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Fabrizio D’Ascenzo, Mario Iannaccone, Gaelle Saint-Hilary, Maurizio Bertaina, Stefanie Schulz-Schüpke, Cheol Wahn Lee, Alaide Chieffo, Gerard Helft, Sebastiano Gili, Umberto Barbero, Giuseppe Biondi Zoccai, Claudio Moretti, Fabrizio Ugo, Maurizio D’Amico, Roberto Garbo, Gregg Stone, Sara Rettegno, Pierluigi Omedè, Federico Conrotto, Christian Templin, Antonio Colombo, Seung-jung Park, Adnan Kastrati, David Hildick-Smith, Mauro Gasparini, Fiorenzo Gaita, Impact of design of coronary stents and length of dual antiplatelet therapies on ischaemic and bleeding events: a network meta-analysis of 64 randomized controlled trials and 102 735 patients, European Heart Journal, Volume 38, Issue 42, 07 November 2017, Pages 3160–3172, https://doi.org/10.1093/eurheartj/ehx437
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Abstract
The differential impact on ischaemic and bleeding events of the type of drug-eluting stent [durable polymer stents [DES] vs. biodegradable polymer stents vs. bioresorbable scaffolds (BRS)] and length of dual antiplatelet therapy (DAPT) remains to be defined.
Randomized controlled trials comparing different types of DES and/or DAPT durations were selected. The primary endpoint was Major Adverse Cardiovascular Events (MACE) [a composite of death, myocardial infarction (MI), and target vessel revascularization]. Definite stent thrombosis (ST) and single components of MACE were secondary endpoints. The arms of interest were: BRS with 12 months of DAPT (12mDAPT), biodegradable polymer stent with 12mDAPT, durable polymer stent [everolimus-eluting (EES), zotarolimus-eluting (ZES)] with 12mDAPT, EES/ZES with <12 months of DAPT, and EES/ZES with >12 months of DAPT (DAPT > 12 m). Sixty-four studies with 150 arms and 102 735 patients were included. After a median follow-up of 20 months, MACE rates were similar in the different arms of interest. EES/ZES with DAPT > 12 m reported a lower incidence of MI than the other groups, while BRS showed a higher rate of ST when compared to EES/ZES, irrespective of DAPT length. A higher risk of major bleedings was observed for DAPT > 12 m as compared to shorter DAPT.
Durable and biodegradable polymer stents along with BRS report a similar rate of MACE irrespective of DAPT length. Fewer MI are observed with EES/ZES with DAPT > 12 m, while a higher rate of ST is reported for BRS when compared to EES/ZES, independently from DAPT length. Stent type may partially affect the outcome together with DAPT length.
Introduction
Percutaneous coronary intervention (PCI) represents the most common revascularization strategy for patients with coronary artery disease (CAD), both for stable angina and for acute coronary syndromes (ACS).1–3
The choice of the appropriate coronary stent and dual antiplatelet therapy (DAPT) duration represents a challenge for the physicians treating and managing these patients.4
Continuous technological developments have led to significant improvements in stent design, struts thickness and anti-proliferative drugs in current second generation drug-eluting stents (DES). Biodegradable materials have been progressively implemented. Recently, completely bioresorbable scaffolds (BRS), bearing the promise of advantages in terms of restoration of coronary physiology, have been introduced, but some concerns have since surfaced regarding an increased risk of stent thrombosis (ST) despite an adequate DAPT length of 12 months.5–8
The optimal duration of DAPT has been investigated in many randomized controlled trials (RCTs) and meta-analyses comparing different DAPT lengths (3, 6, 12, 24 or 30 months) following DES implantation. Prolonged DAPT has been associated with an increased bleeding risk, along with a potential reduction of recurrent myocardial infarction (MI) and ST. However, limited data directly compare different DAPT durations in patients treated with different first and second generation DES or BRS.9 , 10
Consequently, we performed the present analysis to compare BRSs with permanent DES according to length of DAPT.
Methods
The present study was performed according to the Cochrane Collaboration and PRISMA statements.11–14
Search
We searched for randomized trials in The Cochrane Collaboration Central Register of Controlled Trials, EMBASE and MEDLINE/PubMed. We restricted our searches to human studies, clinical trials, controlled trials or randomized trials. We used the keywords and Medical Subject Headings ‘percutaneous coronary intervention’, ‘coronary angiography’, ‘drug eluting stents’, ‘everolimus’, ‘zotarolimus’, ‘paclitaxel’, ‘sirolimus’, ‘bare metal’, ‘bioreabsorbable’, ‘biodegradable polymer’, as well as additional text words in combination with an established search strategy for MEDLINE/PubMed. We also hand-searched bibliographies of identified studies, recent meta-analyses and pulmonary hypertension guidelines.
Selection
Study selection was performed by three independent reviewers (F.D.A., M.I., M.B.), with divergences resolved by consensus. Citations were first scanned at the title/abstract level. Shortlisted studies were then retrieved in full text. They were considered suitable for inclusion if (i) reporting on a RCT, (ii) including at least one type of second generation DES as comparator or (iii) evaluating different DAPT lengths and explicitly reporting data on second generation DES. Studies were excluded if (i) non-randomized, (ii) appraising only first generation DES or (iii) considered less than 100 patients. Corresponding authors of each study were asked to provide more data of their respective paper, especially regarding those on second generation stents with different length of DAPT.
Abstraction and appraisal
Data abstraction and study appraisal were performed by three independent reviewers (F.D.A., M.I., M.B.), with divergences resolved by consensus. In the case of several publications with overlapping study populations, or duplicated publication, the largest sample size study with longest follow-up available was selected. Key study and patient characteristics were extracted, including age, gender, cardiovascular risk factors, clinical presentation, kind and length of lesion, length of stent.
Endpoints
MACE [a composite endpoint of death, MI, target vessel revascularization (TVR)] was the primary endpoint. All cause and cardiovascular death, MI, TVR, target lesion revascularization (TLR) and definite ST (evaluated according to ARC definition15), along with major bleedings were secondary endpoints.
Arms
Competitive arms are shown in Table 1. The interpretation of the results is focused on the comparison among BRS, polymer biodegradable stents and second-generation DES (EES and ZES) with different DAPT lengths.
Arms . | DAPT Duration . |
---|---|
BRS | 12 months |
Polymer biodegradable stents (i.e. BES) | 12 months |
EES/ZES | 12 months |
EES/ZES | Less than 12 months |
EES/ZES | More than 12 moths |
PES | 12 months |
SES | 12 months |
BMS | 12 months |
Arms . | DAPT Duration . |
---|---|
BRS | 12 months |
Polymer biodegradable stents (i.e. BES) | 12 months |
EES/ZES | 12 months |
EES/ZES | Less than 12 months |
EES/ZES | More than 12 moths |
PES | 12 months |
SES | 12 months |
BMS | 12 months |
BRS, bioresorbable stents; BES, biolimus eluting stents; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; DAPT, dual antiplatelet therapy.
Arms . | DAPT Duration . |
---|---|
BRS | 12 months |
Polymer biodegradable stents (i.e. BES) | 12 months |
EES/ZES | 12 months |
EES/ZES | Less than 12 months |
EES/ZES | More than 12 moths |
PES | 12 months |
SES | 12 months |
BMS | 12 months |
Arms . | DAPT Duration . |
---|---|
BRS | 12 months |
Polymer biodegradable stents (i.e. BES) | 12 months |
EES/ZES | 12 months |
EES/ZES | Less than 12 months |
EES/ZES | More than 12 moths |
PES | 12 months |
SES | 12 months |
BMS | 12 months |
BRS, bioresorbable stents; BES, biolimus eluting stents; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; DAPT, dual antiplatelet therapy.
For major bleedings, three competitive arms were created:
Stents with DAPT length <12 months (DAPT <12m)
Stents with DAPT length of 12 months (12mDAPT)
Stents with DAPT length >12 months (DAPT >12m)
Analysis
Descriptive statistics on baseline and angiographic characteristics of the patients in the studies are provided. Binary variables are reported as median percentages (min–max) and continuous variables as mean and standard deviation.
All the statistical methods and the quality assessments of the results are detailed in Supplementary material online, Appendix S 2.
The analyses were conducted using R version 3.2.1 (for the direct comparisons, the data manipulations and the results output) and WinBUGS 1.4.3 (for the NMA, run routinely in ‘batch-mode’ from R).
