Definite Stent Thrombosis Research Articles

Can an ultrathin strut stent design and a polymer free, proendothelializing probucol matrix coating improve early strut healing? The FRIENDLY-OCT trial. An intra-patient randomized study with OCT, evaluating early strut coverage of a novel probucol coated polymer-free and ultra-thin strut sirolimus-eluting stent compared to a biodegradable polymer sirolimus-eluting stent

Backgroundincomplete strut coverage determines the risk of stent thrombosis in the first months after stent implantation. AimsTo evaluate the potential better early healing of a novel probucol coated polymer free ultra-thin strut sirolimus eluting stent (PF-SES). [Clinical trial unique identifier: NCT02785237]. MethodsPatients with two (angiographically similar) lesions with clinical indication for PCI were enrolled. The investigated stent was compared to a thin strut, bioresorbable polymer, sirolimus eluting stent (BP-SES). Every patient received both stents, one in each lesion, assigned in a randomized sequence. OCT was systematically performed at 3 months.Primary end point was the difference in the proportion of covered struts at 3 months (defined as ≥20 μm of tissue coverage). Secondary end points included differences in percentage of uncovered struts (0 μm coverage), mean strut coverage thickness, and malapposed struts' coverage proportion. Major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization, and definite or probable stent thrombosis) at 12 months were also evaluated. Results70 patients were included. At 3 months, a consistent and significantly higher strut coverage rate (≥20 μm) was observed in PF-SES as compared to BP-SES, both for well apposed (87.3% versus 79.1%, p < 0.001) and malapposed struts (50.4% vs 37.8%, p 0.00). Uncoverage rate (0 μm) was also significantly lower for the PF-SES (3.1% vs 5.3%, p < 0.001). There were no differences in clinical endpoints. ConclusionThe probucol coated non-polymeric ultra-thin strut sirolimus eluting stent showed a significantly better early strut coverage at 3 months.

Ten-year patterns of stent thrombosis after percutaneous coronary intervention with new- versus early-generation drug-eluting stents: insights from the DECADE cooperation

Introduction and objectivesThe DECADE cooperation is a pooled analysis of individual patient data from drug-eluting stent (DES) trials with a 10-year follow-up. This analysis reports the risk of definite stent thrombosis (ST) through to 10 years after percutaneous coronary intervention (PCI) in patients treated with early- and new-generation DES. MethodsIndividual patient data from 5 DES trials with a 10-year follow-up were pooled. The primary endpoint was definite ST up to 10 years after PCI. Patients were divided into 2 groups as per the generation of DES implanted (early and new DES). Individual participant data were analyzed using a 1-stage approach. ResultsWe included 9700 patients, 6866 in the new DES group and 2834 in the early DES group. Through to 10 years, definite ST occurred in 69 of 6866 patients treated with new DES and in 91 of 2834 patients treated with early DES (1.0% vs 3.5%, adjusted hazard ratio, 0.32; 95%CI, 0.23-0.45). The rate of definite ST was lower in the new DES group than in the early DES group from 1 to 5 years (rate ratio, 0.14; 95%CI, 0.08-0.26) and from 5 to 10 years (rate ratio, 0.23; 95%CI, 0.08-0.61) after PCI. ConclusionsThe incidence of definite ST through to 10 years after PCI with new-generation DES was 1%. New-generation DES are associated with a lower 10-year incidence of definite ST than early-generation DES, particularly beyond 1 year after PCI.

Comparative efficacy and safety of oral P2Y12 inhibitors after non-ST-elevation acute coronary syndromes: a network meta-analysis

BackgroundCurrently, potent P2Y12 inhibition with the use of prasugrel or ticagrelor is the mainstay of treatment after an acute coronary syndrome (ACS). The 2020 European Society of Cardiology (ESC) Guidelines...

Long-Term Clinical Impact of Contrast-Associated Acute Kidney Injury Following PCI: AnADAPT-DES Substudy.

