Summary of the effects of shorter (3-6 months) vs longer (greater than 6 months) duration of anticoagulation therapy for primary treatment in patients with VTE provoked by chronic risk factors
| 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 | |||||||||||
| 19 per 1000 (9, 10)‡ | 6 fewer per 1000 (from 11 fewer to 0 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 | |||||||||||
| 23 per 1000 (9, 10)‡ | 3 fewer per 1000 (from 9 fewer to 3 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 (13)§ | 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 | |||||||||||
| 19 per 1000 (9, 10)‡ | 6 fewer per 1000 (from 11 fewer to 0 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 | |||||||||||
| 23 per 1000 (9, 10)‡ | 3 fewer per 1000 (from 9 fewer to 3 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 (13)§ | 21 more per 1000 (from 0 more to 63 more) | ||||||||||
The CI around the 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-analysis of 10 cohort studies and 5 randomized trials16 reported that the rate of VTE recurrence was 4.2% per patient-year for patients with a chronic risk factor. Assuming that 45% of the VTE events were PE and 55% were DVT,17 we estimated that, for patients with VTE provoked by chronic risk factors, the risk for PE recurrence was 1.89 per 100 patient-years and DVT recurrence was 2.31 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-months 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%.