We conducted the meta-analysis in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement for studies that evaluate healthcare interventions [9]. We searched the literature in Medline, the Cochrane Library from January 1995 to October 2014, using combinations of the medical subject headings “ultrasound, intravascular”, “IVUS”, “IVUS-guided”, “angiography”, “angiography-guided”, “drug-eluting stent” and “DES”. We used the Science Citation Index as a cross reference to include studies that met the search criteria. We also searched potential studies from the conference proceedings of the American College of Cardiology, the American Heart Association, the European Society of Cardiology and the Transcatheter Cardiovascular Therapeutics. Additionally, we reviewed the reference of the selected articles and earlier meta-analyses for related documents.

Two investigators (PS and CXY) independently conducted the literature search, data extraction and quality evaluation through a standard method. Differences were resolved by consensus with third investigator (ZYJ). Studies were included in the current meta-analysis if they met the following predetermined criteria [4, 10‐28]: (1) clinical research published in peer-reviewed journals with complete data; (2) comparison of IVUS- versus angiography-guided DES implantation; and (3) at least 6 months follow up. Studies that included bare metal stents (BMS) and DES implantation and did not provide separately the DES data were excluded. Two investigators (PS and CXY) extracted the baseline information, which included the study name, study design, sample size, follow-up duration, patients’ baseline characteristics (mean age, sex distribution, and risk factors), lesion and procedural characteristics, and clinical outcomes. The Newcastle-Ottawa-Scale (NOS) scale was used for quality assessment, including assessment of selection of the exposed and unexposed cohort, comparability of the two cohorts, and outcome assessment [29]. The qualities of randomized trials were assessed by the Jadad score [30].

The endpoints of the present analysis included: (1) all-cause death (in 2 studies [11, 13] that only reported cardiac death was included instead), (2) MACE, (3) ST (definite or probable ST, according to the definition of the Academic Research Consortium), (4) MI (in 1 study [14] only the Q-wave MI was reported while others reported both non-Q-wave MI and Q-wave MI), (5) target vessel revascularization (TVR), and (6) target lesion revascularization (TLR). Repeated-analyses were performed in patients with complex lesions or ACS compared to mixed lesions or any presentations and among propensity-matched and randomized studies.

The guideline of the Cochrane Handbook for Systematic Reviews of Interventions was implemented in this meta-analysis [31]. Standard data extraction and calculation were used to improve efficiency and reliability of the analysis [32]. Random-effects model was adopted to measure overall treatment effect expressed as odds ratios (OR) and 95 % confidence intervals (CI). Forest plots were generated for graphical presentations of clinical outcomes with IVUS- versus angiography-guided groups. We assessed heterogeneity of the study using chi-square tests (p > 0.1 showed no significant heterogeneity among studies) and I ² statistic (I ²  > 25 %, >50 %, >75 % showed low, moderate and severe heterogeneity, respectively). All p-values were two-tailed and the statistical significance was considered at <0.05. In case there was heterogeneity among the studies, we conducted sensitivity analyses to clear the source of the heterogeneity. We tested the interaction between patients with complex lesions or ACS versus patients with mixed lesions or any clinical presentations by means of weighted least squares random-effect meta-regression, with weighting provided by the inverse of the variance of each study, patients with complex lesions or ACS (coded as 1 versus patients with mixed or any clinical presentations coded as 0) as random factor, and the natural logarithm of the individual OR as dependent variable [29]. The Egger’s linear regression test was performed for asymmetry of the publication or reporting bias [33]. All statistical analysis was performed with STATA 12.0 (Stata Corp, College Station, TX, USA).

This meta-analysis didn’t require ethical approval.

In total, twenty eligible studies were included in this meta-analysis (Fig. 1). Out of 20 studies, 3 studies were prospective, randomized trials [10‐12], and 17 were observational registries [4, 13‐28]. In addition, 9 of the included studies had performed sub-analysis after propensity score matching [14, 15, 17, 18, 20, 21, 26‐28]. Therefore, 13 studies enrolled only patients with complex lesions or ACS, including 4 for left main disease [13, 15, 26, 28], 3 for bifurcation [16, 17, 21], 1 for chronic total occlusion (CTO) [27], 1 for long lesion [12], 1 for ST-segment elevation MI [24], and 3 for combined complex lesions [10, 11, 24].

Out of 29,068 patients included in this study, 13,552 (46.6 %) patients underwent IVUS-guided DES implantation and 15,516 (53.4 %) angiography-guided DES implantation. The study characteristics are summarized in Table 1. The mean weighted follow-up was 20.8 months. Lesion and procedural characteristics are shown in Table 2.

