Ten-year clinical outcomes after drug-eluting stents implantation according to clinical presentation-Insights from the DECADE cooperation.

BACKGROUND: Investigations of very long-term outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) according to clinical presentation are scarce. Here, we investigated the 10-year clinical outcomes of patients undergoing DES-PCI according to clinical presentation. METHODS: Patient-level data from five randomized trials with 10-year follow-up after DES-PCI were pooled. Patients were dichotomized into acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) groups as per clinical presentation. The primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST) and repeat revascularization involving the target lesion (TLR), target vessel (TVR) or non-target vessel (nTVR). RESULTS: Of the 9700 patients included in this analysis, 4557 presented with ACS and 5143 with CCS. Compared with CCS patients, ACS patients had a higher risk of all-cause death and nTVR in the first year, but comparable risk thereafter. In addition, ACS patients had a higher risk of MI [adjusted hazard ratio 1.21, 95% confidence interval (1.04-1.41)] and definite ST [adjusted hazard ratio 1.48, 95% confidence interval (1.14-1.92)], while the risk of TLR and TVR was not significantly different up to 10-year follow-up. CONCLUSIONS: Compared to CCS patients, ACS patients treated with PCI and DES implantation have an increased risk of all-cause death and repeat revascularization of remote vessels up to 1 year, with no significant differences thereafter and up to 10-year follow-up. ACS patients have a consistently higher risk of MI and definite ST. Whether these differences persist with current antithrombotic and secondary prevention therapies requires further investigation.

Derivation and Validation of the PRECISE-HBR Score to Predict Bleeding After Percutaneous Coronary Intervention.

BACKGROUND: Accurate bleeding risk stratification after percutaneous coronary intervention (PCI) is important for treatment individualization. However, there is still an unmet need for a more precise and standardized identification of high bleeding risk patients. We derived and validated a novel bleeding risk score by augmenting the PRECISE-DAPT score with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. METHODS: The derivation cohort comprised 29,188 patients undergoing PCI, of whom 1136 (3.9%) had a Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding at 1 year, from four contemporary real-world registries and the XIENCE V USA trial. The PRECISE-DAPT score was refitted with a Fine-Gray model in the derivation cohort and extended with the ARC-HBR criteria. The primary outcome was BARC 3 or 5 bleeding within 1 year. Independent predictors of BARC 3 or 5 bleeding were selected at multivariable analysis (p<0.01). The discrimination of the score was internally assessed with apparent validation and cross-validation. The score was externally validated in 4578 patients from the MASTER DAPT trial and 5970 patients from the STOPDAPT-2 total cohort. RESULTS: The PRECISE-HBR score (age, estimated glomerular filtration rate, hemoglobin, white-blood-cell count, previous bleeding, oral anticoagulation, and ARC-HBR criteria) showed an area under the curve (AUC) for 1-year BARC 3 or 5 bleeding of 0.73 (95% CI, 0.71-0.74) at apparent validation, 0.72 (95% CI, 0.70-0.73) at cross-validation, 0.74 (95% CI, 0.68-0.80) in the MASTER DAPT, and 0.73 (95% CI, 0.66-0.79) in the STOPDAPT-2, with superior discrimination than the PRECISE-DAPT (cross-validation: Δ AUC, 0.01; p=0.02; MASTER DAPT: Δ AUC, 0.05; p=0.004; STOPDAPT-2: Δ AUC, 0.02; p=0.20) and other risk scores. In the derivation cohort, a cut-off of 23 points identified 11,414 patients (39.1%) with a 1-year BARC 3 or 5 bleeding risk ≥4%. An alternative version of the score, including acute myocardial infarction on admission instead of white-blood-cell count, showed similar predictive ability. CONCLUSIONS: The PRECISE-HBR score is a contemporary, simple 7-item risk score to predict bleeding after PCI, offering a moderate improvement in discrimination over multiple existing scores. Further evaluation is required to assess its impact on clinical practice.

Prognostic value of a novel artificial intelligence-based coronary CTA-derived ischemia algorithm among patients with normal or abnormal myocardial perfusion.

