Abstract
Background:
Limited data are available on the comparison of clinical outcomes of complete vs. incomplete percutaneous coronary intervention (PCI) for patients with chronic total occlusion (CTO) and multi-vessel disease (MVD). The study aimed to compare their clinical outcomes.
Methods:
A total of 558 patients with CTO and MVD were divided into the optimal medical treatment (OMT) group (n = 86), incomplete PCI group (n = 327), and complete PCI group (n = 145). Propensity score matching (PSM) was performed between the complete and incomplete PCI groups as sensitivity analysis. The primary outcome was defined as the occurrence of major adverse cardiovascular events (MACEs), and unstable angina was defined as the secondary outcome.
Results:
At a median follow-up of 21 months, there were statistical differences among the OMT, incomplete PCI, and complete PCI groups in the rates of MACEs (43.0% [37/86] vs. 30.6% [100/327] vs. 20.0% [29/145], respectively, P = 0.016) and unstable angina (24.4% [21/86] vs. 19.3% [63/327] vs. 10.3% [15/145], respectively, P = 0.010). Complete PCI was associated with lower MACE compared with OMT (adjusted hazard ratio [HR] = 2.00; 95% confidence interval [CI] = 1.23–3.27; P = 0.005) or incomplete PCI (adjusted HR = 1.58; 95% CI = 1.04–2.39; P = 0.031). Sensitivity analysis of PSM showed similar results to the above on the rates of MACEs between complete PCI and incomplete PCI groups (20.5% [25/122] vs. 32.6% [62/190], respectively; adjusted HR = 0.55; 95% CI = 0.32–0.96; P = 0.035) and unstable angina (10.7% [13/122] vs. 20.5% [39/190], respectively; adjusted HR = 0.48; 95% CI = 0.24–0.99; P = 0.046).
Conclusions:
For treatment of CTO and MVD, complete PCI reduced the long-term risk of MACEs and unstable angina, as compared with incomplete PCI and OMT. Complete PCI in both CTO and non-CTO lesions can potentially improve the prognosis of patients with CTO and MVD.
Keywords: Chronic total occlusion, Multi-vessel disease, Treatment, Percutaneous coronary intervention
Introduction
Chronic total occlusion (CTO) remains a significant challenge in the field of interventional cardiology due to the complexity of corrective procedures and the risk of associated complications.[1] Although many cases are asymptomatic, recent data suggest that CTO occurs in about 10–30% of patients with coronary artery disease undergoing coronary angiography.[2–5] Our previous work showed no statistically significant reduction of cardiac death after either successful percutaneous coronary intervention (PCI) or revascularization accomplished by coronary artery bypass graft surgery (CABG) or PCI vs. medical therapy in patients with CTO.[6,7] However, symptom improvement by CTO-PCI was gradually proved, and the risk of major adverse cardiovascular event (MACE) including unstable angina should be reassessed. In actual clinical practice, due to the high radiation exposure, complex technology, and procedural complications of complete percutaneous revascularization, some clinicians are more likely to perform incomplete PCI for non-CTO lesions or CTO lesions for patients with the multi-vessel disease (MVD), and poor revascularization of remaining lesions after incomplete PCI is very common. In addition, MVD, which coexisted in about 80% of CTO patients according to our previous report,[6] was always associated with a poorer prognosis as compared with single-vessel disease,[8] and whether complete PCI improved the prognosis for this subset was still not clear. Therefore, the present study aimed to investigate the clinical outcomes of complete versus incomplete PCI for patients with CTO and MVD.
Methods
Ethics approval
The study protocol was approved by the Institutional Review Board of Dalian Medical University (No. YJ-KY-FB-2017-01) and conducted by the tenets of the Declaration of Helsinki. Study participants have signed informed consent.
Patient population
A total of 11,007 patients underwent coronary angiography at the Department of Cardiology of the First Affiliated Hospital of Dalian Medical University from January 2016 to December 2018. Finally, 558 patients with CTO and MVD were included for analysis.
The inclusion criteria for this study were: (1) aged 18–80 years, (2) at least one CTO, and stenosis of ≥70% of at least one other vessel, as confirmed by coronary angiography, and (3) symptomatic angina and/or functional ischemia, which was assessed by cardiac magnetic resonance, dimensional echocardiography, or single-photon emission computed tomography (SPECT). The exclusion criteria included: (1) acute myocardial infarction (MI) within 3 months, (2) a history of cardiogenic shock or cardiopulmonary resuscitation (New York Heart Association functional classification of grade VI), (3) history of CABG, (4) severe renal insufficiency (estimated glomerular filtration rate [eGFR] <15 mL∙min-1∙1.73 m-2), and (5) current malignancy.
