DOACs, LMWH prevent VTE, but increase bleeding, in major noncardiac surgery

Use of direct oral anticoagulants (DOACs) and low molecular weight heparin (LMWH) appears to reduce venous thromboembolism (VTE) in major noncardiac surgery compared with no active treatment, a study has shown. However, it may also increase major bleeding to a similar extent.

In addition, DOACs seem to be more effective than LMWH in preventing symptomatic VTE at the standard prophylactic dose.

“We showed that pulmonary embolism was consistently rare after noncardiac surgery and that overall reported rates for symptomatic thrombotic events and major bleeding events are rare (<1 percent), but with possible differences across surgical populations and centres,” the researchers said.

“Therefore, we emphasize the need to use our study findings for net effect evaluation of perioperative thromboprophylaxis that accounts for these additional factors,” they added.

In this systematic review and network meta-analyses, the databases of Medline, Embase, and CENTRAL were searched up to August 2021 for randomized controlled trials (RCTs) in adults undergoing noncardiac surgery comparing LMWH with DOACs or with no active treatment.

The researchers abstracted data on participants, interventions, and outcomes, and assessed risk of bias independently in duplicate. They also performed a network meta-analysis with multivariate random effects models and GRADE (grading of recommendations, assessment, development, and evaluation) assessments, which indicated the certainty of the evidence.

Of the 68 RCTs that met the eligibility criteria, 51 dealt with orthopaedic surgery, 10 general, four gynaecological, two thoracic, and one urological, involving 45,445 patients. [BMJ 2022;376:e066785]

Compared with no active treatment, low- (odds ratio [OR], 0.33, 95 percent confidence interval [CI], 0.16‒0.67) and high-dose LMWH (OR, 0.19, 95 percent CI, 0.07‒0.54) and DOACs (OR, 0.17, 95 percent CI, 0.07‒0.41) all prevented symptomatic VTE, with absolute risk differences of 1‒100 per 1,000 patients, depending on baseline risks (certainty of evidence, moderate to high).

None of the active agents, however, were able to effectively reduce symptomatic pulmonary embolism (certainty of evidence, low to moderate).

Moreover, use of DOACs and LMWH resulted in a two- to threefold increase in the likelihood of major bleeding relative to no active treatment (certainty of evidence, moderate to high), with absolute risk differences of 50 per 1,000 in patients at high risk.

High-dose LMWH, compared with the low dose, failed to effectively reduce symptomatic VTE (OR, 0.57, 95 percent CI, 0.26‒1.27) and even increased major bleeding (OR, 1.87, 95 percent CI, 1.06‒3.31). On the other hand, DOACs reduced VTE (OR, 0.53, 95 percent CI, 0.32‒0.89) and did not increase major bleeding (OR, 1.23, 95 percent CI, 0.89‒1.69).

“We believe our work summarizes the current knowledge and can inform decision making, in developing guidelines and in clinical practice,” the researchers said. “Decision makers can use our network relative treatment effects and combine them with trustful (and ideally up-to-date) baseline risk estimates specific to their population and surgery, to obtain absolute treatment effects for benefits and harms.”