Real-world safety of sacubitril/valsartan in Japanese patients with chronic heart failure: A post-marketing surveillance study.

Background: This study evaluated the safety of sacubitril/valsartan for up to 52 weeks in Japanese patients with chronic heart failure (CHF) in real-world settings.

Methods: This was an uncontrolled, multicenter, observational study conducted at 120 sites in Japan. Adult patients on standard of care for CHF and newly initiated on sacubitril/valsartan were included. The primary outcome was the exposure-adjusted incidence rate (EAIR: patients/100 patient-years) of adverse drug reactions (ADRs) and adverse events of interest (related to hypotension, hyperkalemia, renal impairment, and dehydration). The impact of patient risk factors on ADRs and clinical outcomes (EAIR of the composite endpoint [cardiovascular (CV) death or first hospitalization due to heart failure], and its components) were also assessed.

Results: Overall, 682 patients (median age: 78.0 years, male: 61.4 %, age 75 years: 61.9 %) were assessed. Sacubitril/valsartan was typically initiated at 50 mg twice daily and up-titrated to 100 mg or 200 mg sequentially at 2- to 4-week intervals. Dose adjustments were made in 57.2 % of patients. EAIRs of ADRs related to hypotension, hyperkalemia, renal impairment, and dehydration were 7.776, 0.606, 0.913, and 0.151, respectively. The incidence of ADRs was 9.7 %, with hypotension (4.7 %) and decreased blood pressure (1.8 %) being the most common ADRs. Patients with systolic blood pressure (SBP) of ≤120 mmHg at sacubitril/valsartan initiation had a higher risk of ADRs than those in other SBP groups. EAIRs for composite endpoints, CV death, and first hospitalization for heart failure were 9.404, 2.269, and 8.150, respectively.

Conclusions: This study did not show notable differences from the known safety profile of sacubitril/valsartan, and no new safety concerns were identified in Japanese patients with CHF. The EAIR of the composite endpoint of CV death or first hospitalization due to heart failure was lower than that in patients enrolled in clinical studies at the time of approval.