The study cohort included 558 patients who were divided into the optimal medical treatment (OMT) group (n = 86), incomplete PCI group (n = 327), or complete PCI group (n = 145). Baseline clinical, laboratory, and angiographic data were collected from the hospital database and medical records. A median follow-up of 21 months of the enrolled population was performed by reviewing medical records or telephone interviews.
Treatment strategy
OMT included antiplatelet medication, beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, nitrates, and aggressive lipid-lowering agents. The medication doses were maximized as allowed by heart rate, blood pressure, symptoms, and side effects. Coronary interventions were performed according to current standard guidelines.[19] All patients received loading doses of aspirin (300 mg) and clopidogrel (300–600 mg) before PCI unless antiplatelet therapy was administered beforehand. Aspirin treatment was continued indefinitely and clopidogrel was administered for at least 12 months after PCI.
Study definitions and outcomes
CTO was defined as a complete obstruction of a coronary artery with an anterograde Thrombolysis In Myocardial Infarction (TIMI) flow grade of 0 for an estimated duration >3 months based on clinical history or previous angiography.[9] Successful PCI was defined as final residual stenosis of <20% with a TIMI flow grade of ≥2 after stent implantation, as assessed by visual estimation of angiograms. Complete PCI was considered as successful PCI of all vessels with both CTO and non-CTO lesions, while incomplete PCI was defined as revascularization of only a portion of significant lesions, no matter it was due to the failure of CTO lesions or non-CTO lesions. Chronic kidney disease (CKD) stages I–II were defined as eGFR ≥60 mL∙min-1∙1.73 m-2, while CKD stages III–V were defined as eGFR <60 mL∙min-1∙1.73 m-2. The primary outcome was MACE during follow-up, which was defined as a composite of all-cause death, recurrent MI, ischemia-driven repeat revascularization, unstable angina, and heart failure. Unstable angina was defined as the secondary outcome. MI was defined as clinical evidence of myocardial ischemia with an increase and/or decrease in cardiac troponin levels with at least one value above the 99th percentile of the upper reference limit, combined with any of symptom of ischemia, new ischemic changes on an electrocardiograph, development of pathological Q waves, imaging evidence of new loss of viable myocardium, or new regional wall motion abnormality in a pattern consistent with an ischemic etiology, or identification of a coronary thrombus by angiography or autopsy.[10] Periprocedural cardiac enzymes elevation was not included in the definition of MI. Ischemia-driven repeat revascularization was defined as a composite of target vessel revascularization (TVR) and non-TVR treated with PCI or CABG which was driven by ischemia, and scheduled staged PCI was not regarded as ischemia-driven repeat revascularization. Unstable angina was defined as angina required for rehospitalization and supported by evidence of ischemia such as electrocardiographic changes. Heart failure was defined as the breathlessness required for rehospitalization and supported by evidence of impaired cardiac function.
Statistical analysis
Continuous variables were compared using the Student's t-test, one-way analysis of variance, Mann–Whitney U test or Kruskal–Wallis H test, as appropriate, and are presented as the mean ± standard deviation or median with interquartile range. Categorical data were tested using the chi-squared test or Fisher's exact test, and are presented as number and percentage. Survival with no adverse events was evaluated using Kaplan–Meier analysis and compared with the log-rank test. Covariates that were statistically significant by univariate analysis, or were clinically relevant, were included in multivariate models, including age, gender, hypertension, diabetes mellitus, smoking, previous MI, left anterior descending artery (LAD) involvement, left ventricular ejection fraction (LVEF), and eGFR. The adjusted Cox proportional hazard model was used to compare the risks of adverse cardiac events. Additionally, propensity score matching (PSM) was used to balance baseline characteristics between the complete and incomplete PCI groups as sensitivity analysis [Supplementary material, http://links.lww.com/CM9/B497]. A full non-parsimonious model was developed which included each of the variables listed in Table 1. PSM was conducted at a ratio of up to 1:2 using the nearest-neighbor matching algorithm with caliper widths of 0.1. All tests were two-tailed. A probability (P) value of <0.05 was considered statistically significant. All analyses were performed using IBM SPSS Statistics for Windows (version 26.0; IBM Corporation, Armonk, NY, USA) and R software (version 3.5; R Foundation for Statistical Computing, Vienna, Austria).
