BACKGROUND: It is generally assumed by practitioners and guideline authors that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thromboembolism (VTE), defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), or both. This is the second update of the review first published in 2008.
OBJECTIVES: The aim of this review was to assess the efficacy of combined intermittent pneumatic leg compression (IPC) and pharmacological prophylaxis compared to single modalities in preventing VTE.
SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 18 January 2021. We searched the reference lists of relevant articles for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or controlled clinical trials (CCTs) of combined IPC and pharmacological interventions used to prevent VTE compared to either intervention individually.
DATA COLLECTION AND ANALYSIS: We independently selected studies, applied Cochrane's risk of bias tool, and extracted data. We resolved disagreements by discussion. We performed fixed-effect model meta-analyses with odds ratios (ORs) and 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. We assessed the certainty of the evidence using GRADE. The outcomes of interest were PE, DVT, bleeding and major bleeding.
MAIN RESULTS: We included a total of 34 studies involving 14,931 participants, mainly undergoing surgery or admitted with trauma. Twenty-five studies were RCTs (12,672 participants) and nine were CCTs (2259 participants). Overall, the risk of bias was mostly unclear or high. We used GRADE to assess the certainty of the evidence and this was downgraded due to the risk of bias, imprecision or indirectness. The addition of pharmacological prophylaxis to IPC compared with IPC alone reduced the incidence of symptomatic PE from 1.34% (34/2530) in the IPC group to 0.65% (19/2932) in the combined group (OR 0.51, 95% CI 0.29 to 0.91; 19 studies, 5462 participants, low-certainty evidence). The incidence of DVT was 3.81% in the IPC group and 2.03% in the combined group showing a reduced incidence of DVT in favour of the combined group (OR 0.51, 95% CI 0.36 to 0.72; 18 studies, 5394 participants, low-certainty evidence). The addition of pharmacological prophylaxis to IPC, however, increased the risk of any bleeding compared to IPC alone: 0.95% (22/2304) in the IPC group and 5.88% (137/2330) in the combined group (OR 6.02, 95% CI 3.88 to 9.35; 13 studies, 4634 participants, very low-certainty evidence). Major bleeding followed a similar pattern: 0.34% (7/2054) in the IPC group compared to 2.21% (46/2079) in the combined group (OR 5.77, 95% CI 2.81 to 11.83; 12 studies, 4133 participants, very low-certainty evidence). Tests for subgroup differences between orthopaedic and non-orthopaedic surgery participants were not possible for PE incidence as no PE events were reported in the orthopaedic subgroup. No difference was detected between orthopaedic and non-orthopaedic surgery participants for DVT incidence (test for subgroup difference P = 0.19). The use of combined IPC and pharmacological prophylaxis modalities compared with pharmacological prophylaxis alone reduced the incidence of PE from 1.84% (61/3318) in the pharmacological prophylaxis group to 0.91% (31/3419) in the combined group (OR 0.46, 95% CI 0.30 to 0.71; 15 studies, 6737 participants, low-certainty evidence). The incidence of DVT was 9.28% (288/3105) in the pharmacological prophylaxis group and 5.48% (167/3046) in the combined group (OR 0.38, 95% CI 0.21 to 0.70; 17 studies; 6151 participants, high-certainty evidence). Increased bleeding side effects were not observed for IPC when it was added to anticoagulation (any bleeding: OR 0.87, 95% CI 0.56 to 1.35, 6 studies, 1314 participants, very low-certainty evidence; major bleeding: OR 1.21, 95% CI 0.35 to 4.18, 5 studies, 908 participants, very low-certainty evidence). No difference was detected between the orthopaedic and non-orthopaedic surgery participants for PE incidence (test for subgroup difference P = 0.82) or for DVT incidence (test for subgroup difference P = 0.69).
AUTHORS' CONCLUSIONS: Evidence suggests that combining IPC with pharmacological prophylaxis, compared to IPC alone reduces the incidence of both PE and DVT (low-certainty evidence). Combining IPC with pharmacological prophylaxis, compared to pharmacological prophylaxis alone, reduces the incidence of both PE (low-certainty evidence) and DVT (high-certainty evidence). We downgraded due to risk of bias in study methodology and imprecision. Very low-certainty evidence suggests that the addition of pharmacological prophylaxis to IPC increased the risk of bleeding compared to IPC alone, a side effect not observed when IPC is added to pharmacological prophylaxis (very low-certainty evidence), as expected for a physical method of thromboprophylaxis. The certainty of the evidence for bleeding was downgraded to very low due to risk of bias in study methodology, imprecision and indirectness. The results of this update agree with current guideline recommendations, which support the use of combined modalities in hospitalised people (limited to those with trauma or undergoing surgery) at risk of developing VTE. More studies on the role of combined modalities in VTE prevention are needed to provide evidence for specific patient groups and to increase our certainty in the evidence.
