Publications by authors named "Rodrigo Modolo"

125 Publications

Chronic Hemodynamic Performance of a Biorestorative Transcatheter Heart Valve in an Ovine Model.

EuroIntervention 2021 Jul 20. Epub 2021 Jul 20.

Department of Cardiology, National University of Ireland Galway (NUIG), Galway, Ireland.

Background: The Xeltis biorestorative transcatheter heart valve (BTHV) leaflets are made from an eletrospun bioabsorbable supramolecular polycarbonate-urethane and are mounted on a self-expanding nitinol frame. Acute hemodynamic performance of this BTHV was favorable.

Aims: We sought to demonstrate preclinical feasibility of a novel BTHV by evaluating the hemodynamic performances of 5 pilot valve designs up to 12 months in a chronic ovine model.

Methods: Five design iterations (A, B, B', C, and D) of the BTHV were transapically implanted in 46 sheep; chronic data were available in 39 animals. Assessments were performed at implantation, 3-, 6-, and 12-months including quantitative aortography, echocardiography, and histology.

Results: At 12-months, greater than or equal to moderate AR on echocardiography was seen in 0%, 100%, 33.3%, 100%, and 0% in the iterations A, B, B', C, and D, respectively. Furthermore, transprosthetic mean gradients on echocardiography was 10.0±2.8mmHg, 19.0±1.0mmHg, 8.0±1.7mmHg, 26.8±2.4mmHg, and 11.2±4.1mmHg, and effective orifice area was 0.7±0.3cm2, 1.1±0.3cm2, 1.5±1.0cm2, 1.5±0.6cm2, and 1.0±0.4cm2 in the iterations A, B, B', C, and D, respectively. On pathological evaluation, the iteration D demonstrated generally intact leaflets and advanced tissue coverage, while different degrees of structural deterioration were observed in the other design iterations.

Conclusions: Several leaflet material iterations were compared for potential to demonstrate endogenous tissue restoration in an aortic valve in-vivo. The most promising iteration showed intact leaflets and acceptable hemodynamic performance at 12 months, illustrating the potential of BTHV.
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http://dx.doi.org/10.4244/EIJ-D-21-00386DOI Listing
July 2021

Validation of Prosthetic Mitral Regurgitation Quantification Using Novel Angiographic Platform by Mock Circulation.

JACC Cardiovasc Interv 2021 Jul 30;14(14):1523-1534. Epub 2021 Jun 30.

Department of Cardiology, National University of Ireland, Galway (NUIG) and CORRIB Corelab and Center for Research and Imaging, Galway, Ireland.

Objectives: This study aimed to validate a dedicated software for quantitative videodensitometric angiographic assessment of mitral regurgitation (QMR).

Background: Quantitative videodensitometric aortography of aortic regurgitation using the time-density principle is a well-documented technique, but the angiographic assessment of mitral regurgitation (MR) remains at best semi-quantitative and operator dependent.

Methods: Fourteen sheep underwent surgical mitral valve replacement using 2 different prostheses. Pre-sacrifice left ventriculograms were used to assess MR fraction (MRF) using QMR and MR volume (MRV). In an independent core lab, the CAAS QMR 0.1 was used for QMR analysis. In vitro MRF and MRV were assessed in a mock circulation at a comparable cardiac output to the in vivo one by thermodilution. The correlations and agreements of in vitro and in vivo MRF, MRV, and interobserver reproducibility for QMR analysis were assessed using the averaged cardiac cycles (CCs).

Results: In vivo derived MRF by QMR strongly correlated with in vitro derived MRF, regardless of the number of the CCs analyzed (best correlation: 3 CCs y = 0.446 + 0.994x; R = 0.784; p =0.002). The mean absolute difference between in vitro derived MRF and in vivo derived MRF from 3 CCs was 0.01 ± 4.2% on Bland-Altman analysis. In vitro MRV and in vivo MRV from 3 CCs were very strongly correlated (y = 0.196 + 1.255x; R = 0.839; p < 0.001). The mean absolute difference between in vitro MRV and in vivo MRV from 3 CCs was -1.4 ± 1.9 ml. There were very strong correlations of in vivo MRF between 2 independent analysts, regardless of the number of the CCs.

Conclusions: In vivo MRF using the novel software is feasible, accurate, and highly reproducible. These promising results have led us to initiate the first human feasibility study comprising patients undergoing percutaneous mitral valve edge-to-edge repair.
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http://dx.doi.org/10.1016/j.jcin.2021.04.046DOI Listing
July 2021

Effects of Anti-TNF alpha Therapy on Blood Pressure in Resistant Hypertensive Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

Arq Bras Cardiol 2021 03;116(3):443-451

Universidade Estadual de Campinas, Campinas, SP - Brasil.

Background: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in resistant hypertension (RH), but the effects of a TNF-α inhibitor in this population is unknown.

Objective: The aim of this trial was to evaluate whether a single dose of infliximab controlled by placebo acutely reduces blood pressure (BP) in RH subjects.

Methods: A double-blind, placebo-controlled, crossover trial was conducted, and randomized RH subjects received either infliximab or placebo. The primary endpoint was the change in mean BP levels relative to the baseline immediately after the infusion obtained by continuously beat-to-beat non-invasive hemodynamic assessment. Secondary endpoints included changes in office, ambulatory and central BP measurements; endothelial function; and inflammatory biomarkers after 7 days. The level of significance accepted was alpha=0.05.

Results: Ten RH subjects were enrolled. The primary endpoint analysis showed an acute decrease in mean BP values (mean of differences ± standard deviation = -6.3 ± 7.2 mmHg, p=0.02) from baseline, after the application of infliximab compared with placebo. Diastolic BP levels (-4.9 ± 5.5 mmHg, p=0.02), but not systolic BP levels (-9.4 ± 19.7 mmHg, p=0.16), lowered after infliximab infusion. No further significant differences were identified in either the other hemodynamic parameters or in secondary endpoints, except for TNF-α levels, which increased continuously after infliximab infusion. No adverse events were reported during the protocol.

Conclusions: A single-dose of infliximab decreased the mean and diastolic BP levels immediately after its infusion, when compared to the placebo in RH. The anti-TNF-α therapy was found to be safe and well-tolerated. The results of this proof-of-concept are hypothesis-generating and need to be further investigated. (Arq Bras Cardiol. 2021; 116(3):443-451).
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http://dx.doi.org/10.36660/abc.202190703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159563PMC
March 2021

Serum potassium levels provide prognostic information in symptomatic heart failure beyond traditional clinical variables.