Table 1.
Baseline characteristics and related baseline medications in total and post-matched populations of patients with CTO and MVD.
| Variables | Total population | Post-matched population | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
|
OMT (n = 86) |
Incomplete PCI (n = 327) | Complete PCI (n = 145) | χ 2/F/H | P values | Incomplete PCI (n = 190) |
Complete PCI (n = 122) |
χ 2/t/Z | P values | ||
| Age (years) | 63.9 ± 9.5 | 63.4 ± 10.0 | 62.4 ± 9.1 | 0.786§ | 0.456 | 63.5 ± 10.0 | 62.7 ± 9.3 | 0.723** | 0.470 | |
| Male | 69 (80.2) | 241 (73.7) | 113 (77.9) | 2.066|| | 0.356 | 144 (75.8) | 94 (77.0) | 0.065|| | 0.799 | |
| Hypertension | 67 (77.9) | 229 (70.0) | 101 (69.7) | 2.270|| | 0.321 | 128 (67.4) | 85 (69.7) | 0.182|| | 0.670 | |
| Diabetes mellitus | 38 (44.2) | 138 (42.2) | 49 (33.8) | 3.582|| | 0.167 | 72 (37.9) | 40 (32.8) | 0.842|| | 0.359 | |
| Smoking | 38 (44.2) | 152 (46.5) | 50 (34.5) | 5.959|| | 0.051 | 75 (39.5) | 47 (38.5) | 0.028|| | 0.867 | |
| Hyperlipidemia | 72 (83.7) | 272 (83.2) | 126 (86.9) | 1.064|| | 0.587 | 163 (85.8) | 106 (86.9) | 0.075|| | 0.784 | |
| Familial history of CAD | 15 (17.4) | 45 (13.8) | 21 (14.5) | 0.743|| | 0.690 | 22 (11.6) | 18 (14.8) | 0.670|| | 0.413 | |
| Previous MI | 33 (38.4) | 127 (38.8) | 45 (31.0) | 2.749|| | 0.253 | 61 (32.1) | 39 (32.0) | 0.001|| | 0.980 | |
| Previous PCI | 27 (31.4) | 110 (33.6)‡ | 29 (20.0) | 9.074|| | 0.011 | 45 (23.7) | 26 (21.3) | 0.238|| | 0.626 | |
| Previous CVA | 5 (5.8) | 29 (8.9) | 10 (6.9) | 1.138|| | 0.566 | 14 (7.4) | 9 (7.4) | <0.001|| | 0.998 | |
| PVD | 2 (2.3) | 8 (2.4) | 3 (2.1) | 0.063|| | 0.969 | 5 (2.6) | 3 (2.5) | 0.009|| | 0.925 | |
| TC (mmol/L) | 4.5 (3.3–5.2)* | 4.4 (3.5–5.0)‡ | 4.9 (4.0–5.7) | 19.847¶ | <0.001 | 4.6 (3.7–5.5) | 4.8 (3.9–5.6) | -1.222†† | 0.222 | |
| TG (mmol/L) | 1.4 (1.1–2.1) | 1.7 (1.2–2.2) | 1.8 (1.2–2.5) | 5.498¶ | 0.064 | 1.8 (1.2–2.3) | 1.8 (1.3–2.5) | -0.479†† | 0.632 | |
| HDL-C (mmol/L) | 1.0 (0.9–1.2)* | 1.0 (0.9–1.1)‡ | 1.1 (1.0–1.2) | 13.308¶ | 0.001 | 1.0 (0.9–1.2) | 1.1 (0.9–1.2) | -1.048†† | 0.295 | |
| LDL-C (mmol/L) | 2.5 (1.7–3.2) | 2.4 (1.8–3.0)‡ | 2.8 (2.1–3.4) | 14.109¶ | 0.001 | 2.6 (2.0–3.2) | 2.8 (2.1–3.4) | -1.137†† | 0.256 | |
| Creatinine (µmol/L) | 78 (64–87) | 75 (66–87) | 72 (62–80) | 5.995¶ | 0.050 | 71 (65–85) | 74 (65–81) | -0.133†† | 0.894 | |
| eGFR (mL∙min-1∙1.73 m-2) | 87.8 ± 24.4 | 87.0 ± 22.5‡ | 93.5 ± 21.9 | 4.281§ | 0.014 | 89.8 ± 21.4 | 90.4 ± 20.3 | -0.241** | 0.809 | |
| Uric acid (µmol/L) | 355 (293–420) | 358 (301–429) | 361 (310–415) | 0.026¶ | 0.987 | 360 (301–430) | 360 (310–408) | -0.143†† | 0.886 | |
| LVEF (%) | 57 (51–59)* | 57 (54–59)‡ | 58 (56–59) | 12.510¶ | 0.002 | 58 (55–59) | 58 (55–59) | -1.453†† | 0.146 | |
