Dual antiplatelet therapy (DAPT) with ticagrelor and aspirin is effective for secondary prevention after minor ischemic stroke or TIA in adults with CYP2C19 LOF alleles.
Yet, uncertainties remain about the time course of benefit and risk with ticagrelor and aspirin in these patients, the study team explains in JAMA Neurology.
To investigate, they did a secondary time course analysis using data from the CHANCE-2 randomized controlled trial which tested two DAPT regimens (ticagrelor-aspirin and clopidogrel-aspirin) in more than 6,400 Chinese adults aged 40 years and older from 202 hospitals in China with acute minor stroke or TIA and CYP2C19 LOF alleles.
Roughly half were assigned to take ticagrelor-aspirin for 21 days followed by ticagrelor alone for day 22 to 90 days, and half to a similar regimen with clopidogrel-aspirin followed by clopidogrel alone.
The main study results, published last year in the New England Journal of Medicine, showed that the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel and the risk of severe or moderate bleeding did not differ between the two treatment groups.
Results of the time-course analysis show that reduction of major ischemic events with ticagrelor-aspirin predominantly occurred in the first week (absolute risk reduction, 1.34 percentage points) with smaller benefits observed in second, third and fourth weeks (absolute risk reduction, 0.11, 0.14 and 0.04 percentage points, respectively).
The risk of moderate to severe bleeding was "consistently" low in the ticagrelor-aspirin group, report Dr. Yongjun Wang with Beijing Tiantan Hospital and colleagues. The increase in any bleeding seen in the first week (0.87 percentage points) remained in the second, third and fourth weeks (absolute risk increase, 1.21, 0.33 and 0.23 percentage points).
This exploratory time-course analysis, the authors conclude, suggests that the ischemic benefit with ticagrelor-aspirin occurring predominantly in the first week may outweigh the risk of bleeding throughout the 21-day period of DAPT in patients with minor ischemic stroke or TIA who carry CYP2C19 LOF alleles.
"This analysis does not support shortening the 21-day regimen of DAPT with ticagrelor and aspirin demonstrated in the CHANCE-2 trial," Dr. Wang and colleagues add.
In an editorial, Dr. Anthony Kim of UCSF Weill Institute for Neurosciences in San Francisco notes that while this analysis does not fully resolve the question of whether DAPT with clopidogrel-aspirin vs. ticagrelor-aspirin is preferred more generally, there are some consistent lessons learned from these time-course analyses.
One is that TIA remains an emergency and "the consistent time course of benefits reminds us that any delay in initiating DAPT or other prevention interventions risks missing early golden opportunities to prevent a stroke before it can occur because even the best prevention interventions are ineffective to prevent the stroke that has already occurred."
"Second, the pattern of front-loaded risks of recurrent stroke and front-loaded benefits of DAPT combined with low but accumulating bleeding risks over time suggests that shortening the duration of treatment is not supported by current evidence, and that DAPT should be continued for the first few weeks when it is most helpful," Dr. Kim writes.
"Extending DAPT beyond this acute period could have the potential to accrue additional bleeding risk without producing additional benefit. One wonders whether a 21-day prescription would be less likely to be inadvertently refilled compared with a 30-day prescription that could be mistaken as a standing monthly prescription intended to be continued chronically as well," Dr. Kim says.
The researchers did not have commercial funding, but study drugs, placebo and genotyping were provided free of cost by industry.
SOURCE: https://bit.ly/3HHqEYY and https://bit.ly/3b6m1vc JAMA Neurology, online June 21, 2022.
By Reuters Staff
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