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The initiation of dapagliflozin is well-tolerated in transthyretin amyloid cardiomyopathy patients treated with tafamidis.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the latest addition to the portfolio of heart failure (HF) treatments. They have improved clinical outcomes in heart failure patients with reduced ejection fraction (HFrEF) and preserved left ventricular ejection fraction (HFpEF). However, their efficacy and safety profile in tafamidis-treated ATTR-CM patients has yet to be evaluated. Studies have shown that SGLT2i reduces HF-associated hospitalizations and cardiovascular mortality in HFrEF (LVEF <40%) and HF hospitalization in HFpEF. Unlike traditional HF therapy, SGLT2i may not have adverse effects on hemodynamics in ATTR-CM patients. Unlike beta-blockers and RAAS inhibition, they do not reduce heart rate or significantly affect blood pressure. Considering their established safety profile and unique characteristics, SGLT2i may be a suitable treatment option for ATTR-CM patients. Moreover, SGLT-2i is associated with improved clinical outcomes in patients with cardiac failure and reduced left ventricular ejection fraction (LVEF).

A retrospective study published in the ESC Heart Failure journal was conducted to evaluate the effects of dapagliflozin, an SGLT2i, on a selected group of tafamidis-treated ATTR-CM patients. This study assessed the drug’s short-term tolerability, impact on disease stage, required diuretic dosage, kidney function, and NT-proBNP levels.

This study concluded that the dapagliflozin initiation was well-tolerated among ATTR-CM patients treated with tafamidis.

Treatment Outcomes of SGLT-2 Inhibitors in ATTR-CM Patients

In this analysis, no adverse events, including new-onset arrhythmias, worsening heart failure episodes, or death, were observed during the three-month period. Atrial fibrillation was observed in the dapagliflozin cohort at both the baseline and three months. The ATTR-CM cohort participants did not report any side effects associated with SGLT-2i. Weight, HbA1c, use of diuretics, and glomerular filtration rate (GFR) of the patients in control and dapagliflozin cohorts remained stable at three months of dapagliflozin initiation.

Levels of NT-proBNP in Treatment Cohort

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The treatment cohort demonstrated an increase in the median NT-proBNP of 67 pg/mL levels prior to initiation of dapagliflozin. At three months, the median decline in the levels of NT-proBNP was observed to be -190 pg/mL. After the initiation of dapagliflozin, 13/17 patients demonstrated a decline in the levels of NT-proBNP. There was an equal decrease in the NT-proBNP levels in HFpEF and HFrEP patients. A non-significant decline in the levels of NT-proBNP was also observed in the reference cohort.

In this study, the initiation of dapagliflozin was well tolerated in ATTR-CM patients treated with tafamidis. Randomized controlled trials should investigate the efficacy of SGLT-2i treatment in ATTR-CM patients.

Source:

Dobner, S., Bernhard, B., Asatryan, B., Windecker, S., Stortecky, S., Pilgrim, T., Gräni, C., & Hunziker, L. (2023). SGLT2 inhibitor therapy for transthyretin amyloid cardiomyopathy: early tolerance and clinical response to dapagliflozin. ESC Heart Fail, 10(1), 397-404. https://doi.org/10.1002/ehf2.14188