Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial.

Importance: Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown. Objective: To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction. Design, Setting, and Participants: The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals. Interventions: Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg). Main Outcomes and Measures: Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non-infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography-derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52. Results: Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low-density lipoprotein cholesterol level, 152.4 [33.8] mg/dL), 265 (88.3%) underwent serial IVUS imaging in 537 arteries. At 52 weeks, mean change in percent atheroma volume was -2.13% with alirocumab vs -0.92% with placebo (difference, -1.21% [95% CI, -1.78% to -0.65%], P < .001). Mean change in maximum lipid core burden index within 4 mm was -79.42 with alirocumab vs -37.60 with placebo (difference, -41.24 [95% CI, -70.71 to -11.77]; P = .006). Mean change in minimal fibrous cap thickness was 62.67 µm with alirocumab vs 33.19 µm with placebo (difference, 29.65 µm [95% CI, 11.75-47.55]; P = .001). Adverse events occurred in 70.7% of patients treated with alirocumab vs 72.8% of patients receiving placebo. Conclusions and Relevance: Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT03067844.

Acute coronary syndromes in young patients: Phenotypes, causes and clinical outcomes following percutaneous coronary interventions.

BACKGROUND: The prevalence of acute coronary syndromes (ACS) among young individuals is increasing, but the phenotypic characteristics, causes and clinical outcomes in this group have not been well described. METHODS: Between 2009 and 2017, 8712 ACS patients underwent percutaneous coronary intervention (PCI) and were prospectively enrolled. We defined a young patient as female <50 years and male <45 years. The causes of ACS were defined by an adjudication committee. The primary endpoint was the patient-oriented composite endpoint (POCE) of all-cause mortality, myocardial infarction or any revascularization at 12 months. RESULTS: Among 8712 ACS patients, 472 (5.4%) patients were young (26% female). The main cause of ACS in young patients was atherosclerosis (86.5%), followed by coronary artery embolism (9%), and spontaneous coronary artery dissection (SCAD) (4.5%). POCE occurred less frequently in young compared to old patients (8.5% vs. 16.7%, hazard ratio 0.48 (95% confidence interval 0.35-0.66), p < 0.001). The rates of the individual components of the POCE were lower in young including all-cause mortality (3.2% versus 9.5%, 0.32 (0.19-0.54), p < 0.001), myocardial infarction (1.9% versus 3.7%, 0.49 (0.25-0.95), p = 0.035) and any revascularization (5.1% versus 7.4%, 0.65 (0.43-0.97), p = 0.037). Young patients with SCAD had a higher rate of death as compared to those with atherosclerosis, mainly attributed to cardiac deaths. CONCLUSIONS: One out of 20 ACS patients undergoing PCI was young and the principal cause was atherosclerosis. Young carry a lower risk for future events compared to older ACS patients. The underlying cause leading to ACS should be considered in appropriate risk stratification of young patients. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov. NCT02241291.

Effect of Timing of Staged Percutaneous Coronary Intervention on Clinical Outcomes in Patients With Acute Coronary Syndromes.

Background Complete revascularization reduces cardiovascular events in patients with acute coronary syndromes (ACSs) and multivessel disease. The optimal time point of non-target-vessel percutaneous coronary intervention (PCI) remains a matter of debate. The aim of this study was to investigate the impact of early (<4 weeks) versus late (≥4 weeks) staged PCI of non-target-vessels in patients with ACS scheduled for staged PCI after hospital discharge. Methods and Results All patients with ACS undergoing planned staged PCI from 2009 to 2017 at Bern University Hospital, Switzerland, were analyzed. Patients with cardiogenic shock, in-hospital staged PCI, staged cardiac surgery, and multiple staged PCIs were excluded. The primary end point was all-cause death, recurrent myocardial infarction and urgent premature non-target-vessel PCI. Of 8657 patients with ACS, staged revascularization was planned in 1764 patients, of whom 1432 patients fulfilled the eligibility criteria. At 1 year, there were no significant differences in the crude or adjusted rates of the primary end point (7.8% early versus 10.8% late, hazard ratio [HR], 0.72 [95% CI, 0.47-1.10], P=0.129; adjusted HR, 0.80 [95% CI, 0.50-1.28], P=0.346) and its individual components (all-cause death: 1.5% versus 2.9%, HR, 0.52 [95% CI, 0.20-1.33], P=0.170; adjusted HR, 0.62 [95% CI, 0.23-1.67], P=0.343; recurrent myocardial infarction: 4.2% versus 4.4%, HR, 0.97 [95% CI, 0.475-1.10], P=0.924; adjusted HR, 1.03 [95% CI, 0.53-2.01], P=0.935; non-target-vessel PCI, 3.9% versus 5.7%, HR, 0.97 [95% CI, 0.53-1.80], P=0.928; adjusted HR, 1.19 [95% CI, 0.61-2.34], P=0.609). Conclusions In this single-center cohort study of patients with ACS scheduled to undergo staged PCI after hospital discharge, early (<4 weeks) versus late (≥4 weeks) staged PCI was associated with a similar rate of major adverse cardiac events at 1 year follow-up. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02241291.

Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study-Rationale and design of the PACMAN-AMI trial.

BACKGROUND: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. AIMS: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI4 mm) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. METHODS: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI4 mm, and OCT-derived minimal FCT, will be assessed 52 weeks post randomization. SUMMARY: The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. CLINICAL TRIAL REGISTRATION: NCT03067844.

In vivo relationship between near-infrared spectroscopy-detected lipid-rich plaques and morphological plaque characteristics by optical coherence tomography and intravascular ultrasound: a multimodality intravascular imaging study.

AIMS: We assessed morphological features of near-infrared spectroscopy (NIRS)-detected lipid-rich plaques (LRPs) by using optical coherence tomography (OCT) and intravascular ultrasound (IVUS). METHODS AND RESULTS: IVUS-NIRS and OCT were performed in the two non-infarct-related arteries (non-IRAs) in patients undergoing percutaneous coronary intervention for treatment of an acute coronary syndrome. A lesion was defined as the 4 mm segment with the maximum amount of lipid core burden index (maxLCBI4mm) of each LRP detected by NIRS. We divided the lesions into three groups based on the maxLCBI4mm value: <250, 250-399, and ≥400. OCT analysis and IVUS analysis were performed blinded for NIRS. We measured fibrous cap thickness (FCT) by using a semi-automated method. A total of 104 patients underwent multimodality imaging of 209 non-IRAs. NIRS detected 299 LRPs. Of those, 41% showed a maxLCBI4mm <250, 39% a maxLCBI4mm 251-399, and 19% a maxLCBI4mm ≥400. LRPs with a maxLCBI4mm ≥400, as compared with LRPs with a maxLCBI4mm 250-399 and <250, were more frequently thin-cap fibroatheroma (TCFA) (42.1% vs. 5.1% and 0.8%; P < 0.001) with a smaller minimum FCT (80 µm vs. 110 µm and 120 µm; P < 0.001); a higher IVUS-derived percent atheroma volume (53% vs. 53% and 44%; P < 0.001) and a higher remodelling index (1.08 vs. 1.02 and 1.01; P < 0.001). MaxLCBI4mm correlated with OCT-derived FCT (r = 0.404; P < 0.001) and was the best predictor for TCFA with an optimal cut-off value of 401 (area under the curve = 0.882; P < 0.001). CONCLUSION: LRPs with increasing maxLCBI4mm exhibit OCT and IVUS features of presumed plaque vulnerability including TCFA morphology, increased plaque burden, and positive remodelling.

Relationship between arterial remodelling and serial changes in coronary atherosclerosis by intravascular ultrasound: an analysis of the IBIS-4 study.

