2.1 Data sources and search strategy

The study adhered to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) and MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guidelines.^12,13 Medline, Embase, Web of Science, and Cochrane Library were searched from their inception to August 16, 2024. Table S1 details the search strategy. Search results were independently assessed for inclusion by two authors (MFA, AAH). Initial screening was by title and abstract. Further screening of selected full texts determined eligibility. Bibliographies of included articles were manually scanned to identify missed relevant articles. The study was registered in PROSPERO (CRD42024470601).

2.2 Eligibility criteria

Randomised controlled trials (RCTs) and comparative observational studies were eligible for inclusion. Eligible studies included those examining patients undergoing primary elective unilateral THR or TKR and compared those who continued taking aspirin or clopidogrel (antiplatelet group) to those who discontinued these medications or were not taking them before their surgery (non-antiplatelet group). The outcomes of interest are listed in Table 1. Where studies included the results of both patients who discontinued the medications and those who were not previously taking them, data of the former group was preferentially selected for inclusion in the analysis. Data from studies that included revision or bilateral procedures were excluded. Studies examining the effectiveness of initiating antiplatelet medications pre-operatively for prophylaxis against specific conditions such as venous thromboembolism were excluded. Studies in English or with an accessible translation were included. Disagreements regarding study inclusions and marginal studies for eligibility were discussed with the senior author (BLINDED).

2.3 Data extraction and quality assessment

Data was independently extracted using a standardized form, and the methodological quality of the studies were assessed using the Newcastle-Ottawa Scale by two authors (BLINDED, BLINDED).¹⁴ This assesses three domains (selection, comparability, and outcome) across eight items with each scoring one point except for comparability which can be adapted to the specific topic to score up to two points. The two risk factors selected a priori to be most pragmatic and relevant to control for confounding between the comparison groups were body mass index and American Society of Anaesthesiologists grade. Studies scoring less than five points were judged as high risk of bias and excluded, five to seven were considered medium risk, and eight or nine points were deemed low risk.

2.4 Data synthesis and analysis

The meta-analysis was conducted using Review Manager 5.3 (RevMan Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). An inverse variance method was used and random-effects models were applied. Summary measures were abstracted from papers as mean differences (MD) for continuous outcomes and odds ratios (OR) for binary outcomes, along with 95 % confidence intervals (CI). Risk differences (RD) were used to report outcomes when no events occurred in either arm of one or more studies within a comparison. Higgins I² test was performed to provide an estimate of the extent of statistical heterogeneity. 95 % confidence intervals (CI) were calculated for each study with statistical significance set at p ≤ 0.05. Summary estimates of the overall effect are provided as a forest plot. Narrative discussion has been provided where statistical analysis was not possible.

3.1 Study identification and selection

The literature search identified 2721 articles. Fig. 1 illustrates the study selection process. Eight publications met the inclusion criteria (Table 2).^6,15–21

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Fig. 1 PRISMA flow diagram.

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3.2 Study characteristics and study quality

All included studies were observational by design. There were data on 928 THRs and 3526 TKRs. Two studies assessed the outcomes of patients who continued the use of antiplatelets compared to those who discontinued them pre-operatively^19,21 while six studies involved comparison to a group that were not previously taking antiplatelets.^{6,15,16,18,20,22}

Table S2 details the results of the bias assessment.

3.3 Blood loss

3.3.1

3.3.1 Intraoperative blood loss

Pooled analysis found no differences in intraoperative blood loss between groups during both THR and TKR (MD -16.57 mL, 95 % CI -120.75 to 87.61, p = 0.76, and MD -0.06 mL, 95 %CI -6.04 to 5.91, p = 0.98, respectively) (Fig. 2).

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Fig. 2 Mean differences in intraoperative blood loss between patient groups who underwent THR and TKR.

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3.3.2

3.3.2 Post-operative blood loss

Post-operative surgical drain volumes following THR and TKR were not significantly different between groups (MD -32.6 mL, 95 %CI -118.20 to 52.87, p = 0.45, and MD -18.25 mL, 95 %CI -68.26 to 31.76, p = 0.47 respectively) (Fig. 3).

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Fig. 3 Mean differences in post-operative blood drainage volumes between patient groups who underwent THR and TKR.

