Summary of the effects of indefinite vs discontinued antithrombotic therapy for secondary prevention in patients with VTE provoked by chronic risk factors
| Certainty 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 discontinuation of antithrombotic therapy . | With indefinite antithrombotic therapy . | Risk with discontinuation of antithrombotic therapy . | Risk difference with indefinite antithrombotic therapy . | ||||||||
| Mortality: anticoagulants (follow-up: mean 18 mo) | |||||||||||
| 7937 (12 RCTs)26-29,31-38 | Not serious | Not serious | Not serious | Not serious | None | ⨁⨁⨁⨁ HIGH | 57/3553 (1.6) | 36/4384 (0.8) | RR 0.54 (0.36-0.81) | Study population: 19 mo | |
| 16 per 1000 | 7 fewer per 1000 (from 10 fewer to 3 fewer) | ||||||||||
| Mortality rate: 1 y | |||||||||||
| 7 per 1000∗ | 3 fewer per 1000 (from 4 fewer to 1 fewer) | ||||||||||
| Mortality: antiplatelet agents (follow-up: mean 31 mo) | |||||||||||
| 1224 (2 RCTs)39,40 | Not serious | Not serious | Not serious | Very serious† | None | ⨁⨁◯◯ LOW | 23/608 (3.8) | 22/616 (3.6) | RR 0.95 (0.53-1.68) | Study population | |
| 38 per 1000 | 2 fewer per 1000 (from 18 fewer to 26 more) | ||||||||||
| Mortality rate: 1 y | |||||||||||
| 14 per 1000‡ | 1 fewer per 1000 (from 7 fewer to 10 more) | ||||||||||
| Nonfatal PE: anticoagulants (follow-up: mean 17 mo) | |||||||||||
| 7202 (10 RCTs)26-29,31-33,35,36,38 | Not serious | Not serious | Not serious | Not serious | None | ⨁⨁⨁⨁ HIGH | 92/3189 (2.9) | 24/4013 (0.6) | RR 0.25 (0.16-0.41) | Study population | |
| 29 per 1000 | 22 fewer per 1000 (from 24 fewer to 17 fewer) | ||||||||||
| Annualized risk for PE | |||||||||||
| 19 per 1000 (9, 10)§ | 14 fewer per 1000 (from 16 fewer to 11 fewer) | ||||||||||
| Nonfatal PE: antiplatelet agents (follow-up: mean 31 mo) | |||||||||||
| 1224 (2 RCTs)39,40 | Not serious | Not serious | Not serious | Serious‖ | None | ⨁⨁⨁◯ MODERATE | 44/608 (7.2) | 29/616 (4.7) | RR 0.65 (0.41-1.03) | Study population | |
| 72 per 1000 | 25 fewer per 1000 (from 42 fewer to 2 more) | ||||||||||
| Annualized risk for PE | |||||||||||
| 19 per 1000 (9, 10)§ | 7 fewer per 1000 (from 11 fewer to 1 more) | ||||||||||
| DVT: anticoagulants (follow-up: mean 17 mo) | |||||||||||
| 7202 (10 RCTs)26-29,31-33,35,36,38 | Not serious | Not serious | Not serious | Not serious | None | ⨁⨁⨁⨁ HIGH | 198/3189 (6.2) | 33/4013 (0.8) | RR 0.15 (0.10-0.21) | Study population | |
| 62 per 1000 | 53 fewer per 1000 (from 56 fewer to 49 fewer) | ||||||||||
| Annualized risk for DVT | |||||||||||
| 23 per 1000 (9, 10)§ | 20 fewer per 1000 (from 21 fewer to 18 fewer) | ||||||||||
| DVT: antiplatelet agents (follow-up: mean 30 mo) | |||||||||||
| 1347 (3 RCTs)30,39,40 | Not serious | Not serious¶ | Not serious | Serious‖ | None | ⨁⨁⨁◯ MODERATE | 100/671 (14.9) | 58/676 (8.6) | RR 0.44 (0.17-1.13) | Study population | |