AIMS: Arterial remodelling is an important determinant of coronary atherosclerosis. Assessment of the remodelling index, comparing a lesion to a local reference site, is a suboptimal correlate of serial vascular changes. We assessed a novel approach which, unlike the local-reference approach, uses the entire artery's global remodelling as reference. METHODS AND RESULTS: Serial (baseline and 13 months) intravascular ultrasound was performed in 146 non-infarct-related arteries of 82 patients treated with high-intensity statin. Arteries were divided into 3-mm segments (n = 1479), and focal remodelling was characterized in individual segments at both timepoints applying the global arterial reference approach. First, we compared preceding vascular changes in relation to follow-up remodelling. Second, we examined whether baseline remodelling predicts subsequent plaque progression/regression. At follow-up, segments with constrictive vs. compensatory or expansive remodelling had greater preceding reduction of vessel area (-0.67 vs. -0.38 vs. -0.002 mm2; P < 0.001) and lumen area (-0.82 vs. -0.09 vs. 0.40 mm2; P < 0.001). Overall, we found significant regression in percent atheroma volume (PAV) [-0.80% (-1.41 to -0.19)]. Segments with constrictive remodelling at baseline had greater subsequent PAV regression vs. modest regression in the compensatory, and PAV progression in the expansive remodelling group (-6.14% vs. -0.71% vs. 2.26%; P < 0.001). Lesion-level analyses (n = 118) showed no differences when remodelling was defined by the local reference approach at baseline or follow-up. CONCLUSION: Remodelling assessment using a global arterial reference approach, but not the commonly used, local reference site approach, correlated reasonably well with serial changes in arterial dimensions and identified arterial segments with subsequent PAV progression despite intensive statin treatment and overall atheroma regression.

Validation of high bleeding risk criteria and definition as proposed by the academic research consortium for high bleeding risk.

AIMS: To validate the set of clinical and biochemical criteria proposed by consensus by the Academic Research Consortium (ARC) for High Bleeding Risk (HBR) for the identification of HBR patients. These criteria were categorized into major and minor, if expected to carry in isolation, respectively, ≥4% and <4% Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding risk within 1-year after percutaneous coronary intervention (PCI). High bleeding risk patients are those meeting at least 1 major or 2 minor criteria. METHODS AND RESULTS: All patients undergoing PCI at Bern University Hospital, between February 2009 and September 2018 were prospectively entered into the Bern PCI Registry (NCT02241291). Age, haemoglobin, platelet count, creatinine, and use of oral anticoagulation were prospectively collected, while the remaining HBR criteria except for planned surgery were retrospectively adjudicated. A total of 16 580 participants with complete ARC-HBR criteria were included. After assigning 1 point to each major and 0.5 point to each minor criterion, we observed for every 0.5 score increase a step-wise augmentation of BARC 3 or 5 bleeding rates at 1 year ranging from 1.90% among patients fulfilling no criterion, through 4.01%, 5.98%, 7.42%, 8.60%, 12.21%, 12.29%, and 17.64%. All major and five out of six minor criteria, conferred in isolation a risk for BARC 3 or 5 bleeding at 1 year exceeding 4% at the upper limit of the 95% confidence intervals. CONCLUSION: All major and the majority of minor ARC-HBR criteria identify in isolation patients at HBR.

Shear Stress Estimated by Quantitative Coronary Angiography Predicts Plaques Prone to Progress and Cause Events.

OBJECTIVES: This study examined the value of endothelial shear stress (ESS) estimated in 3-dimensional quantitative coronary angiography (3D-QCA) models in detecting plaques that are likely to progress and cause events. BACKGROUND: Cumulative evidence has shown that plaque characteristics and ESS derived from intravascular ultrasound (IVUS)-based reconstructions enable prediction of lesions that will cause cardiovascular events. However, the prognostic value of ESS estimated by 3D-QCA in nonflow limiting lesions is yet unclear. METHODS: This study analyzed baseline virtual histology (VH)-IVUS and angiographic data from 28 lipid-rich lesions (i.e., fibroatheromas) that caused major adverse cardiovascular events or required revascularization (MACE-R) at 5-year follow-up and 119 lipid-rich plaques from a control group that remained quiescent. The segments studied by VH-IVUS at baseline were reconstructed using 3D-QCA software. In the obtained geometries, blood flow simulation was performed, and the pressure gradient across the lipid-rich plaque and the mean ESS values in 3-mm segments were estimated. The additive value of these hemodynamic indexes in predicting MACE-R beyond plaque characteristics was examined. RESULTS: MACE-R lesions were longer, had smaller minimum lumen area, increased plaque burden (PB), were exposed to higher ESS, and exhibited a higher pressure gradient. In multivariable analysis, PB (hazard ratio: 1.08; p = 0.004) and the maximum 3-mm ESS value (hazard ratio: 1.11; p = 0.001) were independent predictors of MACE-R. Lesions exposed to high ESS (>4.95 Pa) with a high-risk anatomy (minimal lumen area <4 mm2 and PB >70%) had a higher MACE-R rate (53.8%) than those with a low-risk anatomy exposed to high ESS (31.6%) or those exposed to low ESS who had high- (20.0%) or low-risk anatomy (7.1%; p < 0.001). CONCLUSIONS: In the present study, 3D-QCA-derived local hemodynamic variables provided useful prognostic information, and, in combination with lesion anatomy, enabled more accurate identification of MACE-R lesions.

