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)

Pharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens.

Tirofiban is a glycoproteine (GP) IIb/IIIa receptor antagonist, which inhibits platelet-platelet aggregation and is a potential adjunctive antithrombotic treatment in patients with acute coronary syndromes (ACS) or high-risk percutaneous coronary interventions (PCI). It is administered intravenously as a bolus followed by continuous infusion. However, the dosage recommendations in the United States (US) and European Union (EU) differ considerably. Furthermore, in routine clinical practice, deviations from the recommendations may occur. The objective of the present study was to investigate the impact of different alterations on tirofiban plasma concentrations in US and EU administration regimens and to give suggestions for delay management in clinical practice. We therefore mathematically simulated the effects of different bolus-infusion delays and infusion interruptions in different scenarios according to the renal function. Here, we provide a systematic assessment of concentration patterns of tirofiban in the US versus EU dosage regimens. We show that differences between the two regimens have important effects on plasma drug levels. Furthermore, we demonstrate that deviations from the proper administration mode affect the concentration of tirofiban. Additionally, we calculated the optimal dosage of a second bolus to rapidly restore the initial concentration without causing overdosage. In conclusion, differences in tirofiban dosing regimens between the U.S and EU and potential infusion interruptions have important effects on drug levels that may impact on degrees of platelet inhibition and thus antithrombotic effects. Thus, the findings of our modelling studies may help to explain differences in clinical outcomes observed in previous clinical trials on tirofiban

Self-reported non-adherence to P2Y12 inhibitors in patients undergoing percutaneous coronary intervention: Application of the medication non-adherence academic research consortium classification.

AIMS The Non-adherence Academic Research Consortium (NARC) has recently developed a consensus-based standardized classification for medication non-adherence in cardiovascular clinical trials. We aimed to assess the prevalence of NARC-defined self-reported non-adherence to P2Y12 inhibitors and its impact on clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS Using a standardized questionnaire administered at 1 year after PCI, we assessed the 4 NARC-defined non-adherence levels including type, decision-maker, reasons, and timing within the Bern PCI registry. The primary endpoint was the patient-oriented composite endpoint (POCE) defined as a composite of death, myocardial infarction, stroke, and any revascularization at 1 year. The recommended P2Y12 inhibitor duration was 12 months. Among 3,896 patients, P2Y12 inhibitor non-adherence was observed in 647 (17%) patients. Discontinuation was permanent in the majority of patients (84%). The decision was mainly driven by a physician (94%), and rarely by patients (6%). The most frequent reason was risk profile change (43%), followed by unlisted reasons (25%), surgery (17%), and adverse events (14%). Non-adherence occurred early (180 days) in 33%. The majority of POCE events (n = 421/502, 84%) occurred during adherence to the prescribed P2Y12 inhibitor. Permanent discontinuation, doctor-driven non-adherence, and risk profile change emerged as independent predictors for POCE. CONCLUSIONS In real-world PCI population treated with 1-year DAPT, non-adherence was observed in nearly one-fifth of patients. Non-adherence to P2Y12 inhibitors was associated with worse clinical outcomes, while the risk was related to underlying contexts. CLINICALTRIALS.GOV IDENTIFIER NCT02241291

Reproducibility of intravascular ultrasound radiofrequency data analysis: Implications for the design of longitudinal studies

Objectives: The purpose of this study was to assess in vivo the reproducibility of tissue characterization using spectral analysis of intravascular ultrasound (IVUS) radiofrequency data (IVUS-VH). Background: Despite the need for reproducibility data to design longitudinal studies, such information remains unexplored. Methods and results: IVUS-VH (Volcano Corp., Rancho Cordova, USA) was performed in patients referred for elective percutaneous intervention and in whom a non-intervened vessel was judged suitable for a safe IVUS interrogation. The IVUS catheters used were commercially available catheters (20 MHz, Volcano Corp., Rancho Cordova, USA). Following IVUS-VH acquisition, and after the disengagement and re-engagement of the guiding catheter, an additional acquisition was performed using a new IVUS catheter. Fifteen patients with 16 non-significant lesions were assessed by 2 independent observers. The relative inter-catheter differences regarding geometrical measurements were negligible for both observers. The inter-catheter relative difference in plaque cross-sectional area (CSA) was 3.2% for observer 1 and 0.5% for observer 2. The limits of agreement for (observer 1 measurements) lumen, vessel, plaque and plaque burden measurements were 0.82, -1.10 mm 2;0.80, -0.66 mm2;1.08, -0.66 mm2; and 5.83, -3.89%; respectively. Limits of agreement for calcium, fibrous, fibrolipidic and necrotic core CSA measurements were 0.22, -0.25 mm2;1.02, -0.71 mm2;0.61, -0.65 mm2; and 0.43, -0.38 mm2 respectively. Regarding the inter-observer agreement, the limits of agreement for lumen, vessel, plaque and plaque burden measurements were 2.61, -2.09 mm2;2.20-3.03 mm2;1.70, -3.04 mm2; and 9.16, -16.41%; respectively, and for calcium, fibrous, fibrolipidic and necrotic core measurements of 0.08, -0.09 mm2;0.89, -1.28 mm2;0.74, -1.06 mm2; and 0.16, -0.20 mm2; respectively. Conclusions: The present study demonstrates that the geometrical and compositional output of IVUS-VH is acceptably reproducible

Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: Patient level meta-analysis

Objectives: To examine the safety and effectiveness of cobalt-chromium everolimus eluting stents compared with bare metal stents.Design: Individual patient data meta-analysis of randomised controlled trials. Cox proportional regression models stratified by trial, containing random effects, were used to assess the impact of stent type on outcomes. Hazard ratios with 95% confidence interval for outcomes were reported.Data sources and study selection: Medline, Embase, the Cochrane Central Register of Controlled Trials. Randomised controlled trials that compared cobalt-chromium everolimus eluting stents with bare metal stents were selected. The principal investigators whose trials met the inclusion criteria provided data for individual patients.Primary outcomes: The primary outcome was cardiac mortality. Secondary endpoints were myocardial infarction, definite stent thrombosis, definite or probable stent thrombosis, target vessel revascularisation, and all cause death.Results: The search yielded five randomised controlled trials, comprising 4896 participants. Compared with patients receiving bare metal stents, participants receiving cobalt-chromium everolimus eluting stents had a significant reduction of cardiac mortality (hazard ratio 0.67, 95% confidence interval 0.49 to 0.91; P=0.01), myocardial infarction (0.71, 0.55 to 0.92; P=0.01), definite stent thrombosis (0.41, 0.22 to 0.76; P=0.005), definite or probable stent thrombosis (0.48, 0.31 to 0.73; P<0.001), and target vessel revascularisation (0.29, 0.20 to 0.41; P<0.001) at a median follow-up of 720 days. There was no significant difference in all cause death between groups (0.83, 0.65 to 1.06; P=0.14). Findings remained unchanged at multivariable regression after adjustment for the acuity of clinical syndrome (for instance, acute coronary syndrome v stable coro

Randomized comparison of operator radiation exposure comparing transradial and transfemoral approach for percutaneous coronary procedures: Rationale and design of the minimizing adverse haemorrhagic events by TRansradial access site and systemic implementation of angioX - RAdiation Dose study (RAD-MATRIX)

Background: Radiation absorbed by interventional cardiologists is a frequently under-evaluated important issue. Aim is to compare radiation dose absorbed by interventional cardiologists during percutaneous coronary procedures for acute coronary syndromes comparing transradial and transfemoral access. Methods: The randomized multicentre MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial has been designed to compare the clinical outcome of patients with acute coronary syndromes treated invasively according to the access site (transfemoral vs. transradial) and to the anticoagulant therapy (bivalirudin vs. heparin). Selected experienced interventional cardiologists involved in this study have been equipped with dedicated thermoluminescent dosimeters to evaluate the radiation dose absorbed during transfemoral or right transradial or left transradial access. For each access we evaluate the radiation dose absorbed at wrist, at thorax and at eye level. Consequently the operator is equipped with three sets (transfemoral, right transradial or left transradial access) of three different dosimeters (wrist, thorax and eye dosimet

Reducing Microvascular Dysfunction in Revascularized Patients with ST-Elevation Myocardial Infarction by Off-Target Properties of Ticagrelor versus Prasugrel. Rationale and Design of the REDUCE-MVI Study

Microvascular injury is present in a large proportion of patients with ST-elevation myocardial infarction (STEMI) despite successful revascularization. Ticagrelor potentially mitigates this process by exerting additional adenosine-mediated effects. This study aims to determine whether ticagrelor is associated with a better microvascular function compared to prasugrel as maintenance therapy after STEMI. A total of 110 patients presenting with STEMI and additional intermediate stenosis in another coronary artery will be studied after successful percutaneous coronary intervention (PCI) of the infarct-related artery. Patients will be randomized to treatment with ticagrelor or prasugrel for 1 year. FFR-guided PCI of the non-infarct-related artery will be performed at 1 month. Microvascular function will be assessed by measurement of the index of microcirculatory resistance (IMR) in the infarct-related artery and non-infarct-related artery, immediately after primary PCI and after 1 month. The REDUCE-MVI study will establish whether ticagrelor as a maintenance therapy may improve microvascular function in patients after revascularized STEMI

Prognostic implications of coronary calcification in patients with obstructive coronary artery disease treated by percutaneous coronary intervention: A patient-level pooled analysis of 7 contemporary stent trials