This study sought to determine correlates and consequences of contrast-associated acute kidney injury (CA-AKI) on clinical outcomes in patients with or without pre-existing chronic kidney disease (CKD). The incidence and impact of CA-AKI on clinical outcomes during contemporary percutaneous coronary intervention (PCI) are not fully defined. The ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study was a prospective, multicenter registry of 8,582 patients treated with≥1 drug-eluting stent(s). CA-AKI was defined as a post-PCI increase in serum creatinine of >0.5mg/dL or a relative increase of≥25% compared with pre-PCI. CKD was defined as estimated glomerular filtration rate<60mL/min/1.73m2. The primary endpoint was the 2-year rate of net adverse clinical events (NACE): All-cause mortality, myocardial infarction (MI), definite or probable stent thrombosis, or major bleeding. Of 7287 (85%) patients with evaluable data, 476 (6.5%) developed CA-AKI. In a multivariable model, older age, female sex, Caucasian race, congestive heart failure, diabetes, hypertension, CKD, presentation with ST-segment elevation MI, Killip class II to IV, radial access, intra-aortic balloon pump use, hypotension, and number of stents were independent predictors of CA-AKI. The 2-year NACE rate was higher in patients with CA-AKI (adjusted HR: 1.88; 95% CI: 1.42-2.49), as was each component of NACE (all-cause mortality, HR: 1.77; 95%CI: 1.22-2.55; MI, HR: 1.67; 95%CI: 1.18-2.36; definite/probable stent thrombosis, HR: 1.71; 95%CI: 1.10-2.65; and major bleeding, HR: 1.38; 95%CI: 1.06-1.80). Compared with the CA-AKI-/CKD- group, the CA-AKI+/CKD- (HR: 1.83; 95%CI: 1.33-2.52), CA-AKI-/CKD+ (HR: 1.56; 95%CI: 1.15-2.13), CA-AKI+/CKD+ (HR: 3.29; 95%CI: 1.92-5.67), and maintenance dialysis (HR: 2.67; 95%CI: 1.65-4.31) groups were at higher risk of NACE. CA-AKI was relatively common after contemporary PCI and was associated with increased 2-year rates of NACE. Patients with pre-existing CKD were at particularly high risk for NACE after CA-AKI.

A Propensity Score-Matched Comparison of Midterm Outcomes Between Drug-Coated Balloons and Drug-Eluting Stents for Patients with Acute Coronary Syndrome.

We conducted a single-center, retrospective, lesion-based study to examine the safety and efficacy of drug-coated balloons (DCBs) for de novo coronary stenosis in patients with acute coronary syndrome (ACS) by comparing them with those of drug-eluting stents (DESs).A total of 309 consecutive lesions in patients with ACS who were successfully treated by emergent procedures using either a DCB (n = 107) or a DES between January 2016 and December 2019 were included in the study. The primary endpoint was the incidence of target lesion failure (TLF), defined as cardiac death without mortality due to ACS, non-fatal myocardial infarction, and any target lesion revascularization, including acute occlusion, after DCB use and definite stent thrombosis after DES placement. A propensity score-matched analysis was used to adjust the 36 baseline variables. Retrospective investigations were conducted in January 2021.Baseline adjustment yielded 91 lesions in each group, with a mean balloon size of 3.02 ± 0.22 mm and a mean length of 20.9 ± 6.2 mm in the DCB group. The frequency of TLF in the DCB group (9.9% during the mean observational interval of 671 ± 508 days) was not significantly different from that in the DES group (13.2% during a period of 626 ± 543 days, P = 0.467). The cumulative TLF-free ratio in the DCB group was not significantly different from that in the DES group (P = 0.475, log-rank test).The present propensity score-matched comparison showed statistically equivalent midterm clinical outcomes after DCB use to those of DES placement for de novo lesions in patients with ACS treated by emergent procedures.

Comparison of Clopidogrel Monotherapy After 1 to 2 Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome

