Imre Ungi

Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial

Importance Reducing levels of low-density lipoprotein cholesterol (LDL-C) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels. Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors produce incremental LDL-C lowering in statin-treated patients; however, the effects of these drugs on coronary atherosclerosis have not been evaluated. Objective To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients. Design, Setting, and Participants The GLAGOV multicenter, double-blind, placebo-controlled, randomized clinical trial (enrollment May 3, 2013, to January 12, 2015) conducted at 197 academic and community hospitals in North America, Europe, South America, Asia, Australia, and South Africa and enrolling 968 patients presenting for coronary angiography. Interventions Participants with angiographic coronary disease were randomized to receive monthly evolocumab (420 mg) (n = 484) or placebo (n = 484) via subcutaneous injection for 76 weeks, in addition to statins. Main Outcomes and Measures The primary efficacy measure was the nominal change in percent atheroma volume (PAV) from baseline to week 78, measured by serial intravascular ultrasonography (IVUS) imaging. Secondary efficacy measures were nominal change in normalized total atheroma volume (TAV) and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated. Results Among the 968 treated patients (mean age, 59.8 years [SD, 9.2]; 269 [27.8%] women; mean LDL-C level, 92.5 mg/dL [SD, 27.2]), 846 had evaluable imaging at follow-up. Compared with placebo, the evolocumab group achieved lower mean, time-weighted LDL-C levels (93.0 vs 36.6 mg/dL; difference, -56.5 mg/dL [95% CI, -59.7 to -53.4]; P < .001). The primary efficacy parameter, PAV, increased 0.05% with placebo and decreased 0.95% with evolocumab (difference, -1.0% [95% CI, -1.8% to -0.64%]; P < .001). The secondary efficacy parameter, normalized TAV, decreased 0.9 mm3 with placebo and 5.8 mm3 with evolocumab (difference, -4.9 mm3 [95% CI, -7.3 to -2.5]; P < .001). Evolocumab induced plaque regression in a greater percentage of patients than placebo (64.3% vs 47.3%; difference, 17.0% [95% CI, 10.4% to 23.6%]; P < .001 for PAV and 61.5% vs 48.9%; difference, 12.5% [95% CI, 5.9% to 19.2%]; P < .001 for TAV). Conclusions and Relevance Among patients with angiographic coronary disease treated with statins, addition of evolocumab, compared with placebo, resulted in a greater decrease in PAV after 76 weeks of treatment. Further studies are needed to assess the effects of PCSK9 inhibition on clinical outcomes. Trial Registration clinicaltrials.gov Identifier: NCT01813422.

Transradial versus transfemoral percutaneous coronary intervention in acute myocardial infarction: Systematic overview and meta-analysis

BACKGROUND Although transradial percutaneous coronary intervention (TRPCI) is widely applied for percutaneous procedures, its safety in the setting of ST-segment elevation (STEMI) is controversial. Our aim was to assess the safety and efficacy of TRPCI versus transfemoral PCI in the context of treating patients suffering acute myocardial infarction with STEMI. METHODS Randomized, case-control, and cohort studies comparing access-related complications were analyzed. Our objective was to determine if radial access reduces major bleeding and thereby reduces death and ischemic events compared to femoral access in this setting. A fixed-effects model was used with random effects for sensitivity analysis. RESULTS Twelve studies involving 3324 patients were identified. Transradial PCI reduced major bleeding compared to transfemoral PCI (P = .0001), and significant reductions were found in the composite of death, myocardial infarction, or stroke (P = .001). Mortality reduction showed a significant toward benefit in the case of TRPCI (2.04% vs 3.06%, OR 0.54 [95% CI 0.33-0.86], P = .01). The fluoroscopic time was longer, and access site crossover was more frequent for TRPCI (P = .001, P < .00001, respectively). CONCLUSIONS Transradial PCI reduces the risk of periprocedural major bleeding and major adverse events in the STEMI setting.

Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): A randomised, open-label, multicentre trial

BACKGROUND Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). METHODS In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. FINDINGS Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (pnon-inferiority=0·0004; hazard ratio [HR] 0·81 [95% CI 0·62-1·06], psuperiority=0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; pnon-inferiority=0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0·82 [95% CI 0·59-1·13]; p=0·23). INTERPRETATION Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI. FUNDING Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

A randomized trial of a dedicated bifurcation stent versus provisional stenting in the treatment of coronary bifurcation lesions

BACKGROUND Bifurcation lesions are frequent among patients with symptomatic coronary disease treated by percutaneous coronary intervention. Current evidence recommends a conservative (provisional) approach when treating the side branch (SB). OBJECTIVES The TRYTON (Prospective, Single Blind, Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries) bifurcation trial sought to compare treatment of de novo true bifurcation lesions using a dedicated bifurcation stent or SB balloon angioplasty. METHODS We randomly assigned patients with true bifurcation lesions to a main vessel stent plus provisional stenting or the bifurcation stent. The primary endpoint (powered for noninferiority) was target vessel failure (TVF) (cardiac death, target vessel myocardial infarction, and target vessel revascularization). The secondary angiographic endpoint (powered for superiority) was in-segment percent diameter stenosis of the SB at 9 months. RESULTS We randomized 704 patients with bifurcation coronary lesions at 58 centers (30 from Europe and 28 from the United States). At 9 months, TVF was 17.4% in the bifurcation stent group compared with 12.8% in the provisional group (p=0.11), mainly because of a higher periprocedural myocardial infarction rate (13.6% vs. 10.1%, p=0.19). The TVF difference of +4.6% (2-sided 95% confidence interval: -1.0 to 10.3; upper limit of the 1-sided 95% confidence interval: 10.3) was not within the pre-specified noninferiority margin of 5.5% (p=0.42 for noninferiority). The SB in-segment diameter stenosis among the angiographic cohort was lower in the bifurcation stent group compared with the provisional group (31.6% vs. 38.6%, p=0.002 for superiority), with no difference in binary restenosis rates (diameter stenosis≥50%) at 9 months follow-up (22.6% vs. 26.8%, p=0.44). CONCLUSIONS Provisional stenting should remain the preferred strategy for treatment of non-left main true coronary bifurcation lesions. (Prospective, Single Blind, Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries [TRYTON]; NCT01258972).

Is Bare-Metal Stent Implantation Still Justifiable in High Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention?: A Pre-Specified Analysis From the ZEUS Trial.

OBJECTIVES This study sought to investigate the ischemic and bleeding outcomes of patients fulfilling high bleeding risk (HBR) criteria who were randomized to zotarolimus-eluting Endeavor Sprint stent (E-ZES) or bare-metal stent (BMS) implantation followed by an abbreviated dual antiplatelet therapy (DAPT) duration for stable or unstable coronary artery disease. BACKGROUND DES instead of BMS use remains controversial in HBR patients, in whom long-term DAPT poses safety concerns. METHODS The ZEUS (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates) is a multinational, randomized single-blinded trial that randomized among others, in a stratified manner, 828 patients fulfilling pre-defined clinical or biochemical HBR criteria-including advanced age, indication to oral anticoagulants or other pro-hemorrhagic medications, history of bleeding and known anemia-to receive E-ZES or BMS followed by a protocol-mandated 30-day DAPT regimen. The primary endpoint of the study was the 12-month major adverse cardiovascular event rate, consisting of death, myocardial infarction, or target vessel revascularization. RESULTS Compared with patients without, those with 1 or more HBR criteria had worse outcomes, owing to higher ischemic and bleeding risks. Among HBR patients, major adverse cardiovascular events occurred in 22.6% of the E-ZES and 29% of the BMS patients (hazard ratio: 0.75; 95% confidence interval: 0.57 to 0.98; p = 0.033), driven by lower myocardial infarction (3.5% vs. 10.4%; p < 0.001) and target vessel revascularization (5.9% vs. 11.4%; p = 0.005) rates in the E-ZES arm. The composite of definite or probable stent thrombosis was significantly reduced in E-ZES recipients, whereas bleeding events did not differ between stent groups. CONCLUSIONS Among HBR patients with stable or unstable coronary artery disease, E-ZES implantation provides superior efficacy and safety as compared with conventional BMS. (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates [ZEUS]; NCT01385319).

