Outcomes of percutaneous coronary intervention for chronic total occlusions in the elderly: A systematic review and meta‐analysis

Abstract Objective This study aimed to compare outcomes of percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) in the elderly (≥75 years) versus nonelderly and assess the impact of successful CTO‐PCI in the elderly. Methods PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched up to October 1, 2020. Mortality rates and major adverse cardiac events (MACE) were compared between elderly and nonelderly patients and successful versus failed CTO‐PCI in the elderly. Results Eight studies were included. Meta‐analysis indicated no statistically significant difference in the risk of in‐hospital mortality (RR: 1.97 95% CI: 0.78, 4.96 I2 = 0% p = .15) but higher tendency of in‐hospital MACE (RR: 2.30 95% CI: 0.99, 5.35 I2 = 49% p = .05) in the elderly group. Risk of long‐term mortality (RR: 3.79 95% CI: 2.84, 5.04 I2 = 41% p < .00001) and long‐term MACE (RR: 1.53 95% CI: 1.14, 2.04 I2 = 80% p = .004) were significantly increased in the elderly versus nonelderly. Elderly patients had a significantly reduced odds of successful PCI as compared to nonelderly patients (OR: 0.63 95% CI: 0.54, 0.73 I2 = 1% p < .00001). Successful CTO‐PCI was associated with reduction in long‐term mortality (HR: 0.51 95% CI: 0.34, 0.77 I2 = 27% p = .001) and MACE (HR: 0.60 95% CI: 0.37, 0.97 I2 = 53% p = .04) as compared to failed PCI in elderly. Conclusions Elderly patients may have a tendency of higher in‐hospital MACE with significantly increased long‐term mortality and MACE after CTO‐PCI. The success of PCI is significantly lower in the elderly. In elderly patients with successful PCI, the risk of long‐term mortality and MACE is significantly reduced.


| Inclusion criteria
The review is conducted as per the guidelines of the PRISMA statement (preferred reporting items for systematic reviews and meta-analyses). 11 We included all studies conducted on elderly patients (≥75 years of age) undergoing PCI for CTO. Studies were included provided they fulfilled one of the following criteria: 1. Studies were to compare outcomes of elderly patients with nonelderly patients (<75 years of age). Outcomes reported were to be mortality and/or major adverse cardiac events (MACE).

| Search strategy
An electronic search was conducted by two reviewers, independent of each other, for the following databases: PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar. The time limit was from the inception of databases to October 1, 2020. The terms used for the literature search included: "percutaneous coronary intervention," "chronic total occlusion," "elderly," "older adults," "geriatric," and "age." Search terms were used in different combinations to find relevant articles. After the deduplication of articles, the search records were analyzed by their titles and abstracts separately by the two reviewers. Articles matching the inclusion criteria were identified and full texts of these were extracted. Individual studies were then assessed for final inclusion in the study. Any disagreements were resolved by discussion. After completion of the search and identification of included studies, the bibliography of included articles was hand searched for any other potential article.

| Data extraction and quality of included studies
The following data were extracted from the included studies: names of first authors, publication year, study type and location, study groups, sample size, demographic details of the sample, medical history of the sample (hypertension, diabetes, hyperlipidemia, chronic heart failure, chronic kidney disease, prior MI, stroke, CABG, or PCI), the success of PCI, CTO location, contrast volume use, procedural time, study outcomes, and follow-up time.
For the first part of the review, mortality and MACE were compared following CTO-PCI in elderly versus nonelderly. We also performed a separate analysis comparing major bleeding, cardiac tamponade, emergent CABG, MI, and cerebrovascular accident (CVA) between the elderly and nonelderly groups. Finally, the success rates of PCI were compared between the elderly and nonelderly groups.
For the second part of the review, we compared mortality and MACE between successful PCI versus failed PCI for CTO in the elderly.
Since only observational studies were included in the review, the risk of a bias assessment tool for nonrandomized studies (RoBANS) was used to assess the quality of included studies. 12 Studies were assessed for the selection of participants, confounding variables, intervention measurements, blinding of outcome assessment, incomplete outcome data, and selective outcome reporting. Two reviewers independently assessed each study. The study was judged to have a "high," "unclear," or "low" risk of bias for each domain. Any disagreements were resolved by discussion.

| Statistical analysis
"Review Manager" (RevMan, version 5.3; Nordic Cochrane Centre [Cochrane Collaboration], Copenhagen, Denmark; 2014) was used for the meta-analysis. Using a random-effects model, all categorical adverse outcomes were summarized using risk ratios (RR) with 95% confidence intervals (CI). The success of PCI between elderly and nonelderly was compared using odds ratios (OR). We also extracted data on hazard ratio (HR) for mortality or MACE if reported by the included studies. The generic inverse variance model of the meta-analysis software was used to pool the HR. Meta-analysis was conducted only if at least three studies reported the same outcome. Heterogeneity was assessed using the I 2 statistic. I 2 values of 25-50% represented low, values of 50-75% medium, and more than 75% represented substantial heterogeneity. As less than 10 studies were included in the meta-analysis, funnel plots were not used to assess publication bias.

| RESULTS
The PRISMA flowchart of the review is presented in Figure 1.

| Elderly versus nonelderly
In-hospital outcomes (i.e., short term outcomes) and long-term outcomes were compared separately for this part of the analysis.  Figure S6).

| DISCUSSION
Our study, which is the first meta-analysis assessing the outcomes of CTO-PCI in the elderly, revealed the following important findings. (1) In-hospital mortality for CTO-PCI may not be different between elderly and nonelderly, but there is a tendency of higher risk of early MACE in the elderly group.   25,26 In this context, an important question that needs to be answered is if CTO-PCI has similar outcomes in elderly and nonelderly subjects?
The concern of poor outcomes in the elderly with CTO arises from the fact that the disease is more extensive in older adults and coronary arteries are more tortuous with heavy calcification of atherosclerotic plaques. 20 9 in a comparative study of ≥75 and < 75-year-old adults reported increased mortality in the older age group. Thomas et al. 29 in an analysis of 152 373 patients undergoing PCI have reported an increased risk of mortality, contrast-induced nephropathy, bleeding, CVA, and vascular complications with increasing age.
The success of PCI for CTO in the literature ranges widely from 59 to 87.5%. 30,31 The success rates for CTO-PCI are significantly lower as compared to nonoccluded lesions and this is attributable to the difficulty in passing the guide-wire through the area of tight stenosis in CTO. 32 In our analysis too, we found an overall lower success rate of CTO-PCI with 70.4% in the elderly group and 78.3% in the nonelderly group. The success of CTO-PCI was significantly reduced by around 37% in older adults. Answering the second question of our review, we found no significant reduction of long-term mortality with successful PCI in the elderly by analyzing absolute events, however, pooled analysis of multivariable-adjusted HR from limited studies did demonstrate that successful CTO-PCI reduced the risk of long-term