Table 4.

—[Recommendation 2.4] Summary of Findings: Early Warfarin (and Shorter Duration Heparin) vs Delayed Warfarin (and Longer Duration Heparin) for Acute VTE^a-d,41,67,68

Outcomes	No. of Participants (Studies), Follow-up	Quality of the Evidence (GRADE)	Relative Effect (95% CI)	Anticipated Absolute Effects
				Risk With Delayed Warfarin Initiation (and Longer Duration Heparin)	Risk Difference With Early Warfarin Initiation (and Shorter Duration Heparin) (95% CI)
Mortality	688 (3 studies), 3 moe	Moderatef,g due to imprecision	RR 0.9 (0.41-1.95)	24 per 1,000h	2 fewer per 1,000 (from 14 fewer to 23 more)
Recurrent VTE	688 (3 studies), 3 moe	Moderatef,g due to imprecision	RR 0.83 (0.4-1.74)	47 per 1,000h	8 fewer per 1,000 (from 28 fewer to 35 more)
Major bleeding	688 (3 studies), 3 moi	Highf,j,k	RR 1.48 (0.68-3.23)	16 per 1,000h	14 more per 1,000 (from 9 fewer to 66 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.

^aMost patients had proximal DVT, some had isolated distal DVT, most DVT were symptomatic (asymptomatic DVT included in Hull et al⁴¹), and few had PE (only included in Gallus et al⁶⁷).

^bThe early initiation of VKA was associated with a fewer number of days of heparin therapy (4.1 vs 9.5 in Gallus et al⁶⁷; 5 vs 10 in Hull et al⁴¹) and a fewer number of days of hospital stay (9.1 vs 13.0 in Gallus et al; 11.7 vs 14.7 in Hull et al; 11.9 vs 16.0 in Leroyer et al⁶⁸).

^cVKA therapy started within 1 day of starting heparin therapy (UFH in two studies and LMWH in one study).

^dVKA therapy delayed for 4 to 10 d.

^eOutcome assessment was at hospital discharge in the study by Gallus et al⁶⁷ (although there was also extended follow-up) and 3 mo in the studies by Hull et al⁴¹ and Leroyer et al.⁶⁸

^fPatients and investigators were not blinded in two studies (Gallus et al⁶⁷ and Leroyer et al⁶⁸) and were blinded in one study (Hull et al⁴¹). Concealment was not clearly described but was probable in the three studies. Primary outcome appears to have been assessed after a shorter duration of follow-up in the shorter treatment arm of one study because of earlier discharge from hospital, and 20% of subjects in this study were excluded from the final analysis postrandomization (Gallus et al).

^gThe 95% CI on relative effect includes both clinically important benefit and clinically important harm.

^hEvent rate corresponds to the median event rate in the included studies.

ⁱBleeding was assessed early (in hospital or in the first 10 d) in two studies (Gallus et al⁶⁷ and Hull et al⁴¹) and at 3 mo in one study (Leroyer et al⁶⁸).

^jIt is unclear whether bleeding was assessed at 10 d in all subjects or just while heparin was being administered, which could yield a biased estimate in favor of short-duration therapy in one study (Hull et al⁴¹).

^kBecause the shorter duration of heparin therapy is very unlikely to increase bleeding, the wide 95% CIs around the relative effect of shorter therapy on risk of bleeding is not a major concern.