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Randomized Controlled Trial
. 2016 Jan 25;11(1):e0147635.
doi: 10.1371/journal.pone.0147635. eCollection 2016.

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

Sadanori Okada  1   2 , Takeshi Morimoto  3 , Hisao Ogawa  4 , Mio Sakuma  3 , Hirofumi Soejima  4 , Masafumi Nakayama  4 , Hideaki Jinnouchi  5 , Masako Waki  6 , Yasuhiro Akai  1 , Hitoshi Ishii  1 , Yoshihiko Saito  2   7 ; Investigators for the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes trial
Affiliations
Randomized Controlled Trial

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

Sadanori Okada et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: Dr. TM reports receiving research grants from Bayer HealthCare and lecturer’s fees from Daiichi-Sankyo, Eisai, Kowa Pharmaceutical, Kyorin Pharmaceutical, and Pfizer Japan for the past three years. Dr. HO reports receiving research grants from AstraZeneca Pharmaceutical, Astellas Pharma, Bayer HealthCare, Boehringer Ingelheim Pharmaceutical, Bristol-Myers, Chugai Pharmaceutical, Daiichi Sankyo, Sumitomo Dainippon Pharma, Kowa Pharmaceutical, MSD, Novartis, Otsuka Pharmaceutical, Pfizer Japan, Sanofi, and Takeda Pharmaceutical and lecturer’s fees from AstraZeneca Pharmaceutical, Bayer HealthCare, Daiichi-Sankyo, MSD, Pfizer Japan, Sanofi, and Taisho Pharmaceutical for the past three years. Dr. HI reports receiving research grant support from Novo Nordisk and Mitsubishi Tanabe Pharma and lecturer’s fees from AstraZeneca Pharmaceutical, Eli Lilly Japan, Sanofi, Daiichi Sankyo, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Novartis Pharma, Novo Nordisk, Boehringer Ingelheim Pharmaceutical, and MSD. Dr. YS reports receiving research grant support from Ono Pharmaceutical, MSD, Mitsubishi Tanabe Pharma, Daiichi Sankyo, Takeda Pharmaceutical, Novartis Pharma, Shionogi, Astellas Pharma, Otsuka Pharmaceutical, St. Jude Medical Japan, and Kyowa Hakko Kirin; lecturer’s fees from MSD, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Daiichi Sankyo, Otsuka Pharmaceutical, and Pfizer Japan; and consulting fees from Ono Pharmaceutical for the past three years. The rest of the authors have declared that no competing interests exist. Our competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials

Figures

Fig 1
Fig 1. Timeline of the JPAD2 cohort study.
A, The timeline of the JPAD trial and the JPAD2 cohort study. RCT indicates randomized controlled trial. B, The flow chart of the JPAD trial and the JPAD2 cohort study.
Fig 2
Fig 2. Incidence of positive urine dipstick albumin in patients on long-term low-dose aspirin therapy in the intention-to-treat analysis.
Positive urine dipstick albumin developed in 297 patients in the aspirin group and 270 patients in the no aspirin group. The intention-to-treat analysis showed that low-dose aspirin did not increase the incidence of positive urine dipstick albumin (HR, 1.17; 95% CI, 0.995 to 1.38; log-rank P = 0.057)
Fig 3
Fig 3. Incidence of positive urine dipstick albumin in patients on long-term low-dose aspirin therapy in the on-treatment analysis.
In the on-treatment analysis, low-dose aspirin had no effect on the incidence of positive urine dipstick albumin (HR, 1.08; 95% CI, 0.92 to 1.28; log-rank P = 0.32).
See this image and copyright information in PMC

References

    1. Antithrombotic Trialists C, Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–60. 10.1016/S0140-6736(09)60503-1 - DOI - PMC - PubMed
    1. Suleyman H, Demircan B, Karagoz Y. Anti-inflammatory and side effects of cyclooxygenase inhibitors. Pharmacol Rep. 2007;59(3):247–58. - PubMed
    1. Morlans M, Laporte JR, Vidal X, Cabeza D, Stolley PD. End-stage renal disease and non-narcotic analgesics: a case-control study. British journal of clinical pharmacology. 1990;30(5):717–23. - PMC - PubMed
    1. Fored CM, Ejerblad E, Lindblad P, Fryzek JP, Dickman PW, Signorello LB, et al. Acetaminophen, aspirin, and chronic renal failure. The New England journal of medicine. 2001;345(25):1801–8. - PubMed
    1. Ibanez L, Morlans M, Vidal X, Martinez MJ, Laporte JR. Case-control study of regular analgesic and nonsteroidal anti-inflammatory use and end-stage renal disease. Kidney international. 2005;67(6):2393–8. - PubMed

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