BACKGROUND: Patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) are at risk of venous thromboembolism (VTE). Australian orthopaedic guidelines recommend aspirin and low-molecular-weight heparin (e.g. enoxaparin) for VTE prophylaxis; however, there is debate in the international literature around the use of aspirin as VTE prophylaxis. This review assesses the risks and benefits of aspirin compared to enoxaparin as VTE prophylaxis for patients undergoing THA or TKA.
METHODS: A systematic review was conducted to identify relevant randomized controlled trials. Studies comparing enoxaparin, aspirin and/or placebo for VTE prophylaxis in THA or TKA patients were included. Network meta-analysis (NMA) was performed to calculate risk ratios (RRs) and confidence intervals (CIs). Quality appraisal was conducted by assessing risk of bias and the strength of the evidence.
RESULTS: Nine randomized controlled trials were eligible for inclusion. The NMA found no statistically significant differences for the investigated outcomes: total DVT rates (RR = 1.21, 95% CI 0.86, 1.72), symptomatic pulmonary embolism (PE) rates (RR = 1.02, 95% CI 0.02, 50.86), major haemorrhage (RR = 0.97, 95% CI 0.02, 50.99) and wound complication (RR = 0.73, 95% CI 0.17, 3.20). The occurrence of PE was rare. Due to limited data, sub-group analysis was not possible. The overall quality of evidence in the NMA is considered to be very low.
CONCLUSION: This review did not find statistically significant differences between aspirin and enoxaparin. Future studies should identify more evidence, particularly for rare outcomes such as PE, as this might help decision-makers to get consensus on the use of aspirin as VTE prophylaxis.
Background: Patients who undergo knee or hip arthroplasty are at a significant risk of venous thromboembolism (VTE) development (pulmonary embolism and/or deep-vein thrombosis). Many different thromboprophylactic strategies have been used for the prevention of VTE in these patients with different outcomes. Therefore, our aim was to evaluate the efficacy and safety of aspirin prophylaxis when compared with placebo or anticoagulants in this population of patients. Methods: A comprehensive electronic database search was conducted for all randomized controlled trials (RCTs) comparing the clinical outcomes of aspirin versus placebo or anticoagulants for the prevention of VTE after knee or hip arthroplasty. The primary outcome was VTE incidence. Secondary outcomes included any bleeding, major bleeding and mortality. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest possible follow-up period. Results: We included 13 RCTs with a total of 20,115 patients with a mean age of 67.15 ± 9.54 and 24.39% males. Aspirin was found to be associated with a non-significantly reduced VTE events compared with other thromboprophylactic methods (RR 0.87; 95% CI: 0.61–1.23; P = 0.43). Compared with placebo, aspirin was associated with significant reduction of VTE (RR 0.65; 95% CI: 0.47–0.89; P = 0.008). There were no significant differences in the clinical outcomes between all groups with regard to mortality (RR 0.98; 95% CI: 0.86–1.11; P = 0.72), major bleeding events (RR 0.96; 95% CI: 0.50–1.84; P = 0.91), and any bleeding events (RR: 1.09; 95% CI: 0.82–1.44; P = 0.56). Conclusion: Among patients who underwent knee or hip arthroplasty, aspirin prophylaxis was found to be associated with similar efficacy and safety outcomes when compared with anticoagulants. When compared with placebo, aspirin prophylaxis was associated with significantly reduced VTE and a comparable safety profile.
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: Venous thromboembolism causes significant morbidity and mortality in patients after total joint arthroplasty. Although network meta-analyses have demonstrated a benefit of various thromboprophylactic agents, there remains a concern in the surgical community regarding the resulting wound complications. There is currently no systematic review of the surgical site bleeding complications of thromboprophylactic agents. The aim of this study was to systematically review the surgical site bleeding outcomes of venous thromboembolism prophylaxis in this population.
METHODS: A systematic review and meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials comparing more than one of low-molecular-weight heparin (LMWH), warfarin, rivaroxaban, apixaban, dabigatran, aspirin, or no pharmacologic treatment in patients after total hip or knee arthroplasty were selected for inclusion. Five meta-analyses were performed to compare LMWH with control, warfarin, apixaban, rivaroxaban, and dabigatran.