ESC Heart Fail 2021 06 18;8(3):2133-2143. Epub 2021 Mar 18.

Faculty of Medical Science, University of Campinas, São Paulo, Brazil.

Aims: Despite of recent advances in the pharmacological treatment, heart failure (HF) maintains significant morbidity and mortality rates. While serum potassium disorders are common and associated with adverse outcomes, the exact recommended potassium level for patients with HF are not entirely established. We aimed to investigate the prognostic role of potassium levels on a cohort of patients with symptomatic chronic HF.

Methods And Results: Patients with symptomatic chronic HF were identified at the referral to 6 min walking test (6MWT) and were prospectively followed up for cardiovascular events. Clinical and laboratorial data were retrospectively obtained. The primary endpoint was the composite of cardiovascular death, hospitalization due to HF, and heart transplantation. The cohort included 178 patients with HF with the mean age of 51 ± 12.76 years, 39% were female, 85% of non-ischaemic cardiomyopathy, and 38% had New York Heart Association Class III with a relatively high Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score (12.91 ± 6.6). The mean left ventricular ejection fraction was 39.98 ± 15.79%, and the mean 6MWT distance was 353 ± 136 m. After a median follow-up of 516 days, there were 22 major cardiovascular events (4 cardiovascular deaths, 13 HF admissions, and 5 heart transplants). Patients were stratified according to cut-point level of serum potassium of 4.7 mmol/L to predict combined cardiac events based on receiver operating characteristic analysis. Individuals with higher potassium levels had worse renal function (glomerular filtration rate, K ≤ 4.7: 102.8 ± 32.2 mL/min/1.73 m vs. K > 4.7: 85.42 ± 36.2 mL/min/1.73 m , P = 0.004), higher proportion of New York Heart Association Class III patients (K ≤ 4.7: 28% vs. K > 4.7: 48%, P = 0.0029), and also higher MAGGIC score (K ≤ 4.7: 12.08 ± 5.7 vs. K > 4.7: 14.9 ± 7.9, P = 0.0089), without significant differences on the baseline pharmacological HF treatment. Both potassium levels [hazard ratio (HR) 4.26, 95% confidence interval (CI) 1.59-11.421, P = 0.003] and 6MWT distance (HR 0.99, 95% CI 0.993-0.999, P = 0.01) were independently associated with the primary outcome. After adjustments for MAGGIC score and 6MWT distance, potassium levels > 4.7 mmol/L maintained a significant association with outcomes (HR 3.57, 95% CI 1.305-9.807, P = 0.013). Patients with K > 4.7 mmol/L were more likely to present clinical events during the follow-up (log rank = 0.005). Adding potassium levels to the model including 6MWT and MAGGIC significantly improved the prediction of events over 2 years (integrated discrimination index 0.105, 95% CI 0.018-0.281, P = 0.012 and net reclassification index 0.447, 95% CI 0.077-0.703, P = 0.028).

Conclusions: Potassium levels were independently associated with worse outcomes in patients with chronic symptomatic HF, also improving the accuracy model for prognostic prediction when added to MAGGIC score and 6MWT distance. The potassium levels above 4.7 mmol/L might identify those patients at an increased risk of cardiovascular events.
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http://dx.doi.org/10.1002/ehf2.13295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120348PMC
June 2021

Gensini Score and Thrombus Burden Add Predictive Value to the SYNTAX Score in Detecting No-Reflow after Myocardial Infarction.

Arq Bras Cardiol 2021 03;116(3):466-472

Universidade Estadual de Campinas,Campinas, SP - Brasil.

Background: No-reflow after percutaneous coronary intervention is associated with poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). SYNTAX score is a good predictor of no-reflow.

Objective: We aimed to evaluate whether atherosclerotic burden (Gensini score) and thrombus burden in the culprit coronary artery would improve the ability of the SYNTAX score to detect no-reflow.

Methods: In this prospective cohort study, consecutive patients with STEMI who presented within 12 h of onset of symptoms were selected for this study. No-reflow was defined as TIMI flow < 3 o r TIMI flow = 3 but myocardial blush grade <2. Thrombus burden was quantified according to the TIMI thrombus grade scale (0 to 5).

Results: A total of 481 patients were included (mean age 61±11 years). No-reflow occurred in 32.8%. SYNTAX score (OR=1.05, 95%CI 1.01-1.08, p<0.01), thrombus burden (OR=1.17, 95%CI 1.06-1.31, p<0.01), and Gensini score (OR=1.37, 95%CI 1.13-1.65, p<0.01) were independent predictors of no-reflow. Combined scores had a larger area under the curve than the SYNTAX score alone (0.78 [0.73-0.82] vs 0.73 [0.68-0.78], p=0.03). Analyses of both categorical (0.11 [0.01-0.22], p=0.02), and continuous net reclassification improvement (NRI>0) (0.54 [0.035-0.73], p<0.001) showed improvement in the predictive ability of no-reflow in the combined model, with integrated discrimination improvement (IDI) of 0.07 (0.04-0.09, p<0.001).

Conclusions: Our findings suggest that, in patients with STEMI undergoing percutaneous coronary intervention, atherosclerotic burden and thrombus burden in the culprit artery add predictive value to the SYNTAX score in detecting the no-reflow phenomenon. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0).
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http://dx.doi.org/10.36660/abc.20200045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159555PMC
March 2021

Online Quantitative Aortographic Assessment of Aortic Regurgitation After TAVR: Results of the OVAL Study.

JACC Cardiovasc Interv 2021 03 10;14(5):531-538. Epub 2021 Feb 10.

Department of Cardiology, National University of Ireland, Galway, Galway, Ireland; Department of Cardiology, Imperial College of London, London, United Kingdom. Electronic address:

Objectives: The aim of this study was to investigate the online assessment feasibility of aortography using videodensitometry in the catheterization laboratory during transcatheter aortic valve replacement (TAVR).

Background: Quantitative assessment of regurgitation after TAVR through aortography using videodensitometry is simple, reproducible, and validated in vitro, in vivo, in clinical trials, and in "real-world" patients. However, thus far the assessment has been done offline.

