Skip to main content
Top
Published in: Diabetology & Metabolic Syndrome 1/2015

Open Access 01-12-2015 | Research

Evaluation of low-dose aspirin for primary prevention of ischemic stroke among patients with diabetes: a retrospective cohort study

Authors: Ye-Jee Kim, Nam-Kyong Choi, Mi-Sook Kim, Joongyub Lee, Yoosoo Chang, Jong-Mi Seong, Sun-Young Jung, Ju-Young Shin, Ji-Eun Park, Byung-Joo Park

Published in: Diabetology & Metabolic Syndrome | Issue 1/2015

Login to get access

Abstract

Background

Low-dose aspirin is recommended to reduce the risk of cardiovascular disease. However, the questions with regard to primary prevention have been raised among patients with diabetes. We evaluated low-dose aspirin use for preventing ischemic stroke in patients with diabetes using a national health insurance database.

Methods

Using data from the Korean Health Insurance Review and Assessment Service database from January 1, 2005, through December 31, 2009, a population-based retrospective cohort study was conducted with incident patients with diabetes aged 40 to 99 years old with the initial use of low-dose aspirin during the index period from January 1, 2006 to December 31, 2007. We matched each low-dose aspirin user to one non-user using a propensity score. The Cox proportional hazards model was used to compare the risk of hospitalization for ischemic stroke in users and nonusers of low-dose aspirin until December 31, 2009.

Results

Out of 261,065 incident patients with diabetes, 15,849 (6.2%) were low-dose aspirin users. Compared to non-users, the adjusted hazard ratio (95% confidence interval) of low-dose aspirin users for hospitalization due to ischemic stroke was 1.73 (95% CI; 1.41-2.12). In a sensitivity analysis of study subjects with more than 1 year follow-up periods, slightly higher adjusted hazard ratio (1.97, 95% CI; 1.51-2.62) was observed. In the subgroup analyses, there were no significant changes in the risk of hospitalization for ischemic stroke irrespective of gender, age, or comorbidity.

