Clinical Study Title:
Ashburner JM, Go AS, Chang Y, et al. Effect of diabetes and glycemic control on ischemic stroke risk in AF patients: ATRIA study. J Am Coll Cardiol. 2016; 26;67(3):239-247.
Fashion Sneaker Oxford Women's Player Taylor Converse Star Star 9546 All Malted Chuck Clinical Study Abstract:
Ashburner and colleagues analyzed stroke rates among diabetic patients with atrial fibrillation, examining coagulation status and glycemic control. Neither poor glycemic control (A1c ≥9.0%, adjusted HR: 1.04, 95% CI: 0.57 to 1.92) nor moderately increased A1c (7.0% to 8.9%, adjusted HR: 1.21, 95% CI: 0.77 to 1.91) were significantly associated with an increased rate of ischemic stroke compared with patients who had A1c <7.0%. Duration of diabetes >3 years was, however, associated with an increased rate of ischemic stroke compared with duration <3 years (adjusted hazard ratio [HR]: 1.74, 95%; confidence interval [CI]: 1.10 to 2.76). These findings led the authors to conclude that the duration of diabetes was a more important predictor of ischemic stroke than glycemic control in patients who have diabetes and atrial fibrillation.
Zachary T. Bloomgarden, MD
Ashburner and colleagues report an analysis of stroke rates among a population of some 2,000 persons with atrial fibrillation and diabetes during periods when anticoagulation was not administered, concluding that longer diabetes duration led to greater risk, while the analysis showed no relationship between glycemic control, as measured by A1c, and stroke risk.a Are we to conclude that glycemic interventions for persons with diabetes are unlikely to offer macrovascular benefit, with duration of diabetes per se of greater importance in predicting adverse outcome? Indeed, studies allowing longer periods of observation do suggest that improvement in glycemic control does track with reduction in macrovascular outcome.
To better understand the findings of the paper, we should recognize that the study was one with relatively short follow-up, of <2 years for the A1c analysis and of ~2.5 years for the duration analysis.b This certainly allows sufficient time to ascertain stroke events, but likely insufficient time to observe a benefit or adverse effect of better or worse levels of glycemic control on macrovascular outcome.
“Indeed, studies allowing longer periods of observation do suggest that improvement in glycemic control does track with reduction in macrovascular outcome.”
This has particularly been observed in individuals who do not have existing macrovascular disease, so that the group studied with underlying atrial fibrillation may indeed have been less likely to show such a beneficial effect. The finding that longer diabetes duration does track with worse outcome is, however, an important one, and may reflect the increasing macrovascular burden among persons with diabetes over time – a factor of particular importance, perhaps, with extant atrial fibrillation.
Clinical Study Title:
Schoos MM, Dangas GD, Mehran R. Impact of hemoglobin A1c levels on residual platelet reactivity and outcomes after insertion of coronary drug-eluting stents (from the ADAPT-DES Study). Am J Cardiol. 2016;117(2):192-200.
Clinical Study Abstract:
While increasing A1c levels predict adverse cardiovascular prognoses, less is known about the relationship between glycemic control, high platelet reactivity (HPR), and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents. In this large-scale study, A1c and HPR were positively associated, but the clinical effect on adverse outcome was driven by poor glycemic control – which predicted stent thrombosis and cardiac death after PCI regardless of platelet reactivity levels, suggesting effort to improve glycemic control after drug eluting stent implantation is warranted.
Zachary T. Bloomgarden, MD
The report by Schoos and coworkers adds further complexity to the consideration of the relationship between A1c and outcome.c This study tracked thrombotic events among 1,145 individuals undergoing PCI. Comparing baseline A1c <6.5%, 6.5-8.5%, and >8.5% over 2-yr follow-up, stent thrombosis rates were 0.9%, 2.7%, and 4.2%, MI occurred in 5%, 9.4%, and 8.5%, and cardiac death in 1.5%, 5.2%, and 5.4%. The antiplatelet effects of aspirin did not appear to track with A1c, while those of clopidogrel were attenuated as A1c increased, suggesting a potential mechanism of the benefit of better levels of glycemic control; however, even after adjusting for clopidogrel-induced platelet effect, the associations of A1c >8.5% with stent thrombosis and with cardiac mortality were seen, suggesting additional effects of poor glycemic control beyond those on platelet reactivity.
“We are left with questions.”
Should efforts be made to improve glycemic control in diabetic persons at risk of cardiovascular disease? In diabetic patients with already existing cardiovascular disease? Certainly, aggressive glucose-lowering therapy carries with it an increase in likelihood of hypoglycemia, which tracks directly with adverse cardiovascular outcome.d However, a recent set of clinical trials of a variety of therapeutic approaches with low likelihood of hypoglycemia, including SGLT-2 inhibitors, GLP-1 receptor agonists, and thiazolidinediones, has shown improved cardiovascular outcomes.e Our prediction is that such approaches will allow rational use of appropriate glycemic treatments in the management of patients with diabetes.