A multicentre comparison of transradial and transfemoral approaches for coronary angiography and PTCA in obese patients: the TROP registry

AIMS The incidence of obesity is increasing continuously in industrial countries. Vascular complications after the transfemoral approach (TF) for either coronary angiography (CA) or angioplasty (PCI) are more frequent in this population. The transradial approach may decrease the risk of such complications. METHODS AND RESULTS We undertook a prospective, multicentre, European registry of overweight patients (BMI >/=35), undergoing CA and/or PCI in centres with broad experience in the transradial approach (TR). The vascular approach was left to the operators discretion. The primary end point was the occurrence of access related complications resulting in delayed hospital discharge 555 patients, (age 60.8+/-10.9 years; males 57.3%; BMI: 38.5+/-3.6 kg/m2) were included in the study. Of these, 157 underwent the transfemoral approach and 398 the transradial. Total procedure time was significantly shorter for the transradial approach in these morbidly obese patients (TR: 35.5+/-25.8 min versus TF: 52.4+/-25.2 min, p=0.0001), and hospital stay after CA or PCI was significantly shorter in the transradial group (TR: 1.8+/-2.3 days versus TF: 2.5+/-4.3 days, p=0.04). Vascular complications delaying hospital discharge occurred in 0.8% of TR patients vs 5.1% TF patients. p=0.0009). CONCLUSIONS The rate of vascular complications in overweight patients after CA or PCI can be significantly decreased by the use of the transradial approach in centres with a large experience.

Five-year experience with transradial coronary angioplasty in ST-segment-elevation myocardial infarction

BACKGROUND AND PURPOSE Percutaneous coronary intervention (PCI) via radial approach has been shown to be an alternative to femoral approach in emergency cases; however, its feasibility has been questioned. This single-center study was performed to compare the outcomes and complication rates between transradial (TR) and transfemoral (TF) PCI in ST-segment-elevation myocardial infarction (STEMI). METHODS AND MATERIALS The clinical and angiographic data of 582 consecutive STEMI patients treated with PCI between 2001 and 2006 were evaluated in a retrospective study. Forty-three patients were excluded from the present study due to cardiogenic shock or rescue PCI. Patients (n=539) were categorized into the TR group (n=167) or the TF group (n=372), and several parameters were evaluated to assess the advantages and drawbacks of TR access: access-site crossover, rate of access-site complications, procedure time, fluoroscopy time, X-ray area dose, major adverse cardiac events (MACE) at 1 month, and consumption of angioplasty equipment. RESULTS In the TR group, the crossover rate to femoral access was 5%, while in the TF group, it was 0.8% (P<.05). There was a significant difference, in both major and minor access-site complications, between the TR group and the TF group (0% vs. 5%, P<.05, and 4% vs. 9%, P<.05, respectively). Consumption of angioplasty equipment proved to be the same for the two groups. The MACE rate was 4% in the TR group and 11% in the TF group (P<.05). CONCLUSIONS Our results suggest that the TR approach is a safe and effective way to treat STEMI; furthermore, site-related complications are less common with this approach.

The effect of aortic valve replacement on coronary flow reserve in patients with a normal coronary angiogram.

