EXpansion of stents after intravascular lithoTripsy versus conventional predilatation in CALCified coronary arteries.

BACKGROUND: Coronary artery calcification is a strong predictor for procedural failure and is independently associated with adverse events after percutaneous coronary intervention (PCI). An important contributor to the impaired outcome is the inability to achieve optimal results due to stent underexpansion or stent deformation/fracture. Intravascular lithotripsy (IVL) has emerged as an alternative technique to change the integrity of calcified plaques. AIMS: Our aim was to investigate if pre-treatment with IVL in severely calcified lesions increases stent expansion, assessed by optical coherence tomography (OCT), when compared to predilatation with conventional and/or specialty balloon strategy. METHODS: EXIT-CALC was a prospective, single-centre, randomised controlled study. Patients with an indication for PCI and severe calcification of the target lesion were allocated to predilatation with conventional angioplasty balloons or pre-treatment with IVL, followed by drug-eluting stenting and mandatory postdilatation. Primary endpoint was stent expansion assessed by OCT. Secondary endpoints were the occurrence of peri-procedural events and major adverse cardiac events (MACE) in hospital and during follow-up. RESULTS: A total of 40 patients were included. The minimal stent expansion in the IVL-group (n = 19) was 83.9 ± 10.3% and 82.2 ± 11.5% in the conventional group (n = 21) (p = 0.630). Minimal stent area was 6.6 ± 1.5 mm2 and 6.2 ± 1.8 mm2, respectively (p = 0.406). No peri-procedural, in-hospital and 30-day follow-up MACE were reported. CONCLUSIONS: In severely calcified coronary lesions we found no significant difference in stent expansion measured by OCT when comparing IVL, as plaque modification, with conventional and/or specialty angioplasty balloons.

Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction.

BACKGROUND: The proprotein convertase subtilisin kexin type-9 inhibitor evolocumab produced coronary atheroma regression in statin-treated patients. OBJECTIVES: The purpose of this study was to determine the effect of evolocumab on optical coherence tomography (OCT) measures of plaque composition. METHODS: Patients with a non-ST-segment elevation myocardial infarction were treated with monthly evolocumab 420 mg (n = 80) or placebo (n = 81) for 52 weeks. Patients underwent serial OCT and intravascular ultrasound imaging within a matched arterial segment of a nonculprit vessel. The primary analysis determined the change in the minimum fibrous cap thickness and maximum lipid arc throughout the imaged arterial segment. Additional analyses determined changes in OCT features in lipid-rich plaque regions and plaque burden. Safety and tolerability were evaluated. RESULTS: Among treated patients (age 60.5 ± 9.6 years; 28.6% women; low-density lipoprotein cholesterol [LDL-C], 141.3 ± 33.1 mg/dL), 135 had evaluable imaging at follow-up. The evolocumab group achieved lower LDL-C levels (28.1 vs 87.2 mg/dL; P < 0.001). The evolocumab group demonstrated a greater increase in minimum fibrous cap thickness (+42.7 vs +21.5 µm; P = 0.015) and decrease in maximum lipid arc (-57.5o vs. -31.4o; P = 0.04) and macrophage index (-3.17 vs -1.45 mm; P = 0.04) throughout the arterial segment. Similar benefits of evolocumab were observed in lipid-rich plaque regions. Greater regression of percent atheroma volume was observed with evolocumab compared with placebo (-2.29% ± 0.47% vs -0.61% ± 0.46%; P = 0.009). The groups did not differ regarding changes in microchannels or calcium. CONCLUSIONS: The combination of statin and evolocumab after a non-ST-segment elevation myocardial infarction produces favorable changes in coronary atherosclerosis consistent with stabilization and regression. This demonstrates a potential mechanism for the improved clinical outcomes observed achieving very low LDL-C levels following an acute coronary syndrome. (Imaging of Coronary Plaques in Participants Treated With Evolocumab; NCT03570697).

