The prevalence of chronic total occlusion (CTO) is reported to be around 18.4% among patients with significant coronary artery disease [
Ultrathin strut polymer-free, sirolimus-probucol coated drug-eluting stents (PF-SES) are safe and effective in large scale all-comers population with low rate of target lesion revascularization (TLR) [
The ISAR 2000 all-comers registry (
Patients 18 years or older with stable angina, objective evidence of myocardial ischemia, and acute coronary syndrome (ACS) who met the requirement for PCI [
PF-SES (Coroflex ISAR, B. Braun Melsungen, Melsungen AG, Germany) were implanted according to each institution’s guidelines and in accordance with proper indications for national reimbursement. The polymer-free stent platform consists of a premounted, thin strut (50/60
Vascular accesses via the femoral or radial artery were both permitted with a recommended introducer sheath of at least 5 Fr in diameter. The technique of stent implantation was up to the operators’ discretion. Intravenous heparin (70 IU/kg) was given to all patients and supplemented on an as-needed basis. Platelet aggregation inhibitor loading was not mandatory but recommended if possible prior to PCI according to institutional preferences of the cardiac center.
The use of various antiplatelet inhibition agents (6 months or more) such as clopidogrel (75 mg/day), prasugrel (10 mg/day), or ticagrelor (90 mg twice daily) was permissible (as recommended by the treating physician) while acetylsalicylic acid 100–325 mg daily was prescribed life-long.
To handle the wealth of the data, an electronic data capture system was used. This database was previously used in prior large scale unselected patient cohorts [
The primary endpoint was the 9-month clinically driven target lesion revascularization (TLR) rate, whereas secondary endpoints were the 9-month major adverse cardiac events (MACE) rate, the in-hospital MACE rate, and the corresponding rates of myocardial infarction (MI) and TLR (coronary artery bypass grafting and percutaneous coronary intervention). Cardiac death was only defined in-hospital, whereas the all-cause death rate was used to define MACE at 9 months (MI, TLR, in-hospital cardiac death, and all deaths post discharge). The Academic Research Consortium (ARC) criteria were used to define acute/subacute stent thrombosis [
For simplicity reason and based on a previous protocol [
The statistical methods were also reported elsewhere [
Ethics committees of all participating centers approved the study protocol prior to patient recruitment. In France, this noninterventional study was nationally approved by Comité Consultative sur le Traitement de I’Information en matière de Recherche dans le domaine de la Santé (CTIRS dossier number 14.613) and the Commission Nationale de I’informatique et des Libertés (CNIL, demande d’autorisation number 915019).
A total of 111 patients with CTO (Table
Patient demographics.
Variable | Patients, |
<25 mm lesion length, |
≥25 mm lesion length, |
| |
---|---|---|---|---|---|
Number of patients | 111 (100%) | 49 (44.1%) | 62 (55.8%) | — | |
Number of lesions | 127 (100%) | 58 (45.7%) | 69 (54.3%) | — | |
Number of DES used | 160 (100%) | 65 (40.6%) | 95 (59.4%) | — | |
Age (years) | 64.9 ± 11.6 | 64.8 ± 12.3 | 65.0 ± 11.0 | 0.942 | |
Male gender | 82 (73.9%) | 35 (71.4%) | 47 (75.8%) | 0.602 | |
Diabetes | 50 (45.0%) | 19 (38.8%) | 31 (50.0%) | 0.238 | |
Hypertension | 79 (71.2%) | 30 (61.2%) | 49 (79.0%) | 0.040 | |
Renal insufficiency | 6 (5.4%) | 3 (6.1%) | 3 (4.8%) | 0.766 | |
Dialysis dependence | 1 (0.9%) | 0 (0.0%) | 1 (1.6%) | 0.372 | |
STEMI | 9 (8.1%) | 2 (4.1%) | 7 (11.3%) | 0.257 | |
NSTEMI | 14 (12.6%) | 8 (16.3%) | 6 (9.7%) | ||
Region | Europe | 71 (64.0%) | 29 (59.2%) | 42 (67.7%) | 0.351 |
Asia | 40 (36.0%) | 20 (40.8%) | 20 (32.3%) |
There were 127 CTO lesions (Table
Lesion characteristics and procedural data.
