Table 2.

—[Section 4.1] Evidence Profile: Question: Should LMWH Rather Than VKA be Used for Long-term Treatment of VTE?^a,13-15

Quality Assessment							Summary of Findings
Participants (Studies), Median Follow-up	Risk of Bias	Inconsistency	Indirectness	Imprecision	Publication Bias	Overall Quality of Evidence	Study Event Rates (%)		Relative Effect, RR (95% CI)	Anticipated Absolute Effectsb
							With VKA	With LMWH		Risk With VKA	Risk Difference With LMWH (95% CI)
Overall mortality (critical outcome)
2,496 (7 RCTs), 6 mo	No serious risk of bias Selective outcome reporting not seriousc	No serious inconsistency	No serious indirectness	Serious imprecision CI includes important benefit and harm	Undetected	Moderate due to imprecision	202/1,231 (16.4)	204/1,265 (16.1)	0.96 (0.81-1.13)	164 deaths per 1,000d	7 fewer deaths per 1,000 (from 31 fewer to 21 more)
Recurrent symptomatic VTE (critical outcome): DVT and PE
2,727 (8 RCTs), 6 mo	Serious risk of bias	No serious inconsistency	No serious indirectness	No serious imprecision	Undetected	Moderate due to risk of bias	105/1,349 (7.8)	67/1,378 (4.9)	0.62 (0.46-0.84)	No cancer
	No studies were blinded									30 VTEs per 1,000d	11 fewer VTE per 1,000 (from 5 fewer to 16 fewer)
										Nonmetastatic cancer
										80 VTEs per 1,000d	30 fewer VTE per 1,000 (from 13 fewer to 43 fewer)
										Metastatic cancer
										200 VTEs per 1,000d	76 fewer VTE per 1,000 (from 32 fewer to 108 fewer)
Major bleeding (critical outcome)
2,737 (8 RCTs), 6 mo	No serious risk of bias Lack of blinding not seriouse	No serious inconsistency	No serious indirectness	Serious imprecision CI includes important benefit and harm	Undetected	Moderate due to imprecision	53/1,351 (3.9)	45/1,386 (3.2)	0.81 (0.55-1.2)	No cancer or nonmetastatic cancer
										20 bleeds per 1,000f	4 fewer bleeds per 1,000 (from 9 fewer to 4 more)
										Metastatic cancer
										80 bleeds per 1,000f	15 fewer bleeds per 1,000 (from 36 fewer to 16 more)
PTS (important outcome): self-reported leg symptoms and signs
100 (1 RCT), 3 mo	Serious risk of bias Patients and investigators not blinded	No serious inconsistency	Serious indirectness Predictive value from 3 mo to long term uncertain	No serious imprecision	Undetected	Low due to risk of bias and indirectness	31/44 (70.5)	34/56 (60.7)	0.85 (0.77- 0.94)	200 PTS per 1,000g	30 fewer per 1,000 (from 12 fewer to 46 fewer)

LMWH = low-molecular-weight heparin; PTS = postthrombotic syndrome; RCT = randomized control trial; RR = risk ratio; VKA = vitamin K agonist. (Kearon C, unpublished data).^h

^aLimited to LMWH regimens that used ≥ 50% of the acute treatment dose during the extended phase of treatment.

^bTime frame is 6 mo for all outcomes except PTS, which is 2 y.

^cOne study did not report deaths: borderline decision.

^dControl event rates from cohort study by Prandoni et al,¹³ adjusted to 6-mo time frame.

^eOutcome less subjective: borderline decision.

^fControl event rates from cohort studies by Prandoni et al¹³ and Beth et al¹⁴ adjusted to 6-mo time frame.

^gControl event rate comes from observational studies in review by Kahn et al¹⁵ adjusted to 2-y time frame. All patients wore pressure stockings.

^hMeta-analysis is based on RCTs as referenced in the article text. The control event rate for mortality comes from this meta-analysis.