after mAVR (high-risk arm). RESULTS: The low-risk arm was terminated for excess cerebral thromboembolic events (3.12% per patient-year vs. 0.29% per patient-year, p = 0.02) in the DAPT group at up to 8.8-year follow-up (631.6 patient-years), with no differences in bleeding or all-cause mortality. High-risk arm patients experienced significantly lower major (1.59% per patient-year vs. 3.94% per patient-year, p = 0.002) and minor (1.27% per patient-year vs. 3.49% per patient-year, p = 0.002) bleeding up to 8.7-year follow-up (2,035.2 patient-years), with no differences in thromboembolism (0.42% per patient-year vs. 0.09% per patient-year, p = 0.20) and all-cause mortality. CONCLUSIONS: DAPT was associated with higher rates of thromboembolism and valve thrombosis compared with control in the low-risk arm. International normalized ratios were safely maintained at 1.5 to 2.0 in high-risk patients, without differences in mortality or thromboembolic complications. (Randomized On-X Anticoagulation Trial [PROACT]; NCT00291525).

Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X valve anticoagulation clinical trial randomized Food and Drug Administration investigational device exemption trial.

OBJECTIVE: Under Food and Drug Administration investigational device exemption, the Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) has been testing the safety of less aggressive anticoagulation than recommended by the American College of Cardiology/American Heart Association guidelines after implantation of an approved bileaflet mechanical valve. METHODS: In this first limb of the PROACT, patients with elevated risk factors for thromboembolism were randomized at 33 US centers to receive lower dose warfarin (test international normalized ratio [INR], 1.5-2.0) or continue standard warfarin (control INR, 2.0-3.0), 3 months after mechanical aortic valve replacement. The INR was adjusted by home monitoring; all patients received 81 mg aspirin daily. Adverse events were independently adjudicated. RESULTS: A total of 375 aortic valve replacement patients were randomized into control (n = 190) and test (n = 185) groups from September 2006 to December 2009. The mean age ± standard deviation was 55.2 ± 12.5 years; 79% were men; and 93% were in sinus rhythm preoperatively. Calcific degeneration was present in 67%; active endocarditis was excluded. Concomitant procedures included coronary artery bypass grafting (27%), aortic aneurysm repair (14%), and other (25%). The follow-up duration averaged 3.82 years (755.7 patient-years [pt-yrs] for control; 675.2 pt-yrs for test). The mean INR was 2.50 ± 0.63 for the control and 1.89 ± 0.49 for the test groups (P < .0001). The test group experienced significantly lower major (1.48% vs 3.26%/pt-yr; P = .047) and minor (1.32% vs 3.41%/pt-yr; P = .021) bleeding rates. The incidence of stroke, transient ischemic attack, total neurologic events, and all-cause mortality were similar between the 2 groups. CONCLUSIONS: INR can be safely maintained between 1.5 and 2.0 after aortic valve replacement with this approved bileaflet mechanical prosthesis. With low-dose aspirin, this resulted in a significantly lower risk of bleeding, without a significant increase in thromboembolism.

Radial artery grafts vs saphenous vein grafts in coronary artery bypass surgery: a randomized trial.

CONTEXT: Arterial grafts are thought to be better conduits than saphenous vein grafts for coronary artery bypass grafting (CABG) based on experience with using the left internal mammary artery to bypass the left anterior descending coronary artery. The efficacy of the radial artery graft is less clear. OBJECTIVE: To compare 1-year angiographic patency of radial artery grafts vs saphenous vein grafts in patients undergoing elective CABG. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized controlled trial conducted from February 2003 to February 2009 at 11 Veterans Affairs medical centers among 757 participants (99% men) undergoing first-time elective CABG. INTERVENTIONS: The left internal mammary artery was used to preferentially graft the left anterior descending coronary artery whenever possible; the best remaining recipient vessel was randomized to radial artery vs saphenous vein graft. MAIN OUTCOME MEASURES: The primary end point was angiographic graft patency at 1 year after CABG. Secondary end points included angiographic graft patency at 1 week after CABG, myocardial infarction, stroke, repeat revascularization, and death. RESULTS: Analysis included 733 patients (366 in the radial artery group, 367 in the saphenous vein group). There was no significant difference in study graft patency at 1 year after CABG (radial artery, 238/266; 89%; 95% confidence interval [CI], 86%-93%; saphenous vein, 239/269; 89%; 95% CI, 85%-93%; adjusted OR, 0.99; 95% CI, 0.56-1.74; P = .98). There were no significant differences in the secondary end points. CONCLUSION: Among Veterans Affairs patients undergoing first-time elective CABG, the use of a radial artery graft compared with saphenous vein graft did not result in greater 1-year patency. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00054847.

Pediatric bridge to heart transplantation: application of the Berlin Heart, Medos and Thoratec ventricular assist devices.

BACKGROUND: Bridge to transplantation (BTT) is an accepted option when a donor heart is not available. Extensive clinical study has been done with BTT in the adult population, but comparatively fewer data are available in the pediatric population with regard to pulsatile devices. METHODS: Ten pediatric patients are presented, all of whom underwent BTT or recovery with pneumatic paracorporeal systems. The Berlin Heart bi-ventricular assist device (BVAD) was utilized in 1 patient, the Medos VAD in 4 patients (1 left ventricular assist device [LVAD], 3 BVADs) and the Thoratec VAD in 5 patients (3 BVADs, 2 LVADs). The pediatric population consisted of 3 females and 7 males. Mean age of the population was 7.4 years, weight 25 kg and body surface area (BSA) 0.88 m(2). Etiology for heart failure consisted of 4 viral, 3 congenital and 3 idiopathic cardiomyopathies. Before implant, all patients had evidence of progressive cardiac failure despite inotropic support, and 2 patients had been on extracorporeal membrane oxygenation (ECMO). Mean duration on the device was 34.3 days (8 to 107 days). RESULTS: Two patients suffered stroke and recovered without sequelae. Two patients died of ischemic stroke and 1 of sepsis. Seven patients survived (6 transplanted and 1 weaned) for a survival rate of 70% compared with survival for ECMO as BTT, which was 40% to 50%. All survivors had complications related to bleeding, thromboembolic events and infections. CONCLUSIONS: The Thoratec VAD can be placed in small patients with large hearts that can accommodate the available cannulas. The Berlin Heart and the Medos VAD have a selection of ventricles with small stroke volumes. All 3 systems can be used successfully in the pediatric population as BTT with better survival than with ECMO.

CardioWest total artificial heart in a moribund adolescent with left ventricular thrombi.

Bridge to transplant is a well-known strategy to enable patients with congestive heart failure to live until transplant. A 15-year-old boy with Beckers' muscular dystrophy and cardiomyopathy was accepted for heart transplantation. He suffered a cardiac arrest and was placed on extracorporeal membrane oxygenator. A paracorporeal biventricular assist device and a total artificial heart were considered for bridge to transplant. A CardioWest total artificial heart was chosen because of the patient's size. Multiple left ventricular thrombi were identified at the time of the ventriculectomy. The patient did well with the total artificial heart was transplanted and discharged home. The unknown presence of significant left ventricular thrombi raises the question of outcome with a paracorporeal ventricular assist device.