Results
Article selection and baseline characteristics
The results of the direct comparisons were consistent with the results of the network meta-analysis described herein. They are provided in the statistical Supplementary material online, Appendix S2.
Four hundred and twenty three studies were screened after the online research; other 49 and 147 were screened from the bibliography of Palmerini et al. 5 and Kang et al.16 network meta-analysis, respectively (see Supplementary material online, Appendix S1). Five hundred and fifty-two papers were excluded because they did not comply with our inclusion criteria or were redundant results. Sixty-seven studies were initially included; 3 of them were subsequently excluded for missing data. Within 64 final studies considered for statistical computation, those comparing just stents in the same analysis group of our network meta-analysis were excluded programmatically (6 studies excluded from the main analysis) (see Figure 1).
The competitive arms were the following, reported as number of study arms and of patients (see Figure 2):
Durable polymer everolimus-eluting stents and zotarolimus-eluting stents (EES/ZES) with 12mDAPT were evaluated in 55 arms with 67 747 patients (respectively EES with 12mDAPT in 43 arms with 49 584 patients and permanent ZES with 12mDAPT in 22 arms with 17 893 patients)
Biodegradable polymer stents with 12mDAPT in 20 with 12 952
BRS in 6 with 2337
EES/ZES with DAPT<12m in 10 with 5731 (respectively, ZES with 1 month of DAPT in 1 with 802 patients, ZES with 3 months of DAPT in 1 with 1563 patients, ZES with 6 months of DAPT in 4 with 1069 patients, EES with 6 months of DAPT in 4 with 2297 patients),
EES/ZES with DAPT>12m in 9 with 5508 (respectively, ZES with 24 months of DAPT in 2 with 527 patients, ZES with 30 months of DAPT in 1 with 642 patients, ZES with 48 months of DAPT in 1 with 75 patients, EES with 24 months of DAPT in 3 with 1563 patients, EES with 30 months of DAPT in 1 with 2345 and EES with 48 of DAPT in 1 with 356)
First generation DES: paclitaxel-eluting stents (PES) with a 12mDAPT in 13 with 5951 and sirolimus-eluting stents with a 12mDAPT in 20 with 15 563
Bare metal stents (BMS) in 7 arms with 5109 patients.
Figure 2 shows direct comparisons among different stent types according to DAPT length. All the comparisons involving EES/ZES with DAPT > 12 m (with the exception of those with 12mDAPT EES/ZES and with DAPT > 12 m EES/ZES) and some of the comparisons of first generation DES and BMS were totally indirect. BRS were compared directly mainly with EES with 12mDAPT.
Baseline features are reported in Table 2. Mean age was 63 ± 4.3 years, 29% (17–77) were of female sex. A high prevalence of cardiovascular risk factors was reported. Overall, 50% of the patients were admitted for stable angina, 17% for ST segment elevation MI (STEMI), 13% for non-ST segment elevation MI (NSTEMI) and 20% for unstable angina (0–100%).
Baseline features . | 150 arms with 102 735 patients . |
---|---|
Female gender (%, min–max) | 29 (17–77) |
BMI (mean ± SD)a | 26.7 ± 1.6 |
Age (years, mean ± SD) | 63 ± 4.3 |
NIDDM (%, min–max) | 25.5 (7–85) |
IDDM (%, min–max) | 11 (4–40) |
Hypertension (%, min–max) | 66 (38–90.6) |
Current smoker (%, min–max) | 26.8 (4.5–59) |
Family history of CAD (%, min–max) | 26.4 (2.9–55) |
Hyperlipidaemia (%, min–max) | 63 (9–92) |
Ranal Insufficiency (%, min–max)b | 8.9 (2.8–15) |
ACS as clinical presentation (%, min–max): | 50 (0–100) |
STEMI (%, min–max) | 17 (0–100) |
NSTEMI (%, min–max) | 13 (0–54) |
UA (%, min–max) | 20 (0–79) |
Stable angina/silent ischaemia (%, min–max) | 50 (0–100) |
Previous AMI (%, min–max) | 21 (1.7–41) |
Previous PCI (%, min–max) | 20 (3–53) |
Previous CABG (%, min–max) | 6 (0–18) |
Angiographic features of included patients | 150 arms with 102 735 patients |
Radial access (% mean, min–max) | 41 (26–56) |
More than two lesions (% mean, min–max) | 22 (0–70) |
Multivessel disease (% mean, min–max)) | 38 (6–86) |
Length of lesion in mm (median ± SD) | 17 ± 4 |
Type B2/C lesion (% mean, min–max)) | 41 (2–100) |
Bifurcation (% mean, min–max) | 19 (6–40) |
Number of stents for patients (median, min–max) | 1.6 (1–2) |
Length of stent in mm (mean, min–max) | 23 (14–46) |
Average stent diameter in mm (mean, min–max) | 3.00 (2.55–3.60) |
Post-dilatation (% mean, min–max) | 56 (15–82) |
Baseline features . | 150 arms with 102 735 patients . |
---|---|
Female gender (%, min–max) | 29 (17–77) |
BMI (mean ± SD)a | 26.7 ± 1.6 |
Age (years, mean ± SD) | 63 ± 4.3 |
NIDDM (%, min–max) | 25.5 (7–85) |
IDDM (%, min–max) | 11 (4–40) |
Hypertension (%, min–max) | 66 (38–90.6) |
Current smoker (%, min–max) | 26.8 (4.5–59) |
Family history of CAD (%, min–max) | 26.4 (2.9–55) |
Hyperlipidaemia (%, min–max) | 63 (9–92) |
Ranal Insufficiency (%, min–max)b | 8.9 (2.8–15) |
ACS as clinical presentation (%, min–max): | 50 (0–100) |
STEMI (%, min–max) | 17 (0–100) |
NSTEMI (%, min–max) | 13 (0–54) |
UA (%, min–max) | 20 (0–79) |
Stable angina/silent ischaemia (%, min–max) | 50 (0–100) |
Previous AMI (%, min–max) | 21 (1.7–41) |
Previous PCI (%, min–max) | 20 (3–53) |
Previous CABG (%, min–max) | 6 (0–18) |
Angiographic features of included patients | 150 arms with 102 735 patients |
Radial access (% mean, min–max) | 41 (26–56) |
More than two lesions (% mean, min–max) | 22 (0–70) |
Multivessel disease (% mean, min–max)) | 38 (6–86) |
Length of lesion in mm (median ± SD) | 17 ± 4 |
Type B2/C lesion (% mean, min–max)) | 41 (2–100) |
Bifurcation (% mean, min–max) | 19 (6–40) |
Number of stents for patients (median, min–max) | 1.6 (1–2) |
Length of stent in mm (mean, min–max) | 23 (14–46) |
Average stent diameter in mm (mean, min–max) | 3.00 (2.55–3.60) |
Post-dilatation (% mean, min–max) | 56 (15–82) |
% are expressed as mean or median value with ranges into brackets.
SD, standard deviation; NIDDM, non-insulin dependent diabetes mellitus; IDDM, insulin dependent diabetes mellitus; ACS, acute coronary syndromes; AMI, acute myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft.
The body-mass index is the weight in kilograms divided by the square of the height in meters.
Renal insufficiency was defined as an estimated glomerular filtration rate of less than 30 mL per minute per 1.73 m2 of body surface area or the need for dialysis. Bifurcation classification follows AHA task force definition modified by Ellis et al. (Circulation 1990;82:1193–1202).
