Real-world data of clazosentan for aneurysmal subarachnoid hemorrhage: a multicenter retrospective cohort study

Abstract Aneurysmal subarachnoid hemorrhage (aSAH) may lead to cerebral vasospasm which is significantly associated with morbidity and mortality. Clazosentan, an endothelin-1 receptor antagonist, has been shown to reduce cerebral vasospasm-related morbidity and all-cause mortality compared to placebo in patients with aSAH. To investigate effectiveness of clazosentan combination therapy we conducted a multicenter, retrospective, observational cohort study of Japanese patients with aSAH (35 female; age 64.4 ± 15.0 years old) between June 2022 and March 2023. Of the 47 cases, 29 (61.7%) had favorable outcomes and 9 (19.1%) had unfavorable outcomes. For postoperative aSAH management, clazosentan, cilostazol, and statins were typically used. Fasudil and ozagrel were used in 18 (38.3%) and 15 cases (31.9%), respectively. In 16 cases (34.0%), vasospasm occurred, but vasospasm-related delayed cerebral ischemia (DCI) was reported in only 4 cases (8.5%). Complications of pulmonary edema and hypotension occurred in 19 cases (40.4%) and 16 cases (34.0%), respectively. Risk factors of pulmonary edema were older age, clazosentan discontinuation, positive fluid balance, and lower serum albumin levels. Lower BMI, higher WFNS grade, lower urine output, lower serum albumin were risk factors of hypotension. The risk factors of vasospasm-related DCI were clazosentan discontinuation and positive fluid balance. Hypotension and vasospasm-related DCI were related to unfavorable outcomes. Combination therapy with clazosentan could be effective in preventing post-aSAH vasospasm-related DCI. However, caution must be taken as combination therapy may increase the risk of hypotension and pulmonary edema compared with clazosentan single therapy. Perioperative fluid balance management may be critical for preventing unfavorable outcomes.