Introduction

Metabolic and bariatric surgery (MBS) is an effective approach for achieving weight loss and resolution of obesity-associated medical problems among patients with obesity [1, 2]. As with any surgical procedure, there is the risk of post-operative venous thromboembolic events (VTE) after MBS, which is exacerbated by the underlying obesity [3]. With the increasing global frequency of MBS [4], VTE presents a particularly serious complication with significant effects on readmission rates and mortality [3, 5, 6].

The literature has shown wide variations in the incidence of VTE after MBS [7, 8]. For instance, previous studies have reported 30-day incidences ranging from 0 to 5.66% [9, 10]. Although the number of meta-analyses on many MBS topics continues to increase [11,12,13], there are no systematic reviews/meta-analyses of the incidence of VTE after MBS. This is despite the available literature that could be meta-analyzed to generate high-quality estimates [5, 7, 10, 14,15,16,17]. To date, global estimates of VTE at different timepoints after MBS remain uncertain, despite the calls for more accurate estimates [7]. The current study is the first to bridge this knowledge gap.

Aim of the Study

The present study aimed to review and synthesize the evidence on the incidence of VTE after MBS. The objectives were to (1) compute global cumulative incidence of VTE at five timepoints after surgery (in-hospital, at 30 days and 3, 6, and 12 months) for studies that utilized mainly laparoscopic approach and those that used predominantly open surgical approach and (2) for the first 30 days investigate the proportions of VTE that occurred in-hospital vs post-discharge. In addition, we subgrouped the studies at each timepoint by two variables, namely, geographic origin and study age (final year of data acquisition) to explore potential sources of heterogeneity, and appraise whether such factors influenced the incidence of VTE. Evaluation of procedure- or patient-related risk factors or prophylaxis and their associations with VTE were not within the scope of this review.

Materials and Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was used to conduct and report this systematic review with meta-analysis [18]. The study protocol was registered a priori (PROSPERO ID: CRD42020184529).

Search Strategy

A systematic search for relevant studies was conducted on 27 April 2022 using PubMed, MEDLINE, and Scopus. The full search strategy, including search terms and medical subject headings (MeSH), is detailed in Supplementary File 1. The reference lists of related reviews were checked for eligible studies that were not captured in the search.

Study Selection

The inclusion criteria were original English language studies of any design, sample size, MBS procedure, or surgical approach that provided cumulative incidence of VTE or sufficient detail to calculate it for the total patient sample. Exclusion criteria included commentaries, letters, practice guidelines, reviews, and conference proceedings; studies that did not include VTE; studies that applied specific limitations to the patient populations they examined, e.g., specific age, weight or BMI cutoffs, obesity associated medical problems, or ethnicity; or questionnaire-based studies reporting subjective recall of VTE from clinicians. Studies were included if they accounted for all VTE including both deep vein thrombosis and pulmonary embolism. Studies that accounted only for specific sub-types of VTE were excluded.

Screening and Data Extraction

Duplicate titles were removed and then all references were independently screened by two authors (WEA, ML) using Covidence (Veritas Health Innovation, Australia). The first stage was title and abstract screening, and studies were excluded if both authors rejected them. In the second stage, full-text articles were screened for eligibility, and studies approved by both authors were included. Conflicts were resolved through discussion between the two authors. Data extraction was undertaken and tabulated by WEA and KE-A and verified by ML and included study identifiers, country, sample size and characteristics, data sources, duration of data acquisition, surgical procedure, approach (laparoscopic, open, robotic), and the reported incidence and timing of VTE. Missing data were calculated where possible or extracted from figures using WebplotDigitizer 4.5 (Ankit Rohatgi, USA).

Outcomes

The outcomes were cumulative incidence of VTE at five timepoints (in-hospital, 30 days, and 3, 6, 12 months) and for the first 30 days, the proportions of VTE that occurred in-hospital vs post-discharge.