Dual versus triple antithrombotic therapy after percutaneous coronary intervention: the prospective multicentre WOEST 2 Study.

BACKGROUND: For patients on oral anticoagulants (OAC) undergoing percutaneous coronary intervention (PCI), European guidelines have recently changed their recommendations to dual antithrombotic therapy (DAT; P2Y12 inhibitor and OAC) without aspirin. AIMS: The prospective WOEST 2 registry was designed to obtain contemporary real-world data on antithrombotic regimens and related outcomes after PCI in patients with an indication for OAC. METHODS: In this analysis, we compare DAT (P2Y12 inhibitor and OAC) to triple antithrombotic therapy (TAT; aspirin, P2Y12 inhibitor, and OAC) on thrombotic and bleeding outcomes after one year. Clinically relevant bleeding was defined as Bleeding Academic Research Consortium classification (BARC) grade 2, 3, or 5; major bleeding as BARC grade 3 or 5. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause mortality, myocardial infarction, stent thrombosis, ischaemic stroke, and transient ischaemic attack. RESULTS: A total of 1,075 patients were included between 2014 and 2021. Patients used OAC for atrial fibrillation (93.6%) or mechanical heart valve prosthesis (4.7%). Non-vitamin K oral anticoagulants (NOAC) were prescribed in 53.1% and vitamin K antagonists in 46.9% of patients. At discharge, 60.9% received DAT, and 39.1% TAT. DAT was associated with less clinically relevant and similar major bleeding (16.8% vs 23.4%; p<0.01 and 7.6% vs 7.7%, not significant), compared to TAT. The difference in MACCE between the two groups was not statistically significant (12.4% vs 9.7%; p=0.17). Multivariable adjustment and propensity score matching confirmed these results. CONCLUSIONS: Dual antithrombotic therapy is associated with a substantially lower risk of clinically relevant bleeding without a statistically significant penalty in ischaemic events.

Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction: Results from the POPular Genetics Trial.

INTRODUCTION: The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI). OBJECTIVE: In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel. METHODS: A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y12 inhibitors, and equal distribution of thrombotic events between the two strategies). RESULTS: Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and €725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant. CONCLUSION: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872.

Two-Year Clinical Outcomes of the REVELATION Study: Sustained Safety and Feasibility of Paclitaxel-Coated Balloon Angioplasty Versus Drug-Eluting Stent in Acute Myocardial Infarction.

OBJECTIVES: The randomized REVELATION (REVascularization With PaclitaxEL-Coated Balloon Angioplasty Versus Drug-Eluting Stenting in Acute Myocardial InfarcTION) trial showed that in the setting of ST-segment elevation myocardial infarction (STEMI), a drug-coated balloon (DCB) strategy was non-inferior to a drug-eluting stent (DES) strategy in terms of fractional flow reserve assessed at 9 months. The aim of the present study is to evaluate the long-term clinical outcome of this treatment strategy. METHODS: Between October 2014 and November 2017, a total of 120 patients with a non-severely calcified culprit lesion in a native coronary artery and a residual stenosis of <50% after predilation were randomized to treatment with DCB or DES. Primary clinical endpoint was the occurrence of major adverse cardiac events, defined as death, recurrent myocardial infarction, or target-lesion revascularization, the occurrence of definite ST, and non-coronary artery bypass grafting (CABG) major bleeding. RESULTS: Complete clinical follow-up at 2 years was available for 109 patients (91%). A major adverse cardiac event occurred in 3 patients (5.4%) in the DCB group and 1 patient (1.9%) in the DES group (hazard ratio, 2.86; 95% confidence interval, 0.30-27.53; P=.34). Between 9 months and 2 years, only 1 additional event occurred (target-lesion revascularization in a patient randomized to DCB). CONCLUSION: In this randomized study of DCB vs DES in selected patients presenting with STEMI, 2-year clinical outcome was excellent and comparable between the DCB and DES groups.