Baseline features . | 150 arms with 102 735 patients . |
---|---|
Female gender (%, min–max) | 29 (17–77) |
BMI (mean ± SD)a | 26.7 ± 1.6 |
Age (years, mean ± SD) | 63 ± 4.3 |
NIDDM (%, min–max) | 25.5 (7–85) |
IDDM (%, min–max) | 11 (4–40) |
Hypertension (%, min–max) | 66 (38–90.6) |
Current smoker (%, min–max) | 26.8 (4.5–59) |
Family history of CAD (%, min–max) | 26.4 (2.9–55) |
Hyperlipidaemia (%, min–max) | 63 (9–92) |
Ranal Insufficiency (%, min–max)b | 8.9 (2.8–15) |
ACS as clinical presentation (%, min–max): | 50 (0–100) |
STEMI (%, min–max) | 17 (0–100) |
NSTEMI (%, min–max) | 13 (0–54) |
UA (%, min–max) | 20 (0–79) |
Stable angina/silent ischaemia (%, min–max) | 50 (0–100) |
Previous AMI (%, min–max) | 21 (1.7–41) |
Previous PCI (%, min–max) | 20 (3–53) |
Previous CABG (%, min–max) | 6 (0–18) |
Angiographic features of included patients | 150 arms with 102 735 patients |
Radial access (% mean, min–max) | 41 (26–56) |
More than two lesions (% mean, min–max) | 22 (0–70) |
Multivessel disease (% mean, min–max)) | 38 (6–86) |
Length of lesion in mm (median ± SD) | 17 ± 4 |
Type B2/C lesion (% mean, min–max)) | 41 (2–100) |
Bifurcation (% mean, min–max) | 19 (6–40) |
Number of stents for patients (median, min–max) | 1.6 (1–2) |
Length of stent in mm (mean, min–max) | 23 (14–46) |
Average stent diameter in mm (mean, min–max) | 3.00 (2.55–3.60) |
Post-dilatation (% mean, min–max) | 56 (15–82) |
Baseline features . | 150 arms with 102 735 patients . |
---|---|
Female gender (%, min–max) | 29 (17–77) |
BMI (mean ± SD)a | 26.7 ± 1.6 |
Age (years, mean ± SD) | 63 ± 4.3 |
NIDDM (%, min–max) | 25.5 (7–85) |
IDDM (%, min–max) | 11 (4–40) |
Hypertension (%, min–max) | 66 (38–90.6) |
Current smoker (%, min–max) | 26.8 (4.5–59) |
Family history of CAD (%, min–max) | 26.4 (2.9–55) |
Hyperlipidaemia (%, min–max) | 63 (9–92) |
Ranal Insufficiency (%, min–max)b | 8.9 (2.8–15) |
ACS as clinical presentation (%, min–max): | 50 (0–100) |
STEMI (%, min–max) | 17 (0–100) |
NSTEMI (%, min–max) | 13 (0–54) |
UA (%, min–max) | 20 (0–79) |
Stable angina/silent ischaemia (%, min–max) | 50 (0–100) |
Previous AMI (%, min–max) | 21 (1.7–41) |
Previous PCI (%, min–max) | 20 (3–53) |
Previous CABG (%, min–max) | 6 (0–18) |
Angiographic features of included patients | 150 arms with 102 735 patients |
Radial access (% mean, min–max) | 41 (26–56) |
More than two lesions (% mean, min–max) | 22 (0–70) |
Multivessel disease (% mean, min–max)) | 38 (6–86) |
Length of lesion in mm (median ± SD) | 17 ± 4 |
Type B2/C lesion (% mean, min–max)) | 41 (2–100) |
Bifurcation (% mean, min–max) | 19 (6–40) |
Number of stents for patients (median, min–max) | 1.6 (1–2) |
Length of stent in mm (mean, min–max) | 23 (14–46) |
Average stent diameter in mm (mean, min–max) | 3.00 (2.55–3.60) |
Post-dilatation (% mean, min–max) | 56 (15–82) |
% are expressed as mean or median value with ranges into brackets.
SD, standard deviation; NIDDM, non-insulin dependent diabetes mellitus; IDDM, insulin dependent diabetes mellitus; ACS, acute coronary syndromes; AMI, acute myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft.
The body-mass index is the weight in kilograms divided by the square of the height in meters.
Renal insufficiency was defined as an estimated glomerular filtration rate of less than 30 mL per minute per 1.73 m2 of body surface area or the need for dialysis. Bifurcation classification follows AHA task force definition modified by Ellis et al. (Circulation 1990;82:1193–1202).
Regarding interventional procedures (see Table 2), multi-vessel disease was reported in 38% (6–86) of the patients, with a median lesion length of 17 ± 4 mm. Type B2/C lesions were reported in 41% (2–100%) of the patients and a median number of 1.6 (1–2) stents per patient, with a mean length of 23 mm (14–46), were implanted. Moreover, technical features of the devices included in the analyses are reported in the appendix (see Supplementary material online, Appendix Table S1a and b).
Endpoint comparison according to dual antiplatelet therapy duration and stent type
After a median follow up of 20 months (18–30), rates of MACE did not differ among EES/ZES, biodegradable polymer stents and BRS (while they were increased in first generation DES and BMS, see Table 3 and Figure 3).
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT <12 m . | vs. EES/ZES with DAPT >12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.03 (0.64–1.64) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 1.05 (0.68–1.62) | 1.02 (0.85–1.23) | — | — | — | — | — | — |
EES/ZES with DAPT< 12 m | 0.91 (0.53–1.56). | 0.89 (0.62–1.28) | 0.87 (0.62–1.21) | — | — | — | — | — |
EES/ZES with DAPT >12 m | 1.07 (0.56–2.05) | 1.04 (0.63–1.74) | 1.01 (0.63–1.64) | 1.17 (0.71–1.94) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.49 (0.9–2.36) | 1.42 (0.9–1.85) | 1.38 (1.12–1.7) | 1.6 (1.1–2.32) | 1.37 (0.81–2.29) | — | — | — |
SES with DAPT ≤ 12 m | 1.06 (0.66–1.68) | 1.03 (0.83–1.28) | 1.01 (0.86–1.18) | 1.16 (0.61–1.87) | 0.99 (0.6–1.64) | 0.73 (0.57–0–93) | — | — |
BMS | 1.69 (0.99–1.68) | 1.58 (1.21–2.08) | 1.54 (1.2–1.98) | 1.78 (1.24–1.59) | 1.52 (0.9–2.57) | 1.11 (0.81–1.53) | 1.53 (1.17–2.04) | — |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT <12 m . | vs. EES/ZES with DAPT >12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.03 (0.64–1.64) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 1.05 (0.68–1.62) | 1.02 (0.85–1.23) | — | — | — | — | — | — |
EES/ZES with DAPT< 12 m | 0.91 (0.53–1.56). | 0.89 (0.62–1.28) | 0.87 (0.62–1.21) | — | — | — | — | — |
EES/ZES with DAPT >12 m | 1.07 (0.56–2.05) | 1.04 (0.63–1.74) | 1.01 (0.63–1.64) | 1.17 (0.71–1.94) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.49 (0.9–2.36) | 1.42 (0.9–1.85) | 1.38 (1.12–1.7) | 1.6 (1.1–2.32) | 1.37 (0.81–2.29) | — | — | — |
SES with DAPT ≤ 12 m | 1.06 (0.66–1.68) | 1.03 (0.83–1.28) | 1.01 (0.86–1.18) | 1.16 (0.61–1.87) | 0.99 (0.6–1.64) | 0.73 (0.57–0–93) | — | — |
BMS | 1.69 (0.99–1.68) | 1.58 (1.21–2.08) | 1.54 (1.2–1.98) | 1.78 (1.24–1.59) | 1.52 (0.9–2.57) | 1.11 (0.81–1.53) | 1.53 (1.17–2.04) | — |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT <12 m . | vs. EES/ZES with DAPT >12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.03 (0.64–1.64) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 1.05 (0.68–1.62) | 1.02 (0.85–1.23) | — | — | — | — | — | — |
EES/ZES with DAPT< 12 m | 0.91 (0.53–1.56). | 0.89 (0.62–1.28) | 0.87 (0.62–1.21) | — | — | — | — | — |
EES/ZES with DAPT >12 m | 1.07 (0.56–2.05) | 1.04 (0.63–1.74) | 1.01 (0.63–1.64) | 1.17 (0.71–1.94) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.49 (0.9–2.36) | 1.42 (0.9–1.85) | 1.38 (1.12–1.7) | 1.6 (1.1–2.32) | 1.37 (0.81–2.29) | — | — | — |
SES with DAPT ≤ 12 m | 1.06 (0.66–1.68) | 1.03 (0.83–1.28) | 1.01 (0.86–1.18) | 1.16 (0.61–1.87) | 0.99 (0.6–1.64) | 0.73 (0.57–0–93) | — | — |
BMS | 1.69 (0.99–1.68) | 1.58 (1.21–2.08) | 1.54 (1.2–1.98) | 1.78 (1.24–1.59) | 1.52 (0.9–2.57) | 1.11 (0.81–1.53) | 1.53 (1.17–2.04) | — |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT <12 m . | vs. EES/ZES with DAPT >12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.03 (0.64–1.64) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 1.05 (0.68–1.62) | 1.02 (0.85–1.23) | — | — | — | — | — | — |
EES/ZES with DAPT< 12 m | 0.91 (0.53–1.56). | 0.89 (0.62–1.28) | 0.87 (0.62–1.21) | — | — | — | — | — |
EES/ZES with DAPT >12 m | 1.07 (0.56–2.05) | 1.04 (0.63–1.74) | 1.01 (0.63–1.64) | 1.17 (0.71–1.94) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.49 (0.9–2.36) | 1.42 (0.9–1.85) | 1.38 (1.12–1.7) | 1.6 (1.1–2.32) | 1.37 (0.81–2.29) | — | — | — |
SES with DAPT ≤ 12 m | 1.06 (0.66–1.68) | 1.03 (0.83–1.28) | 1.01 (0.86–1.18) | 1.16 (0.61–1.87) | 0.99 (0.6–1.64) | 0.73 (0.57–0–93) | — | — |
BMS | 1.69 (0.99–1.68) | 1.58 (1.21–2.08) | 1.54 (1.2–1.98) | 1.78 (1.24–1.59) | 1.52 (0.9–2.57) | 1.11 (0.81–1.53) | 1.53 (1.17–2.04) | — |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
Regarding MI, EES/ZES with DAPT > 12 m showed a trend towards a reduced risk when compared with the pooled cohort of EES/ZES with DAPT < 12 m (odds ratio (OR) 0.71 [0.48–1.03]) and a significant reduction when compared to EES/ZES with 12mDAPT (OR 0.67 [0.49–0.92]), to biodegradable polymer stents with 12mDAPT (OR 0.64 [0.45–0.91]) and to BRS (OR 0.46 [0.28–0.74)]. EES/ZES with 12mDAPT presented a lower incidence of MI than BRS (0.69 [0.47–0.98]), while a trend was noted for EES/ZES with <12 m vs. BRS (OR 0.65 [0.41–1.01], see Table 4 and Figure 4). EES/ZES with DAPT > 12 m was the stent/DAPT length combination with the highest probability to perform best and in the first rank according to the SUCRA values (99%) (see Supplementary material online, Appendix Figures S3 and S4).