| Number of CTOs | 22.810|| | <0.001 | 0.413|| | 0.520 | ||||||
| 1 | 64 (74.4) | 298 (91.1) | 135 (93.1) | 172 (90.5) | 113 (92.6) | |||||
| ≥2 | 22 (25.6)*,† | 29 (8.9) | 10 (6.9) | 18 (9.5) | 9 (7.4) | |||||
| Location of CTO | ||||||||||
| LAD | 31 (36.0) | 80 (24.5)‡ | 53 (36.6) | 9.242|| | 0.010 | 61 (32.1) | 39 (32.0) | 0.001|| | 0.980 | |
| LCX | 27 (31.4) | 132 (40.4)‡ | 40 (27.6) | 7.959|| | 0.019 | 62 (32.6) | 35 (28.7) | 0.539|| | 0.463 | |
| RCA | 50 (58.1) | 143 (43.7) | 62 (42.8) | 6.379|| | 0.041 | 85 (44.7) | 57 (46.7) | 0.118|| | 0.731 | |
| Proximal or mid CTO | 72 (83.7)* | 218 (66.7) | 102 (70.3) | 9.477|| | 0.009 | 130 (68.4) | 84 (68.9) | 0.006|| | 0.936 | |
| Collateral flow ≥ 2 (Rentrop grade) | 63 (73.3)*,† | 169 (51.7) | 62 (42.8) | 20.462|| | <0.001 | 93 (48.9) | 55 (45.1) | 0.445|| | 0.505 | |
| Number of diseased vessels | 0.942|| | 0.625 | 0.002|| | 0.960 | ||||||
| 2 | 53 (61.6) | 199 (60.9) | 95 (65.5) | 122 (64.2) | 78 (63.9) | |||||
| 3 | 33 (38.4) | 128 (39.1) | 50 (34.5) | 68 (35.8) | 44 (36.1) | |||||
| Medication | ||||||||||
| Aspirin | 76 (88.4)*,† | 318 (97.2) | 143 (98.6) | 17.885|| | <0.001 | 187 (98.4) | 120 (98.4) | 0.002|| | 1.000 | |
|
Clopidogrel or ticagrelor |
80 (93.0)*,† | 321 (98.2) | 145 (100.0) | 12.861|| | 0.002 | 190 (100.0) | 122 (100.0) | – | – | |
| ACEI/ARB | 60 (69.8) | 193 (59.0) | 102 (70.3) | 7.225|| | 0.027 | 117 (61.6) | 83 (68.0) | 1.345|| | 0.246 | |
| β-blocker | 68 (79.1) | 243 (74.3) | 115 (79.3) | 1.808|| | 0.405 | 147 (77.4) | 95 (77.9) | 0.011|| | 0.918 | |
| Statins | 85 (98.8) | 316 (96.6) | 143 (98.6) | 2.371|| | 0.465 | 187 (98.4) | 120 (98.4) | 0.002|| | 1.000 | |
| Nitrate | 43 (50.0) | 169 (51.7) | 83 (57.2) | 11.581|| | 0.454 | 108 (56.8) | 68 (55.7) | 0.037|| | 0.848 | |
Data are presented as n (%), mean ± standard deviation, or median (interquartile range). *OMT vs. complete PCI, P <0.05. †OMT vs. incomplete PCI, P <0.05. ‡Incomplete PCI vs. complete PCI, P <0.05. §F value. ||χ2 value. ¶H value. **t value. ††Z value. ACEI: Angiotensin converting enzyme inhibitor; ARB: Angiotensin II receptor blocker; CAD: Coronary artery disease; CTO: Chronic total occlusion; CVA: Cerebrovascular accident; eGFR: Estimated glomerular filtration rate; HDL-C: High-density lipoprotein cholesterol; LAD: Left anterior descending artery; LCX: Left circumflex artery; LDL-C: Low-density lipoprotein cholesterol; LVEF: Left ventricular ejection fraction; MI: Myocardial infarction; MVD: Multi-vessel disease; OMT: Optimal medical treatment; PCI: Percutaneous coronary intervention; PVD: Peripheral vascular disease; RCA: Right coronary artery; TC: Total cholesterol; TG: Total triglyceride; –: Not applicable.
