Table 16.

—[Section 3.1.1-3.1.4] Summary of Findings: Four or Six Weeks vs Three or Six Months as Minimum Duration of Anticoagulation for VTE^{a,b,16,159,167,169,195}

Outcomes	No. of Participants (Studies), Follow-up	Quality of the Evidence (GRADE)	Relative Effect (95% CI)	Anticipated Absolute Effects
				Risk With Control	Risk Difference With 4 or 6 wk vs 3 or 6 mo Months of Anticoagulation (95% CI)
Recurrent VTE	2,185 (5 studiesc), 1-2 yd	Highe-g	RR 1.83 (1.39-2.42)	64 per 1,000	53 more per 1,000 (from 25 more to 91 more)
Major bleeding	2,185 (5 studies), 1-2 y	Highf	RR 0.54 (0.22-1.32)	12 per 1,000	5 fewer per 1,000 (from 9 fewer to 4 more)
Mortality	2,098 (5 studies), 1-2 y	Highe,f,h	RR 0.97 (0.68-1.38)	55 per 1,000	2 fewer per 1,000 (from 18 fewer to 21 more)

The basis for the assumed risk (eg, the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Working group grades of evidence are as follow: High quality, further research is very unlikely to change our confidence in the estimate of effect; moderate quality, further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low quality, further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; very-low quality, we are very uncertain about the estimate. See Table 1 and 3 legends for expansion of abbreviations.

^aPopulations varied among studies: first provoked isolated distal DVT, proximal DVT, or PE provoked in Kearon et al¹⁹⁵; first isolated distal DVT in Pinede et al¹⁶⁷; first isolated distal DVT, proximal DVT, or PE in Schulman et al¹⁶⁹; proximal DVT (21% had cancer) in Levine et al¹⁵⁹; DVT or PE (29% not objectively confirmed) in British Thoracic Society.¹⁶⁰

^bShort vs longer duration of anticoagulation was 6 wk vs 6 mo for Schulman et al¹⁶⁹, 6 wk vs 3 mo for Pinede et al,¹⁶⁷ and 4 wk vs 3 mo for the other three studies.

^cTiming of randomization relative to the start of treatment varied across studies: Pinede et al,¹⁶⁷ Schulman et al,¹⁶⁹ and British Thoracic Society¹⁶⁰ randomized at diagnosis, and Kearon et al¹⁹⁵ and Levine et al¹⁵⁹ randomized to stop or to continue treatment for 2 mo more after the initial 4 wk of treatment.

^dFollow-up was for ∼1 y in all studied except for Schulman et al¹⁶⁹ in which it was 2 y.

^eGenerally, study design was strong. No study stopped early for benefit; two stopped early because of slow recruitment (Kearon et al,¹⁹⁵ Pinede et al¹⁶⁷). In one study (British Thoracic Society¹⁶⁰), 44 randomized patients were excluded centrally as they did not satisfy eligibility criteria. Patients and caregivers were blinded in two studies (Kearon et al, Levine et al¹⁵⁹). Adjudicators of outcomes were blinded in all but one study (British Thoracic Society). All studies appear to have used effective randomization concealment, intention-to-treat analysis, and a low unexplained drop-out frequency.

^fNo heterogeneity with I² = 0%.

^gNo imprecision for overall estimates. However, for the subgroup of patients with isolated distal DVT, who are known to have a very low risk of recurrence, there is imprecision and the possibility that the shorter duration of anticoagulation is adequate and not associated with a clinically important higher risk of recurrence.

^hDifferences in mortality are expected to be mediated by differences in recurrent VTE and bleeding.