Conclusions

In this study of patients with diabetes, the use of low-dose aspirin showed an increased risk of hospitalization for ischemic stroke. These results suggest that low-dose aspirin use for the primary prevention of ischemic stroke should be reconsidered in patients with diabetes.
Literature
1.
go back to reference Preventive US. Services Task Force: Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150(6):396–404.CrossRef Preventive US. Services Task Force: Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150(6):396–404.CrossRef
2.
go back to reference Sacco M, Pellegrini F, Roncaglioni MC, Avanzini F, Tognoni G, Nicolucci A. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Diabetes Care. 2003;26(12):3264–72.CrossRefPubMed Sacco M, Pellegrini F, Roncaglioni MC, Avanzini F, Tognoni G, Nicolucci A. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Diabetes Care. 2003;26(12):3264–72.CrossRefPubMed
3.
go back to reference Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, et al. Prevention of Progression of Arterial Disease and Diabetes Study Group; Diabetes Registry Group; Royal College of Physicians Edinburgh: The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. Brit Med J. 2008;337:a1840.CrossRefPubMedCentralPubMed Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, et al. Prevention of Progression of Arterial Disease and Diabetes Study Group; Diabetes Registry Group; Royal College of Physicians Edinburgh: The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. Brit Med J. 2008;337:a1840.CrossRefPubMedCentralPubMed
4.
go back to reference Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300(18):2134–41.CrossRefPubMed Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300(18):2134–41.CrossRefPubMed
5.
go back to reference Antithrombotic Trialists’ (ATT) Collaboration, 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.CrossRef Antithrombotic Trialists’ (ATT) Collaboration, 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.CrossRef
6.
go back to reference De Berardis G, Sacco M, Strippoli GFM, Pellegrini F, Graziano G, Tognoni G, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials. Brit Med J. 2009;339:b4531.CrossRefPubMedCentralPubMed De Berardis G, Sacco M, Strippoli GFM, Pellegrini F, Graziano G, Tognoni G, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials. Brit Med J. 2009;339:b4531.CrossRefPubMedCentralPubMed
7.
go back to reference American Diabetes Association. Standards of Medical Care in Diabetes-2012. Diabetes Care. 2012;35(1):S11–63. American Diabetes Association. Standards of Medical Care in Diabetes-2012. Diabetes Care. 2012;35(1):S11–63.
8.
go back to reference Kim J, Kim H, Kim H, Min JW, Park SW, Park IB, et al. Current status of the continuity of ambulatory diabetes care and its impact on health outcomes and medical cost in Korea using National Health Insurance database. J Korean Diabetes Assoc. 2006;30(5):377–87.CrossRef Kim J, Kim H, Kim H, Min JW, Park SW, Park IB, et al. Current status of the continuity of ambulatory diabetes care and its impact on health outcomes and medical cost in Korea using National Health Insurance database. J Korean Diabetes Assoc. 2006;30(5):377–87.CrossRef
9.
go back to reference Kwon S. Thirty years of national health insurance in South Korea: lessons for achieving universal health care coverage. Health Policy Plan. 2009;24(1):63–71.CrossRefPubMed Kwon S. Thirty years of national health insurance in South Korea: lessons for achieving universal health care coverage. Health Policy Plan. 2009;24(1):63–71.CrossRefPubMed
10.
go back to reference Seeger JD, Walker AM, Williams PL, Saperia GM, Sacks FM. A propensity score-matched cohort study of the effect of statins, mainly fluvastatin, on the occurrence of acute myocardial infarction. Am J Cardiol. 2003;92(12):1447–51.CrossRefPubMed Seeger JD, Walker AM, Williams PL, Saperia GM, Sacks FM. A propensity score-matched cohort study of the effect of statins, mainly fluvastatin, on the occurrence of acute myocardial infarction. Am J Cardiol. 2003;92(12):1447–51.CrossRefPubMed
11.
go back to reference Sikka R, Xia F, Aubert RE. Estimating medication persistency using administrative claims data. Am J Manag Care. 2005;11(7):449–57.PubMed Sikka R, Xia F, Aubert RE. Estimating medication persistency using administrative claims data. Am J Manag Care. 2005;11(7):449–57.PubMed
12.
go back to reference D’Agostino Jr RB. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17(19):2265–81.CrossRefPubMed D’Agostino Jr RB. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17(19):2265–81.CrossRefPubMed
