Summary of the effects of shorter (3-6 months) vs longer (>6 months) duration of anticoagulation treatment for primary treatment in patients with unprovoked VTE
| Certainty of evidence assessment . | Summary of findings . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Participants (studies) follow-up . | Risk of bias . | Inconsistency . | Indirectness . | Imprecision . | Publication bias . | Overall certainty of evidence . | Study event rates (%) . | Relative effect (95% CI) . | Anticipated absolute effects . | ||
| With short-term anticoagulation (3 to 6 mo) . | With long-term anticoagulation (>6 mo) . | Risk with short-term anticoagulation (3 to 6 mo) . | Risk difference with long-term anticoagulation (>6 mo) . | ||||||||
| Mortality (follow-up: mean 37 mo) | |||||||||||
| 1186 (7 RCTs)20,22,23,26-29 | Not serious | Not serious | Not serious | Serious∗ | None | ⨁⨁⨁◯ MODERATE | 24/594 (4.0) | 34/592 (5.7) | RR 1.43 (0.85-2.41) | Study population | |
| 40 per 1000 | 17 more per 1000 (from 6 fewer to 56 more) | ||||||||||
| Mortality rate: 1 y | |||||||||||
| 14 per 1000† | 6 more per 1000 (from 2 fewer to 20 more) | ||||||||||
| Nonfatal PE (follow-up: mean 35 mo) | |||||||||||
| 1366 (8 RCTs)20-23,26-29 | Not serious | Not serious | Not serious | Serious∗ | None | ⨁⨁⨁◯ MODERATE | 48/686 (7.0) | 31/680 (4.6) | RR 0.66 (0.42-1.02) | Study population | |
| 70 per 1000 | 24 fewer per 1000 (from 41 fewer to 1 more) | ||||||||||
| Annualized risk for PE | |||||||||||
| 36 per 1000 (16, 17)‡ | 12 fewer per 1000 (from 21 fewer to 1 more) | ||||||||||
| DVT (follow-up: mean 33 mo) | |||||||||||
| 1418 (9 RCTs)20-24,26-29 | Not serious | Not serious | Not serious | Serious∗ | none | ⨁⨁⨁◯ MODERATE | 81/711 (11.4) | 69/707 (9.8) | RR 0.85 (0.63-1.14) | Study population | |
| 114 per 1000 | 17 fewer per 1000 (from 42 fewer to 16 more) | ||||||||||
| Annualized risk for DVT | |||||||||||
| 44 per 1000 (16, 17)‡ | 7 fewer per 1000 (from 16 fewer to 6 more) | ||||||||||
| Major bleeding (follow-up: mean 33 mo) | |||||||||||
| 2581 (9 RCTs)20-23,25-29 | Not serious | Not serious | Not serious | Not serious | None | ⨁⨁⨁⨁ HIGH | 11/1307 (0.8) | 36/1274 (2.8) | RR 2.02 (1.02-3.98) | Study population | |
| 8 per 1000 | 8 more per 1000 (from 0 fewer to 24 more) | ||||||||||
| Annualized risk for major bleeding | |||||||||||
| 21 per 1000 (15)§ | 21 more per 1000 (from 0 more to 63 more) | ||||||||||
| Certainty of evidence assessment . | Summary of findings . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Participants (studies) follow-up . | Risk of bias . | Inconsistency . | Indirectness . | Imprecision . | Publication bias . | Overall certainty of evidence . | Study event rates (%) . | Relative effect (95% CI) . | Anticipated absolute effects . | ||
| With short-term anticoagulation (3 to 6 mo) . | With long-term anticoagulation (>6 mo) . | Risk with short-term anticoagulation (3 to 6 mo) . | Risk difference with long-term anticoagulation (>6 mo) . | ||||||||
| Mortality (follow-up: mean 37 mo) | |||||||||||
| 1186 (7 RCTs)20,22,23,26-29 | Not serious | Not serious | Not serious | Serious∗ | None | ⨁⨁⨁◯ MODERATE | 24/594 (4.0) | 34/592 (5.7) | RR 1.43 (0.85-2.41) | Study population | |
| 40 per 1000 | 17 more per 1000 (from 6 fewer to 56 more) | ||||||||||
| Mortality rate: 1 y | |||||||||||
| 14 per 1000† | 6 more per 1000 (from 2 fewer to 20 more) | ||||||||||
| Nonfatal PE (follow-up: mean 35 mo) | |||||||||||
| 1366 (8 RCTs)20-23,26-29 | Not serious | Not serious | Not serious | Serious∗ | None | ⨁⨁⨁◯ MODERATE | 48/686 (7.0) | 31/680 (4.6) | RR 0.66 (0.42-1.02) | Study population | |
| 70 per 1000 | 24 fewer per 1000 (from 41 fewer to 1 more) | ||||||||||
| Annualized risk for PE | |||||||||||
| 36 per 1000 (16, 17)‡ | 12 fewer per 1000 (from 21 fewer to 1 more) | ||||||||||
| DVT (follow-up: mean 33 mo) | |||||||||||
| 1418 (9 RCTs)20-24,26-29 | Not serious | Not serious | Not serious | Serious∗ | none | ⨁⨁⨁◯ MODERATE | 81/711 (11.4) | 69/707 (9.8) | RR 0.85 (0.63-1.14) | Study population | |
| 114 per 1000 | 17 fewer per 1000 (from 42 fewer to 16 more) | ||||||||||
| Annualized risk for DVT | |||||||||||
| 44 per 1000 (16, 17)‡ | 7 fewer per 1000 (from 16 fewer to 6 more) | ||||||||||
| Major bleeding (follow-up: mean 33 mo) | |||||||||||
| 2581 (9 RCTs)20-23,25-29 | Not serious | Not serious | Not serious | Not serious | None | ⨁⨁⨁⨁ HIGH | 11/1307 (0.8) | 36/1274 (2.8) | RR 2.02 (1.02-3.98) | Study population | |
| 8 per 1000 | 8 more per 1000 (from 0 fewer to 24 more) | ||||||||||
| Annualized risk for major bleeding | |||||||||||
| 21 per 1000 (15)§ | 21 more per 1000 (from 0 more to 63 more) | ||||||||||
The CI around absolute estimates does not rule out substantial benefit or substantial harm.
We used the median in the short duration treatment arm from eligible RCTs as the baseline risk and estimated an annualized mortality of 1.4%.
A meta-analysis18 reported that the cumulative incidence of recurrent VTE was 16% at 2 years for patients with unprovoked VTE, and because the median follow-up of our included studies was 24 months, we calculated the baseline risk to be 8% per patient-year. Assuming that 45% of the VTE events were PE and 55% were DVT,17 we estimated that, for patients with unprovoked VTE, the risk for PE recurrence was 3.6 per 100 patient-years and DVT recurrence was 4.4 per 100 patient-years.
A meta-analysis of 13 prospective cohort studies and 56 randomized trials15 showed that, in people with VTE, the risk for major bleeding during a 6-month treatment with anticoagulants was 2.1%. Assuming a risk for major bleeding of close to zero after anticoagulant discontinuation, we estimated an annualized risk for major bleeding of 2.1%.