A meta-analysis on RCTs of direct anterior and conventional approaches in total hip arthroplasty

To conduct a systematic review and meta-analyses on short-term outcomes between total hip arthroplasty (THA) through direct anterior approach (DAA) compared to THA through conventional approaches (CAs) in treatment of hip diseases and fractures. We performed a systematic literature search up to March 1, 2021 to identify RCTs, comparing THA through DAA with THA through CAs. We calculated mean differences (MDs) with 95% confidence intervals (CIs) for continuous outcomes, using the DerSimonian and Laird method and a random effects model. We calculated odds ratios (ORs) with 95% CIs for dichotomous outcomes, using the Mantel–Haenszel method and a random effects model. Ten RCTs met the criteria for final meta-analysis, involving 1053 patients. Four studies were blinded RCTs with a level I evidence, the other 6 studies were non-blinded RCTs with a level II evidence. DAA had a longer operation time than CAs (MD = 17.8, 95% CI  4.8 to 30.8); DAA had similar results compared to CAs for incision length (MD = − 1.1, 95% CI − 4.1 to 1.8), for intraoperative blood loss (MD = 67.2, 95% CI − 34.8 to 169.1), for HHS 3 months postoperatively (MD = 2.4, 95% CI − 0.7 to 5.5), for HHS 6 months postoperatively (MD = 0.8, 95% CI − 1.9 to 3.5), for HHS 12 months postoperatively (MD = 0.9, 95% CI − 0.7 to 2.5), for pain VAS 1 day postoperatively (MD = − 0.9, 95% CI − 2.0 to 0.15), for acetabular cup anteversion angle (MD = − 4.3, 95% CI − 5.2 to − 3.5), for acetabular cup inclination angle (MD = − 0.5, 95% CI − 2.1 to 1.1) and for postoperative complications (OR = 2.4, 95% CI 0.5 to 12.4). Considering the overall results of our meta-analysis, we can conclude that THA through DAA showed similar short-term surgical, functional, radiological outcomes and postoperative complications compared to THA through CAs.

Inclusion/exclusion criteria and outcomes. Inclusion criteria were as follows: RCTs with no restriction to language and publication date, comparing outcomes in THA through DAA and THA through CAs. We included human participants with the following hip pathologies: osteoarthritis, avascular necrosis of the femoral head, dysplasia, femoral neck fracture. We excluded studies on THA through mini-incision approaches as well as surgical techniques, using a computer navigation system. The types of measured outcomes were the following: The operation time in min. was defined as the period of time from the beginning of skin incision to surgical closure. The incision length in cm was measured on graduated scale. The intraoperative blood loss in ml was the total amount of blood from the suction device. The pain Visual Analogue Scale (VAS) 13,14 ranges from 0 to 10 points, with the pain intensity increasing with the number of points. Hip pain was evaluated at day 1 after surgery. The Harris Hip Score (HHS) 15 ranges from 0 to 100 points, with hip function increasing with the number of points. It was evaluated at periodic time intervals after surgery. The acetabular cup anteversion and the inclination have ideal values for positioning: anteversion angle from 10° to 25° and inclination angle from 35° to 45°.
Data extraction and study quality assessment. We extracted data on study characteristics, methods, quality assessment, characteristics of participants, details of the interventions, and measured outcomes into a standard electronic spreadsheet. We contacted corresponding authors for missing data. In case that relevant data was still missing, the concerning study was excluded in order to guarantee a high quality inclusion of RCTs. Risk of bias and level of evidence assessment were performed according to the Cochrane's Risk of Bias 2 (RoB 2) tool 16 and the guidelines of the Centre for Evidence-Based Medicine 17 . Statistical analysis. DAA represented the "experimental group" and CAs represented the "control group".
We tested both fixed and random effects models. The random effects model provided more reliable results, so we proceeded as follows: We calculated mean differences (MDs) with 95% confidence intervals (CIs) for www.nature.com/scientificreports/ continuous outcomes, using the DerSimonian and Laird method and a random effects model. We calculated odds ratios (ORs) with 95% CIs for dichotomous outcomes, using the Mantel-Haenszel method and a random effects model. A common τ 2 was assumed for calculation of the random effects estimates. Study weighting was performed by inverse variance 18 . We evaluated the results and analysed them on basis of the Cochrane Handbook for Systematic Reviews of Interventions 19 . We did not pool study data that were clinically too diverse. Heterogeneity was assessed using a test on Cochrane's Q statistic, which followed a distribution with k-degrees of freedom (p value < 0.10 is indicative of heterogeneity), and a Higgins' test I 2 (low heterogeneity, < 25%; moderate heterogeneity, 25-75%; and high heterogeneity, > 75%) 20 . We performed a traction table subgroup-analysis in order to examine the influence of traction table utilization in THA through DAA.

Results
Study identification and selection. After removal of 824 duplicates, a total of 7,024 studies were found in initial literature search. Forty-one studies were assessed for eligibility after first screening procedure by title and abstract with disagreement between the reviewers concerning one study (κ = 0.98). Thirty-one studies were excluded after full-text screening according to inclusion criteria (κ = 1.0). Four of those studies were excluded because they did not provide any information on standard deviation of the outcome parameters examined [21][22][23][24] .
Characteristics of the RCTs. Risk of bias and level of evidence. Four out of 10 studies were rated with a low risk of bias 10,12,28,31 , 4 studies with a moderate risk of bias 11,26,27,29 and 2 studies with a high risk of bias 25,30 as shown in Table 2. Four out of 10 studies were blinded RCTs with a level I evidence 10,12,28,31 , the other 6 studies were non-blinded RCTs with a level II evidence 11,25-27,29,30 . Incision length. Data on 372 patients were pooled from 4 RCTs (I 2 = 100%, p < 0.01, Fig. 2). There was no difference in incision length (MD = − 1.1, 95% CI − 4.1 to 1.8).

