Abstract
Background
Coronary atherosclerosis often involves small-caliber coronaries, yet the safety and efficacy of 2.25-mm DES have been poorly defined, with a general lack of separation of 2.25 with 2.5-mm performance. No randomized head-to-head 2.25 mm DES studies have been reported. There are several single-arm prospective studies, and we aim to systematically review all published specific 2.25-mm data to estimate composite DES-specific performance and highlight current knowledge gaps.
Methods
We performed a systematic literature search of PubMed, EMBASE, Web of Science and Cochrane database for clinical trials of 2.25-mm DES. Angiographic and composite clinical outcomes were compared with descriptive statistics.
Results
2.25 mm-Paclitaxel (PES), sirolimus (SES), everolimus (EES) and platinum chromium EES DES-specific outcomes have been reported. Death at 12 months for SES, PES, EES and platinum chromium EES was 1.3%, 3.0%, 1.5%, and 4.4%. Rates of target vessel revascularization at 12 months for SES, PES, EES and platinum chromium EES were 5.7%, 13.3%, 8.8%, and 3.3%. Angiographic outcomes at 9 months to one year were as follows: mean late lumen loss (LLL) for SES, PES, and EES was 0.15 ± 0.11-mm, 0.28 ± 0.11-mm, and 0.16 ± 0.41-mm and mean diameter restenosis for SES, PES, and EES were 29.5 ± 6.2%, 34.7 ± 4.2%, and 20.9 ± 22.5%. Reported stent thrombosis rates for 2.25-mm DES were low ranging from 0% to 2.2% in up to 24-months of follow-up.
Conclusions
This systematic review summarizes and tabulates all available specific data on 2.25-mm DES. Based on our descriptive analysis, 2.25-mm DESs have a favorable safety and efficacy profile for the treatment of very small coronary lesions.
Highlights
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Safety and efficacy of 2.25-mm DES have been poorly defined.
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We performed a systematic review on all published 2.25 mm data to estimate composite DES-specific performance and highlight current knowledge gaps.
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We pooled data from 9 clinical studies and 1,476 patients.
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Composite clinical and angiographic data at less than 12 months, 24 months and 60 months were displayed.
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Based on our descriptive analysis, 2.25-mm DESs have a favorable safety and efficacy profile for the treatment of very small coronary lesions.
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Paucity of outcome data on contemporary 2.25-mm DES was highlighted.
1
Introduction
Atherosclerotic coronary involvement often extends to small-caliber coronaries, with angiographic reference vessel diameter of 2.75-mm or less . Up to 20–30% of patients undergoing percutaneous coronary intervention (PCI) may have significant atherosclerosis in relatively small coronary segments . PCI of small vessels is associated with an increased risk of restenosis and adverse outcomes . The use of drug-eluting stents (DESs) in small coronary vessels has been demonstrated to be superior to bare-metal stents (BMS) . With the subsequent availability of 2.25-mm DES, the term “very small coronary vessels” has been proposed for coronary segments where 2.25-mm DESs are used . However, the safety and efficacy of the various types of 2.25-mm DES is not well defined. There has yet to be a systematic overview that would provide a more precise estimate of the outcomes of the various types of 2.25-mm DES. In our systematic review, we aim to summarize clinical and angiographic outcome data from clinical trials of 2.25-mm DES.
2
Materials and methods
2.1
Search strategy
A computerized literature search of the PUBMED, EMBASE, OvidSP, Web of science, and Cochrane database of clinical trials was conducted. The cited references were reviewed to identify randomized, non-randomized as well as single arm or double arm trials that compared the clinical, angiographic and/or procedural outcomes from using 2.25-mm DES. Literature searches were completed in February, 2015. We used the following search keywords: “small vessel”, “small arteries”, “coronary arteries”, “everolimus”, “zotarolimus”, “biolimus”, “umirolimus”, “paclitaxel”, “sirolimus”, “serolimus”, “2.25-mm”, “stent”, “drug-eluting stent”, or “coronary stent”. No time duration, language or study type restriction was used while extracting the data. No restrictions on the subheadings were applied. The PRISMA guidelines were followed in developing a PRISMA flow sheet . All references of relevant trials were also reviewed.
2.2
Study selection
Our primary objective was the description of 2.25-mm DES composite outcomes in all reported clinical trials. Our pre-specified inclusion criteria were as follows: (1) prospective or retrospective data from clinical trials, (2) reports in the English language, (3) single or two-treatment arm containing any of the available 2.25-mm DES, (4) at least 30 days follow up, (6) studies that have at least mentioned device outcomes (angiographic and/or procedural) and patient outcomes . Data published in the form of abstracts without peer-reviewed publication of the manuscripts were not included. Composite outcomes were defined as combination of angiographic outcome and clinical outcome. Two independent individuals (GO and NS) collected the data separately. All studies included were screened against study eligibility criteria.