MACE were reported in 19 of the 20 included studies. The summary result was in favor of IVUS-guided DES implantation in risk of MACE (OR 0.77, 95 % CI 0.71-0.83, P < 0.001; Fig. 2a). Statistical analysis did not show significant heterogeneity (heterogeneity chi-square = 23.40, I² = 23.1 %, p = 0.176).

IVUS guidance was associated with a significantly low risk of mortality, compared with angiography guidance (OR 0.62, 95 % CI 0.54-0.71, p < 0.001; Fig. 2b). Evidence of statistical heterogeneity was not observed among the studies (heterogeneity chi-square = 22.77, I² = 20.9 %, p = 0.200).

The occurrence of definite/probable ST was reported in 19 studies. IVUS guidance appeared to be associated with a significantly low incidence of ST (OR 0.59, 95 % CI: 0.47-0.73, P < 0.001; Fig. 2c). There is no statistical heterogeneity in these studies (heterogeneity chi-square = 19.37, I² = 12.2 %, p = 0.308).

MI was reported in 18 studies and the pooled result showed that IVUS guidance was associated with a significantly low risk of MI (OR 0.64, 95 % CI: 0.55-0.75, P < 0.001; Fig. 2d). The pooled OR for TLR associated with IVUS guidance versus angiography guidance was 0.81 (95 % CI: 0.69-0.94, P = 0.005; Fig. 2e) while the pooled OR for TVR was 0.86 (95 % CI: 0.77-0.97, P = 0.012; Fig. 2f). Statistical heterogeneity was not found in MI (heterogeneity chi-square = 16.80, I² = 4.8 %, p = 0.398), but there was heterogeneity in TLR and TVR (heterogeneity chi-square = 20.27, I² = 45.7 %, p = 0.042; heterogeneity chi-square = 24.33, I² = 46.6 %, p = 0.028, respectively).

In the repeated analysis of propensity-matched and randomized studies, a total of 8,331 patients were included. Repeated analysis confirmed that IVUS guidance was associated with a significant reductions in MACE (OR 0.79, 95 % CI: 0.70-0.88, P < 0.001, Fig. 3a), death (OR 0.64, 95 % CI: 0.52-0.79, P < 0.001, Fig. 3b), ST (OR 0.55, 95 % CI: 0.39-0.78, P = 0.001, Fig. 3c), MI (OR 0.69, 95 % CI: 0.56-0.85, P < 0.001, Fig. 3d), and TVR (OR 0.82, 95 % CI: 0.68-0.98, P = 0.028, Fig. 3f). No statistical difference was observed in TLR (OR 0.92, 95 % CI: 0.76-1.11, P = 0.377, Fig. 3e).

Sub-analysis was performed to compare IVUS-guided versus angiography-guided PCI with DES for patients with complex lesions or ACS. Thirteen studies with 6,393 patients were eligible for this sub-analysis. IVUS guidance was associated with a low risk of MACE (OR 0.69, 95 % CI: 0.60-0.79, p < 0.001), death (OR 0.52, 95 % CI: 0.40-0.67, p < 0.001), and ST (OR 0.41, 95 % CI: 0.25-0.69, p = 0.001) for patients with complex lesions or ACS, when compared to patients with mixed lesions or any clinical presentation (MACE [OR 0.81, 95 % CI: 0.74-0.90, p < 0.001], death [OR 0.67, 95 % CI: 0.56-0.80, p < 0.001], and ST [OR 0.64, 95 % CI: 0.50-0.82, p < 0.001], respectively) (Fig. 4). By employing meta-regression analysis, the benefit of IVUS guidance is significantly pronounced in patients with complex lesions or ACS with respect to death (p = 0.048).

Sensitivity analyses of the lesion subsets did not change the reported results. There was no evidence of publication bias through the Egger’s linear regression analysis (p = 0.455 for MACE, p = 0.395 for death, P = 0.217 for ST, p = 0.319 for MI, p = 0.738 for TLR, P = 0.103 for TVR, Fig. 5). Assessment of publication bias using the logarithm of relative risk showed a symmetric funnel plot and confirmed no evidence of publication bias.

Our study has several limitations. It is a meta-analysis and shares the limitations from the original studies. The inability to adjust the baseline characteristics between the 2 studied groups may introduce remarkable bias. However, the findings consistently showed that IVUS guidance was associated with improved outcomes in the all included studies and the repeated analysis that included matched and randomized studies. The current study was not able to differentiate the impact of IVUS guidance in patients treated with either first or newer generation DES.