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m. . | vs. EES/ZES with DAPT = 12 m. . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.72 (0.48–1.06) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.69 (0.47–0.98) | 0.95 (0.82–1.11) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.65 (0.41–1.01) | 0.9 (0.67–1.21) | 0.95 (0.72–1.24) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.46 (0.28–0.74) | 0.64 (0.45–0.91) | 0.67 (0.49–0.92) | 0.71 (0.47–1.03) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.12 (0.74–1.69) | 1.55 (1.23–1.97) | 1.64 (1.35–1.99) | 1.73 (1.27–2.39) | 2.45 (1.68–3.54) | — | — | — |
SES with DAPT ≤ 12 m | 0.78 (0.52–1.13) | 1.07 (0.89–1.28) | 1.13 (0.97–1.29) | 1.19 (0.89–1.6) | 1.69 (1.18–2.38) | 0.69 (0.85–1.66) | — | — |
BMS | 1.26 (0.81–1.92) | 1.74 (1.39–2.21) | 1.83 (1.46–2.32) | 1.94 (1.44–2.65) | 2.75 (1.85–4–06) | 1.12 (0.84–1.52) | 1.63 (1.26–2.12) | — |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m. . | vs. EES/ZES with DAPT = 12 m. . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.72 (0.48–1.06) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.69 (0.47–0.98) | 0.95 (0.82–1.11) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.65 (0.41–1.01) | 0.9 (0.67–1.21) | 0.95 (0.72–1.24) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.46 (0.28–0.74) | 0.64 (0.45–0.91) | 0.67 (0.49–0.92) | 0.71 (0.47–1.03) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.12 (0.74–1.69) | 1.55 (1.23–1.97) | 1.64 (1.35–1.99) | 1.73 (1.27–2.39) | 2.45 (1.68–3.54) | — | — | — |
SES with DAPT ≤ 12 m | 0.78 (0.52–1.13) | 1.07 (0.89–1.28) | 1.13 (0.97–1.29) | 1.19 (0.89–1.6) | 1.69 (1.18–2.38) | 0.69 (0.85–1.66) | — | — |
BMS | 1.26 (0.81–1.92) | 1.74 (1.39–2.21) | 1.83 (1.46–2.32) | 1.94 (1.44–2.65) | 2.75 (1.85–4–06) | 1.12 (0.84–1.52) | 1.63 (1.26–2.12) | — |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m. . | vs. EES/ZES with DAPT = 12 m. . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.72 (0.48–1.06) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.69 (0.47–0.98) | 0.95 (0.82–1.11) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.65 (0.41–1.01) | 0.9 (0.67–1.21) | 0.95 (0.72–1.24) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.46 (0.28–0.74) | 0.64 (0.45–0.91) | 0.67 (0.49–0.92) | 0.71 (0.47–1.03) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.12 (0.74–1.69) | 1.55 (1.23–1.97) | 1.64 (1.35–1.99) | 1.73 (1.27–2.39) | 2.45 (1.68–3.54) | — | — | — |
SES with DAPT ≤ 12 m | 0.78 (0.52–1.13) | 1.07 (0.89–1.28) | 1.13 (0.97–1.29) | 1.19 (0.89–1.6) | 1.69 (1.18–2.38) | 0.69 (0.85–1.66) | — | — |
BMS | 1.26 (0.81–1.92) | 1.74 (1.39–2.21) | 1.83 (1.46–2.32) | 1.94 (1.44–2.65) | 2.75 (1.85–4–06) | 1.12 (0.84–1.52) | 1.63 (1.26–2.12) | — |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m. . | vs. EES/ZES with DAPT = 12 m. . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.72 (0.48–1.06) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.69 (0.47–0.98) | 0.95 (0.82–1.11) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.65 (0.41–1.01) | 0.9 (0.67–1.21) | 0.95 (0.72–1.24) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.46 (0.28–0.74) | 0.64 (0.45–0.91) | 0.67 (0.49–0.92) | 0.71 (0.47–1.03) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.12 (0.74–1.69) | 1.55 (1.23–1.97) | 1.64 (1.35–1.99) | 1.73 (1.27–2.39) | 2.45 (1.68–3.54) | — | — | — |
SES with DAPT ≤ 12 m | 0.78 (0.52–1.13) | 1.07 (0.89–1.28) | 1.13 (0.97–1.29) | 1.19 (0.89–1.6) | 1.69 (1.18–2.38) | 0.69 (0.85–1.66) | — | — |
BMS | 1.26 (0.81–1.92) | 1.74 (1.39–2.21) | 1.83 (1.46–2.32) | 1.94 (1.44–2.65) | 2.75 (1.85–4–06) | 1.12 (0.84–1.52) | 1.63 (1.26–2.12) | — |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
The risk of definite ST was significantly lower in the EES/ZES group compared to BRS, independently from DAPT length: EES/ZES with DAPT < 12 m (OR 0.17 [0.03;0.79]), EES/ZES with 12mDAPT (OR 0.33 [0.09;0.95]) and EES/ZES with DAPT > 12 m (0.10 [0.01;0.58]). No differences in the rate of ST were observed when comparing EES/ZES and biodegradable polymer stents (OR 0.4 [0.1–1.3]). No significant differences were detected in terms of ST among the different lengths of DAPT with EES/ZES (see Table 5 and Figure 5). EES/ZES with DAPT > 12 m reported the highest probability to perform best and with the first rank according to the SUCRA values (95%) (see Supplementary material online, Appendix Figures S5 and S6).
