Summary of findings 3. Low‐molecular‐weight heparin versus with active control (1).
| LMWH: prophylactic dose compared with intermediate or therapeutic dosefor primary thromboprophylaxis in ambulatory cancer patients receiving chemotherapy | ||||||||
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Patient or population: ambulatory cancer patients receiving chemotherapy Settings: outpatient clinics Intervention: prophylactic dose LMWH Comparison: intermediate or therapeutic dose LMWH | ||||||||
| Outcomes | Control type | Relative effect (95% CI) | Illustrative comparative risks* (95% CI) | Differenceb (95% CI) | No of participants (studies) | Certainty of the evidence (GRADE) | What it means | |
| Assumed riska | Corresponding risk | |||||||
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With intermediate/therapeutic dose LMWH Number of events per 1000 participants |
With prophylactic dose LMWH Number of events per 1000 participants |
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| Intermediate‐risk populationc | ||||||||
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Symptomatic VTE Follow‐up: median 3.5 months |
Intermediate | RR 2.89 (0.12 to 66.75) | 31 per 1000 | 90 per 1000 (4 to 2086) | 59 per 1000 more events (28 fewer events to 2055 more) | 51 (1) | ⊕⊕⊝⊝ Lowd |
Prophylactic‐dose LMWH may be associated with a higher risk of symptomatic VTE when compared to intermediate‐dose LMWH in ovarian cancer. |
| Therapeutic | RR 1.00 (0.07 to 15.15) | 53 per 1000 | 53 per 1000 (4 to 805) | 0 per 1000 fewer events (49 fewer events to 752 more) | 52 (1) | ⊕⊕⊝⊝ Lowd |
We do not know if prophylactic‐dose LMWH is associated with a higher risk of symptomatic VTE when compared to therapeutic‐dose LMWH in ovarian cancer. | |
| Intermediate‐risk populationc | ||||||||
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Major bleeding Follow‐up: median 3.5 months |
Intermediate | Not estimablee | NA | NA | NA | NA | NA | As we have insufficient data to estimate the relative risk, we do not know how prophylactic‐dose LMWH affects major bleeding in ovarian cancer. |
| Therapeutic | Not estimablee | NA | NA | NA | NA | NA | ||
| Intermediate‐risk populationc | ||||||||
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Symptomatic PE Follow‐up: median 3.5 months |
Intermediate | RR 2.89 (0.12 to 66.75) | NAf | NA | NA | NA | NA | As we have insufficient data to estimate the assumed risk, we do not know how prophylactic‐dose LMWH affects symptomatic PE in ovarian cancer. |
| Therapeutic | RR 3.00 (0.13 to 70.42) | NAf | NA | NA | NA | NA | ||
| Intermediate‐risk populationc | ||||||||
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Symptomatic DVT Follow‐up: median 3.5 months |
Intermediate | Not estimablee | NA | NA | NA | NA | NA | We do not know how prophylactic‐dose LMWH affects symptomatic DVT across different cancer types. |
| Therapeutic | RR 0.33 (0.01 to 7.82) | 53 per 1000 | 18 per 1000 (1 to 415) | 36 per 1000 fewer DVT (53 fewer to 362 more) | 52 (1) | ⊕⊕⊝⊝ Lowd |
Prophylactic‐dose LMWH may reduce the risk of symptomatic DVT when compared to therapeutic‐dose LMWH in ovarian cancer, although this seems an implausible finding. | |
| Intermediate‐risk populationc | ||||||||
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Any VTE Follow‐up: NA |
Intermediate |
RR 4.81 (0.24 to 95.58) |
NAf | NA | NA | NA | NA | As we have insufficient data to estimate the assumed risk, we do not know how prophylactic‐dose LMWH affects any VTE across different cancer types. |
| Therapeutic |
RR 5.00 (0.25 to 99.34) |
NAf | NA | NA | NA | NA | ||
| Intermediate‐risk populationc | ||||||||
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1‐year overall mortality Follow‐up: NA |
Intermediate | NAg | NA | NA | NA | NA | NA | We do not know how prophylactic‐dose LMWH affects overall mortality when compared to intermediate or therapeutic‐dose LMWH across different cancer types. |
| Therapeutic | NAg | NA | NA | NA | NA | NA | ||
| Intermediate‐risk populationc | ||||||||
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Clinically relevant bleeding Follow‐up: median 3.5 months |
Intermediate | NAe | NA | NA | NA | NA | NA | We do not know how prophylactic‐dose LMWH affects clinically relevant bleeding across different cancer types. |
| Therapeutic | RR 0.33 (0.01 to 7.82) | 38 per 1000h | 13 per 1000 (0 to 301) | 26 per 1000 fewer clinically relevant bleeding (38 fewer to 262 more) | 52 (1) | ⊕⊕⊝⊝ Lowd |
Prophylactic‐dose LMWH may reduce clinically relevant bleeding when compared to therapeutic‐dose LMWH in ovarian cancer. | |
| *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; NA: not applicable; PE: pulmonary embolism; RR: risk ratio; VTE: venous thromboembolism. | ||||||||
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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 is calculated from the medium observed control group risk in Elit 2012 and Pelzer 2015 for the intermediate‐dose estimation, and from Elit 2012 and Maraveyas 2012 for therapeutic‐dose LMWH. bDifference calculated as the absolute risk difference between the assumed risk and corresponding risk, expressed per 1000. cIntermediate‐risk population refers to the median observed risk to experience symptomatic VTE in the trials contributing to the analyses (31 per 1000 and 53 per 1000). Rates between 2% and 7% are considered intermediate risk (Khorana 2008). dDowngraded two levels because of imprecision. eNot estimable due to zero event count in both trial arms. fWe have insufficient data to estimate the assumed risk due to the zero event rate in both the intermediate‐dose and therapeutic‐dose LMWH. gNo trials contributed to this outcome. hThe assumed risk was based on the small trial by Elit 2012 only (the observed event rate in the control group was 1 out of 26).