Methods: This was a single center, prospective, proof-of-principle, feasibility study. One hundred consecutive patients with aortic stenosis and indications to undergo TAVR were enrolled. All final aortograms were analyzed immediately after acquisition in the catheterization laboratory and were also sent to an independent core laboratory for blinded offline assessment. The primary endpoint of the study was the feasibility of the online assessment of regurgitation (percentage of analyzable cases). The secondary endpoint was the reproducibility of results between the online assessment and the offline analysis by the core laboratory.

Results: Patients' mean age was 81 ± 7 years, and 56% were men. The implanted valves were either SAPIEN 3 (97%) or SAPIEN 3 Ultra (3%). The primary endpoint of online feasibility of analysis was 92% (95% confidence interval [CI]: 86% to 97%) which was the same feasibility encountered by the core laboratory (92%; 95% CI: 86% to 97%). Reproducibility assessment showed a high correlation between online and core laboratory evaluations (R = 0.87, p < 0.001), with an intraclass correlation coefficient of 0.962 (95% CI: 0.942 to 0.975; p < 0.001).

Conclusions: This study showed high feasibility of online quantitative assessment of regurgitation and high agreement between the online examiner and core laboratory. These results may pave the way for the application of videodensitometry in the catheterization laboratory after TAVR. (Online Videodensitometric Assessment of Aortic Regurgitation in the Cath-Lab [OVAL]; NCT04047082).
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http://dx.doi.org/10.1016/j.jcin.2020.11.014DOI Listing
March 2021

Predicting 2-year all-cause mortality after contemporary PCI: Updating the logistic clinical SYNTAX score.

Catheter Cardiovasc Interv 2021 Feb 4. Epub 2021 Feb 4.

Department of Cardiology, National University of Ireland Galway, Galway, Ireland.

Aims: We aimed to update the logistic clinical SYNTAX score to predict 2 year all-cause mortality after contemporary percutaneous coronary intervention (PCI).

Methods And Results: We analyzed 15,883 patients in the GLOBAL LEADERS study who underwent PCI. The logistic clinical SYNTAX model was updated after imputing missing values by refitting the original model (refitted original model) and fitting an extended new model (new model, with, selection based on the Akaike Information Criterion). External validation was performed in 10,100 patients having PCI at Fu Wai hospital. Chronic obstructive pulmonary disease, prior stroke, current smoker, hemoglobin level, and white blood cell count were identified as additional independent predictors of 2 year all-cause mortality and included into the new model. The c-indexes of the original, refitted original and the new model in the derivation cohort were 0.74 (95% CI 0.72-0.76), 0.75 (95% CI 0.73-0.77), and 0.78 (95% CI 0.76-0.80), respectively. The c-index of the new model was lower in the validation cohort than in the derivation cohort, but still showed improved discriminative ability of the newly developed model (0.72; 95% CI 0.67-0.77) compared to the refitted original model (0.69; 95% CI 0.64-0.74). The models overestimated the observed 2 year all-cause mortality of 1.11% in the Chinese external validation cohort by 0.54 percentage points, indicating the need for calibration of the model to the Chinese patient population.

Conclusions: The new model of the logistic clinical SYNTAX score better predicts 2 year all-cause mortality after PCI than the original model. The new model could guide clinical decision making by risk stratifying patients undergoing PCI.
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http://dx.doi.org/10.1002/ccd.29490DOI Listing
February 2021

Valvular heart interventions: advances from 2019 to 2020.

EuroIntervention 2020 Nov;16(10):808-823

Department of Cardiology, National University of Ireland, Galway (NUIG), Galway, Ireland.

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http://dx.doi.org/10.4244/EIJ-D-20-00096DOI Listing
November 2020

Aspirin-Free Prasugrel Monotherapy Following Coronary Artery Stenting in Patients With Stable CAD: The ASET Pilot Study.

JACC Cardiovasc Interv 2020 10 16;13(19):2251-2262. Epub 2020 Sep 16.

Heart Institute - InCor, University of São Paulo, São Paulo, Brazil; Hospital Israelita Albert Einstein, São Paulo, Brazil. Electronic address:

Objectives: The aim of this study was to evaluate the hypothesis that prasugrel monotherapy following successful everolimus-eluting stent implantation is feasible and safe in patients with stable coronary artery disease (CAD).

Background: Recent studies have suggested that short dual-antiplatelet therapy strategies may provide an adequate balance between ischemic and bleeding risks. However, the complete omission of aspirin immediately after percutaneous coronary intervention (PCI) has not been tested so far.

Methods: The study was a multicenter, single-arm, open-label trial with a stopping rule based on the occurrence of definite stent thrombosis (if >3, trial enrollment would be terminated). Patients undergoing successful everolimus-eluting stent implantation for stable CAD with SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores <23 were included. All participants were on standard dual-antiplatelet therapy at the time of index PCI. Aspirin was discontinued on the day of the index procedure but given prior to the procedure; prasugrel was administered in the catheterization laboratory immediately after the successful procedure, and aspirin-free prasugrel became the therapy regimen from that moment. Patients were treated solely with prasugrel for 3 months. The primary ischemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis, and the primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding up to 3 months.

Results: From February 22, 2018, to May 7, 2019, 201 patients were enrolled. All patients underwent PCI for stable CAD. Overall, 98.5% of patients were adherent to prasugrel at 3-month follow-up. The primary ischemic and bleeding endpoints occurred in 1 patient (0.5%). No stent thrombosis events occurred.

Conclusions: Aspirin-free prasugrel monotherapy following successful everolimus-eluting stent implantation demonstrated feasibility and safety without any stent thrombosis in selected low-risk patients with stable CAD. These findings may help underpin larger randomized controlled studies to evaluate the aspirin-free strategy compared with traditional dual-antiplatelet therapy following PCI. (Acetyl Salicylic Elimination Trial: The ASET Pilot Study [ASET]; NCT03469856).
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http://dx.doi.org/10.1016/j.jcin.2020.06.023DOI Listing
October 2020

The ultra-thin strut sirolimus-eluting coronary stent: SUPRAFLEX.

Future Cardiol 2021 03 10;17(2):227-237. Epub 2020 Sep 10.

Department of Cardiology, National University of Ireland Galway, Galway, H91 TK33, Ireland.