Results
Baseline characteristics
A total of 1099 patients were diagnosed with CTO and MVD. The prevalence of CTO and MVD was 9.98% [1099/11,007] in patients undergoing coronary angiography. After exclusion, 86 patients received the OMT, 327 patients received the incomplete PCI and 145 patients received the complete PCI group, according to the initial treatment strategy [Figure 1].
Figure 1.
Flow chart of inclusion and exclusion criteria, and grouping of study population. CABG: Coronary artery bypass graft surgery; CTO: Chronic total occlusion; eGFR: Estimated glomerular filtration rate; NYHA: New York Heart Association; OMT: Optimal medical treatment; PCI: Percutaneous coronary intervention.
The baseline, angiographic data and adverse events during hospitalization of all patients are shown in Table 1 and Supplementary Table 1, http://links.lww.com/CM9/B497. As compared with patients in the incomplete PCI group, those in the complete PCI group had a lower prevalence of previous PCI, and higher total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), eGFR, and LVEF. Besides, patients in the complete PCI group were more likely to have CTO of the LAD, but less likely to have CTO of the left circumflex artery (LCX) as compared with those in the incomplete PCI group. According to the comparison with patients in the OMT group, those in the complete PCI group had a higher TC, HDL-C, and LVEF, lower rate of multiple CTOs and collateral circulation, and a higher rate of therapy with aspirin and adenosine diphosphate P2Y12 receptor antagonists (clopidogrel or ticagrelor) [Table 1]. In addition, patients in the complete PCI group were associated with lower risk of coronary dissection compared with incomplete PCI group [Supplementary Table 1, http://links.lww.com/CM9/B497].
After a PSM ratio of up to 1:2, 190 patients in the incomplete PCI group and 122 in the complete PCI group were retained for comparison [Table 1]. There was no significant difference in the baseline clinical or angiographic data after PSM.
Clinical outcomes
At a median follow-up period of 21 months (interquartile range 12–33 months), there were statistically significant differences among the OMT, incomplete PCI, and complete PCI groups on the rate of MACEs (43.0% [37/86] vs. 30.6% [100/327] vs. 20.0% [29/145], respectively, P = 0.016) and unstable angina (24.4% [21/86] vs. 19.3% [63/327] vs. 10.3% [15/145], respectively, P = 0.010) [Table 2, Figure 2]. Specifically, patients in the complete PCI group had a lower rate of MACE as compared with those in the incomplete PCI group (adjusted hazard ratio [HR] = 1.58; 95% confidence interval [CI] = 1.04–2.39; P = 0.031) and those in the OMT group (adjusted HR = 2.00; 95% CI = 1.23–3.27; P = 0.005). The rate of unstable angina was also lower in the complete PCI group as compared with the incomplete PCI group (adjusted HR = 1.98; 95% CI = 1.13–3.48; P = 0.017) and the OMT group (adjusted HR = 2.41; 95% CI = 1.24–4.67; P = 0.009) [Tables 2 and 3]. However, no significant difference was observed between OMT group and incomplete PCI group in terms of MACE or unstable angina [Supplementary Table 2, http://links.lww.com/CM9/B497].
Table 2.
Clinical outcomes in total population patients with CTO and MVD during follow-up, n (%).
| Items |
OMT (n = 86) |
Incomplete PCI (n = 327) |
Complete PCI (n = 145) |
χ2 | P values |
|---|---|---|---|---|---|
| MACE | 37 (43.0)* | 100 (30.6) | 29 (20.0) | 7.900 | 0.016 |
| All-cause death | 5 (5.8)* | 7 (2.1) | 0 (0) | 3.179‡ | 0.204 |
| Recurrent MI | 4 (4.7) | 13 (4.0) | 6 (4.1) | 1.347 | 0.510 |
| Repeated revascularization | 7 (8.1) | 40 (12.2) | 13 (9.0) | 1.989 | 0.370 |
| Unstable angina | 21 (24.4)* | 63 (19.3)† | 15 (10.3) | 8.034 | 0.010 |
| Heart failure | 4 (4.7) | 13 (4.0) | 4 (2.8) | 0.983 | 0.612 |
*OMT vs. complete PCI, P <0.05. †Incomplete PCI vs. complete PCI, P <0.05. ‡Wald chi-squared test value; CTO: Chronic total occlusion; MACE: Major adverse cardiovascular event; MI: Myocardial infarction; MVD: Multi-vessel disease; OMT: Optimal medical treatment; PCI: Percutaneous coronary intervention.
