Preventing VTE in Outpatients With CancerPreventing VTE in Outpatients With Cancer FREE TO VIEW

We applaud the innovations pioneered by the American College of Chest Physicians evidence-based clinical practice guidelines on antithrombotic therapy and prevention of thrombosis (February 2012). However, we are concerned about the resulting recommendations regarding cancer-associated thrombosis, a significant contributor to the public health burden of VTE and an area of particular interest to us.

Regarding prevention of VTE in nonsurgical patients,¹ the panel suggested that outpatients with solid tumors with additional risk factors for VTE should receive prophylactic-dose low-molecular-weight heparin or low-dose unfractionated heparin (recommendation 4.2.2). Additional risk factors cited by the panel include hormonal therapy and angiogenesis inhibitors. In our opinion, this recommendation (even as a grade 2B) does not reflect an appropriate interpretation of the results of recent studies on cancer thromboprophylaxis and risk assessment. If these recommendations were to be followed, tens of thousands of women with breast cancer or men with prostate cancer on hormonal therapy for extended periods would receive low-molecular-weight heparin or low-dose unfractionated heparin. The rate of VTE in these patients, however, is much lower than other cancer subgroups, and there are no studies showing a benefit of thromboprophylaxis.² Similarly, the linkage between antiangiogenic agents, such as bevacizumab, and VTE has not been consistently demonstrated in pooled analyses.³ (Although thalidomide- and lenalidomide-based regimens are associated with VTE, these are used primarily in myeloma and not solid tumors.) Recommendation 4.2.2 further fails to cite important risk factors, such as site of cancer, and a risk assessment model for chemotherapy-associated VTE that has been externally validated in multiple studies; both are the basis for recent and ongoing prophylaxis studies.⁴

The Institute of Medicine’s 2011 report, Clinical Practice Guidelines We Can Trust, emphasized guideline development group composition and external review.⁵ Inclusion of oncology content experts on the panel or as external reviewers could have provided a different interpretation of the data and more clinically sound recommendations. We urge the panel to consider such multidisciplinary input for the next iteration of the guidelines. Even weak recommendations formulated without scientific evidence can have a negative impact on patient care and future study design. It is quite possible that institutional review boards may identify these suggestions as the standard of care, affecting future study feasibility. As physicians and researchers involved in this field, we disagree with recommendation 4.2.2 and suggest that clinicians consider recommendations from cancer-focused guidelines, such as those of the American Society of Clinical Oncology and the National Comprehensive Cancer Network.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.