Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study
Shadi Yaghi, Liqi Shu, Daniel Mandel, Christopher R. Leon Guerrero, Nils Henninger, Jayachandra Muppa, Muhammad Affan, Omair ul haq Lodhi, Mirjam R. Heldner, Kateryna Antonenko, David Seiffge, Marcel Arnold, Setareh Salehi Omran, Ross Crandall, Evan Lester, Diego López Mena, Antonio Araúz, Ahmad Nehme, Marion Boulanger, Emmanuel Touzé, João André Sousa, João Sargento‐Freitas, Vasco Barata, Paulo Castro‐Chaves, Maria Teresa Brito, Muhib Khan, Dania Mallick, Aaron Rothstein, Ossama Khazaal, Josefin E. Kaufmann, Stefan T. Engelter, Christopher Traenka, Diana Aguiar de Sousa, Mafalda Soares, Sara Rosa, Lily Zhou, Preet Gandhi, Thalia S. Field, Steven Mancini, Issa Metanis, Ronen R. Leker, Kelly Pan, Vishnu Dantu, Karl Baumgartner, Tina Burton, Regina von Rennenberg, Christian H. Nolte, Richard Choi, Jason MacDonald, Reza Bavarsad Shahripour, Xiaofan Guo, Malik Ghannam, Mohammad Almajali, Edgar A. Samaniego, Sebastian Sanchez, Bastien Rioux, Fayçal Zine-Eddine, Alexandre Y. Poppe, Ana Catarina Fonseca, Maria Fortuna Baptista, Diana Cruz, Michele Romoli, Giovanna De Marco, Marco Longoni, Zafer Keser, Kim Griffin, Lindsey Kuohn, Jennifer Frontera, Jordan Amar, James Giles, Marialuisa Zedde, Rosario Pascarella, Ilaria Grisendi, Hipólito Nzwalo, David S. Liebeskind, Amir Molaie, Annie Cavalier, Wayneho Kam, Brian Mac Grory, Sami Al Kasab, Mohammad Anadani, Kimberly Kicielinski, Ali Eltatawy, Lina Chervak, Roberto Chulluncuy‐Rivas, Yasmin Aziz, Ekaterina Bakradze, Thanh Lam Tran, Marc Rodrigo‐Gisbert, Manuel Requena, Faddi Saleh Velez, Jorge Ortiz Gracia, Varsha Mudassani, Adam de Havenon, Venugopalan Y. Vishnu, Sridhara Yaddanapudi, L Adams, Abigail Browngoehl, Tamra Ranasinghe, Randy Dunston
Abstract
BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.