ESSENTIALS: Despite trial data, guidelines have not endorsed direct oral Xa inhibitors above other options. We provide profiles of venous thromboembolism and hemorrhage risk for 12 options. Direct oral Xa inhibitors had a favorable profile compared with low-molecular-weight heparin. Other options did not have favorable profiles compared with low-molecular-weight heparin.
SUMMARY:
BACKGROUND: There are numerous trials and several meta-analyses comparing venous thromboembolism (VTE) prophylaxis options after total hip and knee replacement (THR and TKR). None have included simultaneous comparison of new with older options. Objective To measure simultaneously the relative risk of VTE and hemorrhage for 12 prophylaxis options. METHODS: We abstracted VTE and hemorrhage information from randomized controlled trials published between January 1990 and June 2016 comparing 12 prophylaxis options. We then constructed networks to compute the relative risk for each option, relative to once-daily dosing with low-molecular-weight heparin (LMWH) Low. RESULTS MAIN: Relative to LMWH Low, direct oral Xa inhibitors had the lowest risk of total deep vein thrombosis (DVT)-asymptomatic and symptomatic- (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.35-0.57), translating to 53-139 fewer DVTs per 1000 patients. Vitamin K antagonists (VKAs) titrated to International Normalized Ratio [INR] 2-3 predicted 56% more DVT events (OR, 1.56; 95% CI, 1.14-2.14). Aspirin performed similarly (OR, 0.80; 95% CI, 0.34-1.86), although small numbers prohibit firm conclusions. Direct oral Xa inhibitors did not lead to significantly more bleeding (OR, 1.21; 95% CI, 0.79-1.90). Secondary: Relative to LMWH Low, direct oral Xa inhibitors prevented 4-fold more symptomatic DVTs (OR, 0.25; 95% CI, 0.13-0.47). CONCLUSIONS: Relative to LMWH Low, direct oral Xa inhibitors had a more favorable profile of VTE and hemorrhage risk, whereas VKAs had a less favorable profile. The profile of other agents was not more or less favorable. Clinicians should consider these profiles when selecting prophylaxis options.
BACKGROUND: Major orthopedic surgeries, such as total knee replacement (TKR), total hip replacement (THR), and hip fracture (HFx) surgery, carry a high risk for venous thromboembolism (VTE)—deep vein thrombosis (DVT) and pulmonary embolism (PE).
METHODS: Updating a 2012 review, we compare interventions to prevent VTE after TKR, THR, and HFx surgery. We searched four databases and other sources through June 3, 2016, for randomized controlled trials (RCTs) and large nonrandomized comparative studies (NRCSs) reporting postoperative VTE, major bleeding, and other adverse events. We conducted pairwise meta-analyses, Bayesian network meta-analyses, and strength of evidence (SoE) synthesis.
RESULTS: Overall, 127 RCTs and 15 NRCSs met criteria. For THR: low molecular weight heparin (LMWH) has lower risk than unfractionated heparin (UFH) of various VTE outcomes (moderate to high SoE) and major bleeding (moderate SoE). LMWH and aspirin have similar risks of total PE, symptomatic DVT, and major bleeding (low SoE). LMWH has less major bleeding (low SoE) than direct thrombin inhibitors (DTI), but DTI has lower DVT risks (moderate SoE). LMWH has less major bleeding than vitamin K antagonists (VKA) (high SoE). LMWH and factor Xa inhibitor (FXaI) comparisons are inconsistent across VTE outcomes, but LMWH has less major bleeding (high SoE). VKA has lower proximal DVT risk than mechanical devices (high SoE). Longer duration LMWH has lower risk of various VTE outcome risks (low to high SoE). Higher dose LMWH has lower total DVT risk (low SoE) but more major bleeding (moderate SoE). Higher dose FXaI has lower total VTE risk (low SoE). For TKR: LMWH has lower DVT risks than VKA (low to high SoE), but VKA has less major bleeding (low SoE). FXaI has lower risk than LMWH of various VTE outcomes (low to moderate SoE), but LMWH has less major bleeding (low SoE) and more study-defined serious adverse events (low SoE). Higher dose DTI has lower DVT risk (moderate to high SoE) but more major bleeding (low SoE). Higher dose FXaI has lower risk of various VTE outcomes (low to moderate SoE). For HFx surgery: LMWH has lower total DVT risk than FXaI (moderate SoE).
CONCLUSIONS: VTE prophylaxis after major orthopedic surgery trades off lowered VTE risk with possible adverse events—in particular, for most interventions, major bleeding. In THR, LMWH has lower VTE and adverse event risks than UFH, LMWH and aspirin have similar risks of VTE and major bleeding, DTI has lower DVT risk than LMWH but higher major bleeding risk, and higher dose LMWH has lower DVT risk but higher major bleeding risk than lower dose. In TKR, VKA has higher DVT risk than LMWH but lower major bleeding risk, and higher dose DTI has lower DVT risk but higher major bleeding risk than lower dose. In HFx surgery and for other intervention comparisons, there is insufficient evidence to assess both benefits and harms, or findings are inconsistent. Importantly, though, most studies evaluate “total DVT” (an outcome of unclear clinical significance since it includes asymptomatic and other low-risk DVTs), but relatively few studies evaluate PE and other clinically important outcomes. This limitation yields a high likelihood of selective outcome reporting bias. There is also relatively sparse evidence on interventions other than LMWH.
Despite trial data, guidelines have not endorsed direct oral Xa inhibitors above other options. We provide profiles of venous thromboembolism and hemorrhage risk for 12 options. Direct oral Xa inhibitors had a favorable profile compared with low-molecular-weight heparin. Other options did not have favorable profiles compared with low-molecular-weight heparin.
SUMMARY:
BACKGROUND:
There are numerous trials and several meta-analyses comparing venous thromboembolism (VTE) prophylaxis options after total hip and knee replacement (THR and TKR). None have included simultaneous comparison of new with older options. Objective To measure simultaneously the relative risk of VTE and hemorrhage for 12 prophylaxis options.
METHODS:
We abstracted VTE and hemorrhage information from randomized controlled trials published between January 1990 and June 2016 comparing 12 prophylaxis options. We then constructed networks to compute the relative risk for each option, relative to once-daily dosing with low-molecular-weight heparin (LMWH) Low.
RESULTS MAIN:
Relative to LMWH Low, direct oral Xa inhibitors had the lowest risk of total deep vein thrombosis (DVT)-asymptomatic and symptomatic- (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.35-0.57), translating to 53-139 fewer DVTs per 1000 patients. Vitamin K antagonists (VKAs) titrated to International Normalized Ratio [INR] 2-3 predicted 56% more DVT events (OR, 1.56; 95% CI, 1.14-2.14). Aspirin performed similarly (OR, 0.80; 95% CI, 0.34-1.86), although small numbers prohibit firm conclusions. Direct oral Xa inhibitors did not lead to significantly more bleeding (OR, 1.21; 95% CI, 0.79-1.90). Secondary: Relative to LMWH Low, direct oral Xa inhibitors prevented 4-fold more symptomatic DVTs (OR, 0.25; 95% CI, 0.13-0.47).
CONCLUSIONS:
Relative to LMWH Low, direct oral Xa inhibitors had a more favorable profile of VTE and hemorrhage risk, whereas VKAs had a less favorable profile. The profile of other agents was not more or less favorable. Clinicians should consider these profiles when selecting prophylaxis options.
