Atrial fibrillation and diabetes: lower risk of complications and lower mortality with direct anticoagulants

A recent study, published in the prestigious Annals of Internal Medicine, showed that direct oral anticoagulants were associated with a lower risk of diabetes complications and a lower mortality in diabetic patients, with atrial fibrillation, than in those taking warfarin.

A lower risk of bleeding

In the last decade, direct oral anticoagulants have been progressively replaced the use of vitamin K antagonists in patients with non-valvular atrial fibrillation. These new drugs certainly offer many advantages over their predecessors, particularly reducing the risk of bleeding events.

Furthermore, direct anticoagulants do not require frequent blood sampling to monitor blood coagulation status, thus simplifying the use of these drugs for patients who must take them for the rest of their life.

Although some concerns had been expressed regarding the reversibility of their effect, the development of specific antidotes and, above all, their short half-life, still make them safe even when urgent surgical procedures are required.

On the other hand, the use of direct anticoagulants requires regular monitoring of the patient’s renal function, adjusting their dosage accordingly.

In recent years, other ancillary effects of direct anticoagulants have also been explored and this new study aimed to explore the protective effect of these drugs in patients with diabetes and atrial fibrillation.

Complications of diabetes and mortality

A group of researchers, coordinated by Tzu Chi University, in Taiwan, decided to compare the risk of developing complications and mortality between patients with atrial fibrillation and diabetes mellitus, treated with direct oral anticoagulants or warfarin.

This retrospective study analyzed data from the national database linked to Taiwan’s national health insurance, considering the registrations made between 2012 and 2017.

Four main endpoints were evaluated: macrovascular complications (composite outcome of coronary artery disease, stroke, and peripheral vascular disease), microvascular complications (composite outcome of retinopathy, neuropathy, receiving dialysis, and lower extremity amputations), glycemic emergency (composite outcome of diabetic ketoacidosis, hyperosmolar hyperglycemic state, and hypoglycemia) and all-cause mortality.

Secondary endpoints included the individual components of the composite outcomes and cardiovascular and non-cardiovascular mortality.

Direct anticoagulants versus warfarin

Overall, data from 19,909 patients who had taken direct anticoagulants and 10,300 patients who had used warfarin were included. Patients who had taken direct anticoagulants showed a significantly lower risk of developing macrovascular complications (HR 0.84), microvascular complications (HR, 0.79), and glycemic emergencies (HR, 0.91). Mortality was also lower in subjects treated with direct anticoagulants (HR, 0.78).

The analyses that also considered all the confounding factors, developed using a propensity score, showed similar results.

Analysing the subgroups divided by age, sex and level of the hospital facility, it was also found that in the subgroup of patients under the age of 65, the risk reduction did not reach statistical significance.

Researchers did not develop separate analyses for the different direct anticoagulants used and no information was available on the patients’ lifestyle and their laboratory tests.

Protective mechanisms

This study clearly highlights how diabetic patients with atrial fibrillation treated with direct oral anticoagulants have a lower risk of developing diabetes complications and lower mortality in comparison with patients treated with warfarin.

The authors admit that retrospective research cannot determine what mechanisms are involved in this effect, but they propose some hypotheses. Among these, they favour a negative effect induced by the inhibition of vitamin K, rather than a specific effect of direct anticoagulants. According to the researchers, vitamin K could promote insulin sensitivity, glucose tolerance, suppress oxidative stress and inflammatory responses.

However, It should also be remembered that coagulation factors can favourably influence the cellular processes involved in the pathogenesis of atherosclerosis. In this sense, experimental data are available in animal models that must, however, be confirmed in humans.

This post is also available in: Chinese (Simplified)

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