Risk of Bias Assessment

Potential risk of bias was assessed using the tool by Loney et al. [19], which was developed specifically for studies of prevalence/incidence. The tool was selected for its comprehensiveness and applicability to the study objectives. It comprises eight equally weighted items yielding a maximum score of eight, with higher scores indicating lower risk of bias. Included studies were scored by ML, and then 10% was randomly selected and scored by WEA. Mean percentage agreement across the eight individual items was reported.

Data Synthesis and Statistical Analysis

All studies were cross-checked for duplicated use of data by verifying their data sources (hospital or national/regional registries), sampling timeframe, and included procedures. Where duplicate use of patient data was suspected, only the studies that minimized any overlap were included in the meta-analyses. As many of the included studies were undertaken using large administrative datasets such as NSQIP, MBSAQIP, or NIS, multiple studies included in the same year/s of data from the same registry were meticulously securitized for their procedures, patient samples, and recruitment years, in order to check, confirm, and exclude any potential duplicate use of the data of the same patients. If there was any remaining doubt, the research team undertook the extra step of contacting the authors of such papers for more verification.

Random effects proportional meta-analyses of VTE at the five timepoints were conducted using MetaXL (EpiGear, international Pty Ltd., Queensland, Australia) for Microsoft Excel. Data were transformed using the double arcsine method. This allows inclusion of zero-case studies, stabilizes variance, and has demonstrated advantages [20]. Additionally, categorical meta-analysis assessed pre- versus post-discharge 30-day incidence and was expressed as a proportion of the total number of cases.

Results were presented by surgical approach as pooling both (laparoscopic and open) approaches was deemed inappropriate because most procedures are currently undertaken laparoscopically. Most studies reported a mix of laparoscopic and open approaches; hence, cut-offs were required. As approximately half of the studies that used a majority open approach reported it for 50–80% of their procedures, and almost all studies that used a majority laparoscopic approach reported it for > 80% of their procedures, we subgrouped studies into “ > 80% laparoscopic approach” vs “ > 50% open approach.” Furthermore, subgroup analyses were conducted on cumulative incidences at each timepoint to identify any influence of the subgroups on the pooled estimates, and to assess sources of heterogeneity. In terms of study age, we categorized studies into those with data collected up to the end of 2010 vs after 2010, as an earlier cut-off was not feasible due to a lack of relevant studies. Geographically, it was only feasible to subgroup studies into North America vs “other” countries, as roughly 70% of studies were from North America. This latter comparison was limited to studies with > 80% laparoscopic approach to minimize possible confounding due to surgical approach. Since small samples have potentially lower sensitivity to capture VTE, sensitivity analysis was undertaken excluding the small studies (n < 2000 patients) to assess its influence on pooled incidence of the geographical subgroups.

Heterogeneity

Heterogeneity was measured using Higgin’s I2, Cochrane’s Q, and Chi2. Given the nature of incidence data, high heterogeneity was expected due to large sample sizes and low variance. Therefore, thresholds for heterogeneity [21] were interpreted conservatively in line with recommendations regarding proportional meta-analysis [22].

Publication Bias

We used funnel plots based on sample size (rather than standard error) as they have been shown to be a valid alternative for assessing publication bias in proportional meta-analysis [23], since traditional funnel plots may indicate asymmetry when no publication bias is present [22, 23]. In addition, recent guidelines recommend qualitative methods to appraise publication bias of incidence data [22]. Hence, we assessed publication bias using a combination of both.

Results

Search Results

The PRISMA diagram (Fig. 1) shows that of 3066 retrieved articles, 87 were included in the review [5, 6, 9, 10, 14,15,16,17, 24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102], of which 68 were meta-analyzed. The studies excluded at full text and their reasons, as well as the included studies, and their subgroupings are available in Supplementary File 2.

Fig. 1
figure 1

PRISMA flowchart of search and screening results

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Study Characteristics

Table 1 outlines the studies included in the review (N = 4,991,683 patients). A total of 2,259,886 patients were subsequently excluded from meta-analyses due to data overlap or aggregated data. Data of the remaining 2,731,797 patients were meta-analyzed. The largest study included 540,959 patients [31] and the smallest comprised 39 patients [60].

