Aspirin for primary prevention of cardiovascular disease in diabetes mellitus

Pignone, Michael; Williams, Craig D.

doi:10.1038/nrendo.2010.169

Cited by 45 publications

(25 citation statements)

References 68 publications

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“…However, a recent meta-analysis has not confirmed these findings [49]. Nevertheless, aspirin is effective for the prevention of cardiovascular events in patients with a history of vascular disease and it is reasonable to consider aspirin as one of the potential therapies for cardiovascular disease risk reduction in patients with DM and elevated cardiovascular disease risk [50].…”

Section: Discussionmentioning

confidence: 99%

Four-Year Incidence of Diabetic Retinopathy in a Spanish Cohort: The MADIABETES Study

et al. 2013

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ObjectiveTo evaluate the incidence of diabetic retinopathy in patients with Type 2 Diabetes Mellitus, to identify the risk factors associated with the incidence of retinopathy and to develop a risk table to predict four-year retinopathy risk stratification for clinical use, from a four-year cohort study.DesignThe MADIABETES Study is a prospective cohort study of 3,443 outpatients with Type 2 Diabetes Mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain).ResultsThe cumulative incidence of retinopathy at four-year follow-up was 8.07% (95% CI = 7.04–9.22) and the incidence density was 2.03 (95% CI = 1.75–2.33) cases per 1000 patient-months or 2.43 (95% CI = 2.10–2.80) cases per 100 patient-years. The highest adjusted hazard ratios of associated risk factors for incidence of diabetic retinopathy were LDL-C >190 mg/dl (HR = 7.91; 95% CI = 3.39–18.47), duration of diabetes longer than 22 years (HR = 2.00; 95% CI = 1.18–3.39), HbA1c>8% (HR = 1.90; 95% CI = 1.30–2.77), and aspirin use (HR = 1.65; 95% CI = 1.22–2.24). Microalbuminuria (HR = 1.17; 95% CI = 0.75–1.82) and being female (HR = 1.12; 95% CI = 0.84–1.49) showed a non-significant increase of diabetic retinopathy. The greatest risk is observed in females who had diabetes for more than 22 years, with microalbuminuria, HbA1c>8%, hypertension, LDL-Cholesterol >190 mg/dl and aspirin use.ConclusionsAfter a four-year follow-up, the cumulative incidence of retinopathy was relatively low in comparison with other studies. Higher baseline HbA1c, aspirin use, higher LDL-Cholesterol levels, and longer duration of diabetes were the only statistically significant risk factors found for diabetic retinopathy incidence. This is the first study to demonstrate an association between aspirin use and diabetic retinopathy risk in a well-defined cohort of patients with Type 2 Diabetes Mellitus at low risk of cardiovascular events. However, further studies with patients at high cardiovascular and metabolic risk are needed to clarify this issue.

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Section: Discussionmentioning

confidence: 99%

Four-Year Incidence of Diabetic Retinopathy in a Spanish Cohort: The MADIABETES Study

et al. 2013

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“…27 In patients with diabetes mellitus, however, the JPAD2 study could not demonstrate the benefit of aspirin for primary prevention. Meta-analyses in patients with diabetes mellitus have reported that aspirin has a smaller benefit for primary prevention than in general populations, 26,28,29 although patients with diabetes mellitus are at high risk for cardiovascular events. It seems that there are differential effects of low-dose aspirin therapy on preventing cardiovascular events in patients with and without diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus

et al. 2017

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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.

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“…7 Inhibition of platelet responsiveness with aspirin therapy reduces the relative risk of myocardial infarction and stroke by about 10%. 8 We demonstrated earlier that insulin inhibits aggregation/secretion by platelets and tissue factor synthesis by monocytes. In healthy individuals, insulin interferes with the suppression of cAMP and accumulation of this inhibitor attenuates platelet functions and monocyte responses.…”

Section: Introductionmentioning

confidence: 99%

Induction of insulin resistance by the adipokines resistin, leptin, plasminogen activator inhibitor-1 and retinol binding protein 4 in human megakaryocytes

Gerrits¹,

Gitz²,

Koekman³

et al. 2012

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundIn normal platelets, insulin inhibits agonist-induced Ca 2+ mobilization by raising cyclic AMP. Platelet from patients with type 2 diabetes are resistant to insulin and show increased Ca 2+ mobilization, aggregation and procoagulant activity. We searched for the cause of this insulin resistance. Design and MethodsPlatelets, the megakaryocytic cell line CHRF-288-11 and primary megakaryocytes were incubated with adipokines and with plasma from individuals with a disturbed adipokine profile. Thrombininduced Ca 2+ mobilization and signaling through the insulin receptor and insulin receptor substrate 1 were measured. Abnormalities induced by adipokines were compared with abnormalities found in platelets from patients with type 2 diabetes. ResultsResistin, leptin, plasminogen activator inhibitor-1 and retinol binding protein 4 left platelets unchanged but induced insulin resistance in CHRF-288-11 cells. Interleukin-6, tumor necrosis factor-α and visfatin had no effect. These results were confirmed in primary megakaryocytes. Contact with adipokines for 2 hours disturbed insulin receptor substrate 1 Ser 307 -phosphorylation, while contact for 72 hours caused insulin receptor substrate 1 degradation. Plasma with a disturbed adipokine profile also made CHRF-288-11 cells insulin-resistant. Platelets from patients with type 2 diabetes showed decreased insulin receptor substrate 1 expression. ConclusionsAdipokines resistin, leptin, plasminogen activator-1 and retinol binding protein 4 disturb insulin receptor substrate 1 activity and expression in megakaryocytes. This might be a cause of the insulin resistance observed in platelets from patients with type 2 diabetes.Key words: adipokines, insulin, insulin resistance, megakaryocytes, platelets, obesity, type 2 diabetes.Citation: Gerrits AJ, Gitz E, Koekman CA, Visseren FL, van Haeften TW, and Haematologica 2012;97(08):1149-1157. doi:10.3324/haematol.2011

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Aspirin for primary prevention of cardiovascular disease in diabetes mellitus

Cited by 45 publications

References 68 publications

Four-Year Incidence of Diabetic Retinopathy in a Spanish Cohort: The MADIABETES Study

Four-Year Incidence of Diabetic Retinopathy in a Spanish Cohort: The MADIABETES Study

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus

Induction of insulin resistance by the adipokines resistin, leptin, plasminogen activator inhibitor-1 and retinol binding protein 4 in human megakaryocytes

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