Figure 2.
Kaplan–Meier curves of (A) MACE and (B) unstable angina in all patients with CTO and MVD. CTO: Chronic total occlusion; MACE: Major adverse cardiovascular event; MVD: Multi-vessel disease; OMT: Optimal medical treatment; PCI: Percutaneous coronary intervention.
Table 3.
Cox analyses of the clinical outcomes in total population of patients with CTO and MVD during follow-up.
| Items | OMT vs. complete PCI | Incomplete PCI vs. complete PCI | OMT vs. complete PCI | Incomplete PCI vs. complete PCI | |||||||
|
Unadjusted HR (95% CI) |
P values |
Unadjusted HR (95% CI) |
P values |
Adjusted HR (95% CI) |
P values |
Adjusted HR (95% CI) |
P values | ||||
| MACE | 2.15 (1.32–3.50) | 0.002 | 1.61 (1.07–2.44) | 0.023 | 2.00 (1.23–3.27) | 0.005 | 1.58 (1.04–2.39) | 0.031 | |||
| All-cause death | – | – | – | – | – | – | – | – | |||
| Recurrent MI | 1.12 (0.32–3.98) | 0.858 | 1.01 (0.39–2.67) | 0.978 | 0.46 (0.11–1.91) | 0.288 | 0.80 (0.29–2.16) | 0.653 | |||
| Repeated revascularization | 0.91 (0.36–2.28) | 0.836 | 1.42 (0.76–2.66) | 0.271 | 1.05 (0.41–2.67) | 0.924 | 1.51 (0.80–2.86) | 0.207 | |||
| Unstable angina | 2.41 (1.24–4.67) | 0.009 | 1.98 (1.13–3.48) | 0.017 | 2.41 (1.24–4.67) | 0.009 | 1.98 (1.13–3.48) | 0.017 | |||
| Heart failure | 1.42 (0.35–5.71) | 0.621 | 1.46 (0.48–4.49) | 0.507 | 0.90 (0.20–4.33) | 0.900 | 1.37 (0.43–4.34) | 0.596 | |||
CI: Confidence interval; CTO: Chronic total occlusion; HR: Hazard ratio; MACE: Major adverse cardiovascular event; MI: Myocardial infarction; MVD: Multi-vessel disease; OMT: Optimal medical treatment; PCI: Percutaneous coronary intervention; –: Not applicable.
Additionally, we analyzed patients who received incomplete PCI (n = 327), in which 270 cases failed in CTO revascularization, and 57 cases failed with non-CTO revascularization. Patients who failed in CTO revascularization showed a higher risk of MACE (31.1% [84/270] vs.12.3% [7/57], HR = 0.39, 95% CI = 0.18–0.84, P = 0.017) and unstable angina (17.8% [48/270] vs. 5.3% [3/57], HR = 0.29, 95% CI = 0.09–0.93, P = 0.038) when compared with those who failed with non-CTO revascularization [Supplementary Table 3, http://links.lww.com/CM9/B497].
The multivariate analysis showed that the treatment strategy and CKD stages III–V (adjusted HR = 2.08; 95% CI = 1.37–3.15; P = 0.001) were identified as independent predictive factors for MACEs in the study population according to Cox regression analysis [Supplementary Table 4, http://links.lww.com/CM9/B497]. As a result, Cox analyses of the clinical outcomes stratified by renal function was conducted. The results showed that the benefit of complete PCI was applicable for patients with CKD stages I–II, but not for patients with CKD stages III–V [Supplementary Table 5, http://links.lww.com/CM9/B497].
After PSM, there was still a significant decrease in the rate of MACEs in the complete PCI group as compared with the incomplete PCI group (20.5% [25/122] vs. 32.6% [62/190], respectively; adjusted HR = 0.55, 95% CI = 0.32–0.96, P = 0.035) and the rate of unstable angina (10.7% [13/122] vs. 20.5% [39/190], respectively; adjusted HR = 0.48; 95% CI = 0.24–0.99; P =0.046) [Table 4]. Kaplan–Maier survival curves free from MACEs and unstable angina in the total population and post-matched population are shown in Figures 2 and 3.
Table 4.
