(B-249) DARWIN EU® - Incidence of Myoclonus in Heart Failure: a Descriptive Analysis in Patients Treated with Sacubitril/Valsartan and Other Treatments

Background: Sacubitril/valsartan (Entresto) is used to treat symptomatic chronic heart failure. Some case reports have suggested a potential association between sacubitril/valsartan and myoclonus.

Objectives: To estimate the incidence rate of myoclonus in the general population, in a newly diagnosed (ND) heart failure (HF) population, and in HF population newly initiating treatments: sacubitril/valsartan (first-line [without prior use of ACE inhibitor (ACEi) or angiotensin receptor blockers (ARBs)] and later-line [with prior use of either]), ACEi, and ARBs.

Methods: Population-level cohort study using primary care databases mapped to OMOP Common Data Model (CPRD GOLD, UK; IQVIA DA, Germany; and SIDIAP, Spain) between 2015-2023 in patients aged ≥18 with ≥365 days of database history. Two definitions of myoclonus were used: narrow and broad. Monthly incidence rates (IR [cases/100,000 person-years]) were estimated for the general population. For both the ND HF cohort (index date [ID]: date of diagnosis) and the HF cohort newly initiating treatments of interest (ID: date of treatment initiation), IRs were estimated for predefined consecutive time windows (0–30, 31–90, 91–180, 181–365, and >365 days).

Results: Myoclonus narrow IR were low across all study populations and databases, while the broad definition yielded higher IR in all cases. Myoclonus broad IR in the general population ranged between 60-120 per 100,000 person-years across databases for most of the study period. In the ND HF population, myoclonus broad IR were higher than those observed in the general population in all databases. IR peaked in the earliest time windows, close to first HF diagnosis (ranging from 485-2818 during the 0–30-day window) and stabilised at lower values (212–645) over time. Among HF patients newly initiating treatments, ARBs consistently showed the highest rates, peaking at 893 in SIDIAP during the 0–30-day window (range 503-893). ACEi and sacubitril/valsartan later-line rates ranged between 579-667 and 729 per 100,000 person-years, respectively, during the 0–30-day window. For all treatments, myoclonus broad IR were higher in the earlier time windows following treatment initiation. For sacubitril/valsartan first-line, numbers were too low to estimate myoclonus IR in all databases.

Conclusions: Patients with ND HF consistently exhibited higher myoclonus IR (both narrow and broad narrow) compared to the general population, and to HF patients newly initiating the treatments of interest. For myoclonus broad, the highest IR in the ND HF and treatment initiator cohorts occurred within the 0- 30-day window. Across new initiators of HF treatments of interest, myoclonus broad IR were highest in ARBs initiators, while lower in sacubitril/valsartan (later line) and ACEi initiators.