Percutaneous coronary interventions with drug-eluting stents is currently the preferred revascularization treatment strategy for coronary artery disease. Following the first generation, the second-generation drug-eluting stents was designed with a thinner strut, better biocompatible polymer with/without bioresorbable coating or even polymer-free struts. The SUPRAFLEX stent system has ultra-thin struts (60 μm) across all stent diameters and a biodegradable polymer coating, enabling 70% of the sirolimus elution within 7 days. SUPRAFLEX has been assessed in large scale randomized controlled trials. This review summarizes the design of the SUPRAFLEX stent, the results of the pivotal clinical trials and outlines the ongoing research programs.
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http://dx.doi.org/10.2217/fca-2019-0083DOI Listing
March 2021

Advances in IVUS/OCT and Future Clinical Perspective of Novel Hybrid Catheter System in Coronary Imaging.

Front Cardiovasc Med 2020 31;7:119. Epub 2020 Jul 31.

Department of Cardiology, National University of Ireland, Galway (NUIG), Galway, Ireland.

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed and improved as both diagnostic and guidance tools for interventional procedures over the past three decades. IVUS has a resolution of 100 μm with a high tissue penetration and capability of assessing the entire structure of a coronary artery including the external elastic membrane, whereas OCT has a higher resolution of 10-20 μm to assess endoluminal structures with a limited tissue penetration compared to IVUS. Recently, two companies, CONAVI and TERUMO, integrated IVUS and OCT into a single catheter system. With their inherent strength and limitations, the combined IVUS and OCT probes are complementary and work synergistically to enable a comprehensive depiction of coronary artery. In this review, we summarize the performance of the two intracoronary imaging modalities-IVUS and OCT-and discuss the expected potential of the novel hybrid IVUS-OCT catheter system in the clinical field.
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http://dx.doi.org/10.3389/fcvm.2020.00119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411139PMC
July 2020

Comparative Methodological Assessment of the Randomized GLOBAL LEADERS Trial Using Total Ischemic and Bleeding Events.

Circ Cardiovasc Qual Outcomes 2020 08 30;13(8):e006660. Epub 2020 Jul 30.

Department of Cardiology, National University of Ireland, Galway (NUIG), Ireland (F.S., Y.O., P.W.S.).

Background: Time-to-first-event analysis considers only the first event irrespective of its severity. There are several methods to assess trial outcomes beyond time-to-first-event analysis, such as analyzing total events and ranking outcomes. In the GLOBAL LEADERS study, time-to-first-event analysis did not show superiority of ticagrelor monotherapy following one-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention to conventional 12-month DAPT followed by aspirin monotherapy in the reduction of the primary composite end point of all-cause mortality or new Q-wave myocardial infarction. This study sought to explore various analytical approaches in assessing total ischemic and bleeding events after percutaneous coronary intervention in the GLOBAL LEADERS study.

Methods And Results: Total ischemic and bleeding events were defined as all-cause mortality, any stroke, any myocardial infarction, any revascularization, or Bleeding Academic Research Consortium grade 2 or 3 bleeding. We used various analytical approaches to analyze the benefit of ticagrelor monotherapy over conventional DAPT. For ischemic and bleeding events at 2 years after percutaneous coronary intervention, ticagrelor monotherapy demonstrated a 6% risk reduction, compared with conventional 12-month DAPT in time-to-first-event analysis (hazard ratio, 0.94 [95% CI, 0.88-1.01]; log-rank =0.10). In win ratio analysis, win ratio was 1.05 (95% CI, 0.97-1.13; =0.20). Negative binomial regression and Andersen-Gill analyses which include repeated events showed statistically significant advantage for ticagrelor monotherapy (rate ratio, 0.92 [95% CI, 0.85-0.99; =0.020] and hazard ratio, 0.92 [95% CI, 0.85-0.99; =0.028], respectively), although in weighted composite end point analysis, the hazard ratio was 0.93 (95% CI, 0.84-1.04; log-rank =0.22).

Conclusions: Statistical analyses considering repeated events or event severity showed that ticagrelor monotherapy consistently reduced ischemic and bleeding events by 5% to 8%, compared with conventional 1-year DAPT. Applying multiple statistical methods could emphasize the multiple facets of a trial and result in accurate and more appropriate analyses. Considering the recurrence of ischemic and bleeding events, ticagrelor monotherapy appeared to be beneficial after percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.006660DOI Listing
August 2020

Quantitative Assessment of Acute Regurgitation Following TAVR: A Multicenter Pooled Analysis of 2,258 Valves.

JACC Cardiovasc Interv 2020 06 16;13(11):1303-1311. Epub 2020 Mar 16.

Galway University Hospital, SAOLTA Health Care Group, and National University of Ireland, Galway, Ireland; Department of Cardiology, Imperial College of London, London, United Kingdom. Electronic address:

Objectives: The aim of this study was to assess acute regurgitation following transcatheter aortic valve replacement, comparing different implanted transcatheter heart valves.

Background: Regurgitation following transcatheter aortic valve replacement influences all-cause mortality. Thus far, no quantitative comparison of regurgitation among multiple commercially available transcatheter heart valves has been performed.

Methods: Aortograms from a multicenter cohort of consecutive 3,976 transcatheter aortic valve replacements were evaluated in this pooled analysis. A total of 2,258 (58.3%) were considered analyzable by an independent academic core laboratory using video densitometry. Results of quantitative regurgitation are shown as percentages. The valves evaluated were the ACURATE (n = 115), Centera (n = 11), CoreValve (n = 532), Direct Flow Medical (n = 21), Evolut PRO (n = 95), Evolut R (n = 295), Inovare (n = 4), Lotus (n = 546), Lotus Edge (n = 3), SAPIEN XT (n = 239), and SAPIEN 3 (n = 397). For the main analysis, only valves with more than 50 procedures (7 types) were used.