Clopidogrel monotherapy after short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has not yet been fully investigated in patients with acute coronary syndrome (ACS). To test the hypothesis of noninferiority of 1 to 2 months of DAPT compared with 12 months of DAPT for a composite end point of cardiovascular and bleeding events in patients with ACS. This multicenter, open-label, randomized clinical trial enrolled 4169 patients with ACS who underwent successful PCI using cobalt-chromium everolimus-eluting stents at 96 centers in Japan from December 2015 through June 2020. These data were analyzed from June to July 2021. Patients were randomized either to 1 to 2 months of DAPT followed by clopidogrel monotherapy (n = 2078) or to 12 months of DAPT with aspirin and clopidogrel (n = 2091). The primary end point was a composite of cardiovascular (cardiovascular death, myocardial infarction [MI], any stroke, or definite stent thrombosis) or bleeding (Thrombolysis in MI major or minor bleeding) events at 12 months, with a noninferiority margin of 50% on the hazard ratio (HR) scale. The major secondary end points were cardiovascular and bleeding components of the primary end point. Among 4169 randomized patients, 33 withdrew consent. Of the 4136 included patients, the mean (SD) age was 66.8 (11.9) years, and 856 (21%) were women, 2324 (56%) had ST-segment elevation MI, and 826 (20%) had non-ST-segment elevation MI. A total of 4107 patients (99.3%) completed the 1-year follow-up in June 2021. One to 2 months of DAPT was not noninferior to 12 months of DAPT for the primary end point, which occurred in 65 of 2058 patients (3.2%) in the 1- to 2-month DAPT group and in 58 of 2057 patients (2.8%) in the 12-month DAPT group (absolute difference, 0.37% [95% CI, -0.68% to 1.42%]; HR, 1.14 [95% CI, 0.80-1.62]; P for noninferiority = .06). The major secondary cardiovascular end point occurred in 56 patients (2.8%) in the 1- to 2-month DAPT group and in 38 patients (1.9%) in the 12-month DAPT group (absolute difference, 0.90% [95% CI, -0.02% to 1.82%]; HR, 1.50 [95% CI, 0.99-2.26]). The major secondary bleeding end point occurred in 11 patients (0.5%) in the 1- to 2-month DAPT group and 24 patients (1.2%) in the 12-month DAPT group (absolute difference, -0.63% [95% CI, -1.20% to -0.06%]; HR, 0.46 [95% CI, 0.23-0.94]). In patients with ACS with successful PCI, clopidogrel monotherapy after 1 to 2 months of DAPT failed to attest noninferiority to standard 12 months of DAPT for the net clinical benefit with a numerical increase in cardiovascular events despite reduction in bleeding events. The directionally different efficacy and safety outcomes indicate the need for further clinical trials. ClinicalTrials.gov Identifiers: NCT02619760 and NCT03462498.

Maintained P2Y12 inhibitor monotherapy after shorter-duration of dual antiplatelet therapy in patients undergoing coronary drug-eluting stents implantation: An updated meta-analysis of randomized trials.

It is well known that high in-stent thrombotic risk due to the superimposition of a platelet-rich thrombus was considered as the main origin of major adverse cardiac events after stent implantation. The clinical management of antiplatelet therapy strategy after percutaneous coronary intervention (PCI) remains controversial. This study is sought to explore the efficacy and safety of a maintained P2Y12 inhibitor monotherapy after shorter-duration of dual antiplatelet therapy (DAPT) in these patients. Medline, Google Scholar, Web of Science, and the Cochrane Controlled Trials Registry were searched online for retrieving eligible citations. A composite of all-cause death, myocardial infarction (MI) and stroke was defined as major adverse cardio- and cerebro-vascular events (MACCE), which is analysed as the primary efficacy endpoint. The risk of bleeding events was chosen as safety endpoint. Five randomized clinical trials (RCT) with 32,143 patients were finally analysed. A maintained P2Y12 inhibitor monotherapy after shorter-duration of DAPT cloud not only reduce the incidence of MACCE [odds ratios (OR): 0.89, 95% confidence intervals (CI): 0.79-0.99, p=0.037], but also the bleeding risk (OR 0.61, 95% CI: 0.44-0.85, p=0.003). No higher incidence of any ischaemic events, including MI, stroke or definite stent thrombosis (ST) was observed with respect to this new antiplatelet therapy option. A maintained P2Y12 inhibitor monotherapy after shorter-duration of DAPT was suggested as a more preferable antiplatelet therapy option in patients undergoing coronary drug-eluting stents (DES) placement. Larger and more powerful randomized trials with precise sub-analyses are still necessary for further confirming these relevant benefits.

Aspirin vs. Clopidogrel as a Chronic maintenance monotherapy after PCI in patients with high ischemic risk and high bleeding risk: Subgroup analysis of the HOST-EXAM trial

