In a 2017 review, researchers explored the literature in order to provide evidence-based recommendations for the treatment of patients with type 2 diabetes and atrial fibrillation. The literature suggests similar mechanisms may underlie the two conditions and that non-vitamin K-related oral anticoagulants may be effective for reducing the risk of stroke in patients with both conditions.
Recent study suggests patients suffering from both type 2 diabetes (T2D) and a type of irregular heartbeat called atrial fibrillation (AF) are at increased risk of thromboembolism, the blockage of a blood vessel by a clot that has become lodged within it. Thromboembolisms within the vessels supplying the brain can, in turn, cut off circulation to various regions, resulting in a stroke. Presently, little research has been conducted regarding co-treatment of T2D and AF and the recommendations of therapeutic guidelines are limited.
In a 2017 review published in JAMA Cardiology, researchers explored the literature and current guidelines concerning the treatment of type 2 diabetes and atrial fibrillation in order to provide evidence-based recommendations for the treatment of patients in whom both conditions coexist.
The literature reveals that T2D is associated with a 35-60% increase in the risk of AF, and that those with both conditions are 2.1 times as likely to have a heart attack and 2.65 times as likely to die as those with T2D alone. Though the exact mechanisms underlying diabetes-related AF are unknown, the research suggests obesity, inflammation, sugar and insulin-related cellular pathways, increases in platelets and clot components (which depend upon vitamin K) and decreases in clot-dissolving factors may have significant roles. In addition, having diabetes for ≥3 years has been associated with increased risk of clot-related stroke. The research suggests that in T2D patients without AF, the increased risk of stroke is most likely due to the inflammatory condition atherosclerosis, in which a clot would form due to the buildup of fatty plaque within the vessel, while in patients with AF, the increase is most likely due to the formation and persistence of unstable platelet-based clots due to increases in clot components and decreases in clot-dissolving factors.
In order to combat thromboembolism, at-risk patients are typically prescribed an anticoagulant (blood thinner) such as warfarin, which blocks the action of vitamin K, reducing the effectiveness of its dependent clotting factors. The combined results of recent trials suggest that in T2D patients non-vitamin K-blocking oral anticoagulants (NOACs) are associated with a 3.16% rate of thromboembolism and stroke compared to a rate of 3.96% for warfarin. NOACs are also associated with half the risk of severe bleeding as warfarin.
At present, cardiology societies’ guidelines concerning diabetes treatment recommend screening for AF by physical examination, electrocardiograms, and patient history, and European diabetes societies’ guidelines recommend screening for AF with electrocardiography, a heart monitor, or by feeling for and examining the pulse. Patients with both T2D and AF are recommended to receive vitamin K-blocking drugs, NOACs, aspirin, or clopidogrel. Of note, the use of oral anticoagulants and aspirin in combination significantly increases the risk for severe bleeding. The 2014 North American and 2012 European cardiology societies’ guidelines recommend the use of a CHA2DS2-VASc score, estimating stroke risk in patients with AF based on the presence of congestive heart failure, high blood pressure, and vessel disease, age (65-74 or ≥75), biological sex, and history of stroke. The presence of each item generates a point, with stroke and age ≥75, considered the greatest risk factors, generating 2 points each. The guidelines recommend the administration of an oral and a systemic anticoagulant for scores ≥2, though for a score of 1, systemic anticoagulants are considered optional in the North American guidelines.
In contrast to these recommendations, studies have suggested that in men with a score of 1 and women with a score of 2, the highest risk is actually associated with diabetes and any age over 65, and that vessel disease is associated with increased stroke risks of 1.68 times in men and 2.15 times in women. In a Taiwanese study, age was found to be the greatest stroke risk factor, though was impacted greatly by the presence of other risk factors such as diabetes. Further, stroke rates have been found to vary greatly between populations. In a Swedish study, rates of 0.5-0.9% were observed with a score of 1. In a Danish study, men with a score ≥1 and women with a score of ≥2 had a 3.01 times increase in stroke risk without anticoagulants.
The literature suggests that many of the same mechanisms which underlie type 2 diabetes-related thromboembolism may also underlie atrial fibrillation. Stroke rates were found to vary widely forCHA2DS2-VASc scores of 1, and as such, the appropriate treatment may need to be chosen on a case by case basis. The researchers suggest that NOACs may be of benefit to high-risk T2D-AF co-patients, given their efficacy and safety with respect to warfarin. Due to the varied designs of AF-focused trials and limited data on NOACs, more research is required to compare the safety and efficacy of individual NOACs in the treatment of patients with type 2 diabetes and atrial fibrillation.
Written By: Raishard Haynes, MBS