RESULTS: Forty-five randomized controlled trials of 56,730 patients were included. LMWH had a significantly increased relative risk of surgical site bleeding in comparison with control (relative risk, 2.32; 95% confidence interval, 1.40-3.85) and warfarin (1.54; 1.23-1.94). The relative risk of LMWH trended higher than apixaban (1.27; 1.00-1.63) and was similar to rivaroxaban (0.95; 0.74-1.23). Only 1 study reported the risk of surgical site bleeding in LMWH vs dabigatran (5.97; 2.08-17.11).
CONCLUSION: LMWH increased the risk of surgical site bleeding compared with control, warfarin. and dabigatran and trended toward an increased risk compared with apixaban. The risk of surgical site bleeding was similar with LMWH and rivaroxaban.
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.
AIMS: There is uncertainty regarding the optimal means of thromboprophylaxis following total hip and knee arthroplasty (THA, TKA). This systematic review presents the evidence for acetylsalicylic acid (aspirin) as a thromboprophylactic agent in THA and TKA and compares it with other chemoprophylactic agents.
MATERIALS AND METHODS: A search of literature published between 2004 and 2014 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 13 studies were eligible for inclusion.
RESULTS: Evidence from one good quality randomised controlled trial (RCT) showed no difference in rates of venous thrombo-embolism (VTE) in patients given aspirin or low molecular weight heparin (LMWH) following TKA. There was insufficient evidence from trials with moderate to severe risk of bias being present to suggest aspirin is more or less effective than LMWH, warfarin or dabigatran for the prevention of VTE in TKA or THA. Compared with aspirin, rates of asymptomatic deep vein thrombosis (DVT) in TKA may be reduced with rivaroxaban but insufficient evidence exists to demonstrate an effect on incidence of symptomatic DVT. Compared with aspirin there is evidence of more wound complications following THA and TKA with dabigatran and in TKA with rivaroxaban. Some studies highlighted concerns over bleeding complications and efficacy of aspirin.
CONCLUSION: The results suggest aspirin may be considered a suitable alternative to other thromboprophylactic agents following THA and TKA. Further investigation is required to fully evaluate the safety and efficacy of aspirin. Cite this article: Bone Joint J 2016;98-B:1056-61.
BACKGROUND: Venous thromboembolism (VTE) comprises pulmonary embolism and deep vein thrombosis and is a complication of particular concern in lower limb arthroplasty. In recent years, aspirin has emerged as a potential alternative thromboprophylactic agent, particularly after its acceptance as a recommended agent by the American College of Chest Physicians. Aspirin is favorable due to its relative cost-effectiveness and convenience compared to novel oral anticoagulants and warfarin. However, its efficacy since its inclusion in the American College of Chest Physicians guidelines remains unclear. The present systematic review aimed to establish the efficacy of aspirin in preventing VTE in total hip and knee arthroplasty.
METHODS: Electronic searches were performed using 6 databases from up to June 2015, identifying all relevant studies. Data were extracted and meta-analyzed.
RESULTS: Eleven relevant studies were identified for inclusion in the present meta-analysis. The overall rate of deep vein thrombosis and pulmonary embolism in both hip and knee arthroplasty was 1.2% and 0.6%, respectively. The rate of major bleeding was 0.3%. Pooled mortality rate was 0.2%. All findings demonstrated a high and significant degree of heterogeneity.
CONCLUSION: Aspirin, both alone and in multimodal approaches to thromboprophylaxis, confers a low rate of VTE, with a low risk of major bleeding complications. However, the evidence for its use is limited by the low quality of studies and variation in dose in dosing regimes. Future randomized controlled trials should investigate the efficacy of aspirin, as well as the ideal dosing protocol for its use in thromboprophylaxis in arthroplasty.