Validation of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria in patients undergoing percutaneous coronary intervention and comparison with contemporary bleeding risk scores.

AIMS: The Academic Research Consortium for High Bleeding Risk (ARC-HBR) defined consensus-based criteria for patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI). We aimed to validate the ARC-HBR criteria for the bleeding outcomes using a large cohort of patients undergoing PCI. METHODS AND RESULTS: Between 2009 and 2016, patients undergoing PCI were prospectively included in the Bern PCI Registry. Patients were considered to be at HBR if at least one major criterion or two minor criteria were met. The primary endpoint was Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding at one year; ischaemic outcomes were assessed using the device-oriented composite endpoints (DOCE) of cardiac death, target vessel myocardial infarction, and target lesion revascularisation. Among 12,121 patients, those at HBR (n=4,781, 39.4%) had an increased risk of BARC 3 or 5 bleeding (6.4% vs 1.9%; p<0.001) and DOCE (12.5% vs 6.1%; p<0.001) compared with those without HBR. The degree of risk and prognostic value were related to the risk factors composing the criteria. The ARC-HBR criteria had higher sensitivity than the PRECISE-DAPT score and the PARIS bleeding risk score (63.8%, 53.1%, 31.9%), but lower specificity (62.7%, 71.3%, 86.5%) for BARC 3 or 5 bleeding. CONCLUSIONS: Patients at HBR defined by the ARC-HBR criteria had a higher risk of BARC 3 or 5 bleeding as well as DOCE. The bleeding risk was related to its individual components. The ARC-HBR criteria were more sensitive for identifying patients with future bleedings than other contemporary risk scores at the cost of specificity. ClinicalTrials.gov Identifier: NCT02241291

Everolimus-Eluting Biodegradable Polymer Versus Everolimus-Eluting Durable Polymer Stent for Coronary Revascularization in Routine Clinical Practice.

OBJECTIVES: The aim of this study was to compare the efficacy and safety of a thin-strut, biodegradable-polymer everolimus-eluting stent (BP-EES) (Synergy, Boston Scientific, Marlborough, Massachusetts) and a thin-strut, durable-polymer everolimus-eluting stent (DP-EES) (XIENCE, Abbott Vascular, Abbott Park, Illinois) in an all-comers population. BACKGROUND: BP-EES have been shown to be noninferior to DP-EES in randomized trials in patients at low to moderate risk. METHODS: Among 7,042 consecutive patients who underwent percutaneous coronary intervention between December 2012 and December 2016, 3,870 patients were exclusively treated with BP-EES (n = 1,343) or with DP-EES (n = 2,527). After propensity score matching, the final study population consisted of 1,041 matched patients. The primary endpoint was the device-oriented composite endpoint (cardiac death, target vessel myocardial infarction, and target lesion revascularization) at 12 months. RESULTS: The device-oriented composite endpoint did not differ between the 2 groups (7.8% with BP-EES vs. 7.1% with DP-EES; hazard ratio: 1.12; 95% confidence interval: 0.81 to 1.53; p = 0.49). There were no differences in rates of cardiac death (3.0% vs. 3.0%; p = 1.00), target vessel myocardial infarction (3.6% vs. 3.1%; p = 0.53), and target lesion revascularization (3.0% vs. 2.5%; p = 0.41). The rate of acute stent thrombosis was significantly higher in the BP-EES group compared with the DP-EES group (1.2% vs. 0.3%; hazard ratio: 4.00; 95% confidence interval: 1.13 to 14.19; p = 0.032). At 12 months, the frequency of definite stent thrombosis did not differ (1.5% vs. 0.9%; hazard ratio: 1.67; 95% confidence interval: 0.73 to 3.82; p = 0.22). CONCLUSIONS: In this consecutively enrolled percutaneous coronary intervention population reflecting routine clinical practice, no difference in the device-oriented composite endpoint between BP-EES and DP-EES was observed throughout 12 months. There was a higher rate of acute stent thrombosis with the BP-EES, a difference that disappeared at 1 year. (CARDIOBASE Bern PCI Registry; NCT02241291).