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3.4 Allogenic blood transfusion

Pooled analyses found no significant differences in receipt of a blood transfusion (OR 1.71, 95 %CI 0.84 to 3.49, p = 0.14) or transfused volume (MD -0.04 units, 95 %CI -0.51 to 0.43, p = 0.87) between patient groups following THR (Fig. 4). However, TKR patients who continued antiplatelet therapy experienced a significantly higher transfusion risk (OR 1.63, 95 %CI 1.25 to 2.13, p = 0.0003) and were transfused a greater volume (MD 0.23 units, 95 % CI 0.00 to 0.46, p = 0.05) (Fig. 4).

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Fig. 4 Odds ratios comparing risk of receiving peri-operative blood transfusion (A) and mean differences in number of units of blood transfused (B) between patient groups for both THR and TKR surgery.

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Wu et al. conducted a combined analysis of THR and TKR operations. They found no significant differences between the two groups for allogenic blood transfusion (19.6 % versus 16.7 %, p = 0.28) or volume transfused (2.4 ± 0.8 versus 2.4 ± 1.1 units; p = 0.85).

Meier et al. reported that perioperative transfusion did not significantly differ between groups for both THR and TKR patients.

3.5 Calculated blood loss

Pooled analysis found no significant differences in calculated blood loss between groups for TKR (MD 39.49 mL, 95 %CI -28.87 to 107.84, p = 0.26) (Fig. S1). Similarly, Hang et al. found no differences between patient groups; median 480 ml (interquartile range 298–636) versus 468 ml (interquartile range 318–603), p = 0.724. However, Wu et al. found estimated blood loss was relatively greater among patients taking clopidogrel and undergoing either TKR or THR surgery (mean 1212.3 mL versus 1068.9 mL, p < 0.03).

3.6 Infection

There were no differences in superficial and deep surgical site infection between patient groups who underwent THR surgery at one-year post-operatively (RD 0.01, 95 %CI -0.01 to 0.03, p = 0.43, and RD 0.00, 95 %CI -0.01 to 0.01, p = 0.42 respectively) (Fig. 5A). Meier et al. reported no surgical site infections occurred in either TKR patient group at one year post-operatively (0/17 versus 0/79).

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Fig. 5 Risk differences for superficial and deep surgical site infection between patient groups following THR (A) and following either THR or TKR surgery (B).

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Pooled analysis of studies reporting on both THR and TKR procedures found no difference in superficial and deep surgical site infection (RD 0.00, 95 %CI -0.04 to 0.04, p = 0.89, and RD 0.00, 95 %CI -0.02 to 0.03, p = 0.73, respectively) (Fig. 5B).

3.7 Wound complications

Ashkenazi et al. reported no significant differences in the proportion of patients who experienced post-operative haematomas (2 % versus 2.7 %, p = 0.79) and persistent wound discharge within and after four days following THR (5.4 % versus 6.3 %, p = 0.64, and 7.1 % versus 11.7 %, p = 0.06, respectively). Chen et al. investigated minor wound complications following TKR (including excessive bullae formation, delayed wound healing, and superficial wound infection). They found no differences between groups at one year post-operatively (1.8 % versus 1.6 %, p = 0.478). Cosetto et al. reported none of the patients who underwent THR and TKR experienced wound dehiscence. Similarly, there were no differences in non-infective wound related complications at one year follow-up among TKR patients in the study by Li et al. (2.22 % versus 0.79 %, p = 0.309). Meier et al. found no differences in post-operative haematoma formation following THR (45.8 % versus 36.8 %, p = 0.495) and wound discharge seven days post-operatively following THR and TKR (45.8 % versus 31.6 %, p = 0.276, and 21.5 % versus 17.6 %, p = 0.721, respectively). Wound complications including prolonged discharge, blister formation, haemarthrosis, and skin necrosis were not significantly different between patient groups following TKR and THR in the study by Wu et al. (OR 1.55, 95 %CI 0.74 to 3.21, p = 0.23).

3.8 Length of procedure

THR patients who continued antiplatelet medications experienced relatively shorter operative times (MD -3.97 min, 95 %CI -7.65 to −0.28, p = 0.03) (Fig. 6A). For TKR, only Schwab et al. reported on length of procedure and found no difference between patient groups (MD -3 min, 95 %CI -6.90 to 0.90, p = 0.13). However, several articles on TKR tourniquet time. Pooled analysis demonstrated no differences between groups (MD -1.50 min, 95 %CI -4.41 to 1.40, p = 0.31) (Fig. 6B).