Background: In patients with aortic stenosis and a normal coronary angiogram, a coronary flow reserve (CFR) is impaired. The aim of the present study was to examine the effect of aortic valve replacement (AVR) on the CFR after a long-term follow-up. Patients and Methods: 30 patients with aortic stenosis and a normal coronary angiogram were enrolled in the study. CFR measurements were made on 21 patients 123 ± 137 days before and 497 ± 167 days after AVR. CFR measurements were carried out according to a standard protocol, with a vasodilator stimulus dipyridamole (0.56 mg/kg for 4 min) and peak diastolic velocity measurements at 6 min. Results: Initially, the average peak gradient of aortic stenosis was 89.5 ± 22.4 mm Hg. After AVR, it decreased to 26.2 ± 9 mm Hg. Left ventricular mass was significantly lower after AVR: 354.9 ± 107.9 g versus 223.8 ± 73.6 g (p < 0.001). The average baseline diastolic velocity measured by pulsed Doppler in the left anterior descending coronary artery amounted to 62.2 ± 25.5 cm/s before and 40.1 ± 13.6 cm/s after AVR. The difference was statistically significant (p < 0.01). The average diastolic velocity at maximum stress equaled 117 ± 42.8 cm/s pre- and 91.5 ± 34 cm/s postoperatively (p < 0.005). The calculated CFR before AVR amounted to 1.96 ± 0.5 and increased to 2.37 ± 0.8 postoperatively. The difference was statistically significant (p < 0.05). Conclusion: Prosthetic AVR is of considerable benefit concerning the CFR in patients with a normal coronary angiogram after a long-term follow-up.Hintergrund: Bei Patienten mit Aortenklappenstenose und anatomisch normalem Koronarsystem ist die Koronarflussreserve (CFR) vermindert. Ziel dieser Studie war, die Auswirkungen von Aortenklappenersatzoperationen (AVR) auf die CFR im Langzeitverlauf zu untersuchen. Patienten und Methodik: 30 Patienten mit Aortenklappenstenose wurden in die Studie einbezogen. Die CFR wurde bei 21 Patienten 123 ± 137 Tage vor und 497 ± 167 Tage nach AVR mit einer standardisierten echokardiographischen Methode transösophageal bestimmt. Die Doppler-Messungen erfolgten im Normalzustand und nach maximaler Vasodilatation durch 4-min-Infusion von 0,56 mg/kg Dipyridamol. Ergebnisse: Der durchschnittliche Druckgradient über den Aortenklappen lag bei 89,5 ± 22,4 mm Hg vor und 26,2 ± 9 mm Hg nach AVR. Das linksventrikuläre Gewicht war nach der Operation signifikant vermindert (354,9 ± 107,9 vs. 223,8 ± 73,6 g; p < 0.001). Die durchschnittliche diastolische Geschwindigkeit in den Ramus-interventricularis-anterior-Arterien lag präoperativ bei 62,2 ± 25,5 cm/s und postoperativ bei 40,1 ± 13,6 cm/s (p < 0.01). Die durchschnittliche diastolische Geschwindigkeit bei maximaler Vasodilatation betrug 117 ± 42,8 cm/s vor und 91,5 ± 34 cm/s nach AVR (p < 0.05). Der kalkulierte CFR-Wert lag präoperativ bei 1,96 ± 0,5 und erhöhte sich nach der Operation auf 2,37 ± 0,8 (p < 0,05). Schlussfolgerung: Die Implantation von Aortenklappenprothesen hat eine positive Wirkung auf die CFR von Patienten mit anatomisch normalen Koronararterien.

Outcomes of a Dedicated Stent in Coronary Bifurcations with Large Side Branches: A Subanalysis of the Randomized TRYTON Bifurcation Study

To examine the benefit of the Tryton dedicated side branch (SB) stent compared with provisional stenting in the treatment of complex bifurcation lesions involving large SBs.

Vessel masking improves densitometric myocardial perfusion assessment.

Introduction The objective of treatment in acute myocardial infarction (AMI) is reperfusion of the myocardium at risk. Our goal was to evaluate the effect of vessel masking on videodensitometric assessment of myocardial reperfusion. Methods Epicardial vessels were masked out from the densitometric region of interest, where average rise slope (Gmax/Tmax) of time–density curves (TDC) were measured. Measurements were tested to detect indicators of reperfusion as cumulative creatine-kinase (CK) release and ST-resolution by receiver operating characteristic (ROC) curve analysis. Results When vessel masking was applied before Gmax/Tmax measurement, an improvement has been observed in sensitivity and area under ROC curve to detect indicators of reperfusion as cumulative enzyme release (sensitivity (Se): 85% vs. 61%, area under the curve (AUC): 0.84 vs. 0.76) and ST-resolution (Se: 74% vs. 67%, AUC: 0.83 vs. 0.79). Conclusions Selective myocardial perfusion measurement on coronary angiograms is feasible and serves as an informative method to detect myocardial viability after AMI and revascularization therapy. The present study demonstrated that vessel masking improves results compared to simple densitometric analysis.