Results: The Lotus valve had the lowest mean regurgitation (3.5 ± 4.4%), followed by Evolut PRO (7.4 ± 6.5%), SAPIEN 3 (7.6 ± 7.1%), Evolut R (7.9 ± 7.4%), SAPIEN XT (8.8 ± 7.5%), ACURATE (9.6 ± 9.2%) and CoreValve (13.7 ± 10.7%) (analysis of variance p < 0.001). The only valves that statistically differed from all their counterparts were Lotus (as the lowest regurgitation) and CoreValve (the highest). The proportion of patients presenting with moderate or severe regurgitation followed the same ranking order: Lotus (2.2%), Evolut PRO (5.3%), SAPIEN 3 (8.3%), Evolut R (8.8%), SAPIEN XT (10.9%), ACURATE (11.3%), and CoreValve (30.1%) (chi-square p < 0.001).

Conclusions: In this pooled analysis stemming from daily clinical practice, the Lotus valve was shown to have the best immediate sealing. This analysis reflects the objective evaluation of regurgitation by an academic core laboratory (nonsponsored) in a real-world cohort of patients using a quantitative technique.
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http://dx.doi.org/10.1016/j.jcin.2020.03.002DOI Listing
June 2020

Drug-eluting bioresorbable scaffolds in cardiovascular disease, peripheral artery and gastrointestinal fields: a clinical update.

Expert Opin Drug Deliv 2020 07 27;17(7):931-945. Epub 2020 May 27.

Department of Cardiology, National University of Ireland, Galway (NUIG) , Galway, Ireland.

Introduction: The technology of bioresorbable scaffold (BRS) spread out after the success of the first-in-man trials of the Absorb. However, the randomized trials demonstrated that major adverse cardiac events and scaffold thrombosis rates of the first-generation Absorb were higher than those of the metallic everolimus-eluting stent. To overcome the shortcoming of the firstly commercialized Absorb, novel technologies have been developed.

Areas Covered: In this review, we overviewed the field of BRS in the treatment of coronary, peripheral artery and gastrointestinal fields. To date, 10 BRS devices developed by 6 manufacturers have acquired the CE mark in coronary artery disease. Currently 8 BRS are in clinical trial phase, whereas 7 BRS are in preclinical assessment phase. Most new-generation devices have a strut thickness of less than 100 μm. However, late favorable outcome might be achieved not only by device refinement but also by a proper technique of implantation using intra vascular imaging guidance, as well as with a careful patient and lesion selection.

Expert Opinion: New-generation BRS will be soon tested in the clinical arena to demonstrate improved acute and long-term of safety and efficacy.
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http://dx.doi.org/10.1080/17425247.2020.1764932DOI Listing
July 2020

The impact of pre-procedure heart rate on adverse clinical outcomes in patients undergoing percutaneous coronary intervention: Results from a 2-year follow-up of the GLOBAL LEADERS trial.

Atherosclerosis 2020 06 28;303:1-7. Epub 2020 Apr 28.

Department of Cardiology, National University of Ireland, Galway (NUIG), Galway, Ireland; National Heart and Lung Institute, Imperial College London, London, UK. Electronic address:

Background And Aims: The prognostic impact of pre-procedure heart rate (PHR) following percutaneous coronary intervention (PCI) has not yet been fully investigated. This post-hoc analysis sought to assess the impact of PHR on medium-term outcomes among patients having PCI, who were enrolled in the "all-comers" GLOBAL LEADERS trial.

Methods And Results: The primary endpoint (composite of all-cause death or new Q-wave myocardial infarction [MI]) and key secondary safety endpoint (bleeding according to Bleeding Academic Research Consortium [BARC] type 3 or 5) were assessed at 2 years. PHR was available in 15,855 patients, and when evaluated as a continuous variable (5 bpm increase) and following adjustment using multivariate Cox regression, it significantly correlated with the primary endpoint (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03-1.09, p < 0.001). Using dichotomous cut-off criteria, a PHR>67 bpm was associated with increased all-cause mortality (HR 1.38, 95%CI 1.13-1.69, p = 0.002) and more frequent new Q-wave MI (HR 1.41, 95%CI 1.02-1.93, p = 0.037). No significant association was found between PHR and BARC 3 or 5 bleeding (HR 1.04, 95% CI 0.99-1.09, p = 0.099). There was no interaction with the primary (p-inter = 0.236) or secondary endpoint (p-inter = 0.154) when high and low PHR was analyzed according to different antiplatelet strategies.

Conclusions: Elevated PHR was an independent predictor of all-cause mortality at 2 years following PCI in the "all-comer" GLOBAL LEADERS trial. The prognostic value of increased PHR on outcomes was not affected by the different antiplatelet strategies in this trial.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.04.010DOI Listing
June 2020

Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial.

Can J Cardiol 2021 01 21;37(1):122-130. Epub 2020 Feb 21.

Andrzej Frycz Modrzewski Krakow University, Krakow, Poland; American Heart of Poland, Chrzanow, Poland.

Background: Radial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding.

Methods: Patients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days.

Results: In the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; P = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; P = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant.

Conclusions: Our findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.
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http://dx.doi.org/10.1016/j.cjca.2020.01.029DOI Listing
January 2021

Vulnerable plaques and patients: state-of-the-art.

Eur Heart J 2020 08;41(31):2997-3004

Department of Cardiology, National University of Ireland, Galway, Ireland.

Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term 'vulnerable plaque' was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of 'vulnerability' of a specific lesion to the more comprehensive goal of identifying patient 'cardiovascular vulnerability'. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and 'local' diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevention, and treatment of 'high-risk' plaques occurring in 'vulnerable' patients.
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http://dx.doi.org/10.1093/eurheartj/ehaa227DOI Listing
August 2020

Statistical methods for composite endpoints.

EuroIntervention 2021 Apr 2;16(18):e1484-e1495. Epub 2021 Apr 2.

Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Composite endpoints are commonly used in clinical trials, and time-to-first-event analysis has been the usual standard. Time-to-first-event analysis treats all components of the composite endpoint as having equal severity and is heavily influenced by short-term components. Over the last decade, novel statistical approaches have been introduced to overcome these limitations. We reviewed win ratio analysis, competing risk regression, negative binomial regression, Andersen-Gill regression, and weighted composite endpoint (WCE) analysis. Each method has both advantages and limitations. The advantage of win ratio and WCE analyses is that they take event severity into account by assigning weights to each component of the composite endpoint. These weights should be pre-specified because they strongly influence treatment effect estimates. Negative binomial regression and Andersen-Gill analyses consider all events for each patient -rather than only the first event - and tend to have more statistical power than time-to-first-event analysis. Pre-specified novel statistical methods may enhance our understanding of novel therapy when components vary substantially in severity and timing. These methods consider the specific types of patients, drugs, devices, events, and follow-up duration.
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http://dx.doi.org/10.4244/EIJ-D-19-00953DOI Listing
April 2021

Usefulness of the updated logistic clinical SYNTAX score after percutaneous coronary intervention in patients with prior coronary artery bypass graft surgery: Insights from the GLOBAL LEADERS trial.

