Novel directions for the management of dual antiplatelet therapy in patients with coronary artery disease

Dual antiplatelet therapy has been extensively studied in the last two decades, giving opportunities for thorough evidence-based recommendations. The ESC/EACTS guidelines on DAPT in CAD provide guidance for DAPT type and duration, maintaining a patient-centred focus. Patient-specific and dynamic evaluation of the ischaemic and bleeding risks is key for optimal treatment decisions

Letters Regarding Article by Patti et al, "Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) Study"

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High-Risk Percutaneous Intervention in the Drug-Eluting Stent Era

High-risk Intervention in the Drug-eluting stent era The use of drug-eluting stents in high-risk interventions, including those undertaken to treat the left main coronary artery (Chapter 2), multivessel disease (Chapter 14) or on-going ST-segment elevation myocardial infarction (Chapters 11 and 12) appeared overall beneficial in comparison with traditional metallic stents. In particular, the use of drug eluting stents was associated to a remarkable decrease in late loss (Chapter 3) which ultimately resulted in lower need for re- intervention (Chapter 2), while no clear effect on death and myocardial infarction was observed. The safety profile of these new coronary devices appeared overall consistent with what has been reported in the pivotal trials focusing on selected patient/lesion subsets (Chapters 2, 3, 7, 8, 12, 14, 15, 16). The incidence of possible or confirmed acute, sub-acute or late thrombosis was low in this high-risk subset of patients patients undergoing treatment for left main coronary artery disease (Chapters 2, 3, 7, 8, 12, 14, 15, 16) and importantly we could not confirm previous concerns regarding the potential association between intimal hyperplasia and sudden death in patients undergoing treatment for left main coronary artery disease (Chapters 7 and 8)

Safety and efficacy outcomes of double vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical trials.

Abstract Aims To investigate the safety and efficacy of double vs. triple antithrombotic therapy (DAT vs. TAT) in patients with atrial fibrillation (AF) and acute coronary syndrome or who underwent percutaneous coronary intervention (PCI). Methods and results A systematic review and meta-analysis was performed using PubMed to search for non-vitamin K antagonist oral anticoagulant (NOAC)-based randomized clinical trials comparing DAT vs. TAT in AF patients undergoing PCI. Four trials encompassing 10 234 patients (DAT = 5496 vs. TAT = 4738) were included. The primary safety endpoint (ISTH major or clinically relevant non-major bleeding) was significantly lower with DAT compared with TAT [risk ratio (RR) 0.66, 95% confidence interval (CI) 0.56–0.78; P < 0.0001; I2 = 69%], which was consistent across all available bleeding definitions. This benefit was counterbalanced by a significant increase of stent thrombosis (RR 1.59, 95% CI 1.01–2.50; P = 0.04; I2 = 0%) and a trend towards higher risk of myocardial infarction with DAT. There were no significant differences in all-cause and cardiovascular death, stroke and major adverse cardiovascular events. The comparison of NOAC-based DAT vs. vitamin K antagonist (VKA)-TAT yielded consistent results and a significant reduction of intracranial haemorrhage (RR 0.33, 95% CI 0.17–0.65; P = 0.001; I2 = 0%). Conclusion Double antithrombotic therapy, particularly if consisting of a NOAC instead of VKA and a P2Y12 inhibitor, is associated with a reduction of bleeding, including major and intracranial haemorrhages. This benefit is however counterbalanced by a higher risk of cardiac—mainly stent-related—but not cerebrovascular ischaemic occurrences

Abciximab: a reappraisal of its use in coronary care

Platelet reactivity plays a pivotal role in the pathogenesis of ischemic adverse events during and after acute coronary syndromes (ACS), and percutaneous coronary intervention (PCI). Glycoprotein (GP) IIb/IIIa inhibitors are the strongest antiplatelet agents currently available on the market and three different compounds, namely abciximab, tirofiban, and eptifibatide, have been approved for clinical use. Abciximab has been investigated in the clinical field far more extensively than the other GPIIb/IIIa inhibitors. Abciximab is an anti-integrin Fab fragment of a human – mouse chimeric monoclonal antibody with high affinity and a slow dissociation rate from the GP IIb/IIIa platelet receptor. Abciximab, given shortly before the coronary intervention, is superior to placebo in reducing the acute risk of ischemic complications (EPIC, EPISTENT, EPILOG trials); moreover, in the ISAR-REACT 2 study abciximab has been shown to reduce the risk of adverse events in patients with non ST-segment elevation ACS who are undergoing PCI even after optimal pre-treatment with 600 mg of clopidogrel. Finally, abciximab has been also used in abciximab-coated stent, with only bolus administration regimen and for direct intracoronary use with promising results that may extend and/or modify its current use in clinical practice in future