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf on behalf of the HOST-EXAM investigators Background The HOST-EXAM randomized clinical trial recently performed a comparison of clopidogrel monotherapy vs. aspirin monotherapy in patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention (PCI). This study randomized 5,438 patients who maintained dual antiplatelet therapy without clinical events for 6–18 months after PCI with drug-eluting stents (DES) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. During the 24-month follow-up, the primary outcome (a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater) rate was significantly lower in the clopidogrel group (hazard ratio [HR] 0.73 [95% CI 0.59–0.90]; p = 0.0035). However, it is uncertain whether the beneficial effect of clopidogrel will be consistent in patients with high ischemic risk or those with high bleeding risk. Methods This is a post-hoc analysis of the HOST-EXAM trial. A high ischemic risk was defined as those who had at least 1 of the following procedural features: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI, total stent length &amp;gt;60 mm, or left main PCI. Patients with high bleeding risk were defined according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. The co-primary outcome were thrombotic endpoints (a composite of cardiac death, non-fatal myocardial infarction, ischemic stroke, readmission due to acute coronary syndrome, and definite or probable stent thrombosis) and bleeding endpoints (BARC type ≥2 bleeding events) at 24-month follow-up. Results Among the total population, 22.1% had high ischemic risk and 21.4% had high bleeding risk. Complex PCI was not associated with a higher risk of thrombotic endpoints, nor bleeding endpoints. For patients with a high bleeding risk, these patients had a higher risk of both thrombotic endpoints (HR 1.545, 95% CI 0.141-2.092, p = 0.005) and bleeding endpoints (HR 3.418, 95% CI 2.413-4.840, p &amp;lt; 0.001). The primary results focusing on the interaction between high ischemic risk, high bleeding and the antiplatelet regimen will be presented. Conclusion The current post-hoc analysis of the HOST-EXAM trial will evaluate the efficacy of clopidogrel monotherapy vs. aspirin monotherapy during the chronic maintenance period after PCI, in patients with high ischemic risk or those with high bleeding risk.

One-Month Dual Antiplatelet Therapy After Bioresorbable Polymer Everolimus-Eluting Stents in High Bleeding Risk Patients.

BackgroundIt is unknown whether contemporary drug‐eluting stents have a similar safety profile in high bleeding risk patients treated with 1‐month dual antiplatelet therapy following percutaneous coronary interventions.Methods and ResultsWe performed an interventional, prospective, multicenter, single‐arm trial, powered for noninferiority with respect to an objective performance criterion to evaluate the safety of percutaneous coronary interventions with Synergy bioresorbable‐polymer everolimus‐eluting stent followed by 1‐month dual antiplatelet therapy in patients with high bleeding risk. In case of need for an oral anticoagulant, patients received an oral anticoagulant in addition to a P2Y12 inhibitor for 1 month, followed by an oral anticoagulant only. The primary end point was the composite of cardiac death, myocardial infarction, or definite or probable stent thrombosis at 1‐year follow‐up. The study was prematurely interrupted because of slow recruitment. From April 2017 to October 2019, 443 patients (age, 74.8±9.2 years; women, 29.1%) at 10 Italian centers were included. The 1‐year primary outcome occurred in 4.82% (95% CI, 3.17%–7.31%) of patients, meeting the noninferiority compared with the predefined objective performance criterion of 9.4% and the noninferiority margin of 3.85% (Pnoninferiority <0.001) notwithstanding the lower‐than‐expected sample size. The rates of cardiac death, myocardial infarction, and definite or probable stent thrombosis were 1.88% (95% CI, 0.36%–2.50%), 3.42% (95% CI, 2.08%–5.62%), and 0.94% (95% CI, 0.35%–2.49%), respectively.ConclusionsAmong high bleeding risk patients undergoing percutaneous coronary interventions with the Synergy bioresorbable‐polymer everolimus‐eluting stent, a 1‐month dual antiplatelet therapy regimen is safe, with low rates of ischemic and bleeding events.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03112707.

Impact of diabetes on 1-year clinical outcome in patients undergoing revascularization with the BioFreedom stents or the Orsiro stents from the SORT OUT IX trial.