Background: Hip fracture surgery and lower extremity arthroplasty are associated with increased risk of both venous thromboembolism and bleeding. The best pharmacologic strategy for reducing these opposing risks is uncertain. Purpose: To compare venous thromboembolism (VTE) and bleeding rates in adult patients receiving aspirin versus anticoagulants after major lower extremity orthopedic surgery. Data Sources: Medline, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library through June 2013; reference lists, ClinicalTrials.gov, and scientific meeting abstracts. Study Selection: Randomized trials comparing aspirin to anticoagulants for prevention of VTE following major lower extremity orthopedic surgery. Data Extraction: Two reviewers independently extracted data on rates of VTE, bleeding, and mortality. Data Synthesis: Of 298 studies screened, 8 trials including 1408 participants met inclusion criteria; all trials screened participants for deep venous thrombosis (DVT). Overall rates of DVT did not differ statistically between aspirin and anticoagulants (relative risk [RR]: 1.15 [95% confidence interval {CI}: 0.68-1.96]). Subgrouped by type of surgery, there was a nonsignificant trend favoring anticoagulation following hip fracture repair but not knee or hip arthroplasty (hip fracture RR: 1.60 [95% CI: 0.80-3.20], 2 trials; arthroplasty RR: 1.00 [95% CI: 0.49-2.05], 5 trials). The risk of bleeding was lower with aspirin than anticoagulants following hip fracture repair (RR: 0.32 [95% CI: 0.13-0.77], 2 trials), with a nonsignificant trend favoring aspirin after arthroplasty (RR: 0.63 [95% CI: 0.33-1.21], 5 trials). Rates of pulmonary embolism were too low to provide reliable estimates. Conclusion: Compared with anticoagulation, aspirin may be associated with higher risk of DVT following hip fracture repair, although bleeding rates were substantially lower. Aspirin was similarly effective after lower extremity arthroplasty and may be associated with lower bleeding risk.
CONTEXTE: la thromboprophylaxie optimale pour les patients à risque de saignement reste incertain. Cette méta-analyse a évalué si la compression pneumatique intermittente (CPI) des membres inférieurs était efficace dans la réduction de la maladie thromboembolique veineuse et si la combinaison thromboprophylaxie pharmacologique avec l'IPC devrait améliorer son efficacité.
MÉTHODES ET RÉSULTATS: Deux examinateurs ont fouillé Medline, Embase et le registre des essais contrôlés Cochrane (1966-Février 2013) pour des essais contrôlés randomisés et évalué les résultats et la qualité des essais indépendamment. Des essais comparant l'IPC avec une thromboprophylaxie pharmacologique, bas de dissuasion thromboemboliques, aucune prophylaxie, et une combinaison de l'IPC et pharmacologiques thromboprophylaxie ont été pris en compte. Les essais qui ont utilisé CIB <24 heures ou contre différents types d'IPC ont été exclus. Un total de 16 164 patients hospitalisés provenant de 70 essais répondaient aux critères d'inclusion et ont été soumis à une méta-analyse. IPC était plus efficace que l'absence IPC prophylaxie dans la réduction de la thrombose veineuse profonde (7,3% versus 16,7%; réduction du risque absolu, 9,4%, intervalle de confiance à 95% [IC], 07.09 à 10.09; risque relatif, 0,43, IC 95%, 0,36 0,52, p <0,01; I (2) = 34%) et l'embolie pulmonaire (1,2% versus 2,8%; réduction du risque absolu de 1,6%, IC à 95% 0,9-2,3; risque relatif, 0,48, IC 95%, 0,33 0,69, p <0,01; I (2) = 0%). IPC était également plus efficace que les bas de dissuasion thromboemboliques dans la réduction de la thrombose veineuse profonde et semble être aussi efficace que la thromboprophylaxie pharmacologique, mais avec une réduction du risque de saignement (risque relatif: 0,41, IC 95%, 0,25 à ,65; P <0,01; I ( 2) = 0%). Ajout d'une thromboprophylaxie pharmacologique IPC réduit davantage le risque de thrombose veineuse profonde (risque relatif: 0,54, IC95% 0,32 à 0,91, P = 0,02, I (2) = 0%) par rapport à l'IPC seul.
CONCLUSIONS: CIB a été efficace dans la réduction de la maladie thromboembolique veineuse, et la combinaison de la thromboprophylaxie pharmacologique avec l'IPC était plus efficace que d'utiliser IPC seul.
It is generally assumed by practitioners and guideline authors that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thromboembolism (VTE), defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), or both. This is the second update of the review first published in 2008.
OBJECTIVES:
The aim of this review was to assess the efficacy of combined intermittent pneumatic leg compression (IPC) and pharmacological prophylaxis compared to single modalities in preventing VTE.
SEARCH METHODS:
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 18 January 2021. We searched the reference lists of relevant articles for additional studies.