Validation of High-Risk Features for Stent-Related Ischemic Events as Endorsed by the 2017 DAPT Guidelines.

OBJECTIVES: This study sought to validate European Society of Cardiology guideline-endorsed high-risk features of stent-related recurrent ischemic events for the prediction of ischemic and bleeding outcomes including a stratification according to the PRECISE-DAPT score estimated bleeding risk. BACKGROUND: The 2017 European Society of Cardiology-focused update on dual-antiplatelet therapy endorsed high-risk features of stent-related recurrent ischemic events. Because patients with high ischemic risk also have an increased bleeding risk, appropriate risk stratification for ischemic and bleeding events is crucial. METHODS: Between January 2009 and December 2015, a total of 10,236 consecutive patients undergoing clinically indicated percutaneous coronary intervention were prospectively included in the Bern PCI Registry. Guideline-endorsed high-risk features were retrospectively assessed. The primary ischemic endpoint was device-oriented composite endpoint (DOCE) (cardiac death, target-vessel myocardial infarction, and target lesion revascularization) at 1 year, and the primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) 3-5 at 1 year. RESULTS: A total of 5,323 (52.0%) patients had at least 1 high-risk feature. Among patients with high-risk features, DOCE (12.3% vs. 5.5%; p < 0.001) and BARC 3-5 bleeding (4.9% vs. 2.2%; p < 0.001) occurred more frequently compared with those without. There was a graded risk increase for DOCE (0: 5.5%; 1 to 2: 11.3%; and ≥3: 16.7%; p < 0.001) and BARC 3-5 bleeding (0: 2.2%; 1 to 2: 4.5%; and ≥3: 6.6%; p < 0.001) as the number of high-risk features increased. High-PRECISE-DAPT score (≥25) was associated with an increased risk of DOCE and BARC 3-5 bleeding, irrespective of number of high-risk features. CONCLUSIONS: The European Society of Cardiology guideline-endorsed high-risk features were associated with increased ischemic and bleeding risks following percutaneous coronary intervention in routine clinical practice. (CARDIOBASE Bern PCI Registry; NCT02241291).

Ischemia and Bleeding in Cancer Patients Undergoing Percutaneous Coronary Intervention.

OBJECTIVES: The purpose of this study was to evaluate ischemic and bleeding outcomes of unselected cancer patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: The number of cancer patients undergoing PCI is increasing despite concerns regarding ischemic and bleeding risks. METHODS: Between 2009 and 2017, consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Cancer-specific data including type, date of initial diagnosis, and health status at index PCI were collected. We performed propensity score matching to adjust for baseline differences between patients with and without cancer. The primary ischemic endpoint was the device-oriented composite endpoint (cardiac death, target vessel myocardial infarction, target lesion revascularization) at 1 year, and the primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) 2 to 5 at 1 year. RESULTS: Among 13,647 patients, 1,368 (10.0%) had an established diagnosis of cancer. The 3 leading cancer types were prostate (n = 294), gastrointestinal tract (n = 188), and hematopoietic (n = 177). At index PCI, 179 (13.1%) patients were receiving active cancer treatment. In matched analysis, there was no significant difference in device-oriented composite endpoint (11.5% vs. 10.2%; p = 0.251), whereas cardiac death and BARC 2 to 5 bleeding occurred more frequently among patients with cancer compared with those without cancer (6.8% vs. 4.5%; p = 0.010 and 8.0% vs. 6.0%; p = 0.026, respectively). Cancer diagnosis within 1 year before PCI emerged as an independent predictor for cardiac death and BARC 2 to 5 bleeding at 1 year. CONCLUSIONS: Cancer patients carry an increased risk of cardiac mortality that was not associated with stent-related ischemic events among patients undergoing PCI in routine clinical practice. Higher risk of bleeding in cancer patients undergoing PCI deserves particular attention. (CARDIOBASE Bern PCI Registry; NCT02241291).