Variable | Patients, |
<25 mm lesion length, |
≥25 mm lesion length, |
| |
---|---|---|---|---|---|
Number of lesions | 127 (100%) | 58 (45.7%) | 69 (54.3%) | — | |
Target vessel | LAD | 37 (29.1%) | 15 (25.9%) | 22 (31.9%) | 0.005 |
LCx | 35 (27.6%) | 24 (41.4%) | 11 (15.9%) | ||
RCA | 55 (43.3%) | 19 (32.8%) | 36 (52.2%) | ||
Graft | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | ||
Multivessel disease | 1-vessel | 103 (81.1%) | 46 (79.3%) | 57 (82.6%) | 0.298 |
2-vessels | 22 (17.3%) | 10 (17.2%) | 12 (17.4%) | ||
3-vessels | 2 (1.6%) | 2 (3.4%) | 0 (0.0%) | ||
Thrombus burden | 10 (7.9%) | 5 (8.6%) | 5 (7.2%) | 0.775 | |
Diffuse vessel disease | 83 (65.4%) | 32 (55.2%) | 51 (73.9%) | 0.027 | |
Calcification | 54 (42.4%) | 24 (41.4%) | 30 (43.5%) | 0.812 | |
Ostial lesion | 9 (7.1%) | 5 (8.6%) | 4 (5.8%) | 0.537 | |
Bifurcations | 8 (6.3%) | 5 (8.6%) | 3 (4.3%) | 0.324 | |
In-stent restenosis | 12 (9.4%) | 1 (1.7%) | 11 (15.9%) | 0.006 | |
Severe tortuosity | 17 (13.4%) | 7 (12.1%) | 10 (14.5%) | 0.689 | |
AHA/ACC type B2/C lesion | 121 (95.3%) | 52 (89.7%) | 69 (100.0%) | 0.006 | |
Reference diameter (mm) | 2.76 ± 0.40 | 2.7 ± 0.4 | 2.8 ± 0.4 | 0.059 | |
Lesion length (mm) | 26.8 ± 13.1 | 16.9 ± 4.5 | 35.2 ± 11.9 | <0.001 | |
DESs used | 160 (100%) | 65 (40.6%) | 95 (59.4%) | — | |
DES per patient | 1.8 ± 1.3 | 1.4 ± 1.2 | 2.1 ± 1.4 | 0.008 | |
DES diameter (mm) | 2.7 ± 0.4 | 2.7 ± 0.4 | 2.7 ± 0.4 | 0.690 | |
DES length (mm) | 29.4 ± 15.8 | 20.3 ± 8.4 | 36.9 ± 16.5 | <0.001 | |
DES inflation pressure (atm) | 14.3 ± 3.4 | 14.5 ± 3.2 | 14.2 ± 3.5 | 0.638 | |
Final result (% stenosis) | 4.9 ± 11.3 | 5.7 ± 14.6 | 4.3 ± 7.7 | 0.478 | |
Overall technical success per lesion | 126 (99.2%) | 58 (100.0%) | 68 (98.6%) | 0.357 |
Preprocedural antiplatelet therapy (Tables
Periprocedural drug therapy.
Drug type | Drug | Patients, |
<25 mm lesion length, |
≥25 mm lesion length, |
| |
---|---|---|---|---|---|---|
Pre-PCI | Antiplatelet therapy (APT) | Clopidogrel | 59 (53.9%) | 29 (59.2%) | 30 (48.4%) | 0.391 |
Prasugrel | 18 (16.2%) | 7 (14.3%) | 11 (17.7%) | |||
Ticagrelor | 12 (10.8%) | 7 (14.3%) | 5 (8.1%) | |||
Ticlopidine | 1 (0.9%) | 0 (0.0%) | 1 (1.6%) | |||
Aspirin only | 10 (9.0%) | 2 (4.1%) | 8 (12.9%) | |||
No preloading | 11 (9.9%) | 4 (8.2%) | 7 (11.3%) | |||
Oral anticoagulation (OAC) | All OAC | 1 (0.9%) | 1 (2.0%) | 0 (0.0%) | 0.258 | |
Vitamin K antagonist (VKA) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0.258 | ||
New oral anticoagulation (NOAC) | 1 (0.9%) | 1 (2.0%) | 0 (0.0%) | |||
Post-PCI | Antiplatelet therapy (APT) | Clopidogrel | 92 (82.9%) | 40 (81.6%) | 52 (83.9%) | 0.167 |
Prasugrel | 4 (3.6%) | 0 (0.0%) | 4 (6.5%) | |||
Ticagrelor | 12 (10.8%) | 4 (16.3%) | 4 (6.5%) | |||
Aspirin only | 1 (0.9%) | 0 (0.0%) | 1 (0.9%) | |||
Unknown | 2 (1.8%) | 1 (2.0%) | 1 (0.9%) |
Recommended duration of dual antiplatelet therapy during follow-up.
Variable | Patients, |
<25 mm lesion length, |
≥25 mm lesion length, |
|
---|---|---|---|---|
Number of patients | 111 (100%) | 49 (44.1%) | 62 (55.8%) | — |
DAPT duration in months | 9.7 ± 2.8 | 9.8 ± 2.8 | 9.6 ± 2.9 | 0.773 |
1 month | 1 (0.9%) | 1 (2.0%) | 0 (0.0%) | 0.355 |
1–3 months | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | |
3–6 months | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | |
6 months | 30 (27.0%) | 11 (22.4%) | 19 (30.4%) | |
>6–12 months | 8 (7.2%) | 4 (8.2%) | 4 (6.5%) | |
12 months | 50 (45.0%) | 20 (40.8%) | 30 (48.4%) | |
>12 months | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | |
Unknown status | 22 (19.8%) | 13 (26.5%) | 9 (14.5%) |
At 9 months, there were two patients (2%, 2/101) with TLR (primary endpoint). The rates of acute myocardial infarction (MI) and all-cause death at 9 months were 2% (2/101) and 3% (3/101), respectively. Hence, the composite MACE rate at 9 months was 5.9% (6/101). The in-hospital follow-up was event free except for one acute MI (1%, 1/111). There seems to be a higher 9-month MACE rate for the >25 mm lesion group, but the difference did not reach statistical significance (
Clinical outcomes.
