Table 8.
—[Section 2.5.2] Summary of Findings: LMWH Once vs Twice Daily for Initial Anticoagulation of Acute VTEa,b,81
| Outcomes | No. of Participants (Studies), Follow-up | Quality of the Evidence (GRADE) | Relative Effect (95% CI) | Anticipated Absolute
Effects |
|
| Risk With Twice Daily | Risk Difference With LMWH Once Daily (95% CI) | ||||
| Mortality |
1,261 (3 studies), 3 mo |
Lowc-e due
to inconsistency and imprecision |
RR 1.05 (0.57-1.94) |
31 per 1,000 |
2 more per 1,000 (from 13 fewer to 29 more) |
| VTE recurrence |
1,261 (3 studies), 3 mo |
Lowc,e,f due
to inconsistency and imprecision |
RR 0.86 (0.52-1.42) |
49 per 1,000 |
7 fewer per 1,000 (from 24 fewer to 21 more) |
| Major bleeding | 1,522 (5 studies), 10 d | Moderatec,e due to imprecision | RR 1.13 (0.48-2.66) | 12 per 1,000 | 2 more per 1,000 (from 6 fewer to 20 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.
Of the five included studies, one included patients with PE and DVT and four included only patients with DVT. All studies addressed the initial management of VTE.
The five included studies used four brands of LMWH (enoxaparin, tinzaparin, dalteparin, and nadroparin). In Merli et al,85 enoxaparin 1 mg/kg bid was compared with 1.5 mg/kg once daily. Holmström et al84 adjusted the dose to anti-Xa levels, which resulted in different daily doses after a number of days. In the remaining studies, the dose of the once-daily administration was double the dose of the twice-daily administration (equal total daily dose).
All included studies concealed allocation. Two studies had a double-blind design, and two others were single blind. One study did not mention blinding. Intention to treat likely used in all studies. Participants were lost to follow-up in only two studies (0.3% and 2.2%).
I2 = 37%; point effect estimate in favor of twice-daily dose in Merli et al85 and in favor of once-daily dose in Charbonnier et al.83
Imprecision judged relative to no difference.
I2 = 65%; point effect estimate in favor of twice-daily dose in Merli et al85 and in favor of once-daily dose in Charbonnier.83