Table 1 Characteristics of the 87 original studies included in the current review (4,991,683 patients)
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Geographically, 62 included studies (71.3%) were based on North American data, whereas 25 (28.7%) reported data from other countries. Surgical approach was > 80% laparoscopic in 60 studies (69.0%); > 50% open in 10 (11.5%); did not fulfill the above cut-offs for surgical approach in three (3.44%) [24, 55, 80]; and was not explicitly reported in 14 studies (16.1%). Thirty-two studies (36.8%) included data collected up to the end of 2010, 52 (59.8%) included data collected after 2010, and three studies (3.4%) did not report their data timeframe [16, 53, 99].

Thirty-six studies (41.4%) reported ≥ 3 MBS procedures, 15 (17.2%) undertook only RYGB, 14 (16.1%) included both RYGB and SG, seven (8.0%) undertook strictly SG, four (4.6%) conducted only BPD-DS, six (6.9%) included RYGB and adjustable gastric banding or removal, three (3.4%) reported other combinations [27, 33, 89], and two studies (2.3%) did not report their included procedures [10, 16].

Seventy-three studies (83.9%) reported the sex distribution of their sample, with females comprising a mean of 77.6%. Fourteen (16.1%) did not report sex distribution. Seventy-two studies (82.8%) reported the mean age of their sample, with an average of 42.9 ± 3.02 years, while seven (8%) provided the median age for the sample, and eight studies (9.2%) did not report age. Sixty-four studies (73.6%) reported mean BMI (46.1 ± 6.0 kg/m2 across all studies), six (6.9%) provided their median BMIs, while 17 studies (19.5%) did not report BMI.

Table 2 shows the time point/s of incidence provided by each included study (i.e., the specific meta-analysis/es that each study contributed to, as well as the studies that were excluded from primary (not sub-grouped) meta-analysis of any given time point due to significant overlap in data with other studies. Data sources of each included study are outlined in Supplementary File 3.

Table 2 Timeframe of incidence provided by each included study
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Risk of Bias Appraisal

The mean risk of bias score was 5.82 ± 1.43, with a range of 3–8 (Supplementary File 4). Fifty studies (57.5%) scored six or higher, indicating a low risk of bias. The 20 studies with lower scores of 3–4 were mainly due to small sample sizes, potentially biased sampling frames, or poor reporting. Items 2 and 4 had the lowest number of studies receiving a score for them (50.57% and 42.53%, respectively). Average inter-rater agreement for the 10% of the studies randomly selected was 79.17% ± 17.25 across the nine items.

Meta-analysis

The summary of findings of the meta-analyses at the different time points and their subgroupings is depicted in Table 3. Below, we detail the findings at each time point individually.

Table 3 Summary of findings
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In-Hospital Incidence of VTE

Meta-analysis of in-hospital incidence of VTE included 19 studies (1,083,908 patients, Fig. 2A), reporting a wide range of incidences (0–0.88%). Studies with > 80% laparoscopic approach exhibited lower pooled incidence of VTE (0.15%; I2 = 72%) compared to those with > 50% open approach (0.43%; I2 = 75%). Figure 2 B shows the subgroup analysis: North American studies had slightly lower incidence (0.14%, I2 = 80%) compared to other countries (0.18%; I2 = 0%), and studies using data collected up to the end of 2010 displayed higher incidence (0.32%; I2 = 96%) compared to those after 2010 (0.15%; I2 = 61%).

