by
Angela Wisniewski, Department of Family Medicine and Pharmacy Practice, University at Buffalo
Thuy Nguyen, Pharmacy Department, University of Southern California
David Newberger, Department of Family Medicine, University at Buffalo
Please answer the questions below after reading the article “Long-Term, Low-Intensity Warfarin Therapy for the Prevention of Recurrent Venous Thromboembolism” by P. M Ridker et al. in The New England Journal of Medicine, 348(15): 1425–1434. The tables and figures that appear below are used with permission, copyright © 2003 Massachusetts Medical Society, all rights reserved.
1. What is the most likely design for a study to evaluate the efficacy of this new treatment approach?
2. What information does Table 1 below represent in relation to the similarities and/or differences of the Placebo and Warfarin treatment groups?
| Table 1. Base-Line Characteristics of the Study Participants. | |||
|---|---|---|---|
| Characteristic | Placebo Group (N–253) | Warfarin Group (N–255) | P Value |
| Age (yr) | 0.82 | ||
| Median | 53 | 53 | |
| Interquartile range | 47–64 | 46–65 | |
| Female sex (%) | 47.4 | 47.1 | 0.93 |
| Race or ethnic group (%) | 0.32 | ||
| Non-Hispanic white | 86.6 | 88.2 | |
| Non-Hispanic black | 10.3 | 9.0 | |
| Hispanic | 0.8 | 2.0 | |
| Other | 2.4 | 0.8 | |
| Body-mass index* | 0.89 | ||
| Median | 29.9 | 29.9 | |
| Interquartile range | 26.6–34.3 | 26.6–34.2 | |
| History of Diabetes (%) | 8.7 | 6.7 | 0.39 |
| ≥ Previous venous thromboembolisms (%) | 36.8 | 40.0 | 0.45 |
| Family history of venous thromboembolism (%) | 31.6 | 26.3 | 0.18 |
| Factor V Leiden (%) | 26.6 | 22.0 | 0.23 |
| Prothrombin mutation (%) | 4.8 | 4.7 | 0.98 |
| Duration of full-dose warfarin therapy before enrollment (mo) | 0.15 | ||
| Median | 6.4 | 6.7 | |
| Interquartile range | 5.7–9.0 | 5.9–10.8 | |
| Time between cessation of full-dose warfarin therapy and enrollment (mo) | 0.57 | ||
| Median | 1.4 | 2.0 | |
| Interquartile range | 0.9–5.1 | 0.9–4.3 | |
*The body-mass index is the weight in kilograms divided by the square of the height in meters. | |||
3. Why is the information in Table 1 important in assessing the results of the study?
4. Based on the information in Figure 1 below, were the investigators successful in demonstrating a statistically significant difference between the Placebo and Warfarin Groups in relation to the anticoagulant effect as measured by the INR?
5. Based on the information in Table 2 and Figure 2 below, what do the data suggest with respect to the efficacy of this therapy, specifically in regard to recurrent VTE events and the composite endpoint? Do these results demonstrate a statistically significant difference between the Placebo and Warfarin Groups?
| Table 2. Major Study End Points According to Treatment Group.* | ||||||
|---|---|---|---|---|---|---|
| Outcome | Placebo Group | Warfarin Group | Hazard Ratio (95% CI) | P Value | ||
| No. of Events |
No./100 Person-Yr |
No. of Events |
No./100 Person-Yr |
|||
| Recurrent venous thromboembolism | 37 | 7.2 | 14 | 2.6 | 0.36 (0.19–0.67) | <0.001 |
| Bleeding episode | ||||||
| Major | 2 | 0.4 | 5 | 0.9 | 2.53 (0.49–13.03) | 0.25 |
| Minor | 34 | 6.7 | 60 | 12.8 | 1.92 (1.26–2.93) | 0.002 |
| Death | 8 | 1.4 | 4 | 0.7 | 0.50 (0.15–1.68) | 0.26 |
| Cancer | 9 | 1.6 | 4 | 0.7 | 0.45 (0.14–1.47) | 0.18 |
| Myocardial infarction | 2 | 0.4 | 3 | 0.5 | 1.54 (0.26–9.24) | 0.63 |
| Composite end point (recurrent venous thromboembolism, major bleeding episode, or death) |
41 | 8.0 | 22 | 4.1 | 0.52 (0.31–0.87) | 0.01 |
*Major bleeding episodes were defined as episodes resulting in hospitalization, transfusion of packed red cells, | ||||||
6. What do the data in Table 2 and Figure 2 suggest with respect to the safety of this therapy, specifically in relation to both major and minor bleeding episodes?
7. What information contained within Table 3 below is relevant in your consideration of this new treatment approach for Mr. Cramer?
| Table 3. Rates and Hazard Ratios for Recurrent Venous Thromboembolism in Clinically Important Subgroups, According to Treatment-Group Assignment. | ||||||
|---|---|---|---|---|---|---|
| Characteristic | Placebo Group | Warfarin Group | Hazard Ratio (95% CI)* | P Value for Interaction** | ||
| No. of Events |
No./100 Person-Yr |
No. of Events |
No./100 Person-Yr |
|||
| Factor V Leiden or prothrombin mutation |
0.51 | |||||
| Present | 14 | 8.6 | 3 | 2.2 | 0.25 (0.07–0.87) | |
| Absent | 23 | 6.6 | 11 | 2.7 | 0.42 (0.20–0.86) | |
| Sex | 0.23 | |||||
| Male | 22 | 8.6 | 11 | 3.9 | 0.47 (0.23–0.96) | |
| Female | 15 | 5.9 | 3 | 1.1 | 0.20 (0.06–0.67) | |
| Age | 0.87 | |||||
| 30–44 yr | 8 | 7.6 | 4 | 3.3 | 0.45 (0.14–1.51) | |
| 45–64 yr | 20 | 7.3 | 5 | 1.7 | 0.24 (0.09–0.65) | |
| 65–89 yr | 9 | 6.7 | 5 | 4.0 | 0.57 (0.19–1.70) | |
| No. of previous venous thromboembolic events |
0.42 | |||||
| ≥2 | 21 | 11.4 | 10 | 4.8 | 0.43 (0.20–0.90) | |
| 1 | 16 | 4.9 | 4 | 1.2 | 0.25 (0.08–0.74) | |
| Time since randomization | 0.16 | |||||
| ≤1 yr | 22 | 10.1 | 6 | 2.7 | 0.27 (0.11–0.66) | |
| >1 yr | 15 | 5.1 | 8 | 2.5 | 0.49 (0.21–1.16) | |
| Time since cessation of full-dose warfarin therapy |
0.69 | |||||
| >2 mo | 14 | 5.9 | 7 | 2.5 | 0.42 (0.17–1.04) | |
| ≤2 mo | 23 | 8.4 | 7 | 2.7 | 0.33 (0.14–0.76) | |
* CI denotes confidence interval. | ||||||
8. How would you present the information in Table 3 about this new treatment approach to Mr. Cramer to assist him in making a decision based on the results of this study?
9. Do you feel that you require additional information to make an informed decision regarding therapy for Mr. Cramer? If yes, what information would be helpful?
Originally published at http://www.sciencecases.org/anticoagulant/questions.asp
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