14.
go back to reference Austin PC. A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003. Stat Med. 2008;27(12):2037–49.CrossRefPubMed Austin PC. A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003. Stat Med. 2008;27(12):2037–49.CrossRefPubMed
15.
go back to reference Watala C, Golanski J, Pluta J, Boncler M, Rozalski M, Luzak B, et al. Reduced sensitivity of platelets from type 2 diabetic patients to acetylsalicylic acid (aspirin)-its relation to metabolic control. Thromb Res. 2004;113:101–13.CrossRefPubMed Watala C, Golanski J, Pluta J, Boncler M, Rozalski M, Luzak B, et al. Reduced sensitivity of platelets from type 2 diabetic patients to acetylsalicylic acid (aspirin)-its relation to metabolic control. Thromb Res. 2004;113:101–13.CrossRefPubMed
16.
go back to reference Takahashi S, Ushida M, Komine R, Shimizu A, Uchida T, Ishihara H, et al. Increased basal platelet activity, plasma adiponectin levels, and diabetes mellitus are associated with poor platelet responsiveness to in vitro effect of aspirin. Thromb Res. 2007;119:517–24.CrossRefPubMed Takahashi S, Ushida M, Komine R, Shimizu A, Uchida T, Ishihara H, et al. Increased basal platelet activity, plasma adiponectin levels, and diabetes mellitus are associated with poor platelet responsiveness to in vitro effect of aspirin. Thromb Res. 2007;119:517–24.CrossRefPubMed
17.
go back to reference Ajjan R, Storey RF, Grant PJ. Aspirin resistance and diabetes mellitus. Diabetologia. 2008;51(3):385–90.CrossRefPubMed Ajjan R, Storey RF, Grant PJ. Aspirin resistance and diabetes mellitus. Diabetologia. 2008;51(3):385–90.CrossRefPubMed
18.
go back to reference Pulcinelli FM, Biasucci LM, Riondino S, Giubilato S, Leo A, Di Renzo L, et al. COX-1 sensitivity and thromboxane A2 production in type 1 and type 2 diabetic patients under chronic aspirin treatment. Eur Heart J. 2009;30:1279–86.CrossRefPubMed Pulcinelli FM, Biasucci LM, Riondino S, Giubilato S, Leo A, Di Renzo L, et al. COX-1 sensitivity and thromboxane A2 production in type 1 and type 2 diabetic patients under chronic aspirin treatment. Eur Heart J. 2009;30:1279–86.CrossRefPubMed
19.
go back to reference De Berardis G, Lucisano G, D’Ettorre A, Pellegrini F, Lepore V, Tognoni G, et al. Association of Aspirin Use With Major Bleeding in Patients With and Without Diabetes. JAMA. 2012;307(21):2286–94.CrossRefPubMed De Berardis G, Lucisano G, D’Ettorre A, Pellegrini F, Lepore V, Tognoni G, et al. Association of Aspirin Use With Major Bleeding in Patients With and Without Diabetes. JAMA. 2012;307(21):2286–94.CrossRefPubMed
20.
go back to reference Investigators ETDRS. Aspirin effects on mortality and morbidity in patients with diabetes mellitus. Early Treatment Diabetic Retinopathy Study report 14. ETDRS Investigators. JAMA. 1992;268(10):1292–300.CrossRef Investigators ETDRS. Aspirin effects on mortality and morbidity in patients with diabetes mellitus. Early Treatment Diabetic Retinopathy Study report 14. ETDRS Investigators. JAMA. 1992;268(10):1292–300.CrossRef
21.
go back to reference Henry P, Vermillet A, Boval B, Guyetand C, Petroni T, Dillinger JG, et al. 24-hour time-dependent aspirin efficacy in patients with stable coronary artery disease. Thromb Haemostasis. 2011;105(2):336–44.CrossRef Henry P, Vermillet A, Boval B, Guyetand C, Petroni T, Dillinger JG, et al. 24-hour time-dependent aspirin efficacy in patients with stable coronary artery disease. Thromb Haemostasis. 2011;105(2):336–44.CrossRef
22.
go back to reference Leung WY, So WY, Stewart D, Lui A, Tong PC, Ko GT, et al. Lack of benefits for prevention of cardiovascular disease with aspirin therapy in type 2 diabetic patients–a longitudinal observational study. Cardiovasc Diabetol. 2009;8:57.CrossRefPubMedCentralPubMed Leung WY, So WY, Stewart D, Lui A, Tong PC, Ko GT, et al. Lack of benefits for prevention of cardiovascular disease with aspirin therapy in type 2 diabetic patients–a longitudinal observational study. Cardiovasc Diabetol. 2009;8:57.CrossRefPubMedCentralPubMed
23.
go back to reference Welin L, Wilhelmsen L, Bjornberg A, Oden A. Aspirin increases mortality in diabetic patients without cardiovascular disease: a Swedish record linkage study. Pharmacoepidemiol Drug Saf. 2009;18(12):1143–9.CrossRefPubMed Welin L, Wilhelmsen L, Bjornberg A, Oden A. Aspirin increases mortality in diabetic patients without cardiovascular disease: a Swedish record linkage study. Pharmacoepidemiol Drug Saf. 2009;18(12):1143–9.CrossRefPubMed
24.
