Yoshihiko Saito1, Sadanori Okada2, Hisao Ogawa2, Hirofumi Soejima2, Mio Sakuma2, Masafumi Nakayama2, Naofumi Doi2, Hideaki Jinnouchi2, Masako Waki2, Izuru Masuda2, Takeshi Morimoto2. 1. From First Department of Internal Medicine (Y.S., S.O.) and Department of Diabetology (S.O.), Nara Medical University, Kashihara, Japan; National Cerebral and Cardiovascular Center, Suita, Osaka, Japan (H.O.); Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Cyuo-ku, Japan (H.S.); Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan (M.S., T.M.); Nakayama Cardiovascular Clinic, Amakusa, Kumamoto, Japan (M.N.); Department of Cardiology, Nara Prefecture Western Medical Center, Sango-cho, Ikoma-gun, Japan (N.D.); Diabetes Center, Jinnouchi Hospital, Chuo-ku, Kumamoto, Japan (H.J.); Department of Internal Medicine, Shizuoka City Hospital, Japan (M.W.); and Medical Examination Center, Takeda Hospital, Shimogyo- ku, Kyoto, Japan (I.M.). yssaito@naramed-u.ac.jp. 2. From First Department of Internal Medicine (Y.S., S.O.) and Department of Diabetology (S.O.), Nara Medical University, Kashihara, Japan; National Cerebral and Cardiovascular Center, Suita, Osaka, Japan (H.O.); Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Cyuo-ku, Japan (H.S.); Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan (M.S., T.M.); Nakayama Cardiovascular Clinic, Amakusa, Kumamoto, Japan (M.N.); Department of Cardiology, Nara Prefecture Western Medical Center, Sango-cho, Ikoma-gun, Japan (N.D.); Diabetes Center, Jinnouchi Hospital, Chuo-ku, Kumamoto, Japan (H.J.); Department of Internal Medicine, Shizuoka City Hospital, Japan (M.W.); and Medical Examination Center, Takeda Hospital, Shimogyo- ku, Kyoto, Japan (I.M.).
Abstract
BACKGROUND: The long-term efficacy and safety of low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus are still inconclusive. METHODS: The JPAD trial (Japanese Primary Prevention of Atherosclerosis With Aspirinfor Diabetes) was a randomized, open-label, standard care-controlled trial examining whether low-dose aspirin affected cardiovascular events in 2539 Japanese patients with type 2 diabetes mellitus and without preexisting cardiovascular disease. Patients were randomly allocated to receive aspirin (81 or 100 mg daily; aspirin group) or no aspirin (no-aspirin group) in the JPAD trial. After that trial ended in 2008, we followed up with the patients until 2015, with no attempt to change the previously assigned therapy. Primary end points were cardiovascular events, including sudden death, fatal or nonfatal coronary artery disease, fatal or nonfatal stroke, and peripheral vascular disease. For the safety analysis, hemorrhagic events, consisting of gastrointestinal bleeding, hemorrhagic stroke, and bleeding from any other sites, were also analyzed. The primary analysis was conducted for cardiovascular events among patients who retained their original allocation (a per-protocol cohort). Analyses on an intention-to-treat cohort were conducted for hemorrhagic events and statistical sensitivity. RESULTS: The median follow-up period was 10.3 years; 1621 patients (64%) were followed up throughout the study; and 2160 patients (85%) retained their original allocation. Low-dose aspirin did not reduce cardiovascular events in the per-protocol cohort (hazard ratio, 1.14; 95% confidence interval, 0.91-1.42). Multivariable Cox proportional hazard model adjusted for age, sex, glycemic control, kidney function, smoking status, hypertension, and dyslipidemia showed similar results (hazard ratio, 1.04; 95% confidence interval, 0.83-1.30), with no heterogeneity of efficacy in subgroup analyses stratified by each of these factors (all interaction P>0.05). Sensitivity analyses on the intention-to-treat cohort yielded consistent results (hazard ratio, 1.01; 95% confidence interval, 0.82-1.25). Gastrointestinal bleeding occurred in 25 patients (2%) in the aspirin group and 12 (0.9%) in the no-aspirin group (P=0.03), and the incidence of hemorrhagic stroke was not different between groups. CONCLUSIONS:Low-dose aspirin did not affect the risk for cardiovascular events but increased risk for gastrointestinal bleeding in patients with type 2 diabetes mellitus in a primary prevention setting. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00110448.
RCT Entities:
BACKGROUND: The long-term efficacy and safety of low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus are still inconclusive. METHODS: The JPAD trial (Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes) was a randomized, open-label, standard care-controlled trial examining whether low-dose aspirin affected cardiovascular events in 2539 Japanese patients with type 2 diabetes mellitus and without preexisting cardiovascular disease. Patients were randomly allocated to receive aspirin (81 or 100 mg daily; aspirin group) or no aspirin (no-aspirin group) in the JPAD trial. After that trial ended in 2008, we followed up with the patients until 2015, with no attempt to change the previously assigned therapy. Primary end points were cardiovascular events, including sudden death, fatal or nonfatal coronary artery disease, fatal or nonfatal stroke, and peripheral vascular disease. For the safety analysis, hemorrhagic events, consisting of gastrointestinal bleeding, hemorrhagic stroke, and bleeding from any other sites, were also analyzed. The primary analysis was conducted for cardiovascular events among patients who retained their original allocation (a per-protocol cohort). Analyses on an intention-to-treat cohort were conducted for hemorrhagic events and statistical sensitivity. RESULTS: The median follow-up period was 10.3 years; 1621 patients (64%) were followed up throughout the study; and 2160 patients (85%) retained their original allocation. Low-dose aspirin did not reduce cardiovascular events in the per-protocol cohort (hazard ratio, 1.14; 95% confidence interval, 0.91-1.42). Multivariable Cox proportional hazard model adjusted for age, sex, glycemic control, kidney function, smoking status, hypertension, and dyslipidemia showed similar results (hazard ratio, 1.04; 95% confidence interval, 0.83-1.30), with no heterogeneity of efficacy in subgroup analyses stratified by each of these factors (all interaction P>0.05). Sensitivity analyses on the intention-to-treat cohort yielded consistent results (hazard ratio, 1.01; 95% confidence interval, 0.82-1.25). Gastrointestinal bleeding occurred in 25 patients (2%) in the aspirin group and 12 (0.9%) in the no-aspirin group (P=0.03), and the incidence of hemorrhagic stroke was not different between groups. CONCLUSIONS: Low-dose aspirin did not affect the risk for cardiovascular events but increased risk for gastrointestinal bleeding in patients with type 2 diabetes mellitus in a primary prevention setting. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00110448.
Authors: Mohammed E Al-Sofiani; Lisa R Yanek; Nauder Faraday; Brian G Kral; Rasika Mathias; Lewis C Becker; Diane M Becker; Dhananjay Vaidya; Rita R Kalyani Journal: J Clin Endocrinol Metab Date: 2018-12-01 Impact factor: 5.958
Authors: Safi U Khan; Zain Ul Abideen Asad; Muhammad U Khan; Swapna Talluri; Farman Ali; Muhammad Shahzeb Khan; Ahmad N Lone; Farouk Mookadam; Richard A Krasuski; Edo Kaluski Journal: Eur J Prev Cardiol Date: 2019-01-30 Impact factor: 7.804