Essential Thrombocytosis in Patients <40 Years Old With Acute Coronary Syndromes: A Not So Uncommon Underlying Diagnosis Often Overlooked.

BACKGROUND: In patients under <40 years, traditional cardiovascular (CV)-risk factors are a less likely cause of acute coronary syndromes (ACS) compared to older counterparts. AIMS: To estimate the prevalence of essential thrombocytosis (ET), a hematological disorder and less-prevalent risk factor, in young patients presenting with ACS. METHODS: We constructed a retrospective database of all patients <40 years (n=271) that had consecutively undergone coronary angiography (CAG) after their first ACS within our hospital within the last ten years (2010-2020) and had known thrombocyte counts (n=241). Patients with thrombocytes >450x10*9/L were screened for this hematological disorder. RESULTS: In our database, we identified 15 subjects with thrombocytosis. One was previously known as ET. Of the remaining 14 patients, five were considered reactive/secondary thrombocytosis, and four were lost to follow-up, four were eventually diagnosed with ET, one remains uncertain. The diagnosis was newly established before the initiation of this study in two patients (average delay: six years). Two patients were identified as a result of this study.  Conclusion: With a prevalence of at least 2.1%, ET appears not uncommon in patients <40 years with ACS. Moreover, screening patients with ACS and elevated thrombocytes yielded a novel diagnosis of ET in 27% of patients. The diagnosis was initially missed in all cases. Since the timing of revascularization should be adjusted to thrombocyte count/initiation of ET therapy to prevent thrombotic complications, cardiologists should know, recognize and screen for this pathology in ACS-patients, notably in those with absent traditional CV-risk factors: an 'ACS-protocol' aimed at less-prevalent risk factors could support this.

One-year mortality in NSTEMI patients is unaffected by timing of PCI within the first week of admission: Results of a real-world cohort analysis.

OBJECTIVES: We aimed to explore the impact of time to percutaneous coronary intervention (PCI) (T2P) on 1-year mortality in non-ST-elevation myocardial infarction (NSTEMI) patients. BACKGROUND: The current guidelines recommend an early invasive strategy for NSTEMI patients. However, impact of an early invasive strategy on mortality is a matter of debate. For that reason, real world data are of great value to determine the optimal treatment window. METHODS: This retrospective single center cohort study was performed in a high-volume PCI center in Amsterdam, The Netherlands. Intermediate- and high-risk NSTEMI patients undergoing PCI were included. The main discriminant was timing of PCI after admission (T2P), stratified according to different time windows (<24 h, 24-72 h, 72 h-7 days or >7 days). We analyzed 1-year mortality and the time distribution of overall survival. RESULTS: In total, 848 patients treated between January 1, 2016 and January 1, 2018 were included in the analysis. T2P was <24 h in 145 patients, 24-72 h in 192 patients, 72 h-7 days in 275 patients, and >7 days in 236 patients. The mean GRACE-risk score was 127.1 (SD 28.7), 130.0 (33.1), 133.8 (32.1), and 148.7 (34.6) respectively, p = <0.001. After adjusting for confounders, 1-year mortality in patients with T2P <24 h did not significantly differ when compared with T2P 24-72 h (OR = 1.08; 95% CI = 0.33-3.51) and T2P 72 h-7 days (OR 1.72; 95% CI = 0.57-5.21) but was significantly higher in T2P >7 days (OR = 3.20; 95% CI = 1.06-9.68). CONCLUSIONS: In an unselected cohort of patients with NSTEMI, treatment by PCI <24 h did not lead to improved survival as compared to aT2P <7 days strategy. Delay in PCI >7 days after admission resulted in worse outcome.

Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome: A pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients.

BACKGROUND: Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y12 inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically. METHODS: Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding). RESULTS: A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77-1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66-1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62-1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively. CONCLUSION: In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and patients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in patients using clopidogrel.

Clopidogrel Versus Ticagrelor or Prasugrel After Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype: A POPular Genetics Subanalysis.