Fig. 2
figure 2

In-hospital incidence of venous thromboembolic events. Forest plot showing: A > 80% laparoscopic and > 50% open; B pooled results by two subgroupings—country (North America vs other countries, limited to studies comprising > 80% laparoscopic surgical approach to minimize confounding from surgical approach) and year (last year of data inclusion before and including 2010 vs after 2010, not limited by surgical approach). Square data points: incidence from individual studies; diamond-shaped data points: pooled values from subgroups; hexagonal data points: pooled values from all studies that reported relevant data

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Thirty-Day Cumulative Incidence of VTE

Meta-analysis of 30-day cumulative incidence of VTE included 40 studies (1,402,588 patients, Fig. 3A), reporting a wide range of incidences (0–5.66%). Studies with > 80% laparoscopic approach exhibited lower incidence (0.50%; I2 = 99%) compared to those with > 50% open approach (2.02%; I2 = 60%). Figure 3 B shows the subgroup analysis: North American studies had higher incidence (0.58%; I2 = 100%) compared to other countries (0.34%; I2 = 59%), and studies with data collected up to the end of 2010 demonstrated higher incidence (1.29%, I2 = 91%) compared to those after 2010 (0.43%; I2 = 99%).

Fig. 3
figure 3

Thirty-day cumulative incidence of venous thromboembolic events. Forest plot showing: A > 80% laparoscopic and > 50% open; B pooled results by two subgroupings—country (North America vs other countries, limited to studies comprising > 80% laparoscopic surgical approach to minimize confounding from surgical approach) and year (last year of data inclusion before and including 2010 vs after 2010, not limited by surgical approach). Square data points: incidence from individual studies; diamond-shaped data points: pooled values from subgroups; hexagonal data points: pooled values from all studies that reported relevant data

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Three-Month Cumulative Incidence of VTE

Meta-analysis of the 3-month cumulative incidence of VTE included 15 studies (797,193 patients, Fig. 4A), reporting a wide range of incidences (0%-3.31%). Studies with > 80% laparoscopic approach exhibited lower incidence (0.51%; I2 = 95%) compared to those with > 50% open approach (2.14%; I2 not applicable); Fig. 4B shows the subgroup analysis: North American studies had higher incidence (0.61%; I2 = 98%) compared to other countries (0.37%; I2 = 52%); and studies using data up to the end of 2010 had lower incidence (0.39%; I2 = 87%) compared to those after 2010 (0.48%; I2 = 82%).

Fig. 4
figure 4

Three-month cumulative incidence of venous thromboembolic events. Forest plot showing: A > 80% laparoscopic and > 50% open; B pooled results by two subgroupings—country (North America vs other countries, limited to studies comprising > 80% laparoscopic surgical approach to minimize confounding from surgical approach) and year (last year of data inclusion before and including 2010 vs after 2010, not limited by surgical approach). Square data points: incidence from individual studies; diamond-shaped data points: pooled values from subgroups; hexagonal data points: pooled values from all studies that reported relevant data

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Six-Month Cumulative Incidence of VTE

Meta-analysis of the 6-month cumulative incidence of VTE included 10 studies (256,373 patients, Fig. 5A), reporting a wide range of incidences (0–2.99%). Studies with > 80% laparoscopic approach exhibited lower incidence (0.72%; I2 = 96%) compared to those with > 50% open approach (2.36%; I2 = 64%). Figure 5 B shows the subgroup analysis: North American studies had higher incidence (1.45%; I2 = 96%) compared to other countries (0.31%; I2 = 16%), and studies using data up to the end of 2010 displayed higher incidence (1.67%; I2 = 83%) in comparison with those after 2010 (0.72%; I2 = 96%).

Fig. 5
figure 5

Six-month cumulative incidence of venous thromboembolic events. Forest plot showing: A > 80% laparoscopic and > 50% open; B pooled results by two subgroupings—country (North America vs other countries, limited to studies comprising > 80% laparoscopic surgical approach to minimize confounding from surgical approach) and year (last year of data inclusion before and including 2010 vs after 2010, not limited by surgical approach). Square data points: incidence from individual studies; diamond-shaped data points: pooled values from subgroups; hexagonal data points: pooled values from all studies that reported relevant data

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Twelve-Month Cumulative Incidence of VTE

Meta-analysis of the 12-month cumulative incidence of VTE included six studies (248,809 patients, Fig. 6A). Included studies reported a wide range (0–3.42%) of incidences. Studies with > 80% laparoscopic approach exhibited lower incidence (0.78%; I2 = 98%) compared to those with > 50% open approach (3.38%; I2 not applicable). Figure 6 B shows the subgroup analysis: North American studies had higher incidence (1.60%; I2 = 97%) compared to other countries (0.04%; I2 not applicable), and studies using data up to the end of 2010 displayed higher incidence (1.32%; I2 = 93%) in comparison with those after 2010 (0.78%; I2 = 98%).