Variable | Patients, |
<25 mm lesion length, |
≥25 mm lesion length, |
|
---|---|---|---|---|
Number of patients | 111 (100%) | 49 (44.1%) | 62 (55.8%) | — |
Patients with clinical follow-up at 9 months or early event | 101 (91.0%) | 46 (93.6%) | 55 (88.7%) | 0.345 |
Follow-up time (months) | 8.7 ± 2.5 | 8.1 ± 2.2 | 9.2 ± 2.6 | 0.020 |
Time to discharge median (IQR) (days) | 4.5 ± 16.5 | 3.2 ± 5.7 | 5.6 ± 21.7 | 0.45 |
In-hospital MACE | 1 (1.0%) | 0 (0.0%) | 1 (1.8%) | 0.358 |
In-hospital TLR | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | — |
In-hospital MI | 1 (1.0%) | 0 (0.0%) | 1 (1.8%) | 0.358 |
In-hospital cardiac death | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | — |
9-month MACE | 6 (5.9%) | 2 (4.3%) | 4 (7.3%) | 0.536 |
9-month TLR (Re-PCI/CABG) | 2 (2.0%) | 1 (2.2%) | 1 (1.8%) | 0.898 |
9-month MI | 2 (2.0%) | 0 (0.0%) | 2 (3.6%) | 0.191 |
9-month death all causes | 3 (3.0%) | 1 (2.2%) | 2 (3.6%) | 0.666 |
9-month accumulated definite/probable stent thrombosis | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | — |
Acute stent thrombosis, ≤24 hours | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | — |
Subacute stent thrombosis, 1–30 days | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | |
Late stent thrombosis, ≥30 days | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | |
BARC 1–5 | 6 (5.9%) | 1 (2.2%) | 5 (9.1%) | 0.143 |
BARC 2–5 | 2 (2.0%) | 0 (0.0%) | 2 (3.6%) | 0.191 |
BARC 3–5 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | — |
Despite the conflicting data regarding the clinical benefit [
Unfortunately, due to the technical complexity, relatively lower procedure success rates, and higher periprocedural complications [
For patients to benefit long term and to justify the risk of CTO-PCI, to maintain the target vessel patency is important. A large CTO registry of 800 patients with 6- to 9-month angiographic follow-up reported a reocclusion rate of 7.5% [
Our study described the outcomes of CTO-PCI from “real-world” data using polymer-free ultrathin strut sirolimus-probucol coated drug-eluting stents (PF-SES). CTO-PCIs in this study were conducted in various centers with a broad spectrum of operator experience and revascularization techniques. Overall, the results of this study reflect the unrestricted, day-to-day practice from various European and Asian centers in the treatment of CTO.
The outcome of CTO lesions stented with PF-SES from this study is encouraging. The overall 9-month TLR rate of both <25 mm and >25 mm CTO lesions is low at around 2%. We did not observe any acute, subacute, or late stent thrombosis in this study. The MACE rate at 9-month follow-up is also favorably low at 5.9% (4.3% for lesions < 25 mm and 7.3% for lesions > 25 mm,
The results support the use of PF-SES as an efficacious and safe therapeutic option in the treatment of CTO. The result at least for short term (9 months) is promising, and a longer follow-up would be of interest to determine if PF-SES angioplasty is able to maintain vessel patency in the long-term (>1 year).
The CTO cohort in this study was extracted from the largest all-comers registry under routine use of PF-SES, which can be safely and effectively implanted with favorable rates of TLR and MACE. The data suggest that the use of PF-SES in high-risk patients with complex lesions (diabetes mellitus, ACS, diffuse disease, and CTO) is feasible. However, since this is a subgroup analysis from a “real-world” observational study, data collection and monitoring may not have been as stringent as in randomized control trials with the possibility of some underreporting of events. Although the number of patients reported in this assessment was small, the results nevertheless described the potential of PF-SES performance in the specific cohort of CTO patients. It also would have been useful to provide more details on the chronic kidney disease stages relative to their glomerular filtration rates, which was not done in this assessment. Likewise, the use of the J-SCORE and/or the time course of the occlusion along with the lesion crossing (antegrade/retrograde) would have helped to provide additional details of the performed CTO recanalization.
Florian Krackhardt received lecturing fees, and Matthias W. Waliszewski and Michael Boxberger served full time employment at the Department of Medical Scientific Affairs, B. Braun Melsungen AG.
Ahmad Syadi Mahmood Zuhdi and Muhammad Dzafir Ismail drafted and prepared the manuscript. Florian Krackhardt, Matthias W. Waliszewski, and Michael Boxberger contributed to the conception, design, data analysis, and interpretation. Wan Azman Wan Ahmad critically revised the manuscript for submission. All authors gave final approval of the version to be published.
The authors would like to express gratitude to Denny Herberger (Germany) and Ms. Zoey Hooi (Malaysia) for their relentless efforts providing regulatory and logistic support to conduct this study.