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
Authors: Hankey Graeme J. , Hackett Maree L. , Almeida Osvaldo P. , Flicker Leon , Mead Gillian E. , Dennis Martin S. , Etherton-Beer Christopher , Ford Andrew H. , Billot Laurent , Jan Stephen , Lung Thomas , Lundström Erik , Sunnerhagen Katharina S. , Anderson Craig S. , Thang-Nguyen Huy , Gommans John , Yi Qilong , Murray Veronica , Herbert Robert , Carter Gregory , Donnan Geoffrey A. , Nguyen Huy-Thang , Li Qiang , Bompoint Severine , Barrett Sarah , Claxton Anne , O’Dea Julia , Tang Michelle , Williams Clare , Peterson Shenae , Drummond Christie , Hong Uyen-Ha , My Le Linh-Thi , Bich Ngo Tram-Thi , Mai Yen-Bao , Han Huyen-Thanh , Truong Nhu-Quynh , Nguyen Huong-Thi , Ngo Hai-Thanh , Nguyen Thi Binh , Kieu Ha Oanh-Thi , Huyen Nguyen Trang-Le , Lindley Richard I. , New Peter , Lee Andrew , Tran Thanh-Trung , Truc Mai Le Loan-Tran , Vu Kieu Thuy-Le , Nguyen Sang-Van , Diem Nguyen Thuy-Anh , Dang Tam-Nhat , Truc Phan Hanh-Thi , Ngoc Vo Loan-Thi , Nguyen Mai-Hue , Dang Hanh-Cao , Tran Hong-Thi , Cam Dam Linh-Thi , Kim Ngo Trinh-Thi , Thanh Pham Thai-Nguyen , Pham Binh-Nguyen , Thanh Dao Nha-Thi , Bich Nguyen Huong-Thi , Cam Le Linh-Thi , Do Chi-Minh , Huynh Huy-Quoc , Tran Giau-Thi Kim , Le Oanh-Thi , Khanh Tran Ly-Thi , Duong Chinh-Dinh , Kieu Duong-Van , Le Na , Nguyen Hoa-Ngoc , Le Binh-Van , Nguyen Long-Thanh , Nguyen Long-Van , Dinh Tuan-Quoc , Vo Tan-Van , Bui Tram-Ngoc , To Hoang Uyen-Thi , Bich Nguyen Hien-Thi , Thu Nguyen Ha-Thi , Lam Nga-Thuy , Le Khanh-Kim , Trinh Phuong-Thanh , Huynh Hop-Quang , Thu Nguyen Thao-Thi , Lu Huyen-Ngoc , Pham Tham-Hong , Nguyen Sam-Hoanh , Le Ninh-Hong , Nguyen Giang-Truong , Doan Bich-Thi , Pham Sung-Phuoc , Luong Duong-Huu , Mai Ha-Van , Tran Thuc-Van , Do Phuong-Thi , Le Hoai-Thi , Nguyen Chi-Van , Nguyen Phuong-Doan , Mai Ton-Duy , Dao Phuong-Viet , Nguyen Dung-Tien , Khuong Dai-Quoc , Vuong Trung-Xuan , Vu Lan-Tuong , Ngo Ngoc-Duc , Dang Hanh-Hong , Truong Phuong-Thai , Le Ngan-Thi , Hoang Hoa-Van , Do Chung-Quang , Nguyen Minh-Thao , Dam Anh-Hai , Le Quynh-Nhu , Nguyen Ngoc-Hoang , Nguyen Tuyen-Van , Le Toan-Dinh , Hai Dinh Ha-Thi , Pham Cuong–Van , Ngoc Thach Khanh-Thi , Nguyen Linh-Hai , Nguyen Loan-Thi , Le Vien-Chi , Tran Phuong-Hong , Nguyen Tai-Anh , Le Tuan-Van , Truong Luyen-Van , Bui Tue-Chau , Huynh Ngoc-Xuan , Dinh Lap-Van , Pham An-Gia , Huyen Le Trang-Thi , Nguyen Vy-Tuong , Nguyen Yen-Hai , Nguyen Thang-Ba , Thai Huy , Ngoc Pham Quyen-Thi , Dao Khoa-Duy , Bao Pham Quoc-Nguyen , Huyen Dang Thuong-Thi , To Dinh Huong-Huynh , Tong Trang-Mai , Vu Thuy-Thi , Le Si-Tri , Tran Tai-Ngoc , Tran Phuong-Hoai , Nhu Dinh Ngoc-Thuy , Nguyen Binh-Thanh , Do Vinh-Phuong , Nguyen Anh-Ngoc , Thanh Nguyen Binh-Thi , Nguyen Binh-Thanh , Blacker David , Bunce Lindsey , Tan Ai Ling , Ghia Darshan , Edmonds Gillian , O’Loughlin Nicole , Ewing Megan , Whittaker Kerri-Ann , Deane Lorralee , Gawarikar Yash , Jones Brett , Lopez Maria , Nagesh Koushik , Siracusa Emma , Davis Stephen , McDonald Amy , Tsoleridis Jess , McCoy Rachael , Jackson David , Silver Gab , Bates Timothy R. , Boudville Amanda , Southwell Lynda , Cordato Dennis , McDougall Alan J. , Cappelen-Smith Cecilia , Calic Zeljka , Askar Shabeel , Cheng Qi , Kumar Raymond , Geraghty Richard , Duroux Maree , Ratcliffe Megan , Shone Samantha , McLennan Cassandra , Sahathevan Ramesh , Hair Casey , Levy Stanley , Macdonald Beverley , Nham Benjamin , Rigney Louise , Nathani Dev , Gopinath Sumana , Patel Vishal , Mamun Abul , Trewin Benjamin , Phua Chun , Choong Ho , Tarrant Lauren , Boyle Kerry , Hewitt Luisa , Hourn Monique , Masterson Amanda , Oakley Kim , Ruddell Karen , Sanctuary Colette , Veitch Kimberley , Burdusel Camelia , Lee Lina , Cheuk Gary , Christley Jeremy , Hartwell Tabitha , Davenport Craig , Hickey Kate , Robertson Rosanna , Carr Michelle , Akbari Sam , Coyle Hannah , O’Neill Megan , Redpath Cameron , Roberts Caroline , Tabesh Marjan , Withiel Toni , Abeysuriya Kapila , Granger Andrew , Abraham Angela , Chua Chermaine , Nguyen Dung Do , Surendran Vathani , Daines Melissa , Shivlal David , Latif Mudassar , Mughal Noreen , Morgan Patricia , Krause Martin , Priglinger Miriam , Shandiz Ehsan E. , Day Susan , Kho Lay , Pollack Michael , Dunne Judith , Baines Helen , Rees Merridie , White Jenni , Hourn Monique , Veitch Kimberley , Withanage Aicuratiya , Sanctuary Colette , Delcourt Candice , Carcel Cheryl , Malavera Alejandra , Kunchok Amy , Ray Elizabeth , Pepper Elizabeth , Duckett Emily , White Jenni , Veitch Kimberley , Hewitt Luisa , Hourn Monique , Boyle Kerry , Ormond Sally , Sanctuary Colette , Moey Andrew , Kleinig Timothy , Maxwell Vanessa , Baldwin Chantal , Vallat Wilson , Field Deborah , Markus Romesh , Page Kirsty , Wheelwright Danielle , Bolitho Sam , Faux Steven , Sangvatanakul Fix , Brown Alexis , Walker Susan , Massey Jennifer , Pollack Michael , White Jenni , Veitch Kimberley , Hayes Hillary , Hewitt Luisa , Hourn Monique , Sanctuary Colette , Katrak Pesi , Winker Annie , Zagami Alessandro , Bailey Alanah , Mccormack Sarah , Murray Andrew , Rollason Mark , Taylor Christopher , O’Rourke Fintan , Kuang Ye Min , Burnet Heike , Liu Yvonne , Cheng Qi , Wu Aileen , Akbari Sam , Coyle Hannah , O’Neill Megan , Ramirez Diana , Wijeratne Tissa , Celestino Sherisse , Low Essie , Chen Cynthia , Bergqvist Jennifer , Evans Andrew , Leung Queenie , Jude Martin , McQueen Rachael , Mohr Katherine , Kernaghan Latitia , Stockle Paul , Tan Boon L. , Laubscher Sara , Schmid Diana , Spooner Melissa , Lallu Bhavesh , Pepperell Bronwen , Chalissery John , Mahawish Karim , DeCaigney Susan , Broughton Paula , Knight Karen , Duque Veronica , McNaughton Harry , Lanford Jeremy , Fu Vivian , Wong Lai-Kin 
Published: May 2021

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.