Fig. 6
figure 6

Twelve-month cumulative incidence of venous thromboembolic events. Forest plot showing: A > 80% laparoscopic and > 50% open; B pooled results by two subgroupings—country (North America vs other countries, limited to studies comprising > 80% laparoscopic surgical approach to minimize confounding from surgical approach) and year (last year of data inclusion before and including 2010 vs after 2010, not limited by surgical approach). Square data points: incidence from individual studies; diamond-shaped data points: pooled values from subgroups; hexagonal data points: pooled values from all studies that reported relevant data

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Incidence of VTE Within 30 Days: In-hospital vs Post-Discharge

Meta-analysis of 11 studies that reported both in-hospital and 30-day incidence (Supplementary File 5) showed that 60% (95% CI 57–63%; I2 = 88.16%) of the 30-day VTE occurred after discharge, based on 1073 events.

VTE Over Time

Cumulative incidence of VTE over time is depicted in Fig. 7. Incidence generally increased up to the last timepoint examined (12 months post-MBS). Incidence for > 80% laparoscopic approach was consistently lower compared to the > 50% open approach (Fig. 7A). Subgroup analyses displayed variations across time; incidence from North American studies was higher for most timepoints (based on > 80% laparoscopic procedures only) (Fig. 7C). Sensitivity analysis removing studies with sample sizes < 2000 patients increased the incidence for both subgroups and largely accounted for differences at 30 days (North America 0.43% vs other 0.31%) and 3 months (North America 0.49% vs other 0.51%), but not at 6 months (North America 1.83% vs other 0.48%). Sensitivity analysis was not possible for 12-month data.

Fig. 7
figure 7

Total and sub-grouped cumulative incidence of VTE after metabolic and bariatric surgery across time: A by surgical approach (> 50% open vs > 80% laparoscopic), B by study age (up to and including 2010 vs after 2010), C by geographical origin (North America vs other countries). VTE, venous thromboembolic events

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Publication Bias

Figure 8 depicts the funnel plots of cumulative incidence of VTE. At some timepoints, more studies reported lower incidence (Fig. 8A–C), and there was a relative paucity of studies of moderate sample sizes; hence, studies clustered at the upper (larger sample sizes) and lower (smaller sample sizes) ends of the Y axis (Figs. 8C–E). Qualitatively, countries outside of North America were underrepresented. Roughly three quarters of the studies reported North American data, with many using data registries. For instance, 28 (40.58%) of 69 studies reporting 30-day incidence used North American registry data, introducing considerable overlap of patient data across studies. Figure 8 B shows an unusual ‘stacking’ pattern of very similar incidences of VTE suggesting the duplicate use of patient data by different studies.

Fig. 8
figure 8

Panel of Funnel plots of all included studies presenting data for cumulative incidence of venous thromboembolic events: A in-hospital, B 30-day, C 3-month, D 6-month, and E 12-month. Solid black dots indicate studies included in the primary meta-analysis; open circles indicate studies excluded from the primary meta-analysis due to significant overlap of included patient data

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Discussion

Patients with obesity are at risk of VTE in the post-MBS period [8, 100], and those who develop VTE have an increased risk of mortality [5, 6]. Despite this, no previous study has meta-analyzed the incidence of VTE after MBS. The present systematic review and meta-analysis presented high-quality cumulative incidences of VTE pooled from nearly 5 million patients worldwide. The in-hospital, 30-day, and 3-, 6- and 12-month incidences provide clinically relevant and meaningful information regarding the timing and patterns of VTE, to guide the follow-up, detection, and prevention of this life-threatening complication. The review also explored the influence of surgical approach, geographical origin, and study age on incidence of VTE. To our knowledge, this is the first study to undertake such a task.