PRECISE-DAPT score for bleeding risk prediction in patients on dual or single antiplatelet regimens: insights from the GLOBAL LEADERS and GLASSY

AIMS The 5-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally-adjudicated bleeding endpoints. METHODS AND RESULTS The PRECISE-DAPT was calculated in 14,928 and 7,134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict BARC 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally-adjudicated in GLOBAL LEADERS and GLASSY, respectively.At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 (95% confidence interval [CI]:0.63-0.71) vs. 0.63 (95% CI:0.59-0.67) in GLOBAL LEADERS (p = 0.27), and 0.67 (95% CI:0.61-0.73) vs. 0.66 (95% CI:0.61-0.72) in GLASSY (p = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified 4-item PRECISE-DAPT. CONCLUSIONS The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically-relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints

Randomized comparison between 3-month Cre8 DES vs. 1-month Vision/Multilink8 BMS neointimal coverage assessed by OCT evaluation: The DEMONSTRATE study

AbstractBackgroundIt has been hypothesized that incomplete endothelialization and delayed vascular healing may trigger stent thrombosis events after drug-eluting stent (DES) implantation. We aimed to demonstrate non-inferiority in terms of neointimal coverage of novel Cre8 DES at 3months, compared to Vision/Multilink8 Bare Metal Stent (BMS) at 1month.MethodsThe ranDomizEd coMparisOn betweeN novel Cre8 DES and BMS to assess neoinTimal coveRAge by OCT Evaluation (DEMONSTRATE) was a multicenter, randomized, parallel group study. Thirty-eight patients undergoing angioplasty of de-novo coronary lesion were randomized to Cre8 (19) or Vision/Multilink8 (19) stent placement at 6 OCT-experienced centers. Primary end-point was the Ratio of Uncovered to Total Stent Struts Per Cross Section (RUTTS) score of <30%, determined by OCT at 3 and 1months for Cre8 and Vision/Multilink8, respectively. Percentage of uncovered/malapposed stent struts, neointimal growth and thickness were the main secondary end-points.ResultsThe primary end-point of RUTTS score <30% occurred in 99.8% (899/901) of Cre8 struts and in 99.6% (1116/1121) of Vision/Multilink8 struts (difference 0.2, CI 95% −0.2 to 0.6, p for noninferiority <0.001). The percentage of uncovered/malapposed struts was comparable (0.36±0.64 vs. 0.12±0.24, p=0.145) in the two study groups, while both neointimal percentage area (8.46±5.29 vs. 19.84±15.93, p<0.001) and thickness (0.07±0.04 vs. 0.16±0.12, p<0.001) were significantly reduced by Cre8 stent.ConclusionsThe Cre8 DES at 3months has comparable strut coverage to Vision/Multilink8 BMS at 1month while preserving a greater efficacy in neo-intima formation reduction. Further studies to assess clinical implication of these Cre8 characteristics are warranted

Multivessel percutaneous coronary intervention with thin-strut biodegradable versus durable polymer drug-eluting stents in ST-segment-elevation myocardial infarction: A subgroup analysis of the BIOSTEMI randomized trial.

BACKGROUND Randomized evidence comparing newer-generation drug-eluting stents for multivessel percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is limited. We sought to investigate clinical outcomes in STEMI patients undergoing multivessel PCI with thin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) versus durable polymer everolimus-eluting stents (DP-EES). METHODS We performed a subgroup analysis of the BIOSTEMI (NCT02579031) randomized trial, which included individual patient data from STEMI patients enrolled into the BIOSCIENCE (NCT02579031) study. STEMI patients randomly allocated to BP-SES or DP-EES were divided into those undergoing multivessel versus culprit lesion-only PCI. The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target-vessel myocardial re-infarction or clinically-indicated target lesion revascularization (TLR), within 24 months. RESULTS Among 1707 STEMI patients, 145 patients underwent multivessel PCI. At 2 years, TLF occurred in 2 patients (2.8%) treated with BP-SES and 13 patients (18.7%) treated with DP-EES (hazard ratio [HR], 0.14; 95% confidence interval (CI), 0.03-0.61; p = 0.009) in the multivessel PCI group, and in 40 (5.3%) and 61 (8.2%) patients treated with BP-SES and DP-EES respectively (HR, 0.64; 95%CI, 0.43-0.96; p = 0.03; p for interaction = 0.050) in the culprit lesion-only PCI group. In the multivessel PCI group, the rates of clinically-indicated TLR (0% vs. 12.4%) and target-vessel myocardial re-infarction (0% vs. 4.6%) at 2 years were lower in patients treated with BP-SES compared with DP-EES. CONCLUSION In a subgroup analysis of the BIOSTEMI trial, BP-SES were associated with lower 2-year TLF rates compared to DP-EES in STEMI patients undergoing multivessel PCI