A Cochrane review [Abstract] 1 included 11 studies with a total of 3 716 subjects. The studies compared the following different periods of treatment with vitamin K antagonists (VKA): 4 weeks versus 3 months, 6 weeks versus 12 weeks, 6 weeks versus 6 months, 3 months versus 6 months, 3 months versus one year, 3 months versus 27 months, 4 months versus 27 months, 6 months versus 30 months, and 6 months versus 4 years.
Prolonged treatment with vitamin K antagonists resulted in a consistent reduction for the risk of recurrence of venous thromboembolism (VTE) independent of the period elapsed since the index thrombotic event. Comparisons of two specific durations are shown in table T2. A statistically significant rebound phenomenon (ie, an excess of recurrences shortly after cessation of prolonged treatment) after cessation of treatment was not observed (OR 1.28, 95% CI 0.97 to 1.70). No statistically significant reduction in mortality was noted. Substantial increase in bleeding complications was observed for patients receiving prolonged treatment (table T1).
| Outcome | Relative effect (95% CI) | Assumed risk - short-term treatment | Corresponding risk - long-term treatment (95% CI) | Participants (studies) |
|---|---|---|---|---|
| * Period from cessation of VKA in short arm until VKA cessation in long arm | ||||
| Incidence of recurrent VTE | RR 0.2(0.11 to 0.38) | 88 per 1000 | 18 per 1000(10 to 33) | 3 536(10 studies) |
| Incidence of major bleeding | RR 3.44(1.22 to 9.74) | 4 per 1000 | 15 per 1000(5 to 43) | 1 350(6 studies) |
| Mortality | RR 0.69(0.35 to 1.34) | 38 per 1000 | 26 per 1000(13 to 51) | 1 049(4 studies) |
| Comparison | Reelative effect (95% CI) | Participants (studies) |
|---|---|---|
| VKA 1 month vs 3 months | RR 0.18 (0.04 to 0.79) | 379 (2 studies) |
| VKA 3 months vs 6 months | RR 0.10 (0.02 to 0.43) | 1 113 (4 studies) |
| VKA 3 months vs 12 months | RR 0.18 (0.071 to 0.45) | 610 (3 studies) |
Note: While prolonged use of vitamin K antagonists reduces the risk of recurrent thromboembolism as long as they are used, the absolute risk of recurrent VTE declines over time, although the risk for major bleeding remains. Thus, the efficacy of VKA administration decreases over time from occurrence of the index event.
Primary/Secondary Keywords