Catheter Cardiovasc Interv 2020 11 15;96(5):E516-E526. Epub 2020 Apr 15.

Department of cardiology, National University of Ireland Galway (NUIG), Galway, Ireland.

Objectives: We aimed to investigate the prognostic utility of the anatomical CABG SYNTAX and logistic clinical SYNTAX scores for mortality after percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass grafts (CABG).

Background: The anatomical SYNTAX score evaluated the anatomical complexity of coronary artery disease and helped predict the prognosis of patients undergoing PCI. The anatomical CABG SYNTAX score was derived from the anatomical SYNTAX score in patients with prior CABG, whilst the logistic clinical SYNTAX score was developed by incorporating clinical factors into the anatomical SYNTAX score.

Methods: We calculated the anatomical CABG SYNTAX score and logistic clinical SYNTAX score in 205 patients in the GLOBAL LEADERS trial. The predictive abilities of these scores for 2-year all-cause mortality were evaluated.

Results: Using the median scores as categorical thresholds between low and high score groups, the logistic clinical SYNTAX score was able to discriminate the risk of 2-year mortality, unlike the anatomical CABG SYNTAX score. The logistic clinical SYNTAX was significantly better at predicting 2-year mortality, compared to the anatomical CABG SYNTAX score, as evidenced by AUC values in receiver-operating characteristic curve analysis (0.806 vs. 0.582, p < .001) and integrated discrimination improvement (0.121, p < .001).

Conclusions: The logistic clinical SYNTAX score was superior to the anatomical CABG SYNTAX score in predicting 2-year mortality.
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http://dx.doi.org/10.1002/ccd.28898DOI Listing
November 2020

Association of Pulse Pressure With Clinical Outcomes in Patients Under Different Antiplatelet Strategies After Percutaneous Coronary Intervention: Analysis of GLOBAL LEADERS.

Can J Cardiol 2020 05 19;36(5):747-755. Epub 2019 Oct 19.

Galway University Hospital, National University of Ireland, Galway, Ireland. Electronic address:

Background: We evaluated the association of pulse pressure (PP) and different antiplatelet regimes with clinical and safety outcomes in an all-comers percutaneous coronary intervention (PCI) population.

Methods: In this analysis of GLOBAL LEADERS (n = 15,936) we compared the experimental therapy of 23 months of ticagrelor after 1 month of dual-antiplatelet therapy (DAPT) vs standard DAPT for 12 months followed by aspirin monotherapy in subjects who underwent PCI and were divided into 2 groups according to the median PP (60 mm Hg). The primary end point (all-cause death or new Q-wave myocardial infarction) and the composite end points: patient-oriented composite end points (POCE), Bleeding Academic Research Consortium (BARC) 3 or 5, and net adverse clinical events (NACE) were evaluated.

Results: At 2 years, subjects in the high-PP group (n = 7971) had similar rates of the primary end point (4.3% vs 3.9%; P = 0.058), POCE (14.9% vs 12.7%; P = 0.051), and BARC 3 or 5 (2.5% vs 1.7%; P = 0.355) and higher rates of NACE (16.4% vs 13.7%; P = 0.037) compared with the low-PP group (n = 7965). Among patients with PP < 60 mm Hg, the primary end point (3.4% vs 4.4%, adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.96), POCE (11.8% vs 13.5%, aHR 0.86, 95% CI 0.76-0.98), NACE (12.8% vs 14.7%, aHR 0.85, 95% CI 0.76-0.96), and BARC 3 or 5 (1.4% vs 2.1%, aHR 0.69, 95% CI 0.49-0.97) were lower with ticagrelor monotherapy compared with DAPT. The only significant interaction was for BARC 3 or 5 (P = 0.008).

Conclusions: After contemporary PCI, subjects with high PP levels experienced high rates of NACE at 2 years. In those with low PP, ticagrelor monotherapy led to a lower risk of bleeding events compared with standard DAPT.
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http://dx.doi.org/10.1016/j.cjca.2019.10.015DOI Listing
May 2020

DAPT Score and the Impact of Ticagrelor Monotherapy During the Second Year After PCI.

JACC Cardiovasc Interv 2020 03;13(5):634-646

Department of Cardiology, National University of Ireland, Galway, Galway, Ireland; International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address:

Objectives: This study assessed the ability of the dual-antiplatelet therapy (DAPT) score in stratifying ischemic and bleeding risk in a contemporary percutaneous coronary intervention (PCI) population.

Background: The DAPT score is recommended by guidelines as a tool to stratify ischemic and bleeding risk. Its utility in contemporary PCI is unknown.

Methods: The study studied patients in GLOBAL LEADERS (A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation) who were free of major ischemic and bleeding events and adhered to antiplatelet strategy during the first year after PCI. The primary ischemic endpoint was the composite of myocardial infarction or stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium type 3 or 5. Outcomes from 12 to 24 months after PCI were compared according to the DAPT score.

Results: Of 11,289 patients that were event-free after the first year, 6,882 and 4,407 patients had low (<2) and high (≥2) DAPT scores, respectively. Compared with a low DAPT score, patients with a high DAPT score had a higher rate of the composites of myocardial infarction or stent thrombosis (0.70% vs. 1.55%; p < 0.0001). The rate of Bleeding Academic Research Consortium type 3 or 5 bleeding was 0.54% and 0.30% in the low and high DAPT score groups, respectively (p = 0.058). The effect of ticagrelor versus aspirin monotherapy on primary ischemic and bleeding endpoints during the second year were no different among the 2 groups.

Conclusions: The DAPT score can stratify ischemic but not bleeding risk in a contemporary PCI population during the second year. The score did not provide additional value for selection of antiplatelet strategy beyond the first year.
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http://dx.doi.org/10.1016/j.jcin.2019.12.018DOI Listing
March 2020

Association of diabetes with outcomes in patients undergoing contemporary percutaneous coronary intervention: Pre-specified subgroup analysis from the randomized GLOBAL LEADERS study.