This sub-study of the SORT OUT IX trial sought to compare clinical outcomes between patients with diabetes randomized to implantation of either the polymer-free biolimus A9-coated BioFreedom stent (BF-BES) or the ultra-thin strut, biodegradable polymer sirolimus-eluting Orsiro stent (O-SES). Patients with diabetes have an increased risk of target lesion failure (TLF) after percutaneous coronary intervention (PCI). The impact of different stent types in patients with diabetes is still discussed. A total of 607 of the 3151 patients (19.3%) enrolled in the SORT OUT IX study had diabetes. Randomization was stratified by patients with/without diabetes; 304 received BF-BES and 303 O-SES. The primary endpoint was TLF, which was a composite of cardiac death, myocardial infarction (not related to other than the index lesion) and target lesion revascularization (TLR) within 1 year. After 1 year, patients with diabetes had higher TLF (7.2% vs. 3.7%, incidence rate ratio [IRR]: 1.65; 95% confidence interval [CI]: 1.08-2.50), than patients without diabetes. TLF did not differ significantly between BF-BES and O-SES in patients with diabetes (8.2% vs. 6.3%, IRR: 1.17; 95% CI: 0.63-2.20). In patients with diabetes, cardiac death occurred in 2.3% of BF-BES and in 3.6% of O-SES (IRR: 0.58; 95% CI: 0.23-1.45) and TLR occurred in 5.3% and 2.3% of BF-BES and O-SES, respectively (IRR: 2.12; 95% CI: 0.81-5.56). Definite stent thrombosis rates of 1.3% were found in both stent types. Patients with diabetes had higher 1-year TLF rate after PCI compared to patients without diabetes, whereas TLF did not differ significantly between the two stent types BF-BES and O-SES in patients with diabetes.

Comparison of biodegradable and newer generation durable polymer drug-eluting stents with short-term dual antiplatelet therapy: a systematic review and Bayesian network meta-analysis of randomized trials comprising of 43,875 patients.

Newer generation durable polymer drug-eluting stents (DP-DES) and biodegradable polymer DES (BP-DES) have similar efficacy with dual-antiplatelet therapy (DAPT) duration of > 6months. However, this difference in outcomes have not been well studied in shorter DAPT regime. This study compares the safety and efficacy profiles of DP-DES and BP-DES based on short-term (1-3months), intermediate-term (4-6months) and standard DAPT (6-12months) durations. A search was conducted on Embase and Medline for Randomized Controlled Trials (RCTs) comparing stent types, and DAPT durations. Primary endpoints include cardiac death, myocardial infarction (MI), definite stent thrombosis, stroke, target vessel revascularization (TVR) and major bleeding. Network analysis was conducted to summarize the evidence. A total of 15 RCTs involving 43,875 patients were included. DP-DES was associated with significantly lower major bleeding rates compared to BP-DES (RR 0.44, Crl 0.22-0.83) in short-term DAPT. Among DP-DES patients, short-term DAPT was associated with lower major bleeding risk compared to standard DAPT (RR 0.47, CrI 0.32-0.69). This favorable bleeding profile with short DAPT was not found in BP-DES patients. Cardiacdeath, MI, definite stent thrombosis, stroke and TVR rateswere similar across the various DAPT durations and stent types. Our preliminary findings demonstrated comparable efficacy and safety outcomes between BP-DES and newer generation BP-DES across various DAPT durations. In patients requiring short DAPT, DP-DES had more favourable major bleeding profile compared to BP-DES, without compromising anti-thrombotic efficacy.

Two-year outcomes between ST-elevation and non-ST-elevation myocardial infarction in patients with chronic kidney disease undergoing newer-generation drug-eluting stent implantation.

We evaluated the 2-year clinical outcomes of ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) in patients with chronic kidney disease (CKD) who received newer-generation drug-eluting stents (DES). Overall, 18,875 acute myocardial infarction patients were divided into two groups: CKD (STEMI, n = 1707; NSTEMI, n = 1648) and non-CKD (STEMI, n = 8660; NSTEMI, n = 6860). The occurrence of major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (re-MI), any repeat coronary revascularization, and definite or probable stent thrombosis (ST), was evaluated. After multivariable-adjusted analysis, in the CKD group, the MACE (adjusted hazard ratio [aHR]: 1.365, p = 0.004), all-cause death (aHR: 1.503, p = 0.004), noncardiac death (non-CD; aHR: 1.960, p = 0.004), and all-cause death or MI rates (aHR: 1.458, p = 0.002) were significantly higher in the NSTEMI group than in the STEMI group. In the non-CKD group, the non-CD rate (aHR: 1.78, p = 0.006) was also higher in the NSTEMI group. The CD, re-MI, any repeat revascularization, and ST rates were similar between groups. In the CKD group, from 6 months to 2 years after the index procedure, all-cause death, non-CD, and all-cause death or MI rates were significantly higher in the NSTEMI group than in the STEMI group. These results may be related to the higher non-CD rate in the NSTEMI group. In the era of contemporary newer-generation DES, NSTEMI showed a relatively higher non-CD rate than STEMI in both CKD and non-CKD groups.

Ischemic Events Occur Early in Patients Undergoing Percutaneous Coronary Intervention and Are Reduced With Cangrelor: Findings From CHAMPION PHOENIX.