2.3
Definitions of outcomes
Successful stent deployment was defined as a minimum stenosis diameter reduction of < 20% with final TIMI-3 flow, without side branch occlusion, flow-limiting dissection, distal embolization, or angiographic thrombus. Additional angiographic outcomes included in-stent and in-segment LLL by QCA, binary restenosis and percentage diameter stenosis (DS) . Clinical outcomes including death, target lesion revascularization, target vessel revascularization, stent thrombosis and myocardial infarction (MI) were defined individually as per the recommendations of Academic Research Consortium .
2.4
Statistical analysis
A study-level pooled descriptive analysis was performed to summarize the composite clinical and angiographic outcomes of 2.25-mm DES in all eligible patients. The analysis was performed irrespective of the number of study arms and blinding status. Numerical measures used measure of location such as mean and measure of variation such as standard deviation. Follow-up duration of clinical outcomes was categorized into three categories: ≤ 12 months, 24 months and 60 months respectively.
2
Materials and methods
2.1
Search strategy
A computerized literature search of the PUBMED, EMBASE, OvidSP, Web of science, and Cochrane database of clinical trials was conducted. The cited references were reviewed to identify randomized, non-randomized as well as single arm or double arm trials that compared the clinical, angiographic and/or procedural outcomes from using 2.25-mm DES. Literature searches were completed in February, 2015. We used the following search keywords: “small vessel”, “small arteries”, “coronary arteries”, “everolimus”, “zotarolimus”, “biolimus”, “umirolimus”, “paclitaxel”, “sirolimus”, “serolimus”, “2.25-mm”, “stent”, “drug-eluting stent”, or “coronary stent”. No time duration, language or study type restriction was used while extracting the data. No restrictions on the subheadings were applied. The PRISMA guidelines were followed in developing a PRISMA flow sheet . All references of relevant trials were also reviewed.
2.2
Study selection
Our primary objective was the description of 2.25-mm DES composite outcomes in all reported clinical trials. Our pre-specified inclusion criteria were as follows: (1) prospective or retrospective data from clinical trials, (2) reports in the English language, (3) single or two-treatment arm containing any of the available 2.25-mm DES, (4) at least 30 days follow up, (6) studies that have at least mentioned device outcomes (angiographic and/or procedural) and patient outcomes . Data published in the form of abstracts without peer-reviewed publication of the manuscripts were not included. Composite outcomes were defined as combination of angiographic outcome and clinical outcome. Two independent individuals (GO and NS) collected the data separately. All studies included were screened against study eligibility criteria.
2.3
Definitions of outcomes
Successful stent deployment was defined as a minimum stenosis diameter reduction of < 20% with final TIMI-3 flow, without side branch occlusion, flow-limiting dissection, distal embolization, or angiographic thrombus. Additional angiographic outcomes included in-stent and in-segment LLL by QCA, binary restenosis and percentage diameter stenosis (DS) . Clinical outcomes including death, target lesion revascularization, target vessel revascularization, stent thrombosis and myocardial infarction (MI) were defined individually as per the recommendations of Academic Research Consortium .
2.4
Statistical analysis
A study-level pooled descriptive analysis was performed to summarize the composite clinical and angiographic outcomes of 2.25-mm DES in all eligible patients. The analysis was performed irrespective of the number of study arms and blinding status. Numerical measures used measure of location such as mean and measure of variation such as standard deviation. Follow-up duration of clinical outcomes was categorized into three categories: ≤ 12 months, 24 months and 60 months respectively.
3
Results
3.1
Citations identified
A total of 428 potentially relevant citations were identified. Fig. 1 shows our search strategy, which yielded nine clinical trials with a total of 1,476 patients.
3.2
Patient characteristics and interventions
Table 1 summarizes the characteristics of the 9 studies, of which 7 were non-randomized and the remaining 2 studies were randomized studies comparing DES vs. BMS. Out of 9, 4 studies were single arm without any control , 2 studies used BMS as a control arm , and 3 studies had DES in both arms . Four types of DES-everolimus, platinum chromium everolimus, sirolimus and paclitaxel were used in 2.25-mm DES in reference vessel diameter ranging from 1.86-mm to 2.50-mm.
