The 4-year-rate of cerebrovascular events (CVE) is similar in patients undergoing transcatheter edge-to-edge repair (TEER) plus guideline-directed medical therapy (GDMT) compared with GDMT alone, a new analysis finds. Researchers noted that baseline oral anticoagulation use was associated with a decreased CVE risk after MitraClip (Abbott Vascular) treatment. “By reducing progressive left ventricular dilation and HF, the MitraClip implant may reduce the risk of CVE in patients with SMR [secondary mitral regurgitation] and HF [heart failure],” commented the researchers of the Abbott sponsored and funded trial. “Whether anticoagulation is especially effective at preventing CVE in HF patients treated with MitraClip, as suggested by this report, warrants further study,” the authors, led by Flavien Vincent, MD, from the Cardiovascular Research Foundation in New York, concluded in a manuscript published Monday online and in the June 26 issue of JACC: Cardiovascular Interventions. A multicenter, randomized, controlled, open-label approach The COAPT trial enrolled a total of 614 patients with HF and severe SMR, randomized 1:1 to undergo TEER plus GDMT or GDMT alone. The multicenter, randomized, controlled, open-label trial, then followed these patients at regular intervals for 5 years. In both arms, chronic antiplatelet therapy and oral anticoagulant therapy were otherwise administered. In the TEER arm, a loading dose of clopidogrel (≥300 mg) or aspirin (325 mg) was recommended within 24 hours prior to the procedure with intravenous heparin administered during the procedure. Following MitraClip device placement, antiplatelet therapy with daily clopidogrel (75 mg) and/or aspirin (81 mg) for 6 months or longer was required in the absence of oral anticoagulation use. A CVE was defined as the occurrence of a stroke or transient ischemic attack (TIA) while a disabling stroke was defined as a definite stroke with a modified Rankin Scale (mRS) score ≥2 at 90 days with an increase of ≥1 from baseline. All echocardiograms were analyzed by an independent echocardiographic core laboratory (MedStar Health Research Institute). Results of COAPT trial Results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial revealed 50 CVEs occurred in 48 (7.8%) of the 614 total patients enrolled at 4-year follow-up. The Kaplan-Meier event rates were 12.3% in the TEER group and 10.2% in the GDMT alone group (P=0.91). The findings of the new analysis, which were published Monday online, also noted that within 30 days of randomization, CVE occurred in two (0.7%) patients randomized to TEER and 0% randomized to GDMT (P=0.15). At 2 years after randomization, patients in the GDMT-only group were allowed to cross over to the TEER group. Of the 312 patients in the control group, 62 underwent TEER with the MitraClip at a median 781 days (interquartile range: 739 to 849) after randomization. Of the 22 CVEs that were reported in the GDMT-only group, two occurred after TEER was performed. Renal dysfunction and diabetes were found to be independently associated with increased risk of CVE, while baseline anticoagulation was associated with a reduction of CVE. A significant interaction was present between treatment group and anticoagulation such that TEER compared with GDMT alone was associated with a reduced risk of CVE among patients with anticoagulation (adjusted hazard ratio [HR]: 0.24; 95% confidence interval [CI]: 0.08-0.73). This was compared with an increased risk of CVE in patients without anticoagulation (adjusted HR: 2.27; 95% CI: 1.08-4.81; P interaction=0.001). The researchers suggested that CVE was an independent predictor of death within 30 days after the event (HR: 14.37; 95% CI: 7.61, 27.14; P < 0.0001). MitraClip’s influence on findings Commenting on the impact of the MitraClip implant on CVE, and the interactions between treatment group, anticoagulant use, and the CVE risk, the authors said the TEER procedure exposed systemic circulation to an ongoing risk of device-related thromboemboli prior to complete device endothelialization. Other suggestions included the introduction of left ventricular hemodynamic changes after edge-to-edge repair that may have increased thrombogenicity. The team also pointed out the possibility of functional abnormality recovery in von Willebrand factor after the reduction of transvalvular shear stress that might increase hemostasis. “The present study corroborates the idea, also supported by others, that oral anticoagulation may prevent events after TEER,” said Fabien Praz, MD, and Alec Vahanian, MD, in an accompanying editorial comment. Praz, from Bern University Hospital, University of Bern in Switzerland, and Vahanian, from Université Paris Cité in Paris, pointed out, however, that in the COAPT trial, less than half of patients required oral anticoagulation (47%). Most were treated with vitamin K antagonists, with unknown adherence (direct oral anticoagulation in only 15.6%) with the remaining patients receiving single or dual antiplatelet therapy for at least 6 months. Lack of clear guideline recommendations “The variability of the proposed antithrombotic treatment regimens after TEER is explained by the lack of clear guideline recommendations on both sides of the Atlantic,” the editorialists wrote. “In addition, further clarity is needed regarding the role of atrial fibrillation, as a previous subanalysis of the COAPT trial revealed an overall worse prognosis among patients with atrial fibrillation but a lower risk for stroke in those treated with TEER, which may be linked to diverging antithrombotic treatments.” They suggested a concomitant transcatheter left atrial appendage occlusion using the same transseptal access as an alternative in in patients at high bleeding risk, despite existing studies using small patient cohorts. CRTonline.org Managing Editor Jason Wermers contributed to this report. Sources: Vincent F, Redfors B, Kotinkaduwa LN, et al. Cerebrovascular Events After Transcatheter Edge-to-Edge Repair and Guideline-Directed Medical Therapy in the COAPT Trial. JACC Cardiovasc Interv. 2023;16: 1448–1459. Praz F, Alec Vahanian A. Stroke After Mitral TEER:A Grain of Sand in the Stapler? JACC Cardiovasc Interv. 2023;16:1460–1462. Image Credit: highwaystarz – stock.adobe.com