What is the clinical evidence from this study?

Study design: Cohort. Population: Cancer-related ischemic stroke (n=2285). Intervention: Anticoagulant drugs vs. Antiplatelet drugs. Primary outcome: Major bleeding (HR 1.35, 95% CI 1.20-1.52, p=<0.001).

May 9, 2023Open Access

Bleeding risk and mortality according to antithrombotic agents’ exposure in cancer-related stroke patients: nationwide population-based cohort study in South Korea

Q: What are the key findings of this study?

Anticoagulant exposure significantly increased the risk of major bleeding compared to antiplatelet exposure in patients with cancer-related stroke (HR 1.35).

Q: What does this research mean for the field?

Anticoagulant exposure significantly increases the risk of major bleeding compared to antiplatelet exposure in patients with cancer-related stroke. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

Anticoagulant exposure significantly increased the risk of major bleeding compared to antiplatelet exposure in patients with cancer-related stroke (HR 1.35).

Study Design

Type

Cohort (n=2,285)

Structured PICO

Does anticoagulation increase bleeding risk and mortality compared to antiplatelet therapy in cancer-related stroke patients?

Population

2,285 subjects with cancer-related stroke (diagnosed with ischemic stroke within six months before and 12 months after a cancer diagnosis), mean age 68.94, 69.19% male, South Korea.

Intervention

Anticoagulants (warfarin, low molecular weight heparin, or direct oral anticoagulant) or combination of anticoagulants and antiplatelets

Comparator

Antiplatelet drugs only (aspirin, clopidogrel, cilostazol, ticlopidine, triflusal, or dipyridamole)

Outcome

Major bleeding events (combination of anemia due to acute bleeding, intracranial hemorrhage, and gastrointestinal bleeding) and all-cause mortalitysafety

In cancer-related stroke patients, the use of anticoagulants or combination therapy is associated with a significantly higher risk of major bleeding and mortality compared to antiplatelet therapy alone.

Main Result

Effect estimate: HR 1.35 (95% CI 1.20-1.52)

p-value: p=<0.001

Limitations

Retrospective observational design cannot establish causal relationships.
Lack of laboratory and imaging data to evaluate anticoagulation control quality and stroke severity.
Potential inclusion of strokes caused by etiologies other than active cancer due to operational definitions.
Inability to evaluate stroke recurrence risk due to database limitations.
Results may not be generalizable to non-Asian populations.

Abstract

BACKGROUND: Ischemic stroke with active cancer is thought to have a unique mechanism compared to conventional stroke etiologies. There is no gold standard guideline for secondary prevention in patients with cancer-related stroke, hence, adequate type of antithrombotic agent for treatment is controversial. METHODS: Subjects who were enrolled in National Health Insurance System Customized Research data during the period between 2010 and 2015 were observed until 2019. Subject diagnosed with ischemic stroke within six months before and 12 months after a cancer diagnosis was defined as cancer-related stroke patient. To solve immeasurable time bias, the drug exposure evaluation was divided into daily units, and each person-day was classified as four groups: antiplatelet, anticoagulant, both types, and unexposed to antithrombotic drugs. To investigate bleeding risk and mortality, Cox proportional hazards regression model with time-dependent covariates were used. RESULTS: Two thousand two hundred eighty-five subjects with cancer-related stroke were followed and analyzed. A group with anticoagulation showed high estimated hazard ratios (HRs) of all bleeding events compared to a group with antiplatelet (major bleeding HR, 1.35; 95% confidence interval CI, 1.20-1.52; p < 0.001). And the result was also similar in the combination group (major bleeding HR, 1.54; 95% CI, 1.13-2.09; p = 0.006). The combination group also showed increased mortality HR compared to antiplatelet group (HR, 1.72; 95% CI, 1.47-2.00; p < 0.001). CONCLUSIONS: Bleeding risk increased in the anticoagulant-exposed group compared to antiplatelet-exposed group in cancer-related stroke patients. Thus, this result should be considered when selecting a secondary prevention drug.

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