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.41 (0.1–1.3) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.33 (0.09–0.95) | 0.81 (0.51–1.34) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.17 (0.03–0.79) | 0.42 (0.11–1.31) | 0.52 (0.14–1.58) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.1 (0.01–0.58) | 0.25 (0.06–1.21) | 0.31 (0.07–1.25) | 0.61 (0.12–3.38) | — | — | — | — |
PES with DAPT ≤ 12 m | 0.84 (0.19–2.91) | 2.06 (0.95–4.42) | 2.54 (1.32–4.71) | 4.91 (1.36–20.15) | 8.13 (1.73–39.78) | — | — | — |
SES with DAPT ≤ 12 m | 0.45 (0.11–1.41) | 1.12 (0.61–1.93) | 1.38 (0.82–1.12) | 2.66 (0.81–9.85) | 4.42 (0.96–19.36) | 0.54 (0.25–1.14) | — | — |
BMS | 0.63 (0.14–2.25) | 1.54 (0.77–3.11) | 1.9 (0.94–3.9) | 3.66 (1.29–12.79) | 6.13 (1.4–29.72) | 0.75 (0.31–1.96) | 1.37 (0.66–3.19) | — |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.41 (0.1–1.3) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.33 (0.09–0.95) | 0.81 (0.51–1.34) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.17 (0.03–0.79) | 0.42 (0.11–1.31) | 0.52 (0.14–1.58) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.1 (0.01–0.58) | 0.25 (0.06–1.21) | 0.31 (0.07–1.25) | 0.61 (0.12–3.38) | — | — | — | — |
PES with DAPT ≤ 12 m | 0.84 (0.19–2.91) | 2.06 (0.95–4.42) | 2.54 (1.32–4.71) | 4.91 (1.36–20.15) | 8.13 (1.73–39.78) | — | — | — |
SES with DAPT ≤ 12 m | 0.45 (0.11–1.41) | 1.12 (0.61–1.93) | 1.38 (0.82–1.12) | 2.66 (0.81–9.85) | 4.42 (0.96–19.36) | 0.54 (0.25–1.14) | — | — |
BMS | 0.63 (0.14–2.25) | 1.54 (0.77–3.11) | 1.9 (0.94–3.9) | 3.66 (1.29–12.79) | 6.13 (1.4–29.72) | 0.75 (0.31–1.96) | 1.37 (0.66–3.19) | — |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.41 (0.1–1.3) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.33 (0.09–0.95) | 0.81 (0.51–1.34) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.17 (0.03–0.79) | 0.42 (0.11–1.31) | 0.52 (0.14–1.58) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.1 (0.01–0.58) | 0.25 (0.06–1.21) | 0.31 (0.07–1.25) | 0.61 (0.12–3.38) | — | — | — | — |
PES with DAPT ≤ 12 m | 0.84 (0.19–2.91) | 2.06 (0.95–4.42) | 2.54 (1.32–4.71) | 4.91 (1.36–20.15) | 8.13 (1.73–39.78) | — | — | — |
SES with DAPT ≤ 12 m | 0.45 (0.11–1.41) | 1.12 (0.61–1.93) | 1.38 (0.82–1.12) | 2.66 (0.81–9.85) | 4.42 (0.96–19.36) | 0.54 (0.25–1.14) | — | — |
BMS | 0.63 (0.14–2.25) | 1.54 (0.77–3.11) | 1.9 (0.94–3.9) | 3.66 (1.29–12.79) | 6.13 (1.4–29.72) | 0.75 (0.31–1.96) | 1.37 (0.66–3.19) | — |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.41 (0.1–1.3) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.33 (0.09–0.95) | 0.81 (0.51–1.34) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.17 (0.03–0.79) | 0.42 (0.11–1.31) | 0.52 (0.14–1.58) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.1 (0.01–0.58) | 0.25 (0.06–1.21) | 0.31 (0.07–1.25) | 0.61 (0.12–3.38) | — | — | — | — |
PES with DAPT ≤ 12 m | 0.84 (0.19–2.91) | 2.06 (0.95–4.42) | 2.54 (1.32–4.71) | 4.91 (1.36–20.15) | 8.13 (1.73–39.78) | — | — | — |
SES with DAPT ≤ 12 m | 0.45 (0.11–1.41) | 1.12 (0.61–1.93) | 1.38 (0.82–1.12) | 2.66 (0.81–9.85) | 4.42 (0.96–19.36) | 0.54 (0.25–1.14) | — | — |
BMS | 0.63 (0.14–2.25) | 1.54 (0.77–3.11) | 1.9 (0.94–3.9) | 3.66 (1.29–12.79) | 6.13 (1.4–29.72) | 0.75 (0.31–1.96) | 1.37 (0.66–3.19) | — |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
Regarding the risk of TVR, TLR, death or cardiovascular death, no significant differences were detected among BRS, EES/ZES and biodegradable polymer stents (see Tables 6–9 and Supplementary material online, Appendix Figures S7–S14).
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.02 (0.66–1.61) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.95 (0.63–1.42) | 0.92 (0.75–1.13) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.79 (0.46–1.34) | 0.77 (0.53–1.11) | 0.84 (0.59–1.17) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.62 (0.25–1.49) | 0.6 (0.26–1.34) | 0.66 (0.29–1.44) | 0.78 (0.34–1.78) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.42 (0.88–2.29) | 1.39 (1.01–1.89) | 1.5 (1.16–1.93) | 1.79 (1.19–2.75) | 2.29 (1.5–35) | — | — | — |
SES with DAPT ≤ 12 m | 0.83 (0.53–1.32) | 0.81 (0.62–1.05) | 0.88 (0.71–1.08) | 1.05 (0.72–1.56) | 1.34 (0.59–3.12) | 0.59 (0.43–0.80) | — | — |
BMS | 2.13 (1.29–3.51) | 2.08 (1.5–2.85) | 2.25 (1.66–3.06) | 2.69 (1.79–4.12) | 3.43 (1.5–8.15) | 1.5 (1.02–2.21) | 2.56 (1.82–3.62) | – |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.02 (0.66–1.61) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.95 (0.63–1.42) | 0.92 (0.75–1.13) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.79 (0.46–1.34) | 0.77 (0.53–1.11) | 0.84 (0.59–1.17) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.62 (0.25–1.49) | 0.6 (0.26–1.34) | 0.66 (0.29–1.44) | 0.78 (0.34–1.78) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.42 (0.88–2.29) | 1.39 (1.01–1.89) | 1.5 (1.16–1.93) | 1.79 (1.19–2.75) | 2.29 (1.5–35) | — | — | — |
SES with DAPT ≤ 12 m | 0.83 (0.53–1.32) | 0.81 (0.62–1.05) | 0.88 (0.71–1.08) | 1.05 (0.72–1.56) | 1.34 (0.59–3.12) | 0.59 (0.43–0.80) | — | — |
BMS | 2.13 (1.29–3.51) | 2.08 (1.5–2.85) | 2.25 (1.66–3.06) | 2.69 (1.79–4.12) | 3.43 (1.5–8.15) | 1.5 (1.02–2.21) | 2.56 (1.82–3.62) | – |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.02 (0.66–1.61) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.95 (0.63–1.42) | 0.92 (0.75–1.13) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.79 (0.46–1.34) | 0.77 (0.53–1.11) | 0.84 (0.59–1.17) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.62 (0.25–1.49) | 0.6 (0.26–1.34) | 0.66 (0.29–1.44) | 0.78 (0.34–1.78) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.42 (0.88–2.29) | 1.39 (1.01–1.89) | 1.5 (1.16–1.93) | 1.79 (1.19–2.75) | 2.29 (1.5–35) | — | — | — |
SES with DAPT ≤ 12 m | 0.83 (0.53–1.32) | 0.81 (0.62–1.05) | 0.88 (0.71–1.08) | 1.05 (0.72–1.56) | 1.34 (0.59–3.12) | 0.59 (0.43–0.80) | — | — |
BMS | 2.13 (1.29–3.51) | 2.08 (1.5–2.85) | 2.25 (1.66–3.06) | 2.69 (1.79–4.12) | 3.43 (1.5–8.15) | 1.5 (1.02–2.21) | 2.56 (1.82–3.62) | – |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.02 (0.66–1.61) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.95 (0.63–1.42) | 0.92 (0.75–1.13) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.79 (0.46–1.34) | 0.77 (0.53–1.11) | 0.84 (0.59–1.17) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 0.62 (0.25–1.49) | 0.6 (0.26–1.34) | 0.66 (0.29–1.44) | 0.78 (0.34–1.78) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.42 (0.88–2.29) | 1.39 (1.01–1.89) | 1.5 (1.16–1.93) | 1.79 (1.19–2.75) | 2.29 (1.5–35) | — | — | — |
SES with DAPT ≤ 12 m | 0.83 (0.53–1.32) | 0.81 (0.62–1.05) | 0.88 (0.71–1.08) | 1.05 (0.72–1.56) | 1.34 (0.59–3.12) | 0.59 (0.43–0.80) | — | — |
BMS | 2.13 (1.29–3.51) | 2.08 (1.5–2.85) | 2.25 (1.66–3.06) | 2.69 (1.79–4.12) | 3.43 (1.5–8.15) | 1.5 (1.02–2.21) | 2.56 (1.82–3.62) | – |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
. | vs. BRS with DAPT = 12 m. . | vs. Polymer biodegradable with DAPT ≤ 12 m. . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.82 (0.41–1.16) | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m. | 0.88 (0.47–1.65) | 1.08 (0.8–1.44) | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.73 (0.3–1.77) | 0.9 (0.45–1.75) | 0.83 (0.43.1.55) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.39 (0.69–2.81) | 1.7 (1.13–2.58) | 1.58 (1.15–2.16) | 1.9 (0.96–3.77) | — | — | — |
SES with DAPT ≤ 12 m | 0.68 (0.34–1.36) | 0.84 (0.58–1.2) | 0.78 (0.58–1.02) | 0.93 (0.47–1.89) | 0.49 (0.33–0.73) | — | — |