| Authors | Year | Design | Control | Stent | Drug | RVD (mm) | Primary endpoint | Secondary endpoint | Follow up |
|---|---|---|---|---|---|---|---|---|---|
| Ardissino et al. | 2004 | Prospective, randomized, single-blind, multicenter | BMS 2.25-mm | Cypher SES 2.25-mm | Sirolimus | 2.22 ± 0.29 | Angiographic binary restenosis rate at 12 m | Procedural success, 8 m in segment MLD, late loss, MACE, CVA. | 8 m angiography |
| Cannon et al. | 2012 | Prospective, non-randomized, multi-center | None | Xience Nano 2.25-mm EES | Everolimus | ≥ 2.25– < 2.5 | TLF at 1 year post PCI (defined as cardiac death, MI in target vessel, CI-TLR) | MACE (cardiac death, MI, TLR, TVF, TVR) | 1 m, 8 m, and 1 year clinical, 8 m angiography |
| Lemos et al. | 2004 | Prospective, non-randomized, single center, | None | Cypher SES 2.25 mm | Sirolimus | 1.88 ± 0.34 | Late lumen loss/binary restenosis at 6 m angiography, 12 m clinical outcome | Not specified | 12 m clinical, 6 m angiography |
| Moses et al. | 2006 | Prospective, non-randomized, multi-center | None | Cypher SES 2.25-mm | Sirolimus | 2.04 ± 0.29 | In-lesion binary restenosis at 6 m | Death, MI, TLR, TVR, MACE. In-stent or in-segment binary restenosis | 6 m angiography and clinical |
| Ormiston et al. ⁎ | 2012 | Prospective, non-randomized, multi-center | Taxus Express 2.25-mm PES | Taxus Liberte 2.25-mm PES | Paclitaxel | 2.2–2.5 | Non-inferiority of 9-month in-segment DS versus historical Taxus Express control subjects | QCA and clinical endpoints at 60 m | 60 m clinical |
| Stone et al. | 2005 | Prospective, randomized, double-blind, multi-center | BMS 2.25-mm | Taxus Express PES 2.25-mm | Paclitaxel | 2.07 ± 0.31 | Incidence of ischemia-driven TVR at 12 months | 9 m follow up angiographic DS% | 1 m and 9 m clinical. 9 m angiography |
| Tanimoto et al. | 2007 | Prospective, non-randomized, single center | None | 2.25-mm SES and PES | Sirolimus Paclitaxel | 1.86 ± 0.37 (SES) 1.95 ± 0.38 (PES) | To compare clinical outcomes-safety and efficacy at 2 years after implantation | Not specified | 1, 12, 24 m clinical |
| Teirstein et al. | 2015 | Prospective, single-arm, multicenter study | None | Platinum chromium EES | Everolimus | 2.04 ± 0.29 | TLF at 12 m | Not specified | 1, 6, 12, 18 m, 2 years clinical. |
| Turco et al. | 2008 | Prospective, non-randomized, multi-center | Taxus Express 2.25-mm PES | Taxus Liberte 2.25-mm PES | Paclitaxel | ≥ 2.2– < 2.5 | Non-inferiority of 9-month in-segment DS vs. historical Taxus Express control subjects | QCA and clinical endpoints at 12 m | 9 m angiography, 12 m clinical |
⁎ Ormiston et al. 2012 study is 5-year results of initially reported by Turco et al. 2008 1-year follow-up data.
Table 2 describes baseline clinical characteristics, while Table 3 describes baseline target vessel characteristics of the studies included.
| Authors | Sample size | DES type | Age (years, mean ± SD) | Male (%) | Tobacco user (%) | DM (%) | HTN (%) | Hyperlipidemia (%) | Previous MI (%) | Previous UA (%) | Previous PCI (%) | Previous CABG (%) | LVEF (mean ± SD) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ardissino et al. a | 61 | SES | 63 ± 12 | 77 | 19 | 19 | 65 | 61 | 30 | NA | 20 | 10 | NA |
| Cannon et al. | 144 | EES | 63 ± 11 | 62 | 23 | 39 | 82 | 87 | 28 | 27 | NA | NA | NA |
| Lemos et al. | 91 | SES | 64 ± 12 | 62 | 23 | 26 | 56 | NA | 32 | NA | 25 | 11 | NA |
| Moses et al. | 100 | SES | 63 ± 10 | 64 | 20 | 40 | 84 | 86 | 35 | 17 | 63 | 29 | 53 ± 10 |
| Ormiston et al. b | 75 | PES | 65 ± 9 | 67 | 71 | 44 | 81 | 77 | 32 | 28 | NA | 21 | NA |
| 261 | PES | 63 ± 11 | 56 | 58 | 36 | 77 | 82 | 29 | 28 | NA | 13 | NA | |
| Stone et al. | 108 | PES | 63 ± 11 | NA | NA | 47 | NA | NA | NA | NA | NA | NA | NA |
| Tanimoto et al. | 107 | SES | 61 ± 11 | 70 | 19 | 19 | 44 | 67 | 33 | 31 | 26 | 8 | 50 ± 10 |
| 90 | PES | 63 ± 12 | 66 | 31 | 22 | 49 | 61 | 44 | 33 | 28 | 7 | 51 ± 9 | |
| Terstein et al. | 94 | Platinum Chromium EES | 64 ± 11 | 72 | 17 | 43 | 80 | 82 | 30 | 25 | NA | NA | NA |
| Turco et al. | 75 | PES | 65 ± 9 | 67 | 71 | 44 | 81 | 77 | 32 | 28 | NA | 21 | NA |
| 261 | PES | 63 ± 11 | 56 | 58 | 36 | 77 | 82 | 29 | 28 | NA | 13 | NA |
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