| 149 per 1000 | 83 fewer per 1000 (from 124 fewer to 19 more) | ||||||||||
| Annualized risk for DVT | |||||||||||
| 23 per 1000 (9, 10)§ | 13 fewer per 1000 (from 19 fewer to 3 fewer) | ||||||||||
| Major bleeding: anticoagulants (follow-up: mean 19 mo) | |||||||||||
| 8210 (13 RCTs)26-29,31-38,41 | Not serious | Not serious | Not serious | Not serious | None | ⨁⨁⨁⨁ HIGH | 20/3687 (0.5) | 50/4523 (1.1) | RR 1.98 (1.18-3.30) | Study population | |
| 5 per 1000 | 5 more per 1000 (from 1 more to 12 more) | ||||||||||
| Annualized risk for major bleeding | |||||||||||
| 4 per 1000# | 4 more per 1000 (from 1 more to 9 more) | ||||||||||
| Major bleeding: antiplatelet agents (follow-up: mean 31 mo) | |||||||||||
| 1224 (2 RCTs)39,40 | Not serious | Not serious | Not serious | Very serious† | None | ⨁⨁◯◯ LOW | 7/608 (1.2) | 9/616 (1.5) | RR 1.28 (0.48-3.41) | Study population | |
| 12 per 1000 | 3 more per 1000 (from 6 fewer to 29 more) | ||||||||||
| Annualized risk for major bleeding | |||||||||||
| 4 per 1000# | 1 more per 1000 (from 2 fewer to 10 more) | ||||||||||
| Certainty 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 discontinuation of antithrombotic therapy . | With indefinite antithrombotic therapy . | Risk with discontinuation of antithrombotic therapy . | Risk difference with indefinite antithrombotic therapy . | ||||||||
| Mortality: anticoagulants (follow-up: mean 18 mo) | |||||||||||
| 7937 (12 RCTs)26-29,31-38 | Not serious | Not serious | Not serious | Not serious | None | ⨁⨁⨁⨁ HIGH | 57/3553 (1.6) | 36/4384 (0.8) | RR 0.54 (0.36-0.81) | Study population: 19 mo | |
| 16 per 1000 | 7 fewer per 1000 (from 10 fewer to 3 fewer) | ||||||||||
| Mortality rate: 1 y | |||||||||||
| 7 per 1000∗ | 3 fewer per 1000 (from 4 fewer to 1 fewer) | ||||||||||
| Mortality: antiplatelet agents (follow-up: mean 31 mo) | |||||||||||
| 1224 (2 RCTs)39,40 | Not serious | Not serious | Not serious | Very serious† | None | ⨁⨁◯◯ LOW | 23/608 (3.8) | 22/616 (3.6) | RR 0.95 (0.53-1.68) | Study population | |
| 38 per 1000 | 2 fewer per 1000 (from 18 fewer to 26 more) | ||||||||||
| Mortality rate: 1 y | |||||||||||
| 14 per 1000‡ | 1 fewer per 1000 (from 7 fewer to 10 more) | ||||||||||
| Nonfatal PE: anticoagulants (follow-up: mean 17 mo) | |||||||||||
| 7202 (10 RCTs)26-29,31-33,35,36,38 | Not serious | Not serious | Not serious | Not serious | None | ⨁⨁⨁⨁ HIGH | 92/3189 (2.9) | 24/4013 (0.6) | RR 0.25 (0.16-0.41) | Study population | |
| 29 per 1000 | 22 fewer per 1000 (from 24 fewer to 17 fewer) | ||||||||||
| Annualized risk for PE | |||||||||||
| 19 per 1000 (9, 10)§ | 14 fewer per 1000 (from 16 fewer to 11 fewer) | ||||||||||
| Nonfatal PE: antiplatelet agents (follow-up: mean 31 mo) | |||||||||||
| 1224 (2 RCTs)39,40 | Not serious | Not serious | Not serious | Serious‖ | None | ⨁⨁⨁◯ MODERATE | 44/608 (7.2) | 29/616 (4.7) | RR 0.65 (0.41-1.03) | Study population | |
