PCC does not improve outcomes for Chinese patients with DOAC-associated ICH

Prothrombin complex concentrate (PCC) treatment does not improve functional outcomes or reduce haematoma expansion or mortality in Chinese atrial fibrillation (AF) patients with direct-acting oral anticoagulant (DOAC)–associated intracerebral haemorrhage (ICH), researchers from the Chinese University of Hong Kong (CUHK) have reported.

ICH is a rare complication of DOAC use, occurring in 0.1 percent of cases, which is potentially life-threatening primarily due to rapid expansion of the haematoma. While haemostasis may be achieved by PCC treatment, data supporting its effectiveness are scarce. [JAMA Netw Open 2024;doi:10.1001/jamanetworkopen.2023.54916]

“To our knowledge, this is the world’s first population-based study that evaluated outcomes of PCC treatment among Chinese patients with DOAC-associated ICH,” pointed out Dr Bonaventure Ip of the Department of Medicine and Therapeutics, CUHK.

The researchers identified 232 Chinese AF patients (mean age, 77.2 years; female, 43.5 percent; median last-known-well-to-CT time, 3.4–3.9 hours) with DOAC-associated ICH who were admitted to public hospitals in Hong Kong from 1 January 2016 to 31 December 2021. Fifty percent of patients received conservative treatment with blood pressure control, and 44 percent received PCC. Using an artificial intelligence (AI)–imaging algorithm developed by CUHK’s Department of Computer Science and Engineering, the researchers compared clinical outcomes of the two treatment approaches.

Overall, 74 patients (32.0 percent) patients had good neurological recovery and 92 (40.0 percent) died within 90 days, indicating high risks of mortality and morbidity in Chinese patients with DOAC-associated ICH.

Compared with conservative management, PCC was not associated with improved neurological recovery at 90 days (adjusted odds ratio [aOR], 0.62; 95 percent confidence interval [CI], 0.33–1.16; p=0.14). PCC also did not reduce risks of mortality at 90 days (aOR, 1.03; 95 percent CI, 0.70–1.53; p=0.88), in-hospital mortality (aOR, 1.11; 95 percent CI, 0.69–1.79; p=0.66), and haematoma expansion (aOR, 0.94; 95 percent CI, 0.38–2.31; p=0.90) vs conservative management.

Higher baseline haematoma volume (aOR, 0.97; 95 percent CI, 0.96–0.99; p=0.002), lower Glasgow coma scale on admission (aOR, 1.27; 95 percent CI, 1.09–1.47; p=0.002), and intraventricular haemorrhage (aOR, 0.24; 95 percent CI, 0.08–0.71; p=0.01) were associated with lower odds of good neurological recovery.

PCC is currently listed as one of the treatment options in international ICH management guidelines. However, the recommendation for its use is based solely on animal models or expert opinion. [Stroke 2022;53:e282-e361; Stroke 2011;42:3594-3599; Stroke 2013;44:771-778]

“Our findings underscore the urgency of seeking better treatment strategies for ICH patients,” commented Professor Thomas Leung, Head of Division of Neurology, CUHK.

“[In contrast,] high-quality research data now suggest that specific anticoagulant reversal agents [eg, idarucizumab for dabigatran and andexanet alfa for factor Xa inhibitors] and timely blood pressure control have significant therapeutic effects in treatment of acute ICH,” noted Ip.

“DOACs are generally highly effective and safe, with DOAC-associated ICH being a rare complication,” emphasized Ip. “Patients with AF treated with DOACs should actively manage risk factors of ICH, including hypertension, impaired liver or kidney function, alcohol abuse, head injuries, and poor drug compliance.”