Estimating risk of venous thromboembolism in patients with cancer in the presence of competing mortality. (14th January 2015)

• Record Type: Journal Article
• Authors: Ay, C.; Posch, F.; Kaider, A.; Zielinski, C.; Pabinger, I.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 13:Number 3(2015:Mar.)
• Page Start: 390
• Page End: 397
• Publication Date: 2015-01-14
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.12825
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth12825-abs-0001"> <title>Summary</title> <sec id="jth12825-sec-0001" sec-type="section"> <title>Background</title> <p>In studies on cancer‐associated venous thromboembolism (VTE), patients not only are at risk for VTE but also may die from their underlying malignancy.</p> </sec> <sec id="jth12825-sec-0002" sec-type="section"> <title>Objectives</title> <p>In this competing‐risk (CR) scenario, we systematically compared the performance of standard (Kaplan–Meier estimator [1‐KM]), log‐rank test, and Cox model) and specific CR methods for time‐to‐VTE analysis.</p> </sec> <sec id="jth12825-sec-0003" sec-type="section"> <title>Patients and Methods</title> <p>Cancer patients (1542) were prospectively followed for a median of 24 months. VTE occurred in 112 (7.3%) patients, and 572 (37.1%) patients died.</p> </sec> <sec id="jth12825-sec-0004" sec-type="section"> <title>Results</title> <p>In comparison with the CR method, 1‐KM slightly overestimated the cumulative incidence of VTE (cumulative VTE incidence at 12 and 24 months [1‐KM vs. CR]: 7.22% vs. 6.74%, and 8.40% vs. 7.54%, respectively). Greater bias was revealed in tumor entities with high early mortality (e.g., pancreatic cancer, n = 99, 24‐month cumulative VTE incidence: 28.37% vs. 19.30%). Comparing the (subdistribution) hazard of VTE between patients with low and high baseline D‐dimer, the Cox model yielded a higher estimate than the corresponding CR model (hazard vs. subdistribution hazard ratio [95% CI] 2.85 [1.92–4.21] vs. 2.47 [1.67–3.65]). For this comparison, the log‐rank test yielded a higher test statistic and smaller <italic>P</italic>‐value than Gray's test (χ<sup>2</sup> on 1 degree of freedom: 29.88 vs. 21.34).</p> </sec> <sec id="jth12825-sec-0005" sec-type="section"> <title>Conclusion</title> <p>In patients with cancer who are at risk for VTE and death, standard and CR methods for time‐to‐VTE analysis can generate differing results. For 1‐KM, the magnitude of bias is a direct function of competing mortality. Consequently, bias tends to be negligible in cancer patient populations with low mortality but can be considerable in populations at high risk of death.</p> </sec> </abstract>