Summary of findings 2. Low‐molecular‐weight heparin versus no thromboprophylaxis.

LMWH compared with no thromboprophylaxis for primary thromboprophylaxis in ambulatory cancer patients receiving chemotherapy
Patient or population: ambulatory cancer patients receiving chemotherapy Settings: outpatient clinics Intervention: LMWH Comparison: no thromboprophylaxis (placebo or no LMWH)
Outcomes	Relative effect (95% CI)	Illustrative comparative risk (95% CI)*		Difference (95% CI)b	No of participants (studies)	Certainty of the evidence (GRADE)	What it means
		Assumed riska	Corresponding risk
		With no thromboprophylaxis Number of events per 1000 participants	With LMWH Number of events per 1000 participants
Symptomatic VTE Follow‐up: median 10 months	RR 0.62 (0.46 to 0.83)	High‐risk populationc		27 per 1000 fewer events (12 fewer to 39 fewer)	3931 (11)	⊕⊕⊕⊕ Highd	LMWH decreases the incidence of symptomatic VTE across different cancer types.
		71 per 1000	44 per 1000 (33 to 59)
Major bleeding Follow‐up: median 10 months	RR 1.63 (1.12 to 2.35)	High‐risk populationc		7 per 1000 more major bleeds (1 more to 15 more)	7282 (15)	⊕⊕⊕⊝ Moderatee	LMWH probably increases major bleedings across different cancer types.
		11 per 1000	18 per 1000 (12 to 26)
Symptomatic PE Follow‐up: median 8 months	RR 0.60 (0.42 to 0.88)	High‐risk populationc		7 per 1000 fewer events (2 fewer to 11 fewer)	5324 (8)	⊕⊕⊕⊝ Moderatef	LMWH probably decreases the incidence of symptomatic PE across different cancer types.
		18 per 1000	11 per 1000 (8 to 16)
Symptomatic DVT Follow‐up: median 10 months	RR 0.48 (0.35 to 0.67)	High‐risk populationc		15 per 1000 fewer events (9 fewer to 18 fewer)	5408 (9)	⊕⊕⊕⊕ Highg	LMWH decreases the incidence of symptomatic DVT across different cancer types.
		28 per 1000	14 per 1000 (10 to 19)
Any VTE Follow‐up: median 8 months	RR 0.57 (0.46 to 0.71)	High‐risk populationc		38 per 1000 fewer events (26 fewer to 48 fewer)	5743 (10)	⊕⊕⊕⊕ Highh	LMWH decreases the incidence of any VTE across different cancer types.
		90 per 1000	52 per 1000 (43 to 64)
1‐year overall mortality Follow‐up: median 12 months	RR 0.94 (0.83 to 1.07)	High‐risk populationc		35 per 1000 fewer deaths (100 fewer to 41 more)	2681 (9)	⊕⊕⊝⊝ Lowi	LMWH may decrease the incidence of death across different cancer types.
		586 per 1000	551 per 1000 (486 to 627)
Clinically relevant bleeding Follow‐up: median 11 months	RR 3.40 (1.20 to 9.63)	High‐risk populationc		40 per 1000 more clinically relevant bleeds (3 more to 145 more)	3105 (4)	⊕⊕⊕⊝ Moderatej	LMWH probably increases the incidence of clinically relevant bleeding across different cancer types.
		17 per 1000	57 per 1000 (20 to 162)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DVT: deep vein thrombosis; LMWH: low‐molecular‐weight heparin; PE: pulmonary embolism; RR: risk ratio; VTE: venous thromboembolism.
GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: 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 certainty: we are very uncertain about the estimate.

^aThe assumed risk was calculated from the median control group risk across the studies.
^bDifference calculated as the absolute risk difference between the assumed risk and corresponding risk, expressed per 1000.
^cHigh‐risk population refers to the median observed risk to experience symptomatic VTE in the trials contributing to the analyses. It corresponds to 71 per 1000 for symptomatic VTE, which is consistent with previous literature, suggesting that rates of 7% or higher identify individuals at high risk of symptomatic VTE (Khorana 2008). The high‐risk label for other outcomes is based on the risk profile for symptomatic VTE.
^dAlthough 7/11 trials were not double‐blind, and 3/11 trials used dosages exceeding typical prophylactic dosages, results were consistent across trials, so we did not downgrade.
^eDowngraded one level because 10/15 trials contributing to the analyses were not double‐blind, and 4/15 trials did not use standard definitions to ascertain major bleeding. Overall, no relevant inconsistency was detected, so that the effects of non‐blinding, definitions, and other study characteristics were deemed to be small. One study reported zero events in both the intervention and control arm, and was not considered in the 'Summary of findings' table (Zwicker 2013).
^fDowngraded one level because risk of selective outcome reporting, with only 8/15 trials reporting symptomatic PE.
^gAlthough 5/9 trials were not double‐blind, and 2/9 trials used dosages exceeding typical prophylactic dosages, results were very consistent across trials, so we did not downgrade.
^hAlthough 7/10 trials were not double‐blind, and 4/10 trials used dosages exceeding typical prophylactic dosages, results were very consistent across trials, so we did not downgrade.
ⁱDowngraded two levels because the 95% CI included both small and appreciable benefit or harm; with some variability in estimates across trials due to heterogeneity other than sampling error (chance).
^jDowngraded one level due to unexplained between‐trial variation.