Atherosclerosis 2020 02 15;295:45-53. Epub 2020 Jan 15.

Department of Cardiology, National University of Ireland Galway, Galway, Ireland; NHLI, Imperial College London, London, United Kingdom. Electronic address:

Background And Aims: Diabetes has been well recognized as a strong predictor for adverse outcomes after percutaneous coronary intervention (PCI), however, studies in the era of drug-eluting stent and potent P2Y12 inhibitors have shown conflicting results. We aimed to assess ischemic and bleeding outcomes after contemporary PCI according to diabetic status.

Methods: We studied 15,957 patients undergoing PCI for stable or acute coronary syndrome in the GLOBAL LEADERS study with known baseline diabetic status. The primary endpoint was all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was major bleeding defined as bleeding academic research consortium (BARC) type 3 or 5.

Results: A quarter of the study cohort were diabetic (4038/15,957), and these patients had a significantly higher risk of primary endpoint at 2 years compared to non-diabetics (adjusted hazard ratio [HR] 1.38; 95% confidence interval [CI] 1.17-1.63). The difference was driven by a significantly higher risk of all-cause mortality at 2 years in diabetics (adjusted HR 1.47, 95% CI 1.22-1.78). The risk of BARC 3 or 5 bleeding was comparable between the two groups (adjusted HR 1.09, 95% CI 0.86-1.39). The antiplatelet strategy (experimental versus reference strategy) had no significant effect on the rates of primary endpoint and secondary safety endpoint at 2 years in patients with and without diabetes.

Conclusions: Diabetic patients had higher risk of ischemic events after PCI than non-diabetic patients, whilst bleeding risk was comparable. The outcomes of diabetic patients following PCI were not affected by the two different antiplatelet strategies.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.01.002DOI Listing
February 2020

The association of body mass index with long-term clinical outcomes after ticagrelor monotherapy following abbreviated dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: a prespecified sub-analysis of the GLOBAL LEADERS Trial.

Clin Res Cardiol 2020 Sep 31;109(9):1125-1139. Epub 2020 Jan 31.

Department of Cardiology, NUIG (National University of Ireland, University Road, Galway)Galway, H91 TK33, Ireland.

Background: The efficacy of antiplatelet therapies following percutaneous coronary intervention (PCI) may be affected by body mass index (BMI).

Methods And Results: This is a prespecified subgroup analysis of the GLOBAL LEADERS trial, a prospective, multicenter, open-label, randomized controlled trial in an all-comer population undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with a reference regimen (12-month aspirin monotherapy following 12-month DAPT). A total of 15,968 patients were stratified by baseline BMI with prespecified threshold of 27 kg/m. Of those, 6973 (43.7%) patients with a BMI < 27 kg/m had a higher risk of all-cause mortality at 2 years than those with BMI ≥ 27 kg/m (adjusted HR 1.24, 95% CI 1.02-1.49). At 2 years, the rates of the primary endpoint (all-cause mortality or new Q-wave myocardial infarction) were similar between treatment strategies in either BMI group (p = 0.51). In acute coronary syndrome, however, the experimental strategy was associated with significant reduction of the primary endpoint compared to the reference strategy in patients with BMI < 27 kg/m (HR 0.69, 95% CI 0.51-0.94), but not in the ones with BMI ≥ 27 kg/m (p = 0.047). In chronic coronary syndrome, there was no between-group difference in the efficacy and safety of the two antiplatelet strategies.

Conclusions: Overall, BMI did not influence the treatment effect seen with ticagrelor monotherapy; however, a beneficial effect of ticagrelor monotherapy was seen in ACS patients with BMI < 27 kg/m.

Trial Registration: The trial has been registered with ClinicalTrials.gov, Number NCT01813435.
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http://dx.doi.org/10.1007/s00392-020-01604-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449952PMC
September 2020

Impact of renal function on clinical outcomes after PCI in ACS and stable CAD patients treated with ticagrelor: a prespecified analysis of the GLOBAL LEADERS randomized clinical trial.

Clin Res Cardiol 2020 Jul 10;109(7):930-943. Epub 2020 Jan 10.

University Hospital of Wales, Cardiff, UK.

Background: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF.

Methods: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m).

Results: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35-1.98, p = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61-1.11, p = 0.192, p = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71-1.71, p = 0.656, p = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (p = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (p = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF.

Conclusions: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy.

Clinical Trial Registration: The trial has been registered with ClinicalTrials.gov, number NCT01813435.
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http://dx.doi.org/10.1007/s00392-019-01586-9DOI Listing
July 2020

The influence of implantation techniques on lesion oriented-outcomes in Absorb BVS and Xience EES lesions treated in routine clinical practice at complete three year follow-up: AIDA trial QCA substudy.

Int J Cardiovasc Imaging 2020 Apr 2;36(4):565-575. Epub 2020 Jan 2.

Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

It has been hypothesized that dedicated optimized Absorb BVS implantation techniques might mitigate the risk of adverse events such as target vessel failure and device thrombosis. In this explorative AIDA trial QCA substudy, we sought to investigate the influence of implantation techniques on lesion-oriented outcomes in both the Absorb BVS and Xience EES arm at complete 3-year follow-up. The current analysis includes 2152 study lesions treated with at least one study device, of which the baseline angiogram was suited for offline QCA analysis, including Dmax analysis. The lesion-oriented composite outcome (LOCE) of this analysis was a composite of definite device thrombosis, target lesion revascularization and target-vessel myocardial infarction. In Absorb BVS, the Lesion-oriented composite endpoint (LOCE) occurred numerically less in correctly QCA sized vessels when compared to incorrectly sized vessels 8.5% (58/696) versus 11.1% (39/358), p = 0.151. In Xience EES, LOCE had occurred more frequently in incorrectly sized devices according to device diameter/RVD matching; 2.2% (4/187) in correctly sized devices versus 7.1% (63/911) in incorrectly sized devices (p = 0.014). In this AIDA trial QCA substudy, rates of LOCE were significantly lower in Xience EES treated lesions in which devices were correctly sized according to the definitions of device diameter/RVD matching.
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http://dx.doi.org/10.1007/s10554-019-01756-wDOI Listing
April 2020

Impact of chronic obstructive pulmonary disease and dyspnoea on clinical outcomes in ticagrelor treated patients undergoing percutaneous coronary intervention in the randomized GLOBAL LEADERS trial.

