Dual antiplatelet treatment (DAPT) has emerged as the gold standard of treatment for patients with coronary artery disease (CAD). Combining two antiplatelet drugs makes sense. Aspirin inhibits the enzyme cyclooxygenase-1 (COX-1), which reduces the production of thromboxane A2, a potent platelet activator. A second agent, such as clopidogrel, ticagrelor, or prasugrel, blocks the P2Y12 receptor on the platelet surface, preventing adenosine diphosphate (ADP) mediated platelet activation and aggregation. This synergistic effect offers a better prognosis for patients and has been recommended by cardiology societies from both North America and Europe. ,
Individuals with active cancers are increasingly represented in the cohort of patients with CAD because of the increased survival achieved by novel and effective therapies for cancer. Yet, these patients are excluded or poorly represented in trials of DAPT or antiplatelet agents. Patients with cancer generally have a higher incidence of bleeding, anemia, and thrombocytopenia because of several reasons, including chemotherapy. Active cancer is also thought to be one of the major risk factors for bleeding after coronary interventions. Synergistic effects of DAPT also expose these patients to increased chances of major bleeding. All these factors make it difficult to offer evidence-based treatment to this subset of patients.
Clinical questions important in this incipient group of cardiac patients with active cancers are threefold. First, is DAPT effective in reducing the mortality and other major complications of CAD? Second, which one of the antiplatelet agents, i.e., clopidogrel, ticagrelor, or prasugrel, is most effective in preventing adverse outcomes and increasing survival? Third, is DAPT going to increase the chances of major bleeding in patients with active cancer? The paper by Cole and colleagues published in the journal addresses these significant questions.
In a uniquely designed retrospective study of 8,000 propensity-matched cohorts derived from a patient registry, the authors found that after acute myocardial infarction in active cancer patients, prasugrel showed the lowest 5-year mortality rate (20%) compared to clopidogrel (28%) and ticagrelor (27%), which was statistically significant. Interestingly, the prasugrel group did not exhibit any increased major bleeding rates compared to the other 2 antiplatelet drugs. This is reassuring since bleeding risk in patients with active cancers could have been augmented by the use of a potent antiplatelet agent such as prasugrel.
These findings mirror the results of studies in patients with CAD and no active cancer. Potent P2Y12 inhibitors may be more effective in reducing platelet-mediated thrombosis and thus improving the prognosis. Interestingly, authors also noticed that clopidogrel was the most used medication, in about 80% of patients analyzed. Older patients and patients with comorbidities received clopidogrel more often, probably out of concern for increased bleeding with the other 2 stronger antiplatelet agents.
The authors used patient data from a patient registry known as TriNetX, which is a large global health research network funded privately. This was a novel approach. The registry gives researchers access to deidentified patient data from electronic medical records and claims-based data from more than 100 healthcare organizations across 30 countries. Currently, the TriNetX registry includes 145 million patients globally, and the data are updated every 2 to 4 weeks. Apparently, the frequent rapid ongoing updates offer several advantages compared to infrequent massive data dumps. This feature allows tracking of the emerging diseases, new treatments, and following patients in near real-time.
However, there are a few caveats to the study. The retrospective nature of the study might introduce several confounding variables and biases that the authors could not control. The propensity matching method used by the authors does help in reducing some of those variables. However, unknown or unmeasured confounding variables can still tarnish the results of the study. Propensity matching can also reduce the number of patients studied, limiting the generalizability of a study.
The patient data were obtained from a wide variety of sources and deidentified in the registry. This might have limited the granularity of the patient-level data and resulted in missing parameters. Overall data quality is also unknown because the registry is essentially dependent on the quality of the electronic medical record data from participating organizations. The registry was also not optimized for detailed laboratory data analysis. Original data were obtained mainly from large academic institutions with largely insured patient populations, which may not represent the broad general population.
Overall, the study sheds new light on the use of antiplatelet treatment in patients with active cancer and CAD. Prasugrel was found to be the most effective drug with the lowest 5-year mortality, with similar rates of major bleeding as clopidogrel and ticagrelor. Practical challenges of using prasugrel in patients with active cancer, such as individual variability, side effects, costs, and logistics of real-world implementation, have to be teased out in light of the findings from this retrospective analysis. Further prospective randomized trials will be able to answer these questions more definitively.
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