BMS | 1.93 (0.87–4.19) | 2.36 (1.44–3.86) | 2.19 (1.33–3.53) | 2.62 (1.34–5.22) | 1.39 (0.79–2.44) | 2.81 (1.62–4.87) | — |
. | vs. BRS with DAPT = 12 m. . | vs. Polymer biodegradable with DAPT ≤ 12 m. . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.82 (0.41–1.16) | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m. | 0.88 (0.47–1.65) | 1.08 (0.8–1.44) | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.73 (0.3–1.77) | 0.9 (0.45–1.75) | 0.83 (0.43.1.55) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.39 (0.69–2.81) | 1.7 (1.13–2.58) | 1.58 (1.15–2.16) | 1.9 (0.96–3.77) | — | — | — |
SES with DAPT ≤ 12 m | 0.68 (0.34–1.36) | 0.84 (0.58–1.2) | 0.78 (0.58–1.02) | 0.93 (0.47–1.89) | 0.49 (0.33–0.73) | — | — |
BMS | 1.93 (0.87–4.19) | 2.36 (1.44–3.86) | 2.19 (1.33–3.53) | 2.62 (1.34–5.22) | 1.39 (0.79–2.44) | 2.81 (1.62–4.87) | — |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
. | vs. BRS with DAPT = 12 m. . | vs. Polymer biodegradable with DAPT ≤ 12 m. . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.82 (0.41–1.16) | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m. | 0.88 (0.47–1.65) | 1.08 (0.8–1.44) | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.73 (0.3–1.77) | 0.9 (0.45–1.75) | 0.83 (0.43.1.55) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.39 (0.69–2.81) | 1.7 (1.13–2.58) | 1.58 (1.15–2.16) | 1.9 (0.96–3.77) | — | — | — |
SES with DAPT ≤ 12 m | 0.68 (0.34–1.36) | 0.84 (0.58–1.2) | 0.78 (0.58–1.02) | 0.93 (0.47–1.89) | 0.49 (0.33–0.73) | — | — |
BMS | 1.93 (0.87–4.19) | 2.36 (1.44–3.86) | 2.19 (1.33–3.53) | 2.62 (1.34–5.22) | 1.39 (0.79–2.44) | 2.81 (1.62–4.87) | — |
. | vs. BRS with DAPT = 12 m. . | vs. Polymer biodegradable with DAPT ≤ 12 m. . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 0.82 (0.41–1.16) | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m. | 0.88 (0.47–1.65) | 1.08 (0.8–1.44) | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.73 (0.3–1.77) | 0.9 (0.45–1.75) | 0.83 (0.43.1.55) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.39 (0.69–2.81) | 1.7 (1.13–2.58) | 1.58 (1.15–2.16) | 1.9 (0.96–3.77) | — | — | — |
SES with DAPT ≤ 12 m | 0.68 (0.34–1.36) | 0.84 (0.58–1.2) | 0.78 (0.58–1.02) | 0.93 (0.47–1.89) | 0.49 (0.33–0.73) | — | — |
BMS | 1.93 (0.87–4.19) | 2.36 (1.44–3.86) | 2.19 (1.33–3.53) | 2.62 (1.34–5.22) | 1.39 (0.79–2.44) | 2.81 (1.62–4.87) | — |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.09 (0.55–2.1) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 1.04 (0.54–1.96) | 0.95 (0.82–1.11) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.98 (0.48–1.95) | 0.9 (0.67–1.2) | 0.94 (0.71–1.23) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 1.04 (0.47–2.21) | 0.95 (0.61–1.45) | 1 (0.65–1.49) | 1.06 (0.71–1.58) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.25 (0.62–2.45) | 1.15 (0.86–1.51) | 1.2 (0.94–1.53) | 1.28 (0.9–1.82) | 1.21 (0.75–1.94) | — | — | — |
SES with DAPT ≤ 12 m | 1.09 (0.55–2.08) | 1 (0.83–1.2) | 1.05 (0.92–1.2) | 1.11 (0.83–1.51) | 1.05 (0.69–1.63) | 0.87 (0.67–1.15) | — | — |
BMS | 1.13 (0.56–2.2) | 1.04 (0.83–1.28) | 1.09 (0.88–1.34) | 1.16 (0.88–1.54) | 1.09 (0.71–1.7) | 0.91 (0.66–1.25) | 1.04 (0.82–1.31) | — |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.09 (0.55–2.1) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 1.04 (0.54–1.96) | 0.95 (0.82–1.11) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.98 (0.48–1.95) | 0.9 (0.67–1.2) | 0.94 (0.71–1.23) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 1.04 (0.47–2.21) | 0.95 (0.61–1.45) | 1 (0.65–1.49) | 1.06 (0.71–1.58) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.25 (0.62–2.45) | 1.15 (0.86–1.51) | 1.2 (0.94–1.53) | 1.28 (0.9–1.82) | 1.21 (0.75–1.94) | — | — | — |
SES with DAPT ≤ 12 m | 1.09 (0.55–2.08) | 1 (0.83–1.2) | 1.05 (0.92–1.2) | 1.11 (0.83–1.51) | 1.05 (0.69–1.63) | 0.87 (0.67–1.15) | — | — |
BMS | 1.13 (0.56–2.2) | 1.04 (0.83–1.28) | 1.09 (0.88–1.34) | 1.16 (0.88–1.54) | 1.09 (0.71–1.7) | 0.91 (0.66–1.25) | 1.04 (0.82–1.31) | — |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.09 (0.55–2.1) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 1.04 (0.54–1.96) | 0.95 (0.82–1.11) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.98 (0.48–1.95) | 0.9 (0.67–1.2) | 0.94 (0.71–1.23) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 1.04 (0.47–2.21) | 0.95 (0.61–1.45) | 1 (0.65–1.49) | 1.06 (0.71–1.58) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.25 (0.62–2.45) | 1.15 (0.86–1.51) | 1.2 (0.94–1.53) | 1.28 (0.9–1.82) | 1.21 (0.75–1.94) | — | — | — |
SES with DAPT ≤ 12 m | 1.09 (0.55–2.08) | 1 (0.83–1.2) | 1.05 (0.92–1.2) | 1.11 (0.83–1.51) | 1.05 (0.69–1.63) | 0.87 (0.67–1.15) | — | — |
BMS | 1.13 (0.56–2.2) | 1.04 (0.83–1.28) | 1.09 (0.88–1.34) | 1.16 (0.88–1.54) | 1.09 (0.71–1.7) | 0.91 (0.66–1.25) | 1.04 (0.82–1.31) | — |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1.09 (0.55–2.1) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 1.04 (0.54–1.96) | 0.95 (0.82–1.11) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.98 (0.48–1.95) | 0.9 (0.67–1.2) | 0.94 (0.71–1.23) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 1.04 (0.47–2.21) | 0.95 (0.61–1.45) | 1 (0.65–1.49) | 1.06 (0.71–1.58) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.25 (0.62–2.45) | 1.15 (0.86–1.51) | 1.2 (0.94–1.53) | 1.28 (0.9–1.82) | 1.21 (0.75–1.94) | — | — | — |
SES with DAPT ≤ 12 m | 1.09 (0.55–2.08) | 1 (0.83–1.2) | 1.05 (0.92–1.2) | 1.11 (0.83–1.51) | 1.05 (0.69–1.63) | 0.87 (0.67–1.15) | — | — |
BMS | 1.13 (0.56–2.2) | 1.04 (0.83–1.28) | 1.09 (0.88–1.34) | 1.16 (0.88–1.54) | 1.09 (0.71–1.7) | 0.91 (0.66–1.25) | 1.04 (0.82–1.31) | — |
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1 (0.35–2.62) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.95 (0.34–2.48) | 0.95 (0.79–1.15) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.94 (0.32–2.55) | 0.94 (0.67–1.32) | 0.99 (0.72–1.36) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 1.02 (0.33–3.02) | 1.02 (0.59–1.76) | 1.07 (0.63–1.8) | 1.08 (0.65–1.81) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.02 (0.34–2.74) | 1.01 (0.7–1.45) | 1.06 (0.77–1.46) | 1.08 (0.69–1.68) | 0.99 (0.54–1.82) | — | — | — |
SES with DAPT ≤ 12 m | 1 (0.36–2.62) | 1 (0.8–1.25) | 1.05 (0.88–1.25) | 1.06 (0.75–1.52) | 0.98 (0.57–1.7) | 0.99 (0.69–1.41) | — | — |
BMS | 1.21 (0.42–3.23) | 1.21 (0.94–1.56) | 1.27 (0.99–1.62) | 1.28 (0.94–1.77) | 1.18 (0.69–2.04) | 1.19 (0.81–1.78) | 1.21 (0.91–1.61) | — |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1 (0.35–2.62) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.95 (0.34–2.48) | 0.95 (0.79–1.15) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.94 (0.32–2.55) | 0.94 (0.67–1.32) | 0.99 (0.72–1.36) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 1.02 (0.33–3.02) | 1.02 (0.59–1.76) | 1.07 (0.63–1.8) | 1.08 (0.65–1.81) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.02 (0.34–2.74) | 1.01 (0.7–1.45) | 1.06 (0.77–1.46) | 1.08 (0.69–1.68) | 0.99 (0.54–1.82) | — | — | — |
SES with DAPT ≤ 12 m | 1 (0.36–2.62) | 1 (0.8–1.25) | 1.05 (0.88–1.25) | 1.06 (0.75–1.52) | 0.98 (0.57–1.7) | 0.99 (0.69–1.41) | — | — |
BMS | 1.21 (0.42–3.23) | 1.21 (0.94–1.56) | 1.27 (0.99–1.62) | 1.28 (0.94–1.77) | 1.18 (0.69–2.04) | 1.19 (0.81–1.78) | 1.21 (0.91–1.61) | — |
Table to be read from left to right and from the first row to the last one. OR refers to row-defining group (on left side).
