We, therefore, sought to investigate the effect of the SGLT2i dapagliflozin on the incidence and total number of AF/AFL events in post hoc analyses. 5, 12–14 In addition, mitigation of inflammation, endothelial and left ventricular dysfunction, and improved glucose control may improve atrial remodeling and thereby favorably impact the incidence of AF/AFL.
11 Although the exact mechanisms of the nonglycemic benefit of SGLT2i are incompletely understood, in addition to the aforementioned favorable metabolic effects (including lowering of glycated hemoglobin A 1c, blood pressure, and weight), multiple pleiotropic properties, including a modest diuretic effect, improved myocardial efficiency, improved oxygen delivery, a reduction of inflammation and oxidative stress, and restoration of the tubuloglomerular feedback, have been suggested to contribute to the salutary cardiorenal effects. 10 These findings suggest glucose-independent, direct cardiac protective effects of SGLT2i.
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9 The DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) showed that dapagliflozin reduced the risk of the composite of worsening of HF or cardiovascular death by 26% in patients with and without T2DM who had HF and reduced ejection fraction. 5–8 We have shown that the SGLT2i dapagliflozin reduces the composite of cardiovascular death and hospitalization for HF (HHF) by 17%, primarily driven by a 27% reduction in HHF, and was noninferior with regard to major adverse cardiovascular events (the composite of myocardial infarction, ischemic stroke, and cardiovascular death) in patients with T2DM. 5 Moreover, SGLT2i lower blood pressure without increasing the heart rate, reduce body weight, have protective effects on atherosclerotic cardiovascular disease (ASCVD) and HF-related outcomes, and prevent the progression of chronic kidney disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) block glucose and sodium reabsorption in the proximal tubule of the kidney and thereby lower glucose without increasing the risk of hypoglycemia in patients with type 2 diabetes mellitus (T2DM). 1–3 Diabetes mellitus–induced myocardial remodeling and changes in the electrical properties of the heart are associated with a propensity to develop these common cardiac arrhythmias. Dapagliflozin also reduced the total number (first and recurrent) of AF/AFL events (337 versus 432 incidence rate ratio, 0.77 P=0.005).ĭiabetes mellitus and diabetes mellitus–related comorbidities including obesity, hypertension, chronic kidney disease, and heart failure (HF) are associated with an increased incidence of atrial fibrillation (AF) and atrial flutter (AFL). Moreover, there was no effect modification by sex, history of ischemic stroke, glycated hemoglobin A 1c, body mass index, blood pressure, or estimated glomerular filtration rate (all P for interaction >0.20).
Similarly, presence of atherosclerotic cardiovascular disease (HR, 0.83 ) versus multiple risk factors (HR, 0.78 P for interaction 0.72) or a history of HF (HF: HR, 0.78 No HF: HR, 0.81 P for interaction 0.88) did not modify the reduction in AF/AFL events observed with dapagliflozin. The reduction in AF/AFL events was consistent regardless of presence or absence of a history of AF/AFL at baseline (previous AF/AFL: HR, 0.79 no AF/AFL: HR, 0.81 P for interaction 0.89).
Customer Service and Ordering Informationĭapagliflozin reduced the risk of AF/AFL events by 19% (264 versus 325 events 7.8 versus 9.6 events per 1000 patient-years hazard ratio, 0.81 P=0.009).Stroke: Vascular and Interventional Neurology.
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