Is Long-Term Low-Dose Aspirin Therapy Associated with Renal Dysfunction in Patients with Type 2 Diabetes? JPAD2 Cohort Study

Sadanori Okada; Takeshi Morimoto; Hisao Ogawa; Mio Sakuma; Hirofumi Soejima; Masafumi Nakayama; Hideaki Jinnouchi; Masako Waki; Yasuhiro Akai; Hitoshi Ishii; Yoshihiko Saito; Investigators for the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes trial

doi:10.1371/journal.pone.0147635

Is Long-Term Low-Dose Aspirin Therapy Associated with Renal Dysfunction in Patients with Type 2 Diabetes? JPAD2 Cohort Study

PLoS One. 2016 Jan 25;11(1):e0147635. doi: 10.1371/journal.pone.0147635. eCollection 2016.

Affiliations

¹ Department of Diabetology, Nara Medical University, Kashihara, Nara, Japan.
² First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
³ Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
⁴ Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
⁵ Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan.
⁶ Division of Endocrinology and Metabolism, Department of Internal Medicine, Shizuoka City Hospital, Shizuoka, Japan.
⁷ Department of Regulatory Medicine of Blood Pressure, Nara Medical University, Kashihara, Nara, Japan.

Abstract

Background: Low-dose aspirin is widely recommended for patients at high risk for cardiovascular disease (CVD); however, it remains uncertain whether long-term treatment adversely affects renal function in patients with diabetes. We investigated whether long-term low-dose aspirin affects renal dysfunction in patients with diabetes.

Methods: We conducted a randomized controlled trial (RCT), the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, to evaluate low-dose aspirin as primary prevention for CVD in patients with type 2 diabetes. We followed the patients with negative urine dipstick albumin of the JPAD trial in a cohort study after the RCT period was completed. Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily, aspirin group) or no aspirin (no aspirin group). After the RCT, the treating physician decided whether to administer aspirin. We evaluated the incidence of positive urine dipstick albumin and annual changes in estimated glomerular filtration rate (eGFR).

Results: Positive urine dipstick albumin developed in 297 patients in the aspirin group (n = 1,075) and 270 patients in the no aspirin group (n = 1,098) during follow-up (median, 8.5 years). Intention-to-treat analysis showed low-dose aspirin did not increase the incidence of positive urine dipstick albumin (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.995-1.38). On-treatment analysis yielded similar results (HR, 1.08; 95% CI, 0.92-1.28). Multivariable analysis showed the incidence of positive urine dipstick albumin was higher among the elderly and those with elevated serum creatinine, high hemoglobin A1c, or high blood pressure; however, low-dose aspirin did not increase the risk of positive urine dipstick albumin. There were no significant differences in annual changes in eGFR between the groups (aspirin, -0.8 ± 2.9; no aspirin, -0.9 ± 2.5 ml/min/1.73 m(2)/year).

Conclusion: Long-term low-dose aspirin does not affect eGFR and positive urine dipstick albumin in patients with type 2 diabetes.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aspirin / administration & dosage*
Aspirin / adverse effects
Cohort Studies
Diabetes Mellitus, Type 2 / physiopathology*
Dose-Response Relationship, Drug
Female
Glomerular Filtration Rate
Humans
Kidney / drug effects*
Kidney / physiopathology
Male
Middle Aged

Substances

Aspirin

Grants and funding

This study was supported by the Ministry of Health, Labour and Welfare of Japan (HO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.