Unselected Use of Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Coronary Revascularization.

BACKGROUND: Biodegradable polymer sirolimus-eluting stents (BP-SESs) have been reported to be noninferior compared with durable polymer everolimus-eluting stents (DP-EES) in a randomized clinical trial. We sought to compare the efficacy and safety of an ultrathin strut BP-SES with a DP-EES in an all-comers population. METHODS AND RESULTS: Among 7640 consecutive patients who underwent percutaneous coronary intervention between March 2011 and June 2015, 4638 patients were exclusively treated with BP-SES (N=1896; 3137 lesions) or DP-EES (N=2742; 4468 lesions). After propensity score matching within strata of clinical indications, the final study population consisted of 2902 matched patients (BP-SES 2406 lesions and DP-EES 2368 lesions). The primary device-oriented composite end point (DOCE) included cardiac death, target vessel myocardial infarction, and target lesion revascularization at 1 year. BP-SES (6.9%) was noninferior to DP-EES (8.0%) with respect to device-oriented composite end point (hazard ratio [HR], 0.85; 95% CI, 0.65-1.11; P for noninferiority <0.001; P for superiority=0.24). No differences in cardiac death (BP-SES, 2.3% versus DP-EES, 3.0%; HR, 0.76; 95% CI, 0.49-1.20; P=0.25), myocardial infarction (BP-SES, 4.6% versus DP-EES, 4.6%; HR, 1.00; 95% CI, 0.71-1.40; P=0.99), or target lesion revascularization (BP-SES, 2.8% versus DP-EES, 2.5%; HR, 1.11; 95% CI, 0.71-1.74; P=0.65) were observed. The rate of periprocedural myocardial infarction was comparable between the 2 groups (2.1% versus 2.2%; HR, 0.97; 95% CI, 0.59-1.58; P=0.89). The rate of definite stent thrombosis was similarly low throughout 1 year (BP-SES, 0.8% versus DP-EES, 0.8%; HR, 1.00; 95% CI, 0.45-2.22; P=1.00). CONCLUSIONS: In a consecutively enrolled percutaneous coronary intervention population reflecting routine clinical practice, BP-SES was noninferior to DP-EES for device-oriented composite end point at 1 year. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02241291.

Progression of cardiac allograft vasculopathy assessed by serial three-vessel quantitative coronary angiography.

BACKGROUND: The purpose of the present study was to assess the short- and long-term progression of cardiac allograft vasculopathy (CAV) using serial 3-vessel quantitative coronary angiography (QCA). METHODS: CAV progression was assessed using serial 3-vessel QCA analysis at baseline, 1-year and long-term angiographic follow-up (8.5±3.7 years) after heart transplantation. The change in minimal lumen diameter (MLD) and percent diameter stenosis (%DS) was serially assessed within matched segments. Patients were graded according to the ISHLT-CAV classification and grouped as ISHLT-CAV0 and ISHLT-CAV1-3. The primary endpoint was mean change in MLD and %DS. RESULTS: A total of 41 patients and 520 matched segments were available for serial 3-vessel QCA. Overall, MLD decreased non-significantly from baseline to 1-year follow-up and significantly from 1-year to the long-term angiographic follow-up (Δ-0.08mm/year [95%CI -0.11 to -0.05], P<0.001). %DS increased significantly from baseline to 1-year (Δ+0.96%/year [95%CI 0.04 to 1.88], P = 0.041) and from 1-year to long-term angiographic follow-up (Δ+0.61%/year [95%CI 0.33 to 0.88], P<0.001). ISHLT-CAV1-3 at 1 year and at long-term angiographic follow-up was observed in 22% and 61%, respectively. Between baseline and long-term angiographic follow-up, a significant reduction in MLD was observed within both groups without a significant difference in the reduction between the two groups (ISHLT-CAV0: median -0.49mm [IQR -0.54 to -0.43] vs. ISHLT-CAV1-3: median -0.40mm [IQR -0.44 to -0.35], P = 0.4). CONCLUSION: The current data suggest that QCA can't predict CAV beyond 1 year, but, QCA affirmed that CAV progresses to a similar extent in patients who do not develop visual CAV during long-term follow-up.