[Figure: see text].

Transulnar coronary intervention complicated by compartment syndrome.

We describe a case of a compartment syndrome after transulnar coronary intervention. As far as we are aware of, this is the first report of such a complication after a transulnar approach described in the literature. Compartment syndrome is a very rare but possibly devastating complication of coronary angiography and percutaneous coronary interventions. We retrospectively observed an incidence rate of 0.007% after 13,948 coronary angiographies or 0.013% after 7532 interventions performed through the wrist in our centre in the last 5 years. Rapid recognition and treatment of this rare complication may prevent long-term morbidity and are thus of utmost importance. General measures should be taken to reduce this incidence of this serious complication.

An immediate or early invasive strategy in non-ST-elevation acute coronary syndrome: The OPTIMA-2 randomized controlled trial.

BACKGROUND: In intermediate- and high-risk non-ST elevated acute coronary syndrome (NSTE-ACS) patients, a routine invasive approach is recommended. The timing of coronary angiography remains controversial. To assess whether an immediate (<3 hours) invasive treatment strategy would reduce infarct size and is safe, compared with an early strategy (12-24 hours), for patients admitted with NSTE-ACS while preferably treated with ticagrelor. METHODS: In this single-center, prospective, randomized trial an immediate or early invasive strategy was randomly assigned to patients with NSTE-ACS. At admission, the patients were preferably treated with a combination of aspirin, ticagrelor and fondaparinux. The primary endpoint was the infarct size as measured by area under the curve (AUC) of CK-MB in 48 hours. Secondary endpoints were bleeding outcomes and major adverse cardiac events (MACE): composite of all-cause death, MI and unplanned revascularization. Interim analysis showed futility regarding the primary endpoint and trial inclusion was terminated. RESULTS: In total 249 patients (71% of planned) were included. The primary endpoint of in-hospital infarct size was a median AUC of CK-MB 186.2 ng/mL in the immediate group (IQR 112-618) and 201.3 ng/mL in the early group (IQR 119-479). Clinical follow-up was 1-year. The MACE-rate was 10% in the immediate and 10% in the early group (hazard ratio [HR] 1.13, 95% CI: 0.52-2.49). CONCLUSIONS: In NSTE-ACS patients randomized to either an immediate or an early-invasive strategy the observed median difference in the primary endpoint was about half the magnitude of the expected difference. The trial was terminated early for futility after 71% of the projected enrollment had been randomized into the trial.

Impact of different anticoagulation management strategies on outcomes in atrial fibrillation: Dutch and Belgian results from the GARFIELD-AF registry.

BACKGROUND: The uptake rate of non-vitamin K oral anticoagulants (NOAC) for the treatment of non-valvular atrial fibrillation (AF) was far lower in the Netherlands (NL) compared to Belgium (BE). Also, patients on VKA in NL were treated with a higher target international normalized ratio (INR) range of 2.5 to 3.5. OBJECTIVES: To explore the effect of these differences on thromboembolism (TE) and bleeding. METHODS: Data from the GARFIELD-AF registry was used. Patients with new-onset AF and ≥1 investigator-determined risk factor for stroke were included between 2010 and 2016. Event rates from 2 years of follow-up were used. RESULTS: In NL and BE, 1186 and 1705 patients were included, respectively. Female sex (42.3% vs 42.2%), mean age (70.7 vs 71.3 years), CHA2 DS2 -VASc (3.1 vs 3.1), and HAS-BLED score (1.4 vs 1.5) were comparable between NL and BE. At diagnosis in NL vs BE, 72.1% vs 14.6% received vitamin K antagonists (VKA) and 17.8% vs 65.5% NOACs, varying greatly across cohorts. Mean INR was 2.9 (±1.0) and 2.4 (±1.0) in NL and BE, respectively. Event rates per 100 patient-years in NL and BE, respectively, of all-cause mortality (3.38 vs 3.90; hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65-1.15), ischemic stroke/TE (0.82 vs 0.72; HR 1.14, 95% CI 0.62-2.11), and major bleeding (2.06 vs 1.54; HR 1.33, 95% CI 0.89-1.99) did not differ significantly. CONCLUSIONS: In GARFIELD-AF, despite similar characteristics, patients on anticoagulants were treated differently in NL and BE. Although the rate of major bleeding was 33% higher in NL, variations in bleeding, mortality, and TE rates were not statistically significant.