Cox analyses of clinical outcomes between the complete vs. incomplete PCI groups after PSM.
| Variables |
Incomplete PCI (n = 190) |
Complete PCI (n = 122) |
Unadjusted HR (95% CI) | P values | Adjusted HR (95% CI) | P values |
|---|---|---|---|---|---|---|
| MACE | 62 (32.6) | 25 (20.5) | 0.61 (0.38–0.96) | 0.034 | 0.55 (0.32–0.96) | 0.035 |
| All-cause death | 4 (2.1) | 0 (0) | – | – | – | – |
| Recurrent MI | 6 (3.2) | 5 (4.1) | 1.26 (0.38–4.13) | 0.703 | 0.70 (0.13–3.82) | 0.684 |
| Repeated revascularization | 26 (13.7) | 11 (9.0) | 0.63 (0.31–1.28) | 0.203 | 0.73 (0.33–1.59) | 0.427 |
| Unstable angina | 39 (20.5) | 13 (10.7) | 0.50 (0.27–0.93) | 0.030 | 0.48 (0.24–0.99) | 0.046 |
| Heart failure | 7 (3.7) | 3 (2.5) | 0.69 (0.18–2.68) | 0.595 | 0.47 (0.04–5.26) | 0.536 |
Data are presented as n (%). CI: Confidence interval; HR: Hazard ratio; MACE: Major adverse cardiovascular event; MI: Myocardial infarction; PCI: Percutaneous coronary intervention; PSM: Propensity score matching; –: Not applicable.
Figure 3.
Kaplan–Meier curve of (A) MACE and (B) unstable angina between the complete and incomplete PCI groups after PSM. MACE: Major adverse cardiovascular event; PCI: Percutaneous coronary intervention; PSM: Propensity score matching.
Discussion
In this study, the clinical outcomes of different percutaneous strategies in patients with CTO and MVD were investigated. The results showed that complete PCI was associated with a reduced long-term risk of MACEs and unstable angina for patients with CTO and MVD, as compared with incomplete PCI and OMT. However, there was no improvement in all-cause death and other adverse events.
MVD and CTO often coexist. A large registry of 15,619 consecutive patients after coronary angiography showed that the prevalence of CTO and MVD was 8.1%,[4] and CTO was the main reason for incomplete PCI in patients with MVD.[11] In the present study, the prevalence of CTO and MVD was 9.98% and the right coronary artery was the most common site of CTO. Those findings agreed with previous reports.[4,12] For management of CTO, previous trials suggested that PCI was superior in improving symptoms and quality of life, as compared with OMT,[13,14] with similar improvement in MACEs in patients with multiple CTOs.[15] According to recent guidelines, ischemic symptoms are the primary indication for PCI.[9] Therefore, we defined MACE as a composite including unstable angina required for rehospitalization, which represented the improvement of symptoms to some extent. Similarly, in the present study, the rates of MACEs and unstable angina were lower in the complete PCI group as compared with the OMT group.
However, in actual clinical practice, a large portion of patients with MVD and CTO are treated with incomplete PCI to avoid high radiation exposure, high failure rate of the procedure, and poor revascularization of remaining lesions. With the development of technologies and strategies, the rate of successful PCI has greatly increased to 80%.[9,16] Recent studies have reported that successful PCI can achieve better clinical outcomes as compared with failed PCI in patients with CTO lesions.[17,18] However, the efficacy of complete percutaneous revascularization in patients with CTO and MVD remains uncertain, as there are limited data on clinical outcomes. A lower rate of MACEs in patients undergoing complete PCI was reported in a randomized trial, as compared with patients undergoing non-CTO PCI.[18] However, the latter group of the trial was defined as medical treatment with or without non-CTO PCI, and patients with the single-vessel disease were also enrolled. Thus, the efficacy of PCI for patients with CTO and MVD remains unclear. Additionally, a subgroup analysis in patients with CTO and MVD showed that complete revascularization by CABG or PCI was associated with a significantly better long-term combined endpoint, including death and Q-wave MI.[19] However, the superiority of PCI in avoiding MACEs was not observed in the another trial,[20] and the outcomes of complete vs. incomplete PCI for patients with CTO and MVD were still not clear.