Thrombotic events are reduced with cangrelor, an intravenous P2Y12 inhibitor. We sought to characterize the timing, number, and type of early events (within 2 hours of randomization) in CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention). CHAMPION PHOENIX was a double-blind, placebo-controlled trial that randomized patients undergoing percutaneous coronary intervention to cangrelor or clopidogrel. For this analysis, we evaluated the efficacy of cangrelor in the first 2 hours postrandomization with regards to the primary end point (death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis). Sensitivity analyses were performed evaluating a secondary, post hoc end point (death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis). The majority of events (63%) that occurred in the trial occurred within 2 hours of randomization. The most common early event was myocardial infarction; next were stent thrombosis, ischemia driven revascularization, and death. In the first 2 hours after randomization, cangrelor significantly decreased the primary composite end point compared with clopidogrel (4.1% versus 5.4%; hazard ratio, 0.76 [95% CI, 0.64-0.90], P=0.002). Similar findings were seen for the composite end point of death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium stent thrombosis at 2 hours (0.9% versus 1.6%; hazard ratio, 0.57 [95% CI, 0.40-0.80], P=0.001). Between 2 and 48 hours, there was no difference in the primary composite end point (0.6% versus 0.5%; odds ratio, 1.17 [95% CI, 0.71-1.93]; P=0.53). Early (≤2 hours of randomization) GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events were infrequent, and there was no significant difference with cangrelor compared with clopidogrel (0.2% [n=10] versus 0.1% [n=4]; adjusted odds ratio, 1.41 [95% CI, 0.37-5.40]; P=0.62). The reductions in ischemic events and overall efficacy seen with cangrelor in CHAMPION PHOENIX occurred early and during the period of time in which patients were being actively treated with cangrelor. These findings provide evidence that supports the importance of potent platelet inhibition during percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01156571.

Amphilimus- vs. zotarolimus-eluting stents in patients with diabetes mellitus and coronary artery disease: the SUGAR trial.

AimPatients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes.Methods and resultsWe did an investigator-initiated, randomized, controlled, assessor-blinded trial at 23 sites in Spain. Eligible patients had diabetes and required percutaneous coronary intervention. A total of 1175 patients were randomly assigned (1:1) to receive Cre8 EVO or Resolute Onyx stents. The primary endpoint was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization at 1-year follow-up. The trial had a non-inferiority design with a 4% margin for the primary endpoint. A superiority analysis was planned if non-inferiority was confirmed. There were 106 primary events, 42 (7.2%) in the Cre8 EVO group and 64 (10.9%) in the Resolute Onyx group [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.44–0.96; Pnon-inferiority < 0.001; Psuperiority = 0.030]. Among the secondary endpoints, Cre8 EVO stents had significantly lower rate than Resolute Onyx stents of target-vessel failure (7.5% vs. 11.1%, HR: 0.67, 95% CI: 0.46–0.99; P = 0.042). Probable or definite stent thrombosis and all-cause death were not significantly different between groups.ConclusionIn patients with diabetes, Cre8 EVO stents were non-inferior to Resolute Onyx stents with regard to target-lesion failure composite outcome. An exploratory analysis for superiority at 1 year suggests that the Cre8 EVO stents might be superior to Resolute Onyx stents with regard to the same outcome.Clinical trial registrationClinicalTrials.gov: NCT03321032.

