Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration
Graeme J. Hankey, Maree L. Hackett, Osvaldo P. Almeida, Leon Flicker, Gillian Mead, Martin Dennis, Christopher Etherton‐Beer, Andrew H. Ford, Laurent Billot, Stephen Jan, Thomas Lung, Erik Lundström, Katharina S. Sunnerhagen, Craig S. Anderson, Huy Thang-Nguyen, John Gommans, Qilong Yi, Veronica Murray, Rob Herbert, Gregory Carter, Geoffrey A. Donnan, Huy‐Thang Nguyen, Qiang Li, Séverine Bompoint, Sarah Barrett, Anne Claxton, Julia O’Dea, Michelle Tang, Clare Williams, Shenae Peterson, Christie Drummond, Uyen-Ha Hong, Linh-Thi My Le, Tram-Thi Bich Ngo, Yen-Bao Mai, Huyen-Thanh Han, Nhu-Quynh Truong, Huong-Thi Bich Nguyen, Hai-Thanh Ngo, Thi Binh Nguyen, Oanh-Thi Kieu Ha, Trang-Le Huyen Nguyen, Richard I. Lindley, Peter W. New, Andrew Lee, Thanh-Trung Tran, Loan-Tran Truc Mai Le, Thuy-Le Vu Kieu, Sang-Van Nguyen, Thuy-Anh Diem Nguyen, Tam-Nhat Dang, Hanh-Thi Truc Phan, Loan-Thi Ngoc Vo, Mai-Hue Nguyen, Hanh-Cao Dang, Hong-Thi Tran, Linh-Thi Cam Dam, Trinh-Thi Kim Ngo, Thai-Nguyen Thanh Pham, Binh-Nguyen Pham, Nha-Thi Thanh Dao, Huong-Thi Bich Nguyen, Linh-Thi Cam Le, Chi-Minh Do, Huy-Quoc Huynh, Giau-Thi Kim Tran, Oanh-Thi Le, Ly-Thi Khanh Tran, Chinh-Dinh Duong, Duong-Van Kieu, Ngoc‐Anh Le, Hoa-Ngoc Nguyen, Binh-Van Le, Long-Thanh Nguyen, Long-Van Nguyen, Tuan-Quoc Dinh, Tan-Van Vo, Tram-Ngoc Bui, Uyen-Thi To Hoang, Hien-Thi Bich Nguyen, Ha-Thi Thu Nguyen, Nga-Thuy Lam, Khanh-Kim Le, Phuong-Thanh Trinh, Hop-Quang Huynh, Thao-Thi Thu Nguyen, Huyen-Ngoc Lu, Tham-Hong Pham, Sam-Hoanh Nguyen, Ninh-Hong Le, Giang-Truong Nguyen, Bich-Thi Doan, Sung-Phuoc Pham, Duong-Huu Luong, Ha-Van Mai, Thuc-Van Tran, Phuong-Thi Do, Hoai-Thi Le, Chi-Van Nguyen, Phuong-Doan Nguyen
Abstract
Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921.