Author + information
- Babak B. Navi, MD, MS∗ (, )
- Anne S. Reiner, MPH,
- Hooman Kamel, MD,
- Costantino Iadecola, MD,
- Peter M. Okin, MD,
- Mitchell S.V. Elkind, MD, MS,
- Katherine S. Panageas, DrPH and
- Lisa M. DeAngelis, MD
- ↵∗Department of Neurology and Brain and Mind Research Institute, Weill Cornell Medicine, 525 East 68th Street, Room F610, New York, New York 10065
We agree with Dr. Sorigue and colleagues that besides cancer stage, cancer histology might also affect arterial thromboembolism risk, particularly in patients with non-Hodgkin lymphoma (NHL). To investigate this hypothesis, we performed the subgroup analyses suggested by the correspondents. Using the International Classification of Diseases for Oncology, 3rd edition scheme outlined in their letter, we categorized patients with new diagnoses of NHL from 2002 to 2011 in the Surveillance Epidemiology and End Results-Medicare database into aggressive or indolent subgroups. As in our original study, patients with NHL were matched individually by demographics and comorbidities to a Medicare enrollee without cancer, and each pair was followed through 2012 for an arterial thromboembolism outcome, defined as myocardial infarction or ischemic stroke (1). Cumulative incidence rates accounting for the competing risk of death were calculated. Cox regression was used to compare rates between groups at discrete time points.
We identified 15,669 pairs of patients with NHL and matched control subjects without NHL. Aggressive histologies were diagnosed in 9,786 patients with NHL (62%), and indolent histologies were diagnosed in 5,883 (38%). Forty-nine percent of patients with aggressive histologies and 50% of patients with indolent histologies were Ann Arbor Stages 3 or 4 at diagnosis. Patients with aggressive histologies had substantially higher absolute and relative risks of arterial thromboembolism than those with indolent histologies, although even patients with indolent histologies had significantly increased risks of arterial thromboembolism as compared with control subjects without NHL (Figure 1). The 6-month cumulative incidence of arterial thromboembolism was 6.5% (95% confidence interval [CI]: 6.0% to 6.9%) in patients with aggressive NHL histologies compared with 2.2% (95% CI: 1.9% to 2.5%) in control patients (hazard ratio: 3.0; 95% CI: 2.6 to 3.5). Meanwhile, the 6-month cumulative incidence of arterial thromboembolism was 3.7% (95% CI: 3.2% to 4.2%) in patients with indolent NHL histologies compared with 2.2% (95% CI: 1.8% to 2.5%) in control patients (hazard ratio: 1.8; 95% CI: 1.4 to 2.2). For all histologies, patients with NHL had higher incidences of ischemic stroke than myocardial infarction, but their relative risks for myocardial infarction were consistently higher than for ischemic stroke. Excess risks attenuated in all patients with NHL over time, although less so in those with aggressive histologies, and at 2 years from diagnosis, aggressive NHLs were still associated with a roughly 40% increased cumulative incidence of arterial thromboembolism as compared with matched control subjects. The association between aggressive NHL histologies and arterial thromboembolism risk was materially unchanged in a sensitivity analysis (n = 7,398) that excluded patients with nonspecific International Classification of Diseases for Oncology, 3rd edition histology codes of 9590, 9591, and 9596 from the aggressive NHL subgroup (6-month hazard ratio: 3.1; 95% CI: 2.6 to 3.7).
Dr. Leening and colleagues astutely point out that recurrent arterial thromboembolism despite antithrombotic therapy can sometimes serve as a clue to occult cancer. This phenomenon, although reported previously (2), requires more investigation, particularly surrounding risk markers and optimal screening strategies for occult cancer.
We agree with Frere and colleagues that cancer therapies might contribute to the heightened short-term risk of arterial thromboembolism in newly diagnosed patients with cancer, especially platinum-based and anti-angiogenesis chemotherapies (3,4). Although this hypothesis was beyond the scope of our initial study (1), which intended to define the risk of arterial thromboembolism in patients with incident cancer according to cancer type and stage, we are planning future large-scale studies to delineate the effects of commonly used cancer treatments on arterial thromboembolism risk.
Please note: This work was supported by the National Institutes of Health grants KL2TR000458 (Dr. Navi and Dr. DeAngelis), K23NS091395 (Dr. Navi), and P30CA008748 (Ms. Reiner, Dr. Panageas, and Dr. DeAngelis), and the Florence Gould Endowment for Discovery in Stroke (Dr. Navi). Funding sources had no role in the design or conduct of the study, the collection, analysis, or interpretation of the data, or in the preparation, review, or approval of the manuscript. Dr. Kamel has been a consultant for Genentech, Medtronic, and IRhythm; and served on the speakers bureau for Genentech. Dr. Elkind has provided expert witness testimony to Merck/Organon, Bristol-Myers Squibb-Sanofi Partnership, and Hi-Tech Pharmaceuticals regarding litigation related to stroke; received honoraria from UpToDate for chapters on stroke; and served on advisory boards for Biotelemetry/Cardionet, Boehringer-Ingelheim, Bristol-Myers Squibb-Pfizer Partnership, and Sanofi-Regeneron. Dr. DeAngelis has served on scientific advisory boards for Juno Therapeutics, Sapience, and Roche. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
- Navi B.B.,
- Reiner A.S.,
- Kamel H.,
- et al.
- Li S.H.,
- Chen W.H.,
- Tang Y.,
- et al.