752 Acute coronary syndrome in young patients: long-term follow-up and quality of life assessment

Abstract Aims Early onset acute coronary syndrome (ACS) is associated with a more aggressive evolution and its consequences can be devastating to the quality of life (QOL), affecting the patient’s psychology, ability to work, and the socioeconomic burden. In the last decade, the incidence of ACS in young patients (≤45 years old) is increased but unfortunately, little is known about long-term follow-up and impact on quality of life. The aim of this study was to analyse the clinical evolutions and the QOL in this specific group of patients. Methods and results We included 91 consecutive young patients (≤45 years at the time of presentation) with ACS referred from October 2013 until March 2021 to our clinic. All enrolled patients underwent angiography. We analysed the clinical presentation, echocardiography, and therapy at the time of discharge. Furthermore, patients underwent telephone follow-up after 40 months: new hospitalizations, cardiovascular events, bleeding, and relevant changes in medical therapy were investigated. In addition, patients were also invited to participate to a survey to investigate QOL, sexual, and socioeconomic changes after ACS. QOL was explored through the EQ-5D scale using the time trade-off (TTO) and visual analogue scale (VAS) technique based on European values. Mean age was 40.6 ± 3.6 years and 17.6% were women. Most patients had obstructive coronary artery disease at angiography (90.1%) and 85.7% underwent PCI. At a median follow-up of 40 months, major adverse cardiovascular events (MACE) a composite of death, myocardial infarction, stroke and definite stent thrombosis, occurred in 12% of patients (Figure 1). Patient reported bleeding occurred in 29.8%, while bleeding requiring hospitalization in 3.6%. Univariate predictors of MACE were previous stroke, Killip class at presentation, current drug use, left ventricle ejection fraction, wall motion score index (WMSI), and haemoglobin at admission. Young patients showed reduced levels of QOL (TTO: 0.85 ± 0.17—VAD: 0.79 ± 0.17), with higher levels among individuals without obstructive coronary artery disease (Figure 2). Predictors of lower quality of life were WMSI, left anterior descending (LAD) stenting, left ventricular aneurysm and ventricular thrombus (Figure 3). After 12 months from the index event, 31.5% of patients were still on dual antiplatelet therapy, and the mean number of medications was 4.65 ± 2.3. Conclusions In conclusion, young patients have a high residual risk of ischaemic and bleeding events and impaired QOL. Optimization of medical therapy and better patient information is of upmost importance to mitigate residual risk of adverse events.

Instantaneous wave-free ratio for guiding treatment of nonculprit lesions in patients with acute coronary syndrome: A retrospective study.

The aim of this study was to analyze the feasibility of a physiological coronary evaluation with the instantaneous wave-free ratio (iFR) of nonculprit lesions in patients with acute coronary syndrome (ACS) successfully revascularized. A multicenter registry including patients of four high-volume PCI centers with ACS and underwent successful revascularization of the culprit vessel and had other nonculprit lesions that were physiologically evaluated with the iFR between January 2017 and December 2019. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction, probable or definitive stent thrombosis and new revascularization (MACEs). A total of 356 patients with 472 nonculprit lesions were included. The mean age was 66 ± 11 years. The clinical presentation was ACS without persistent ST-segment elevation (NSTE-ACS) in 235 patients (66%) and ST-segment elevation myocardial infarction (STEMI) in 121 patients (34%). After a median follow-up period of 21 (14-30) months, the primary endpoint occurred in 32 patients (9%). There were no differences in outcomes regarding clinical presentation (NSTEMI vs. NSTE-ACS, 9.1 vs. 8.9%, padj =0.570) or iFR induced treatment strategy (patients with all lesions revascularized vs. patients with at least one lesion with an iFR > 0.89 deferred for revascularization, 10.5 vs. 8.4%, padj =0.476). The use of the iFR to guide percutaneous coronary intervention decision making in nonculprit lesions seems to be feasible, with an acceptable percentage of MACEs at the mid-term follow-up. Patients with deferred revascularization of lesions without physiological significance and patients undergoing complete revascularization had a similar risk of MACEs.

Stenting techniques for coronary bifurcation disease: a systematic review and network meta-analysis demonstrates superiority of double-kissing crush in complex lesions

ObjectiveThis study was aimed to compare different stenting techniques for coronary bifurcation disease (CBD).BackgroundPercutaneous coronary intervention (PCI) remains controversial for CBD; over the years, several stent techniques for bifurcation lesions have been used. Current guidelines recommend a provisional single-stent strategy as the preferred method for coronary artery bifurcation lesions. However, several randomized controlled trials (RCT) indicated that two-stent techniques showed better clinical outcomes.MethodsWe systematically searched Embase, PubMed, and Web of Science to include RCTs. The primary endpoint was the major adverse cardiovascular event (MACE). Secondary outcomes were cardiac death, myocardial infarction (MI), target-lesion or target-vessel revascularization (TLR or TVR), and definite or probable stent thrombosis (ST). Finally, we used 26 RCTs and a total of 7257 individuals were randomly assigned to one of the 6 stent techniques and included in this network meta-analysis.ResultsIn our network meta-analysis, double-kissing (DK) crush was significantly more superior to other 5 stent techniques in MACEs: OR vs. provisional 0.40 (95% CI 0.28–0.55); vs. culotte 0.40 (95% CI 0.26–0.60). DK crush ranked the most effective treatment for MACE (100%), MI (75%), ST (83%), and TLR (100%) in the rank probabilities analysis. In patients with complex bifurcation lesion defined by DEFINITION criteria, DK crush was notably more efficacious than provisional, culotte, and T-stenting/T-stenting and protrusion (TAP) in MACEs (OR vs. provisional 0.26, 95% CI 0.13–0.52) and TLR (OR vs. provisional 0.24, 95% CI 0.10–0.58).ConclusionCompared with other stenting techniques, DK crush had a lower incidence of MACEs in CBD. DK crush was significantly associated with a lower rate of MACEs in patients with complex bifurcation lesions defined by the DEFINITION criterion.Graphical abstract