A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI.

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.).

Paclitaxel-Coated Balloon Angioplasty Versus Drug-Eluting Stent in Acute Myocardial Infarction: The REVELATION Randomized Trial.

OBJECTIVES: This study sought to assess the efficacy and safety of a drug-coated balloon (DCB) strategy versus drug-eluting stent (DES) in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: In primary percutaneous coronary intervention for STEMI, stenting has proved to be beneficial with regard to repeat revascularization, but not recurrent myocardial infarction or death, compared with balloon angioplasty alone. A strategy of DCB angioplasty without stenting might abolish the potential disadvantages of stent implantation while reducing the probability of restenosis observed in plain old balloon angioplasty. METHODS: In the prospective, randomized, single-center REVELATION trial, we compared DCB with DES in patients presenting with STEMI. Patients with a new, nonseverely calcified culprit lesion in a native coronary artery and a residual stenosis of <50% after pre-dilatation were randomized to treatment with a DCB or DES. The primary endpoint was fractional flow reserve at 9 months, allowing for a functional measurement of the infarct-related lesion. RESULTS: A total of 120 patients were included. At 9 months after enrolment, the mean fractional flow reserve value was 0.92 ± 0.05 in the DCB group (n = 35) and 0.91 ± 0.06 in the DES group (n = 38) (p = 0.27). One abrupt vessel closure requiring treatment occurred after treatment with DCB. Up to 9-months follow-up, 2 patients required nonurgent target lesion revascularization (1 in each group). CONCLUSIONS: In the setting of STEMI, the DCB strategy was noninferior to DES in terms of fractional flow reserve assessed at 9 months. Furthermore, it seemed to be a safe and feasible strategy. (Revascularization With Paclitaxel-Coated Balloon Angioplasty Versus Drug-Eluting Stenting in Acute Myocardial Infarction [REVELATION]; NCT02219802).

Web-based distress management for implantable cardioverter defibrillator patients: A randomized controlled trial.

OBJECTIVE: Sudden cardiac arrest caused by cardiac arrhythmias is 1 of the leading causes of death worldwide. Implantable cardioverter defibrillators (ICDs) are considered as standard care for patients with increased risk of arrhythmias. However, 1 in 4 ICD patients experiences psychological distress post-ICD implantation. The WEB-based distress management program for ICD patients (WEBCARE) was developed to mitigate anxiety and depression and enhance health-related quality of life in ICD patients. This study investigates the 6- and 12-months outcomes. METHOD: A total of 289 consecutive ICD patients from 6 referral hospitals in the Netherlands were randomized to either the WEBCARE (n = 146) or usual care (n = 143) group. Patients in the WEBCARE group received an online, 12-weeks fixed, 6 lesson behavioral treatment based on problem solving therapy. Patients in the usual care group receive care as usual. RESULTS: Current findings show no significant difference on anxiety, depression or quality of life between the WEBCARE and Usual Care group at 6- and 12-months postimplantation. CONCLUSIONS: In this clinical trial of a Web-based behavioral intervention for ICD patients, the Web-based treatment was not superior to usual care on the long-term regarding patient reported outcomes. Future studies are warranted to examine the applicability of blended-care models and focus on further personalizing the program in order to increase adherence and improve outcomes. (PsycINFO Database Record

REVascularization with paclitaxEL-coated balloon angioplasty versus drug-eluting stenting in acute myocardial infarcTION-A randomized controlled trial: Rationale and design of the REVELATION trial.