| 72 per 1000 | 25 fewer per 1000 (from 42 fewer to 2 more) | ||||||||||
| Annualized risk for PE | |||||||||||
| 19 per 1000 (9, 10)§ | 7 fewer per 1000 (from 11 fewer to 1 more) | ||||||||||
| DVT: anticoagulants (follow-up: mean 17 mo) | |||||||||||
| 7202 (10 RCTs)26-29,31-33,35,36,38 | Not serious | Not serious | Not serious | Not serious | None | ⨁⨁⨁⨁ HIGH | 198/3189 (6.2) | 33/4013 (0.8) | RR 0.15 (0.10-0.21) | Study population | |
| 62 per 1000 | 53 fewer per 1000 (from 56 fewer to 49 fewer) | ||||||||||
| Annualized risk for DVT | |||||||||||
| 23 per 1000 (9, 10)§ | 20 fewer per 1000 (from 21 fewer to 18 fewer) | ||||||||||
| DVT: antiplatelet agents (follow-up: mean 30 mo) | |||||||||||
| 1347 (3 RCTs)30,39,40 | Not serious | Not serious¶ | Not serious | Serious‖ | None | ⨁⨁⨁◯ MODERATE | 100/671 (14.9) | 58/676 (8.6) | RR 0.44 (0.17-1.13) | Study population | |
| 149 per 1000 | 83 fewer per 1000 (from 124 fewer to 19 more) | ||||||||||
| Annualized risk for DVT | |||||||||||
| 23 per 1000 (9, 10)§ | 13 fewer per 1000 (from 19 fewer to 3 fewer) | ||||||||||
| Major bleeding: anticoagulants (follow-up: mean 19 mo) | |||||||||||
| 8210 (13 RCTs)26-29,31-38,41 | Not serious | Not serious | Not serious | Not serious | None | ⨁⨁⨁⨁ HIGH | 20/3687 (0.5) | 50/4523 (1.1) | RR 1.98 (1.18-3.30) | Study population | |
| 5 per 1000 | 5 more per 1000 (from 1 more to 12 more) | ||||||||||
| Annualized risk for major bleeding | |||||||||||
| 4 per 1000# | 4 more per 1000 (from 1 more to 9 more) | ||||||||||
| Major bleeding: antiplatelet agents (follow-up: mean 31 mo) | |||||||||||
| 1224 (2 RCTs)39,40 | Not serious | Not serious | Not serious | Very serious† | None | ⨁⨁◯◯ LOW | 7/608 (1.2) | 9/616 (1.5) | RR 1.28 (0.48-3.41) | Study population | |
| 12 per 1000 | 3 more per 1000 (from 6 fewer to 29 more) | ||||||||||
| Annualized risk for major bleeding | |||||||||||
| 4 per 1000# | 1 more per 1000 (from 2 fewer to 10 more) | ||||||||||
We used the median in the discontinued treatment arm from eligible RCTs as the baseline risk and estimated an annualized mortality of 0.7%.
The optimal information size was not met and the wide CI around the absolute estimates does not rule out substantial benefit or substantial harm, and so we downrate the quality by 2 levels for impression.
We used the median in the discontinued 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.
The CI around the absolute estimates does not rule out substantial benefit or substantial harm, and thus we downrated the quality by 1 level for impression.
Although I2 = 85%, the treatment effects were all in favor of indefinite antithrombotic therapy and we therefore did not rate down the quality for inconsistency.
We used the median in the discontinued treatment arm from eligible RCTs as the baseline risk and estimated the annualized risk for bleeding to be 0.4%.