Frequency, Reasons, and Impact of Premature Ticagrelor Discontinuation in Patients Undergoing Coronary Revascularization in Routine Clinical Practice: Results From the Bern Percutaneous Coronary Intervention Registry.

BACKGROUND: Although ticagrelor has improved clinical outcomes among patients with acute coronary syndrome compared with clopidogrel, adherence to this new antiplatelet agent in real-world practice has not been fully investigated. METHODS AND RESULTS: Between November 2011 and June 2014, 1278 of 4831 consecutive patients (26.5%) undergoing percutaneous coronary intervention at a tertiary care center were treated with ticagrelor. Premature ticagrelor cessation was categorized into (1) change, when ticagrelor was replaced by prasugrel; (2) de-escalation, when ticagrelor was replaced by clopidogrel; and (3) premature discontinuation, when ticagrelor was discontinued without P2Y12 inhibitor replacement. Of 1278 patients treated with ticagrelor, premature treatment cessation occurred in 212 patients (17%). De-escalation to clopidogrel was the most frequent scenario (57%; n=120), followed by premature discontinuation (28%; n=60) and change to prasugrel (15%; n=32). Reasons for ticagrelor cessation included adverse effects (49%), initiation of oral anticoagulation (19%), and unspecified general practitioner preference (10%). Most frequent adverse effects leading to premature ticagrelor cessation were bleeding (41%), dyspnea (29%), and gastrointestinal symptoms (18%). Premature ticagrelor cessation was not associated with an increased risk of cardiac death, myocardial infarction, or stroke (hazard ratio, 0.73; 95% confidence interval: 0.40-1.32; P=0.29). CONCLUSIONS: Premature ticagrelor cessation in routine clinical practice occurred in 1 of 6 patients and was primarily related to adverse effects among which bleeding and dyspnea were the most frequent. Although premature ticagrelor cessation was not associated with adverse cardiovascular outcomes, this finding requires careful interpretation in view of the modest sample size. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02241291.

Ten-year clinical outcomes of first-generation drug-eluting stents: the Sirolimus-Eluting vs. Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) VERY LATE trial.

AIMS: Compared with bare metal stents, first-generation drug-eluting stents (DES) are associated with an increased risk of late restenosis and stent thrombosis (ST). Whether this risk continues or attenuates during long-term follow-up remains unknown. METHODS AND RESULTS: We extended the follow-up of 1012 patients [sirolimus-eluting stent (SES): N = 503 and paclitaxel-eluting stent (PES): N = 509] included in the all-comers, randomized Sirolimus-Eluting vs. Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) trial to 10 years. Follow-up was complete in 895 patients (88.4%) at 10 years. At 1, 5, and 10 years of follow-up, rates of ischaemia-driven target lesion revascularization (ID-TLR) were 8.1%, 14.6% and 17.7%, respectively, and rates of ST were 1.9%, 4.5% and 5.6%, respectively. The annual risks of ID-TLR and definite ST were significantly higher between 1 and 5 years as compared with the 5- to 10-year period [ID-TLR: 1.8% vs. 0.7%/year, hazard ratio (HR) 0.36, 95% confidence intervals (95% CI) 0.21-0.62, P < 0.001; definite ST: 0.67% vs. 0.23%/year, HR 0.31, 95% CI 0.13-0.75, P = 0.01]. The attenuation of the risk of ID-TLR and ST beyond 5 years was independent of age. Major adverse events (cardiac death, myocardial infarction, and ID-TLR) occurred in 33.7% of SES- and 33.8% of PES-treated patients (P = 0.72). CONCLUSIONS: During long-term follow-up through 10 years, the annual risks of ID-TLR and definite ST significantly decreased beyond 5 years after first-generation DES implantation. These findings may have important implications for secondary prevention after percutaneous coronary intervention with first-generation DES including long-term antiplatelet therapy. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00297661.