AIM: In primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI), stenting has proved to reduce the need for repeat revascularization compared with balloon angioplasty alone. The incidence of cardiac death or recurrent myocardial infarction, though, is not reduced by stenting. This is in part attributable to stent-related complications like stent thrombosis which may occur even years after implantation. A strategy of drug coated balloon (DCB) angioplasty without stenting would abolish the potential disadvantages of stent implantation while reducing the probability of restenosis observed in plain old balloon angioplasty. Our aim is to evaluate the efficacy and safety of a DCB only strategy versus drug-eluting stents (DES) in PPCI for STEMI. STUDY DESIGN: The REVELATION trial is a prospective, single center, randomized study, in which 120 patients presenting with STEMI will be allocated to treatment with a DCB versus DES. Appertaining to the established prognostic value of fractional flow reserve (FFR) rather than angiographic lesion severity, the functional assessment of the infarct-related lesion by FFR at 9 months after initial treatment is the primary end point. Assuming an FFR value of 0.90 after stenting and an increased risk of adverse events if post-PCI FFR <0.85, we decided to accept an FFR value of ≥0.85 after DCB only at follow-up as noninferiority margin. Secondary end points include major adverse cardiac events up to 5-year follow-up. CONCLUSION: Our trial will address the efficacy and safety of DCB angioplasty versus DES in the setting of PPCI for STEMI. The REVELATION trial will introduce the recognized prognostic significance of physiologic assessment of the infarct-related lesion by FFR at 9 months follow-up as primary end point. © 2015 Wiley Periodicals, Inc.

Effect of the BET Protein Inhibitor, RVX-208, on Progression of Coronary Atherosclerosis: Results of the Phase 2b, Randomized, Double-Blind, Multicenter, ASSURE Trial.

BACKGROUND: Bromodomain and extra-terminal (BET) proteins regulate transcription of lipoprotein and inflammatory factors implicated in atherosclerosis. The impact of BET inhibition on atherosclerosis progression is unknown. METHODS: ASSURE was a double-blind, randomized, multicenter trial in which 323 patients with angiographic coronary disease and low high-density lipoprotein cholesterol (HDL-C) levels were randomized in a 3:1 fashion to treatment with the BET protein inhibitor RVX-208 200 mg or placebo for 26 weeks. Plaque progression was measured with serial intravascular ultrasound imaging. Lipid levels, safety, and tolerability were also assessed. RESULTS: During treatment, apolipoprotein (apo)A-I increased by 10.6% with placebo (P < 0.001 compared with baseline) and 12.8% with RVX-208 (P < 0.001 compared with baseline), between groups P = 0.18. HDL-C increased by 9.1% with placebo (P < 0.001 compared with baseline) and 11.1% with RVX-208 (P < 0.001 compared with baseline), between groups P = 0.24. Low-density lipoprotein cholesterol (LDL-C) decreased by 17.9% with placebo (P < 0.001 compared with baseline) and 15.8% with RVX-208 (P < 0.001 compared with baseline), between groups P = 0.55. The primary endpoint, the change in percent atheroma volume, decreased 0.30% in placebo-treated patients (P = 0.23 compared with baseline) and 0.40% in the RVX-208 group (P = 0.08 compared with baseline), between groups P = 0.81. Total atheroma volume decreased 3.8 mm(3) in the placebo group (P = 0.01 compared with baseline) and 4.2 mm(3) in the RVX-208 group (P < 0.001 compared with baseline), P = 0.86 between groups. A greater incidence of elevated liver enzymes was observed in RVX-208-treated patients (7.1 vs. 0%, P = 0.009). CONCLUSION: Administration of the BET protein inhibitor RVX-208 showed no greater increase in apoA-I or HDL-C or incremental regression of atherosclerosis than administration of placebo. TRIAL REGISTRATION: ClinicalTrials.gov identifier-NCT01067820.