In the present study, patients who underwent complete PCI had a lower prevalence of history of PCI and higher TC, HDL-C, LDL-C, eGFR, and LVEF, and were less likely to have CTO of the LCX as compared with those in the incomplete PCI group. To balance baseline characteristics, PSM analysis was performed and the results showed the rates of MACEs and unstable angina were lower in the complete PCI group, as determined by both pre-matched and post-matched analyses. Those data indicated the potential clinical benefit of complete PCI rather than incomplete PCI on CTO lesions or non-CTO lesions. The results of this study suggest that complete revascularization should possibly be achieved in patients with CTO and MVD in clinical practice. However, the mechanism by which complete percutaneous revascularization improves MACE events is unclear. As reducing the presence or extent of myocardial ischemia might contribute to the benefit of revascularization,[13,14] complete PCI might alleviate unstable angina and confer a better long-term clinical outcome, as observed in the pre- and post-matched populations of this and previous studies.[21] Regretfully, imaging evaluations, such as cardiovascular magnetic resonance (CMR), positron emission tomography (PET)/computed tomography (CT), and SPECT, to assess the ischemic area in patients with CTO or MVD were not performed in every patient. Therefore, the results might be insufficient to determine whether incomplete revascularization by CTO or non-CTO PCI can resolve ischemia.
On the contrary, several trials showed no benefit in clinical outcomes between complete CTO PCI and non-CTO PCI in patients with ST-elevation MI,[22,23] and an even worse prognosis due to complete CTO PCI in patients with MI-related cardiogenic shock.[24] The majority of patients in this study had stable coronary disease, which may explain the discrepancy with previous trials. Thus, aggressive complete PCI should possibly be limited to only patients with stable coronary disease.
As some patients who received incomplete PCI were likely to arrange scheduled secondary revascularization, but this "revascularization" was not regarded as the MACE event in this study, which avoided misjudgment of MACE events. A sub-analysis in patients with CTO and MVD showed comparable rates of cardiac death between the complete CTO-PCI and non-CTO PCI groups[25], which concurred with the results of the present study. However, non-CTO PCI was not equal to incomplete PCI, and our study showed that different incomplete PCI strategy might cause different impact on long-term prognosis. Hence, further observational studies and randomized trials are needed to verify the long-term prognosis of complete vs. incomplete PCI and to provide clinical guidance and support.
In addition to complete PCI treatment, the results of the present study identified CKD stages III–IV as a predictor of MACEs in patients with CTO and MVD. Moreover, a previous study verified that PCI reduced the rate of MACEs as compared with medical treatment in patients with CKD stages I–II,[26] which was consistent with our subgroup analysis. However, limited by the small sample size of patients with CKD stages III–V in the present study, more prospective study should be conducted to determine whether complete PCI is appropriate for this subset.
The results of this study confirmed that for patients with CTO and MVD, complete PCI reduced the long-term risk of MACEs and unstable angina as an initial strategy as compared with incomplete PCI. Despite observational evidence, an optimal initial strategy remains unclear. Hence, ongoing randomized controlled trials, such as "The Success of Opening Concurrent Chronic Total Occlusion Lesion to Improve Cardiac Function Trial in Patients with Multi-vessel Disease", may provide answers.
There were some limitations in this study that should be addressed. First, this was an observational study, and thus, the results may have been significantly affected by confounding factors, and we performed PSM to further balance the baseline characteristics among the groups. Second, the patients were not stratified by SYNTAX scores or Rentrop classification. So the severity of coronary heart disease and quantitative analysis of collateral circulation were not comprehensively evaluated. Third, imaging evaluations (e.g., CMR, PET/CT, and SPECT) were not performed in every patient to assess the ischemic area of patients with CTO and MVD to further explain the ability of incomplete revascularization to alleviate myocardial ischemia.
In conclusion, for treatment of CTO and MVD, complete PCI reduced the long-term risk of MACEs and unstable angina, as compared with incomplete PCI and OMT. These findings suggest that complete percutaneous revascularization of both CTO and non-CTO lesions can potentially improve the prognosis of patients with CTO and MVD.
Acknowledgements
We thank Shanshan Wu (Department of Clinical Epidemiology and EBM, Beijing Friendship Hospital, Capital Medical University) for guiding the statistical analysis.
Funding
This study was supported by grants from the Beijing United Heart Foundation, Cardiacare Sponsored Optimizing Antithrombotic Research Fund (No. BJUHFCSOARF 201801-02) and the Summit Talent Plan, Beijing Hospital Management Center (No. DFL20190101).
Conflicts of interest
None.
Supplementary Material
Footnotes
How to cite this article: Li ZY, Zhou ZR, Guo L, Zhong L, Xiao JN, Meng SK, Wang YD, Ding HY, Zhang B, Zhu H, Zhou XC, Huang RC. Effect of complete percutaneous revascularization on improving long-term outcomes of patients with chronic total occlusion and multi-vessel disease. Chin Med J 2023;136:959–966. doi: 10.1097/CM9.0000000000002653
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