A majority of patients with atrial fibrillation (AF) do not have an indication for sodium-glucose co-transporter 2 inhibitor (SGLT2i) therapy but have a substantial risk for cardiovascular events, according to a study in the Canadian Journal of Cardiology.

Researchers pooled data from the Randomized Evaluation of Long Term Anticoagulant Therapy With Dabigatran Etexilate (RE-LY; Clinicaltrials.gov identifier: NCT00262600) and Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE W; Clinicaltrials.gov identifier: NCT00243178) randomized controlled trials (RCTs) to estimate the proportion of patients with AF who would be eligible for SGLT2is and compare the rate of cardiovascular events between SGLT2i-eligible and ineligible AF patients.

Participants who met the key enrollment criteria from at least 1 of the phase 3 SGLT2i RCTs of empagliflozin, dapagliflozin, and canagliflozin were included in the SGLT2i-eligible group and the others were in the SGLT2i-ineligible group.

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The primary outcome was a composite of hospitalization for heart failure or cardiovascular death.

Data from 21,484 patients with AF who received oral anticoagulation therapy were included from RE-LY (n=12,091 on dabigatran and n=6022 on vitamin K antagonist; target international normalized ratio [INR] 2.0-3.0) and ACTIVE W (n=3371 on vitamin K antagonist; target INR 2.0-3.0). The group were aged mean 71.2 ± 8.8 years, the median CHA2DS2-VASc score was 3 (IQR, 2-4), and 36.1% were women.

A total of 8845 (41.2%) patients with AF met the definitions for SGLT2i eligibility according to the enrollment criteria from the trials.

After a median follow-up of 1.9 years, the primary composite outcome of cardiovascular death or hospitalization for heart failure occurred in 946 patients (10.7%) from the SGLT2i-eligible group and 751 patients (5.9%) from the ineligible group (5.8 vs 3.2 events/100 person-years; P <.001).

SGLT2i-eligible patients with AF had a significantly higher rate of cardiovascular death (3.9 vs 1.5 events/100 person-years; P <.001), hospitalization for heart failure (2.5 vs 1.9 events/100 person-years; P <.001), hospitalization for AF (3.1 vs 2.8 events/100 person-years; P =.021), and thromboembolic events (2.3 vs 2.0 events/100 person-years; P =.012) compared with the ineligible participants.

After adjustment for age and sex, SGLT2i-eligible patients with AF had a significantly increased risk for hospitalization for heart failure or cardiovascular death (hazard ratio [HR], 1.97; 95% CI, 1.79-2.17; P <.001), thromboembolic events (HR, 1.29; 95% CI, 1.12-1.48; P <.001), cardiovascular death (HR, 2.75, 95% CI, 2.41-3.13; P <.001),  and hospitalization for heart failure (HR, 1.41; 95% CI, 1.23-1.62; P <.001) compared with the ineligible patients.

The researchers noted that their study is limited by its retrospective, observational nature, and the RCTs used complex sets of enrollment criteria in their design and study protocols. In addition, information on hemoglobin A1C and low-density lipoprotein cholesterol levels was lacking, as was detailed information about heart failure medications and their dosing levels. Furthermore, the participants represent the AF population who are eligible for oral anticoagulant therapy.

“The majority of AF patients are not currently eligible to receive an SGLT2i,” wrote the investigators. “Although cardiovascular event rates are lower in SGLT2i-ineligible AF patients, these patients are still at substantial risk of cardiovascular death and hospitalization for heart failure. Future randomized trials should focus on testing the safety and efficacy of SGLT2is in reducing future AF events, cardiovascular death, and hospitalization for heart failure in patients with AF.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Oraii A, Healey JS, Benz AP, et al. Association of eligibility for a sodium-glucose co-transporter 2 inhibitor and cardiovascular events in patients with atrial fibrillation. Can J Cardiol. Published online May 9, 2022. doi:10.1016/j.cjca.2022.05.004