Stent-Related Adverse Events as Related to Dual Antiplatelet Therapy in First- vs Second-Generation Drug-Eluting Stents.

There are limited data on the long-term stent-related adverse events as related to the duration of dual antiplatelet therapy (DAPT) in second-generation (G2) drug-eluting stents (DES) compared with first-generation (G1) DES. This study sought to compare the long-term stent-related outcomes of G2-DES with those of G1-DES. The study group consisted of 15,009 patients who underwent their first coronary revascularization with DES from the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) Registry Cohort-2 (first-generation drug-eluting stent [G1-DES] period; n=5,382) and Cohort-3 (second-generation drug eluting stent [G2-DES] period; n=9,627). The primary outcome measures were definite stent thrombosis (ST) and target vessel revascularization (TVR). The cumulative 5-year incidences of definite ST and TVR were significantly lower in the G2-DES group than in the G1-DES group (0.7% vs 1.4%; P< 0.001; and 16.2% vs 22.1%; P< 0.001, respectively). The lower adjusted risk of G2-DES relative to G1-DES for definite ST and TVR remained significant (HR: 0.53; 95%CI: 0.37-0.76; P< 0.001; and HR: 0.74; 95%CI: 0.68-0.81; P< 0.001, respectively). In the landmark analysis that was based on the DAPT status at 1 year, the lower adjusted risk of on-DAPT status relative to off-DAPT was significant for definite ST beyond 1 year in the G1-DES stratum (HR: 0.42; 95%CI: 0.24-0.76; P=0.004) but not in the G2-DES stratum (HR: 0.66; 95%CI: 0.26-1.68; P=0.38) (P interaction=0.14). G2-DES compared with G1-DES were associated with a significantly lower risk for stent-related adverse events, including definite ST and TVR. DAPT beyond 1 year was associated with a significantly lower risk for very late ST ofG1-DES but not for that of G2-DES.

Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction.

Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y12-inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry). In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days. Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y12-inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78-1.17], P=0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70-1.45], P=0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45-1.28], P=0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81-1.33], P=0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18-0.96], P=0.04). In patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y12-inhibitors rate of the composite of all-cause death, MI, or major bleeding was not lower in those randomized to receive bivalirudin as compared with heparin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.

One-year outcomes of novel BioMime Morph tapered stent in long and multiple coronary artery lesions.

Even with the immense progress achieved in the field of percutaneous coronary interventions (PCIs), treatment of diffuse long atherosclerotic coronary artery disease continues to remain a challenge for durable outcomes. The downstream reduction in diameter along the lesion length of a coronary artery may compel the cardiologist to use either 2 overlapping stents of different diameters or a single long stent leading to stent-vessel mismatch at the edges. Recently, Meril Life Sciences Pvt. Ltd., India, has introduced a long-tapered sirolimus-eluting stent (SES) system, BioMime Morph, which conforms to the normal tapered geometry of coronary arteries along with adequate lesion coverage. In this study, we aimed to provide real world experience regarding the safety and efficacy of the BioMime Morph SES over a follow-up of one year. This was a single center, retrospective study involving 172 participants who underwent PCI with the BioMime Morph SES. Mean length of the target lesion was 34.4±10.4 mm, and mean stent length was 53.2±8.7 mm. The most frequent revascularized vessel was the left anterior descending artery (LAD) in 97 lesions (54.4%). Major adverse cardiac events (MACE) (defined as a composite of target vessel myocardial infarction, target lesion revascularization, and death due to a cardiac cause) at 1, 6, and 12 months were seen in 4 (2.3%), 7 (4.0%), and 8 (4.7%) patients, respectively. Overall, 5 cardiac deaths and 2 definite stent thrombosis were observed in the study. The study suggests that the novel BioMime Morph SES is an effective and a safe option for PCI in the treatment of long diffuse atherosclerotic lesions.