In terms of the incidence of VTE at the five timepoints under examination, our observed cumulative incidence of VTE exhibited an increasing trend in-hospital, and at 30 days and 3, 6 and 12 months, for the > 80% laparoscopic approach (0.15%, 0.50%, 0.51%, 0.72%, and 0.78% respectively) and for the > 50% open approach (0.43%, 2.02%, 2.14%, 2.36%, and 3.38% respectively). Such increasing pattern is consistent with two studies that reported incidences of VTE after MBS of 0.88%in-hospital, 2.17%1 month, and 2.99%6 month [93] and 0.3%7 days, 1.9%30 days, 2.1%3 months, and 2.1%6 months [43]. Therefore, MBS patients require clinical vigilance to continue for an extended period, in order to identify VTE and reduce the risk of morbidity and mortality.

Individual studies reported a wide range of incidences at each timepoint. Such variations could be due to patient features such as age, BMI, or comorbidity [103]; surgical characteristics, such as operative time [103], MBS procedure, or surgical approach [100, 104, 105]; or study characteristics, such as study design, years of data acquisition, and sample size.

Across studies that reported both in-hospital and 30-day VTE, 60% of events occurred after discharge, concurring with previous reports where up to 80% of VTE occurred after discharge [52, 93, 100]. Higher post-discharge incidence of VTE might be partly attributed to short in-hospital stays of only a few days [106, 107], compared to longer post-discharge periods. Similarly, we found that most VTE occurred within the first 30 days, consistent with observations from some of the included studies [43, 52]. This further highlights the importance of vigilance during this period.

The present study noted that cumulative incidence across the > 80% laparoscopic studies was consistently lower than the > 50% open approach for all timepoints, consistent with previous findings at 30 days [105], 90 days [100], and 5 years [104]. Notwithstanding, some literature has demonstrated no differences in VTE outcomes between laparoscopic vs open approaches [108,109,110].

As for the subgroup analyses, we explored the effects of study age and geographical origin.

Studies using data up to the end of 2010 demonstrated higher incidences at most timepoints, compared to more recent studies, likely due to the larger proportion of > 50% open approach studies in the former subgroup. Factors that have contributed to the reduction in VTE since the turn of the century include the shift from open to laparoscopic approaches, MBS technical advancements, pre-/post-surgery thromboprophylaxis, and enhanced recovery regimens [68, 111,112,113,114,115].

To explore geographical differences, we compared North American studies to other countries. Despite limiting this to > 80% laparoscopic studies to minimize confounding from surgical approach, incidence from North American studies was higher for most timepoints. Sensitivity analysis removing studies with less than 2000 patients increased the incidence of the other countries group closer to that of North American studies at 30 days and 3 months, the timepoints where both subgroups used large samples from registry data, indicating the influence of sample size.

The current review identified only one study that assessed outcomes beyond the first few years after MBS [16]. This study found that over a median of 10.7 years post-surgery, MBS patients exhibited significantly less VTE compared to non-MBS patients matched for sex, age, and baseline BMI [16]. This suggests that despite our observed shorter-term incidence of VTE, MBS appears to offer “protection” (e.g., decreases in BMI), resulting in lower long-term risk of VTE [7]. Future research should include longer-term assessment of VTE after MBS.

Collectively, the above suggests that a deeper understanding of the variations in VTE across time must consider the interrelationships between surgical approach (and hence study age) and sample size (and hence the use of data registries and geographical origin), amongst other factors.