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1 (0.35–2.62) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.95 (0.34–2.48) | 0.95 (0.79–1.15) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.94 (0.32–2.55) | 0.94 (0.67–1.32) | 0.99 (0.72–1.36) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 1.02 (0.33–3.02) | 1.02 (0.59–1.76) | 1.07 (0.63–1.8) | 1.08 (0.65–1.81) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.02 (0.34–2.74) | 1.01 (0.7–1.45) | 1.06 (0.77–1.46) | 1.08 (0.69–1.68) | 0.99 (0.54–1.82) | — | — | — |
SES with DAPT ≤ 12 m | 1 (0.36–2.62) | 1 (0.8–1.25) | 1.05 (0.88–1.25) | 1.06 (0.75–1.52) | 0.98 (0.57–1.7) | 0.99 (0.69–1.41) | — | — |
BMS | 1.21 (0.42–3.23) | 1.21 (0.94–1.56) | 1.27 (0.99–1.62) | 1.28 (0.94–1.77) | 1.18 (0.69–2.04) | 1.19 (0.81–1.78) | 1.21 (0.91–1.61) | — |
. | vs. BRS with DAPT = 12 m . | vs. Polymer biodegradable with DAPT ≤ 12 m . | vs. EES/ZES with DAPT = 12 m . | vs. EES/ZES with DAPT < 12 m . | vs. EES/ZES with DAPT > 12 m . | vs. PES with DAPT ≤ 12 m . | vs. SES with DAPT ≤ 12 m . | vs. BMS . |
---|---|---|---|---|---|---|---|---|
Polymer biodegradable with DAPT ≤ 12 m | 1 (0.35–2.62) | — | — | — | — | — | — | — |
EES/ZES with DAPT = 12 m | 0.95 (0.34–2.48) | 0.95 (0.79–1.15) | — | — | — | — | — | — |
EES/ZES with DAPT < 12 m | 0.94 (0.32–2.55) | 0.94 (0.67–1.32) | 0.99 (0.72–1.36) | — | — | — | — | — |
EES/ZES with DAPT > 12 m | 1.02 (0.33–3.02) | 1.02 (0.59–1.76) | 1.07 (0.63–1.8) | 1.08 (0.65–1.81) | — | — | — | — |
PES with DAPT ≤ 12 m | 1.02 (0.34–2.74) | 1.01 (0.7–1.45) | 1.06 (0.77–1.46) | 1.08 (0.69–1.68) | 0.99 (0.54–1.82) | — | — | — |
SES with DAPT ≤ 12 m | 1 (0.36–2.62) | 1 (0.8–1.25) | 1.05 (0.88–1.25) | 1.06 (0.75–1.52) | 0.98 (0.57–1.7) | 0.99 (0.69–1.41) | — | — |
BMS | 1.21 (0.42–3.23) | 1.21 (0.94–1.56) | 1.27 (0.99–1.62) | 1.28 (0.94–1.77) | 1.18 (0.69–2.04) | 1.19 (0.81–1.78) | 1.21 (0.91–1.61) | — |
Table to be read from left to right and from the first row to the last one. OR refers to row-defining group (on left side).
BRS, bioresorbable stents; DAPT, dual antiplatelet therapy; EES, everolimus eluting stents; ZES, zotarolimus eluting stents; PES, paclitaxel eluting stents; SES, sirolimus eluting stents; BMS, bare metal stents; OR, odds ratio.
Pertaining major bleedings, an increased risk was reported for all the stents with >12mDAPT as compared both to stents with DAPT < 12 m (OR 2.06 [1.33;3.44]) and DAPT = 12 m (1.64 [1.1–2.48]) (see Table 10 and Supplementary material online, Appendix Figures S15 and S16).
. | vs. Stents with DAPT < 12 m . | vs. Stents with DAPT = 12 m . | vs. Stents with DAPT > 12 . |
---|---|---|---|
Stents with DAPT = 12 m | 1.26 (0.89–1.88) | — | — |
Stents with DAPT > 12 m | 2.06 (1.33–3.44) | 1.64 (1.1–2.48) | — |
. | vs. Stents with DAPT < 12 m . | vs. Stents with DAPT = 12 m . | vs. Stents with DAPT > 12 . |
---|---|---|---|
Stents with DAPT = 12 m | 1.26 (0.89–1.88) | — | — |
Stents with DAPT > 12 m | 2.06 (1.33–3.44) | 1.64 (1.1–2.48) | — |
DAPT, dual antiplatelet therapy.
. | vs. Stents with DAPT < 12 m . | vs. Stents with DAPT = 12 m . | vs. Stents with DAPT > 12 . |
---|---|---|---|
Stents with DAPT = 12 m | 1.26 (0.89–1.88) | — | — |
Stents with DAPT > 12 m | 2.06 (1.33–3.44) | 1.64 (1.1–2.48) | — |
. | vs. Stents with DAPT < 12 m . | vs. Stents with DAPT = 12 m . | vs. Stents with DAPT > 12 . |
---|---|---|---|
Stents with DAPT = 12 m | 1.26 (0.89–1.88) | — | — |
Stents with DAPT > 12 m | 2.06 (1.33–3.44) | 1.64 (1.1–2.48) | — |
DAPT, dual antiplatelet therapy.
Quality assessment of the analysis
The quality assessment of the analysis is detailed in the Supplementary material online, Appendix S2, including the assessment of convergence, goodness-of-fit, heterogeneity, inconsistencies, the presence of small study effects and sensitivity analyses. After thinning, the autocorrelations were satisfactory, and the chains converged according to the Brooks–Gelman–Rubin diagnostic tool. The residual deviances of the models suggest that the quality of fit is questionable for MI and death. Moreover, for each endpoint, a certain number of points are identified as contributing to the models’ poor fit, with decreasing proportion: ST (5/84, i.e. 6% of the data points), death (7/121, 5.8%), MI (6/123, 4.9%), major bleeding (1/22, 4.5%), CV death (5/114, 4.4%), TLR (3/98, 3.1%), TVR (3/110, 2.7%) and MACE (2/110, 1.8%). None of the omnibus tests for consistency are significant, and P-values are large. Using the node-splitting analysis, no inconsistency was detected for MACE, death, ST and major bleeding. Three inconsistencies were detected for MI, one for CV death, two for TVR and one for TLR. Small study effects are detected for ST (P-value = 0.01 for the slope of regression line), suggesting that less experimental interventions are favoured in small trials for this endpoint. The slope of the regression line appears quite important for major bleeding, but is driven by few data points and is not significant (P = 0.14). No small study effects are detected for the other endpoints. By the GRADE evaluation, the most of the comparisons were assessed as ‘very low’ while eight were assessed as ‘low’.