Objective To investigate the long- Term prognostic implications of coronary calcification in patients undergoing percutaneous coronary intervention for obstructive coronary artery disease. Methods Patient-level data from 6296 patients enrolled in seven clinical drug-eluting stents trials were analysed to identify in angiographic images the presence of severe coronary calcification by an independent academic research organisation (Cardialysis, Rotterdam, The Netherlands). Clinical outcomes at 3-years follow-up including all-cause mortality, death-myocardial infarction (MI), and the composite end-point of all-cause death-MI- Any revascularisation were compared between patients with and without severe calcification. Results Severe calcification was detected in 20% of the studied population. Patients with severe lesion calcification were less likely to have undergone complete revascularisation (48% vs 55.6%, p<0.001) and had an increased mortality compared with those without severely calcified arteries (10.8% vs 4.4%, p<0.001). The event rate was also high in patients with severely calcified lesions for the combined end-point death-MI (22.9% vs 10.9%; p<0.001) and death-MI- Any revascularisation (31.8% vs 22.4%; p<0.001). On multivariate Cox regression analysis, including the Syntax score, the presence of severe coronary calcification was an independent predictor of poor prognosis (HR: 1.33 95% CI 1.00 to 1.77, p=0.047 for death; 1.23, 95% CI 1.02 to 1.49, p=0.031 for death-MI, and 1.18, 95% CI 1.01 to 1.39, p=0.042 for death-MI- Any revascularisation), but it was not associated with an increased risk of stent thrombosis. Conclusions Patients with severely calcified lesions have worse clinical outcomes compared to those without severe coronary calcification. Severe coronary calcification appears as an independent predictor of worse prognosis, and should be considered as a marker of advanced atherosclerosis

Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: A systematic review and meta-analysis

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/)Aims:The value of elective coronary revascularisation plus medical therapy over medical therapy alone in managing stable patients with coronary artery disease is debated. We reviewed all trials comparing the two strategies in this population. Methods and results:From inception through November 2020, Medline, Embase, Google Scholar and other databases were searched for randomised trials comparing revascularisation to medical therapy alone in clinically stable coronary artery disease patients. Treatment effects were measured by rate ratios (RR) with 95% confidence intervals using random-effects models. Cardiac mortality was the prespecified primary endpoint. Spontaneous myocardial infarction (MI) and its association with cardiac mortality were secondary endpoints. Further endpoints included all-cause mortality, any MI and stroke. Longest follow-up data were abstracted. The study is registered with PROSPERO (CRD42021225598). Twenty-five trials involving 19,806 patients (10,023 randomised to revascularisation plus medical therapy and 9,783 to medical therapy alone) were included. Compared to medical therapy alone, revascularisation was associated with a lower risk of cardiac death (RR 0.79 [0.67-0.93], p<0.01) and spontaneous MI (RR 0.74 [0.64-0.86], p<0.01). By meta-regression, the cardiac death risk reduction after revascularisation, compared to medical therapy alone, was linearly associated with follow-up duration (RR per 4-year follow-up: 0.81 [0.69-0.96], p=0.008) and spontaneous MI absolute difference (p=0.01). Trial sequential and sensitivity analyses confirmed the reliability of the cardiac mortality findings. All cause mortality (0.94 [0.87-1.01], p=0.11), any MI (p=0.14) and stroke risk (p=0.30) did not differ significantly between strategies. Conclusion:In stable coronary artery disease patients, randomisation to elective coronary revascularisation plus medical therapy led to reduced cardiac mortality compared to medical management alone. The cardiac survival benefit after revascularisation improved with longer follow-uptimes and was associated with fewer spontaneous MIs.Peer reviewedFinal Published versio

Sirolimus-Eluting Versus Paclitaxel-Eluting Stent Implantation for the Percutaneous Treatment of Left Main Coronary Artery Disease A Combined RESEARCH and T-SEARCH Long-Term Analysis

ObjectivesThe purpose of this study was to investigate the long-term clinical and angiographic profile of sirolimus-eluting stent (SES) versus paclitaxel-eluting stent (PES) in patients undergoing percutaneous intervention for left main (LM) coronary disease.BackgroundThe long-term clinical and angiographic impact of SES as opposed to PES implantation in this subset of patients is unknown.MethodsFrom April 2002 to March 2004, 110 patients underwent percutaneous intervention for LM stenosis at our institution; 55 patients were treated with SES and 55 with PES. The two groups were well balanced for all baseline characteristics.ResultsAt a median follow-up of 660 days (range 428 to 885), the cumulative incidence of major adverse cardiovascular events was similar (25% in the SES group vs. 29%, in the PES group; hazard ratio 0.88 [95% confidence interval 0.43 to 1.82]; p = 0.74), reflecting similarities in both the composite death/myocardial infarction (16% in the SES group and 18% in the PES group) and target vessel revascularization (9% in the SES group and 11% in the PES group). Angiographic in-stent late loss (mm), evaluated in 73% of the SES group and in 77% of the PES group, was 0.32 ± 74 in the main and 0.36 ± 0.59 in the side branch in the SES group vs. 0.46 ± 0.57 (p = 0.36) and 0.52 ± 0.42 (p = 0.41) in the PES group, respectively.ConclusionsIn consecutive patients undergoing percutaneous LM intervention, PES may perform closely to SES both in terms of angiographic and long-term clinical outcome