In terms of the quality of estimates, risk of bias within and across studies and heterogeneity, slightly more than half of the included studies exhibited low risk of bias. Some of the studies displaying higher risk of bias were due to small sample sizes, potentially biased sampling frames, or poor reporting. North American studies were over-represented, with many utilizing large national/regional registries. This led to considerable overlap of patient data, which increased our efforts to identify and exclude overlapping data to ensure the validity of the meta-analysis. Heterogeneity in the overall meta-analyses was high at all timepoints. Subgrouping reduced some heterogeneity; however, it remained high for the > 80% laparoscopic approach and the North American subgroups, both of which included the studies with the largest sample sizes and lowest variance. This is consistent with others who noted that measures of heterogeneity such as Higgin’s I2 may indicate high heterogeneity in proportional meta-analysis, even when data are consistent [22].

This review has some limitations. Many studies reported 30-day incidence, while others reported inconsistent timepoints, rendering interpretations of incidence across individual studies difficult. However, this variation enabled us to assess cumulative incidence and its patterns over time. Additionally, as most studies were retrospective, based on patient charts/records, pooled incidences are likely to reflect symptomatic VTE. As it was only possible to use the > 80% laparoscopic and > 50% open subgroups, this would have resulted in some contamination within the subgroups, suggesting that our observed VTE differences between surgical approaches could be underestimated. It would have been beneficial to include elements of the prophylaxis undertaken as well as operative time in the analysis. However, the extent of non-reporting, aggregated or undetailed reporting of these items, and in the case of prophylaxis, the numerous and wide variations in the chemo/mechanical prophylaxis protocols used singly or in combination at different times and durations of administration, with or without inferior vena cava filters, transfusions, or stoppage of chemical thromboprophylaxis where required would result in countless combinations thereof, which mitigated against a meaningful analysis. Notwithstanding, some of the included studies reported that duration of surgery for patients who experienced VTE after MBS was longer than that of matched control patients [29], and that operative time was significantly longer in patients who experienced a post-operative VTE [52] and a significant predictor of or associated with of post-operative VTE [40, 44].

Future studies would benefit from prospective designs, better (non-aggregated) reporting of sample/procedure characteristics and timeframes, assessment of longer-term VTE, and greater representation from outside of North America. Future meta-analyses should be aware of studies utilizing large national/regional registries that could lead to considerable overlap of patient data. Future researchers should be mindful of the differences across data registries when conducting research to ensure that significant proportions of events are not missed. The current study clearly demonstrated that the time course of VTE post-surgery is dynamic. As such, researchers presenting primary research on such complications need to clearly relate reported incidences to a given timeframe post-surgery, and those synthesizing such studies should be careful not to aggregate incidences related to different timeframes, since this would render any reported values meaningless.

This study has many strengths. We assessed the pooled incidence of VTE after MBS at five timepoints. Subgroup analysis included surgical approach, geographical origin of the studies, and study age. We meticulously identified potential overlap of patient data, including that from large registries, and excluded such studies from the meta-analysis, enhancing the internal validity [116]. The extremely large number of patients worldwide enhances the external validity and generalizability of the findings. To our knowledge, this is the most extensive and comprehensive systematic review/meta-analysis of VTE after MBS over several timepoints that has been undertaken, and probably the largest systematic review/meta-analysis conducted to date in the field of surgery/health in general in terms of the number of patients.

Conclusion

We pooled a large number of studies and patients worldwide to provide high-quality estimates of VTE and valuable insights into its patterns over time. For studies that utilized a mainly laparoscopic approach, in-hospital incidence of VTE and cumulative incidence at 30 days and 3, 6 and 12 months were 0.15%, 0.50%, 0.51%, 0.72%, and 0.78% respectively. Most VTE occurred in the first 30 days, of which 60% was after discharge, although we observed some VTE up to our last timepoint. Incidence was consistently lower for laparoscopic compared to open MBS. Lower incidences from studies outside of North America were largely due to smaller sample sizes. Deeper understanding of the variations in VTE across time must consider the interrelationships between surgical approach, geographical origin, study age, and sample size, amongst other factors. Post-operative surveillance needs to be particularly vigilant after discharge and continue thereafter for an extended period to detect VTE and reduce the risk of associated morbidity and mortality. These findings provide clinically relevant estimates of VTE to inform policy, clinical practice, and research.