Contemporary Oral Medication Use and Frequency in Patients with Transthyretin Amyloid Cardiomyopathy

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure (HF), with a higher prevalence in older patients with comorbidities requiring concomitant medical therapy. Acoramidis is a next-generation transthyretin stabilizer with near-complete protein stabilization (≥ 90%) administered orally twice daily (BID) for treatment of ATTR-CM. We report on oral medication use in patients with ATTR-CM using two complementary sources: the ATTRibute-CM trial and real-world claims data.

In the ATTRibute-CM study, participants with ATTR-CM were randomly assigned 2:1 to receive 800 mg of acoramidis hydrochloride or matching placebo BID for 30 months. Participants from acoramidis and placebo groups were pooled for this analysis. Baseline oral medication use was collected upon enrollment in the study. Real-world data were obtained from patients with ATTR-CM in Optum's deidentified Clinformatics Data Mart Database (Optum CDM) who met the stability criteria. Patients meeting the stability criteria had: (1) ≥ 2 years of continuous enrollment with ≥ 3-months look-back and a 12-month look-forward from index diagnosis, during the study period of 2018-2021 and (2) ≥ 28 days of continuous treatment for a given dosing frequency within the 12-month look-forward period.

The ATTRibute-CM study randomly assigned 632 participants with ATTR-CM (mean [± SD] age: 77.3 [6.6] years). At entry to the study, 407 (64.4%) participants were using a medication that was administered BID, three times daily (TID), or four times daily (QID), and 392 (62.0%) participants were using at least one medication administered BID. The most frequent BID medications were apixaban, furosemide, metformin, metoprolol, and carvedilol. In ATTRibute-CM, accountability to acoramidis was high (97.1%). From a pool of 2.46 million patients with HF and cardiomyopathy identified in the Optum CDM, 12,116 patients (mean [± SD] age: 76.3 [9.4] years) met the criteria for ATTR-CM, and 5601 patients met the stability criteria. Analysis from this real-world database demonstrated that 4351 (92.1%) patients were prescribed a medication that was administered BID, TID, or QID and 4166 (88.2%) patients were prescribed at least one BID medication. The most frequent medications regardless of dosing frequency included furosemide, atorvastatin, metoprolol, apixaban, and carvedilol. The most frequent BID medications were apixaban, carvedilol, furosemide, metoprolol, and potassium chloride.

Patients with ATTR-CM take oral medications administered multiple times a day for the treatment of HF and other comorbidities. As a BID medication, acoramidis does not appear to deviate from non-ATTR-CM pharmacotherapy strategies, and is therefore not expected to impose additional burden in a real-world setting. These data suggest that acoramidis may align with and could possibly be incorporated into patients' existing non-ATTR-CM pharmacotherapeutic regimens.

NCT03860935.