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Fig. 6 Mean difference in operative time between patient groups undergoing THR (A) and mean difference in tourniquet time between patient groups undergoing TKR (B).

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3.9 Length of hospital stay

Pooled analysis found no differences in length of hospital stay between patient groups for TKR (MD -0.09 days, 95 %CI -0.20 to 0.02, p = 0.12) (Fig. 7). Similarly, Hang et al. found no differences in length of hospital stay between patient groups who underwent TKR (median 3 days, IQR 3 to 5 versus 3 days, IQR 3 to 4, p = 0.869). Wu et al. also reported no significant differences following THR and TKR (mean 4.5 days, range 2–10 versus mean 5.2 days, range 2–27, p = 0.16).

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Fig. 7 Mean difference in length of hospital stay between patient groups who underwent TKR surgery.

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3.10 Venous thromboembolism

Pooled analysis demonstrated no differences in the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) between patient groups undergoing TKR at minimum of 90 days post-operatively (RD 0.00, 95 %CI -0.02 to 0.02, p = 0.76, and RD 0.00, 95 %CI -0.01 to 0.01, p = 1.00, respectively) (Fig. 8). Li et al. evaluated venous thromboembolism as a composite outcome (DVT and PE) and found no differences at one year post-operatively following TKR (3/180 versus 17/380, p = 0.570).

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Fig. 8 Risk differences in incidence of deep vein thrombosis and pulmonary embolism following TKR.

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Wu et al. reported that none of the THR patients in their study experienced a DVT at 90 days post-operatively (0/15 versus 0/27). However, one patient in the non-antiplatelet group experienced a PE (0/56 versus 1/240). It is not known whether this occurred in a patient who had undergone THR or TKR.

Cossetto et al. analysed outcomes of both THR and TKR procedures together and reported that three patients in each group developed a DVT (3/63 versus 3/76) however none experienced a PE.

3.11 Re-admissions and re-operations

Ashkenazi et al. reported on all-cause 30-day and operation-related one-year hospital re-admission following THR and found no difference between patient groups (15/552 versus 5/205, and 5/552 versus 3/205, p = 0.78, respectively). Similarly, Wu et al. found no differences in return to the emergency room within 30 days of THR or TKR surgery (OR 0.86, 95 %CI 0.36 to 2.07, p = 0.83). The authors also found no differences in return to the operating room (OR 4.35, 95 %CI 0.27 to 7.1, p = 0.34).

3.12 Cardiac and cerebral adverse events

Four studies reported on cardiac and cerebral adverse events.

Two of these studies made comparisons to patients who discontinued antiplatelet pre-operatively. Meier et al. reported no differences between patient groups for cardiac and cerebral complications following THR (0 % versus 11.7 %, p = 0.119, and 5.3 % versus 1.7 %, p = 0.392, respectively) and TKR (0 % versus 2.5 %, p = 0.507, and 0 % versus 0 %, respectively) at one-year post-operatively. Wu et al. analysed THR and TKR procedures together, and found no differences in transient ischaemic attacks and strokes (0/56 versus 6/240) and acute myocardial infarction (1/56 versus 7/240) between patient groups (OR 0.32, 95 %CI 0.04 to 2.48, p = 0.48).

Two studies compared results to patients who were not previously taking antiplatelet medications. Li et al. found no differences in cardiac (18.18 % versus 25 %, p = 0.944) and cerebrovascular events (9.09 % versus 12.50 %, p = 1.00) between TKR patient groups at one-year follow up. Chen et al. reported that none of the TKR patients experienced a cardiac or cerebrovascular event at one-year post-operatively (0/217 versus 0/1078).

3.13 Mortality

Wu et al. compared results to patients who discontinued their antiplatelet medication pre-operatively. They found no significant differences in 90-day post-operative mortality between patient groups undergoing either THR or TKR (0/56 versus 1/240). Chen et al. reported there was no in-hospital mortality between patient groups who underwent TKR (0/217 versus 0/1078). Ashkenazi et al. reported on mortality at one month and one-year following THR and found no differences between groups (1/205 versus 1/552, p = 0.47, and 4/205 versus 3/552, p = 0.40, respectively).