Discussion
The main findings of our study are:
The type of stent partially influences the risk of events when different DAPT durations are prescribed.
Even if prolonged DAPT in patients treated with EES/ZES did not reduce the overall rate of MACE at follow up, a lower incidence of MI, a secondary endpoint and one of the single components of MACE, was observed in these patients when compared with all the other types of stents or DAPT durations. A longer DAPT duration, however, is associated with a higher bleeding rate.
BRS seem to perform similarly to EES/ZES in terms of overall MACE rate, irrespective of DAPT duration, but not in terms of the secondary endpoints ST and MI.
No differences were observed in terms of TLR, TVR and death (either cardiovascular or not) among the different combinations of stent and DAPT duration.
This is the first study assessing the impact of different types of stents on cardiovascular events when different DAPT durations are prescribed. Several studies and meta-analysis evaluated the impact of DAPT length on MACE,17–19 most of them investigating the association between outcomes and baseline clinical features of the patients.20
Many grey zones persist regarding the appropriate identification of the patients beneficiating from a prolonged (or shorter) DAPT. The focused guidelines21 on DAPT duration issued by the American College of Cardiology/American Heart Association suggest to select the patients eligible for DAPT prolongation after the first year of therapy based on the ‘DAPT score’ calculation, which includes clinical and procedural variables.22 However, this score is not devoid of limitations: for example, diabetes is considered as a parameter relating to a higher risk of events and thus deserving a longer DAPT duration, even when recent data showed that diabetic patients treated with second generation DES do not seem to beneficiate from a prolonged DAPT.23 Furthermore, the aforementioned score considers only the implantation of first generation DES, which are nowadays outdated and almost completely replaced by second generation DES and BRS. Recently, a new simple 5-items tool has been proposed to best select DAPT duration following PCI. According to this tool, only patients with a lower ‘PRECISE-DAPT’ score would gain a net clinical advantage from DAPT prolongation, while higher risk patients seem to beneficiate more from a shorter DAPT duration.24
Notably, based on our meta-analysis, some differences in the performance of the different types of second generation DES in combination with different DAPT durations can be detected: EES/ZES with longer DAPT duration showed a lower risk of MI as compared with EES/ZES with shorter DAPT and with all the other stents. EES/ZES with 12mDAPT showed a significant reduction of MI versus BRS. All EES/ZES, irrespective of DAPT duration, reported a lower rate of ST than BRS.
Regarding the second generation DES with durable polymer, no relevant differences between ZES and EES were noted. In a sensitivity analysis assessing separately these different DES, ZES showed a slight increase of MACE compared with EES when 12 months DAPT was prescribed. However, this difference was not significant when considering Resolute™ ZES separately from Endeavour™ ZES, meaning probably that this latter type of ZES is the culprit of this conflicting result, confirming some previous conflicting reports concerning ZES. Our global results, however, are in line with those reported by previous studies: the comprehensive network meta-analyses by Palmerini et al. 25 , 26 reported no significant differences in terms of performance of ZES versus EES on a long term follow-up.
Evidences about the impact of DAPT duration on patients treated with BRS are lacking; moreover, despite being recently approved by the U.S. Food and Drugs Administration, they were not considered in the aforementioned DAPT guidelines.21 According to our data, BRS perform similarly to the other second generation DES in terms of MACE, irrespective of DAPT duration; however, despite the general safety of this device, our analysis reported an increased risk of definite ST during the follow-up, confirming the findings of the latest three major trials assessing the Abbott Absorb BRS27–29 and of the network meta-analysis by Kang et al. 16 The mechanisms underlying the increased rate of ST, especially of very-late ST, of BRS are to date not completely understood, as they could be device-related, implantation-related or caused by incorrect patients or lesions selection.30 In any case, it is plausible that a longer DAPT duration could provide a decrease in ST with these devices, even if more data are needed, particularly to appraise the risk-benefit balance of a longer DAPT duration with BRS. Generally speaking, indeed, an increased risk of definite ST when a reduced DAPT duration is prescribed is a well-known problem, shared by all the types of stent.17 For this reason, the choice of a shortened DAPT not only with BRS but also with all current stents, should be considered only in patients in whom the increased bleeding risk would expose them to an increased mortality risk for non-cardiovascular causes in case of longer DAPT durations.
Despite the large amount of data evaluated in our analysis, its results should be interpreted carefully and in light of some important considerations. Half of the patients included were admitted for ACS: while for selected patients with stable CAD a shortened DAPT could represent a safe choice, in patients with ACS a shortened DAPT may lead to a higher rate of adverse events. As reported by Palmerini et al. 31 a 3-month (but not a 6-month) DAPT may expose patients with ACS to an increased risk of MI and ST. Concerning the reduction of the rate of MI associated with EES/ZES with prolonged DAPT, this result was probably due to a decreased rate of atherothrombotic events unrelated to stent implantation, which represent almost half of the adverse events that occur in the first three years after PCI. Moreover, patients treated with BRS experienced a higher rate of MI as compared to patients treated with EES/ZES with 12mDAPT. This result, partly guided by ST, is probably also dependent on stent-related MI without proper ST; this means that the choice of the stent may reduce the rate of MI independently of the DAPT length. Consequently, when deciding between short- and long-term DAPT, the choice of the stent (that is, durable polymer vs. biodegradable polymer vs. BRS) should be considered, along with ischaemic and bleeding risk.
Finally, EES/ZES with DAPT > 12 months were ranked at the first place for ischaemic cerebral events, while were not for MACE, major bleedings and death. This may be explained by the detrimental and largely demonstrated effect of major bleeding on survival. Also, few studies reported net adverse cardiac events (NACE) consequently the above explained finding may be reported as deductive and not inferential.
Study limitations
A meta-analysis of multiple trials inherently shares the limitations of each trial. The potential biases in each study can affect the analyses.
For each endpoint, a certain number of points are identified as contributing to the models’ poor fit. Therefore, the results should be interpreted with caution. The quality of fit for MACE, the primary endpoint, seems however acceptable.
The results of a network meta-analysis can be biased when heterogeneity is present in terms of populations or interventions among studies. Indeed, we pooled trials with different designs, enrolment criteria, follow-up and medication protocols. The results suggest that heterogeneity is reasonable for death, CV death, MI and major bleeding, and is fairly high for MACE, TVR, TLR and ST.
None of the omnibus tests for consistency suggests that inconsistency models do not fit better than the standard consistency model. Therefore, the global consistency of the models seems satisfying. By the node-splitting analysis, inconsistencies were detected for MI, one for CV death, two for TVR and one for TLR. Thus, this finding from this analysis should be considered as exploratory since the presence of inconsistency may have been overestimated due to multiplicity of the tests, leading to too pessimistic conclusions. In any case, no interpretation and no claims are made for these comparisons.
Six studies out of 64 (9%) had at least one high risk of bias and were excluded from the first sensitivity analysis. They had a minimal impact on the results of the NMA, and the results of this sensitivity analysis and of the main analysis are consistent. Thirty-one studies out of 64 (48%) had at least one high, medium or unclear risk of bias and were excluded from the second sensitivity analysis. For some comparisons, the sizes of the effects obtained with this sensitivity analysis differ noticeably from those of the main analysis. However, they are not conflicting (all the differences are in the same direction) and the precision of the sensitivity analysis is much lower. By the GRADE analysis, most of the indirect comparisons were assessed as ‘very low’ or ‘low’, thus our results have to be considered as hypothesis generating. Due to the limited sample size, two studies evaluating a DAPT length of 3 months were combined with the studies that explored 6-months DAPT. Indeed by the GRADE quality assessment most of the comparisons were graded as ‘low’ or ‘very low’ due to the indirect nature of most of the comparisons.
Conclusions
The type of stent seems to impact partially the risk of adverse events at follow-up, when different DAPT durations are chosen. BRS seems to perform similarly to second generation DES in term of MACE, but showed an increased risk of ST, irrespective of DAPT duration, and also of MI. A prolonged DAPT in patients treated with EES/ZES seems to reduce the occurrence of MI during follow-up compared with all the other types of stents, even if longer DAPT duration is associated with an increased risk of bleedings.
Supplementary material
Supplementary material is available at European Heart Journal online.
Conflict of interest: F.D.A is consultant for Abbott SRL, Medtronic SRL, Chiesi SRL. G.S.H is a consultant for Servier and AstraZeneca.
References