go back to reference Sasso FC, Marfella R, Pagano A, Porta G, Signoriello G, Lascar N, et al. Lack of effect of aspirin in primary CV prevention in type 2 diabetic patients with nephropathy: results from 8 years follow-up of NID-2 study. Acta Diabetol 2014 Aug 11. [Epub ahead of print] Sasso FC, Marfella R, Pagano A, Porta G, Signoriello G, Lascar N, et al. Lack of effect of aspirin in primary CV prevention in type 2 diabetic patients with nephropathy: results from 8 years follow-up of NID-2 study. Acta Diabetol 2014 Aug 11. [Epub ahead of print]
25.
go back to reference Ong G, Davis TME, Davis WA. Aspirin Is Associated With Reduced Cardiovascular and All-Cause Mortality in Type 2 Diabetes in a Primary Prevention Setting - The Fremantle Diabetes Study. Diabetes Care. 2010;33(2):317–21.CrossRefPubMedCentralPubMed Ong G, Davis TME, Davis WA. Aspirin Is Associated With Reduced Cardiovascular and All-Cause Mortality in Type 2 Diabetes in a Primary Prevention Setting - The Fremantle Diabetes Study. Diabetes Care. 2010;33(2):317–21.CrossRefPubMedCentralPubMed
26.
go back to reference Psaty BM, Siscovick DS. Minimizing bias due to confounding by indication in comparative effectiveness research: the importance of restriction. JAMA. 2010;304:897–8.CrossRefPubMed Psaty BM, Siscovick DS. Minimizing bias due to confounding by indication in comparative effectiveness research: the importance of restriction. JAMA. 2010;304:897–8.CrossRefPubMed
27.
go back to reference Park BJ, Sung JH, Park KD, Seo SW, Kim SW. Report of the evaluation for validity of discharged diagnoses in Korean Health Insurance database. Seoul: Seoul National University; 2003. Park BJ, Sung JH, Park KD, Seo SW, Kim SW. Report of the evaluation for validity of discharged diagnoses in Korean Health Insurance database. Seoul: Seoul National University; 2003.
28.
go back to reference Kim JY. Strategies to enhance the use of National Health Insurance Claims Database in generating health statistics. Seoul: Health Insurance Review and Assessment Services; 2005. Kim JY. Strategies to enhance the use of National Health Insurance Claims Database in generating health statistics. Seoul: Health Insurance Review and Assessment Services; 2005.
29.
go back to reference Task Force Team for Basic Statistical Study of Korean Diabetes Mellitus of Korean Diabetes Association, Park IB, Kim J, Kim DJ, Chung CH, Oh JY, et al. Diabetes epidemics in Korea: reappraise nationwide survey of diabetes “diabetes in Korea 2007”. Diabetes Metab J. 2013;37(4):233–9.CrossRefPubMedCentral Task Force Team for Basic Statistical Study of Korean Diabetes Mellitus of Korean Diabetes Association, Park IB, Kim J, Kim DJ, Chung CH, Oh JY, et al. Diabetes epidemics in Korea: reappraise nationwide survey of diabetes “diabetes in Korea 2007”. Diabetes Metab J. 2013;37(4):233–9.CrossRefPubMedCentral
30.
go back to reference Park IB, Kim DJ, Kim J, Kim H, Kim H, Min KW, et al. Current status of aspirin user in Korean Diabetic Patients Using Korean Health Insurance Database. J Kor Diabetes Assoc. 2006;30(5):363–71.CrossRef Park IB, Kim DJ, Kim J, Kim H, Kim H, Min KW, et al. Current status of aspirin user in Korean Diabetic Patients Using Korean Health Insurance Database. J Kor Diabetes Assoc. 2006;30(5):363–71.CrossRef
31.
go back to reference American Diabetes Association. Standards of Medical Care in Diabetes-2015. 8. Cardiovascular Disease and Risk Management. Diabetes Care. 2015;38 Suppl 1:S49–57.CrossRef American Diabetes Association. Standards of Medical Care in Diabetes-2015. 8. Cardiovascular Disease and Risk Management. Diabetes Care. 2015;38 Suppl 1:S49–57.CrossRef
32.
go back to reference De Berardis G, Sacco M, Evangelista V, Filippi A, Giorda CB, Tognoni G, et al. Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D): design of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins. Trials. 2007;8:21.CrossRefPubMedCentralPubMed De Berardis G, Sacco M, Evangelista V, Filippi A, Giorda CB, Tognoni G, et al. Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D): design of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins. Trials. 2007;8:21.CrossRefPubMedCentralPubMed
Metadata
Title
Evaluation of low-dose aspirin for primary prevention of ischemic stroke among patients with diabetes: a retrospective cohort study
Authors
Ye-Jee Kim
Nam-Kyong Choi
Mi-Sook Kim
Joongyub Lee
Yoosoo Chang
Jong-Mi Seong
Sun-Young Jung
Ju-Young Shin
Ji-Eun Park
Byung-Joo Park
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2015
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-015-0002-y

Other articles of this Issue 1/2015

Diabetology & Metabolic Syndrome 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.