SELECTION CRITERIA:
We included randomised controlled trials (RCTs) or controlled clinical trials (CCTs) of combined IPC and pharmacological interventions used to prevent VTE compared to either intervention individually.
DATA COLLECTION AND ANALYSIS:
We independently selected studies, applied Cochrane's risk of bias tool, and extracted data. We resolved disagreements by discussion. We performed fixed-effect model meta-analyses with odds ratios (ORs) and 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. We assessed the certainty of the evidence using GRADE. The outcomes of interest were PE, DVT, bleeding and major bleeding.
MAIN RESULTS:
We included a total of 34 studies involving 14,931 participants, mainly undergoing surgery or admitted with trauma. Twenty-five studies were RCTs (12,672 participants) and nine were CCTs (2259 participants). Overall, the risk of bias was mostly unclear or high. We used GRADE to assess the certainty of the evidence and this was downgraded due to the risk of bias, imprecision or indirectness. The addition of pharmacological prophylaxis to IPC compared with IPC alone reduced the incidence of symptomatic PE from 1.34% (34/2530) in the IPC group to 0.65% (19/2932) in the combined group (OR 0.51, 95% CI 0.29 to 0.91; 19 studies, 5462 participants, low-certainty evidence). The incidence of DVT was 3.81% in the IPC group and 2.03% in the combined group showing a reduced incidence of DVT in favour of the combined group (OR 0.51, 95% CI 0.36 to 0.72; 18 studies, 5394 participants, low-certainty evidence). The addition of pharmacological prophylaxis to IPC, however, increased the risk of any bleeding compared to IPC alone: 0.95% (22/2304) in the IPC group and 5.88% (137/2330) in the combined group (OR 6.02, 95% CI 3.88 to 9.35; 13 studies, 4634 participants, very low-certainty evidence). Major bleeding followed a similar pattern: 0.34% (7/2054) in the IPC group compared to 2.21% (46/2079) in the combined group (OR 5.77, 95% CI 2.81 to 11.83; 12 studies, 4133 participants, very low-certainty evidence). Tests for subgroup differences between orthopaedic and non-orthopaedic surgery participants were not possible for PE incidence as no PE events were reported in the orthopaedic subgroup. No difference was detected between orthopaedic and non-orthopaedic surgery participants for DVT incidence (test for subgroup difference P = 0.19). The use of combined IPC and pharmacological prophylaxis modalities compared with pharmacological prophylaxis alone reduced the incidence of PE from 1.84% (61/3318) in the pharmacological prophylaxis group to 0.91% (31/3419) in the combined group (OR 0.46, 95% CI 0.30 to 0.71; 15 studies, 6737 participants, low-certainty evidence). The incidence of DVT was 9.28% (288/3105) in the pharmacological prophylaxis group and 5.48% (167/3046) in the combined group (OR 0.38, 95% CI 0.21 to 0.70; 17 studies; 6151 participants, high-certainty evidence). Increased bleeding side effects were not observed for IPC when it was added to anticoagulation (any bleeding: OR 0.87, 95% CI 0.56 to 1.35, 6 studies, 1314 participants, very low-certainty evidence; major bleeding: OR 1.21, 95% CI 0.35 to 4.18, 5 studies, 908 participants, very low-certainty evidence). No difference was detected between the orthopaedic and non-orthopaedic surgery participants for PE incidence (test for subgroup difference P = 0.82) or for DVT incidence (test for subgroup difference P = 0.69).
AUTHORS' CONCLUSIONS:
Evidence suggests that combining IPC with pharmacological prophylaxis, compared to IPC alone reduces the incidence of both PE and DVT (low-certainty evidence). Combining IPC with pharmacological prophylaxis, compared to pharmacological prophylaxis alone, reduces the incidence of both PE (low-certainty evidence) and DVT (high-certainty evidence). We downgraded due to risk of bias in study methodology and imprecision. Very low-certainty evidence suggests that the addition of pharmacological prophylaxis to IPC increased the risk of bleeding compared to IPC alone, a side effect not observed when IPC is added to pharmacological prophylaxis (very low-certainty evidence), as expected for a physical method of thromboprophylaxis. The certainty of the evidence for bleeding was downgraded to very low due to risk of bias in study methodology, imprecision and indirectness. The results of this update agree with current guideline recommendations, which support the use of combined modalities in hospitalised people (limited to those with trauma or undergoing surgery) at risk of developing VTE. More studies on the role of combined modalities in VTE prevention are needed to provide evidence for specific patient groups and to increase our certainty in the evidence.