Eur Heart J Cardiovasc Pharmacother 2020 07;6(4):222-230

Department of Cardiology, National University of Ireland Galway, Galway, Ireland.

Aims: To evaluate long-term safety and efficacy of ticagrelor monotherapy in patients undergoing percutaneous coronary interventions (PCIs) in relation to chronic obstructive pulmonary disease (COPD) at baseline and the occurrence of dyspnoea reported as adverse event (AE) that may lead to treatment non-adherence.

Methods And Results: This is a non-prespecified, post hoc analysis of the randomized GLOBAL LEADERS trial (n = 15 991), comparing the experimental strategy of 23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after PCI with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy. Impact of COPD and dyspnoea AE (as a time-dependent covariate) on clinical outcomes was evaluated up to 2 years. The primary endpoint was a 2-year all-cause mortality or non-fatal, centrally adjudicated, new Q-wave myocardial infarction. The presence of COPD (n = 832) was the strongest clinical predictor of 2-year all-cause mortality after PCI [hazard ratio (HR) 2.84; 95% confidence interval (CI) 2.21-3.66; P adjusted = 0.001] in this cohort (n = 15 991). No differential treatment effects on 2-year clinical outcomes were found in patients with and without COPD (primary endpoint: HR 0.88; 95% CI 0.58-1.35; P = 0.562; P int = 0.952). Overall, at 2 years dyspnoea was reported as an AE in 2101 patients, more frequently among COPD patients, irrespective of treatment allocation (27.2% in experimental arm vs. 14.5% in reference arm, P = 0.001). Its occurrence was not associated with a higher rate of the primary endpoint (P adjusted = 0.640) in the experimental vs. the reference arm.

Conclusion: In this exploratory analysis, COPD negatively impacted long-term prognosis after PCI. Despite higher incidence of dyspnoea in the experimental arm, in particular among COPD patients, the safety of the experimental treatment strategy appeared not to be affected.

Clinical Trial Registration Unique Identifier: NCT01813435.
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http://dx.doi.org/10.1093/ehjcvp/pvz052DOI Listing
July 2020

Impact of established cardiovascular disease on outcomes in the randomized global leaders trial.

Catheter Cardiovasc Interv 2020 12 19;96(7):1369-1378. Epub 2019 Dec 19.

Department of Cardiology, National University of Ireland Galway, Galway, Ireland.

Objective: To investigate the impact of different anti-platelet strategies on outcomes after percutaneous coronary intervention (PCI) in patients with established cardiovascular disease (CVD).

Methods: GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing one-month dual anti-platelet therapy (DAPT) with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. Established CVD was defined as ≥1 prior myocardial infarction, PCI, coronary artery bypass operation, stroke, or established peripheral vascular disease. The primary endpoint was a composite of all-cause death or new Q-wave MI at 2-years. The secondary safety endpoint was BARC 3 or 5 bleeding. Exploratory secondary endpoints were the patient-orientated composite endpoint and net adverse clinical events.

Results: Among the 15,761 patients in this cohort were 6,693 patients (42.5%) with established CVD. Compared to those without established CVD, these patients had significantly higher rates of the primary (5.1 vs. 3.3%, HR1.59[1.36-1.86], p < .001) and secondary composite endpoints with no significant differences in bleeding. There was a nonsignificant reduction in the primary endpoint in patients with established CVD receiving the experimental treatment (4.6 vs. 5.6%, HR0.82[0.66-1.02], p = .07). When comparing patients without CVD to those with one or three territories of CVD, the hazard ratio for the primary endpoint increased in unadjusted and adjusted models.

Conclusions: The poorer outcomes in patients with established CVD are not mitigated by prolonged monotherapy with a potent P2Y12 inhibitor suggesting a greater need to focus on modifiable risk factors.
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http://dx.doi.org/10.1002/ccd.28649DOI Listing
December 2020

Ticagrelor monotherapy beyond one month after PCI in ACS or stable CAD in elderly patients: a pre-specified analysis of the GLOBAL LEADERS trial.

EuroIntervention 2020 Apr 3;15(18):e1605-e1614. Epub 2020 Apr 3.

Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands.

Aims: Antiplatelet treatment in the elderly post percutaneous coronary interventions (PCI) remains a complex issue. Here we report the results of the pre-specified subgroup analysis of the GLOBAL LEADERS trial evaluating the long-term safety and cardiovascular efficacy of ticagrelor monotherapy among patients categorised according to the pre-specified cut-off value of 75 years of age.

Methods And Results: This was a pre-specified analysis of the randomised GLOBAL LEADERS trial (n=15,991), comparing 23-month ticagrelor monotherapy (after one month of DAPT) with the reference treatment (12-month DAPT followed by 12 months of aspirin). Among elderly patients (>75 years; n=2,565), the primary endpoint (two-year all-cause mortality or new Q-wave core lab-adjudicated myocardial infarction [MI]) occurred in 7.2% and 9.4% of patients in the ticagrelor monotherapy and the reference group, respectively (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.58-0.99, p=0.041; pint=0.23); BARC-defined bleeding type 3/5 occurred in 5.2% and 4.1%, respectively (HR 1.29, 95% CI: 0.89-1.86; p=0.180; pint=0.06). The elderly with stable CAD had a higher rate of BARC 3/5 type bleeding (HR 2.05, 95% CI: 1.18-3.55) with ticagrelor monotherapy versus the reference treatment (pint=0.02). Elderly patients had a lower rate of definite or probable stent thrombosis (ST) with ticagrelor monotherapy (0.4% vs 1.4%, p=0.015, pint=0.01), compared with the reference group.

Conclusions: In this pre-specified, exploratory analysis of the overall neutral trial, there was no differential treatment effect of ticagrelor monotherapy (after one-month dual therapy with aspirin) found in elderly patients undergoing PCI with respect to the rate of the primary endpoint of all-cause death or new Q-wave MI. The lower rate of ST in the elderly with ticagrelor monotherapy is hypothesis-generating. ClinicalTrials.gov identifier: NCT01813435.
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http://dx.doi.org/10.4244/EIJ-D-19-00699DOI Listing
April 2020
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