Discussion
Main findings. In order to overcome the limitations of the related previous systematic reviews and metaanalyses 1-9 , we conducted our meta-analysis with a more extensive literature search, with restriction to RCTs and with implementation of high-quality statistical methods, testing both fixed and random effects models. Our direct comparison in meta-analysis on short-term outcomes between THA through DAA and CAs included 10 RCTs and 1,053 patients. Four out of 10 studies were blinded RCTs with a level I evidence 10,12,28,31 , the other 6 studies were non-blinded RCTs with a level II evidence 11,[25][26][27]29,30 . THA through DAA showed overall similar surgical, functional, radiological outcomes and postoperative complications compared to THA through CAs. Both approaches showed overall sufficient results in acetabular cup positioning. THA through DAA showed a longer operation time compared to THA through CAs. We found no influence of traction table utilization on outcomes in THA through DAA.
Operation time. Our meta-analysis found that the operation time of THA through DAA was 17.8 min.
longer than the operation time of THA through CAs. The mean operation time varied from 59.9 to 121.0 min. for DAA and from 45.7 to 78.2 min. for CAs. The meta-analyses by Kucukdurmaz et al. 3 and Yue et al. 7 found similarly prolonged operation times in THA through DAA. In contrast, the meta-analyses by Higgins et al. 1 and Wang et al. 6 found no difference. Operation time is an outcome parameter that is very difficult to generalize, as there are certainly some confounding factors. During the surgeon's learning curve period, there usually is a prolonged operation time. However, it remains unclear whether THA through DAA were implanted by learners, skilled surgeons, or experts. It is possible to significantly reduce operation time in THA through DAA by acqui- www.nature.com/scientificreports/ sition of surgical skills 32 . The wide variation in operation times in THA through DAA from 59.9 to 121 min. supports the idea that the surgeon's proficiency plays an important role and shows that there is potential for a shorter operation time.
Incision length. Our meta-analysis found no difference in incision length of THA through DAA compared to THA through CAs. The mean incision length varied from 9.1 to 13.7 cm for DAA and from 10.4 to 14.8 cm for CAs. In contrast, the meta-analyses by Kucukdurmaz et al. 3 found that THA through DAA had a 3.2 cm shorter incision length than THA through other approaches. The meta-analysis by Wang et al. 6 showed a 3.5 cm shorter incision length of THA through DAA than THA through posterior approach.

Intraoperative blood loss.
Our meta-analysis found no difference in intraoperative blood loss of THA through DAA compared to THA through CAs. The mean intraoperative blood loss varied from 165.9 to 1344.0 ml for DAA and from 123.8 to 1644.0 ml for CAs. The meta-analysis by Higgins et al. 1 also showed no difference in intraoperative blood loss. The meta-analysis by Wang et al. 6 showed a lower postoperative blood loss of 67 ml in THA through DAA compared to THA through posterior approach. The meta-analysis by Yue et al. 7 showed no difference in postoperative blood transfusion rates between THA through DAA and THA through lateral approach. However, sufficient conclusions about the extent of the tissue trauma cannot be drawn only by determining the intraoperative blood loss. Further outcome parameters such as total blood loss and laboratory parameters such as CRP, IL-6, IL-10, IL-1a, ESR, and CK must also be considered. The overall results showed a weak tendency towards better outcome in THA through DAA compared to THA through posterior approach. The meta-analysis by Kucukdurmaz et al. 3 found a 5.6 points higher HHS and a 3.1 points lower WOMAC 1.5 months postoperatively in THA through than THA through other approaches. In contrast to the HHS, in WOMAC a lower result is considered as better and a higher result as worse. The meta-analysis by Miller et al. 4 showed an overall 0.3 point higher HHS in THA through DAA than THA through posterior approach. The HHS was measured at different time points 3 months postoperatively. The network meta-analysis by Putananon et al. 5 ranked four hip approaches in order from best to fourth best with regard to the HHS 1-1.5 months postoperatively as follows: DAA, lateral approach, posterior and posterior-2-incision approach. THA through DAA had a 2.6 points higher HHS than THA through lateral approach, a 4.8 points higher HHS than THA through posterior approach and a 10.8 higher HHS than THA through posterior-2-incision approach. The meta-analysis by Wang et al. 6 found that THA through DAA had a 7.4 higher HHS 0.5 months postoperatively than THA through posterior approach and a 6. The improved functional outcome, which several meta-analyses found in THA through DAA, follows the lower tissue and muscle damage, presumably due to operating in a muscle-sparing anatomical plane. Lower tissue and muscle damage in DAA was determined by measuring the levels of relevant laboratory parameters such as CRP, IL-6, IL-10, IL-1a, ESR, and CK in several studies 28,31,33,34 .

Limitations
We identified the following limitations to our study: First, the long-term outcomes in THA were not considered. Second, due to insufficient data, important outcome parameters such as hospitalization time, postoperative drainage volume and postoperative gait analysis could not be considered. Third, we did not consider the possible influence of the surgeon operating skills, the utilization of tranexamic acid and anticoagulants, bone cement or the types of implants for THA. Lastly, conventional approaches were summarized in one group, although they differ greatly from one another.

Conclusion
Considering the overall results of our meta-analysis, we can conclude that THA through DAA showed similar short-term surgical, functional, radiological outcomes and postoperative complications compared to THA through CAs.

Data availability
The data are available from the corresponding author upon reasonable request.