Earlier anticoagulation reversal tied to improved survival in ICH patients

In anticoagulation-associated intracerebral haemorrhage (ICH), earlier administration of reversal treatments is associated with reduced in-hospital mortality or discharge to hospice, according to data presented at ISC 2024.

“To our knowledge, this would be the first description showing [this outcome],” said Dr Kevin Sheth from the Yale University School of Medicine, New Haven, Connecticut, US, during his presentation at ISC 2024.

In the adjusted model, patients who were administered a reversal agent within 60 minutes of hospital arrival had a lower likelihood of dying in the hospital as opposed to those who had a door-to-treatment (DTT) time of >60 minutes (adjusted odds ratio [aOR], 0.83; 95 percent confidence interval [CI], 0.69–1.00).

“However, the aOR just hits the border of significance, Sheth noted. When discharge to hospice care was included in the outcome, it yielded an aOR of 0.82 [95 percent CI, 0.69–0.99], which then crossed the threshold of significance,” he continued.

Treatment within 60 minutes of hospital arrival was also tied to a higher likelihood of discharge to home or inpatient rehabilitation (aOR, 1.23; 95 percent CI, 1.02–1.49). [Sheth K, et al, ISC 2024, abstract 145]

Factors associated with DTT time ≤60 minutes include non-Hispanic White race (p=0.0029), higher systolic blood pressure (BP; per 5 mm Hg increase; p=0.0130), admission NIHSS* score (p<0.0001), and average annual number of reversals (p=0.0027).

“The association with White patients signifies that they were getting treatment faster … The association with systolic BP was a very small absolute effect, [which could] be a marker of haemorrhage severity,” said Sheth.

Overall, the use of a reversal agent was tied to reduced in-hospital mortality in both unadjusted (OR, 0.78; 95 percent CI, 0.70–0.87) and adjusted analyses (OR, 0.74; 95 percent CI, 0.62–0.88).

Time is brain

For acute ischaemic stroke, there is data to support the concept that ‘time is brain’, suggesting the “need to move faster to extend the gains that reperfusion can provide,” said Sheth. “For ICH however, we do not have a data-based paradigm [despite numerous] discussions about target ICH and code ICH [improving] quickly especially for reversal treatments.”

The 2018 American Heart Association (AHA) performance measures suggest a 90 minute DTT time target for reversal treatment. According to Sheth, this is, in some cases, twice the time target of 45 minutes for door to tPA** in ischaemic stroke.

“For anticoagulation-related ICH, mortality is quite high. In some reports, it is as high as 50 percent and often, deterioration is mediated through ICH expansion,” Sheth said.

Specific reversal agents have emerged of late for both vitamin K antagonists and direct-acting oral anticoagulants; however, it is unclear whether there is a time-dependent treatment effect. Existing evidence have not had adequate power or precision to assess for a time-treatment interaction.

To ascertain whether DTT time was tied to outcomes in anticoagulation-related ICH patients, the team evaluated 9,492 patients who presented with ICH within 24 hours of symptom onset across 465 US hospitals between 2015 and 2021. Of those with documented DTT time (n=5,224; median age 77 years; men, 57 percent), 60.8 percent were on warfarin prior to admission, 22.5 percent were on apixaban while 15.3 percent were on rivaroxaban. Only a few patients were on dabigatran (1.4 percent) and edoxaban (<0.2 percent). Median DTT time was 82 minutes.

AHA GWTG Haemorrhagic Stroke Initiative

The participants were extracted from the Get With The Guidelines^® (GWTG) – Stroke quality improvement registry provided by the AHA, a database of nearly 500K patients screened for eligible diagnosis of haemorrhagic stroke.

In February 2023, there was a national rollout of ICH measures to all GWTG – Stroke hospitals, with 20 phase I hospital sites initially serving as mentors through a focus collaborative to guide national ICH quality improvement work.

“Key insights were obtained, educational platforms were developed and deployed in the 20 hospitals across a number of acute measures that have now been rolled out nationally. Subcommittees have been implemented on certain aspects of prehospital and acute hospital care. Now, there is a plan for national development and dissemination,” Sheth shared.

What’s next?

The registry represents real-world data and is dependent on the accuracy of abstraction, noted Sheth. However, given the observational study design, data from the registry may be vulnerable to unmeasured confounding factors. Also, the exclusion of patients who lacked data on reversal treatment status or timing of administration could have led to biases in the study.

“Clinical trials and other large observational studies should replicate the results. Quality improvement programmes and educational initiatives should identify and mitigate barriers to earlier DTT time in ICH,” he said.

The stroke community should consider intensive efforts to accelerate evaluation and treatment of patients with this devastating form of stroke, Sheth continued. “We can start to pull together data like what we have today to [reinforce] the statement that for ICH, time is also brain.”