BACKGROUND: Among patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA), downstream positron emission tomography (PET) perfusion imaging can be performed to assess the presence of myocardial ischemia. A novel artificial-intelligence-guided quantitative computed tomography ischemia algorithm (AI-QCTischemia) aims to predict ischemia directly from coronary CTA images. We aimed to study the prognostic value of AI-QCTischemia among patients with obstructive CAD on coronary CTA and normal or abnormal downstream PET perfusion. METHODS: AI-QCTischemia was calculated by blinded analysts among patients from the retrospective coronary CTA cohort at Turku University Hospital, Finland, with obstructive CAD on initial visual reading (diameter stenosis ≥50%) being referred for downstream 15O-H2O-PET adenosine stress perfusion imaging. All coronary arteries with their side branches were assessed by AI-QCTischemia. Absolute stress myocardial blood flow ≤2.3 â€‹ml/g/min in ≥2 adjacent segments was considered abnormal. The primary endpoint was death, myocardial infarction, or unstable angina pectoris. The median follow-up was 6.2 [IQR 4.4-8.3] years. RESULTS: 662 of 768 (86%) patients had conclusive AI-QCTischemia result. In patients with normal 15O-H2O-PET perfusion, an abnormal AI-QCTischemia result (n â€‹= â€‹147/331) vs. normal AI-QCTischemia result (n â€‹= â€‹184/331) was associated with a significantly higher crude and adjusted rates of the primary endpoint (adjusted HR 2.47, 95% CI 1.17-5.21, p â€‹= â€‹0.018). This did not pertain to patients with abnormal 15O-H2O-PET perfusion (abnormal AI-QCTischemia result (n â€‹= â€‹269/331) vs. normal AI-QCTischemia result (n â€‹= â€‹62/331); adjusted HR 1.09, 95% CI 0.58-2.02, p â€‹= â€‹0.794) (p-interaction â€‹= â€‹0.039). CONCLUSION: Among patients with obstructive CAD on coronary CTA referred for downstream 15O-H2O-PET perfusion imaging, AI-QCTischemia showed incremental prognostic value among patients with preserved perfusion by 15O-H2O-PET imaging, but not among those with reduced perfusion.

Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy.

BACKGROUND AND AIMS: The effects of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on endothelial function as assessed by flow-mediated dilation (FMD) in patients with acute myocardial infarction (AMI) are unknown. Therefore, we aimed to investigate the effects of the PCSK9 inhibitor alirocumab added to high-intensity statin on FMD, and its association with coronary atherosclerosis in non-infarct related arteries using intracoronary intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT). METHODS: This was a pre-specified substudy among patients recruited at Bern University Hospital, Switzerland, for the randomized-controlled, double-blind, PACMAN-AMI trial, which compared the effects of biweekly alirocumab 150 mg vs. placebo added to rosuvastatin. Brachial artery FMD was measured at 4 and 52 weeks, and intracoronary imaging at baseline and 52 weeks. RESULTS: 139/173 patients completed the substudy. There was no difference in FMD at 52 weeks in the alirocumab (n = 68, 5.44 ± 2.24%) versus placebo (n = 71, 5.45 ± 2.19%) group (difference = -0.21%, 95% CI -0.77 to 0.35, p = 0.47). FMD improved throughout 52 weeks in both groups similarly (p < 0.001). There was a significant association between 4 weeks FMD and baseline plaque burden (IVUS) (n = 139, slope = -1.00, p = 0.006), but not with lipid pool (NIRS) (n = 139, slope = -7.36, p = 0.32), or fibrous cap thickness (OCT) (n = 81, slope = -1.57, p = 0.62). CONCLUSIONS: Among patients with AMI, the addition of alirocumab did not result in further improvement of FMD as compared to 52 weeks secondary preventative medical therapy including high-intensity statin therapy. FMD was significantly associated with coronary plaque burden at baseline, but not with lipid pool or fibrous cap thickness.

Pretreatment With P2Y12 Inhibitors in ST-Segment Elevation Myocardial Infarction: Insights From the Bern-PCI Registry.

BACKGROUND: Evidence to support immediate P2Y12 inhibitor loading in ST-segment elevation myocardial infarction (STEMI) is limited. OBJECTIVES: This study sought to compare outcomes of STEMI patients receiving immediate or delayed P2Y12 inhibitor treatment. METHODS: Using data from the prospective Bern-PCI registry between 2016 and 2020, we stratified STEMI patients undergoing percutaneous coronary intervention according to time periods with different institutional recommendations regarding P2Y12 inhibitor pretreatment. In cohort 1 (October 2016-September 2018), immediate P2Y12 inhibitor treatment was recommended. In cohort 2 (October 2018-September 2020), P2Y12 inhibitor treatment was recommended after coronary anatomy was confirmed. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events (MACCEs) defined as all-cause death, recurrent myocardial infarction, stroke, or definite stent thrombosis at 30 days. Sensitivity analysis included only patients in whom these recommendations were followed. RESULTS: Cohort 1 included 1,116 patients; pretreatment was actually given in 708 (63.4%). Cohort 2 included 847 patients; pretreatment was withheld in 798 (94.2%). The mean age was 65 ± 13 years, and 24% were female. Baseline characteristics were well-balanced between groups. The median difference for P2Y12 loading to angiography was 52 minutes between cohort 1 and 2 and 100 minutes between patients receiving vs not receiving pretreatment. Rates of MACCEs were similar between cohort 1 and cohort 2 (10.1% vs 8.1%; adjusted HR: 0.91; 95% CI: 0.65-1.28; P = 0.59) and between patients receiving vs not receiving pretreatment (7.1% vs 8.4%; adjusted HR: 1.17; 95% CI: 0.78-1.74; P = 0.45). CONCLUSIONS: In this cohort study of patients with STEMI undergoing primary percutaneous coronary intervention, P2Y12 inhibitor pretreatment was not associated with improved MACCEs.

Quantitative Flow Ratio to Predict Non-Target-Vessel Events Before Planned Staged Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome.

BACKGROUND: The optimal time point of staged percutaneous coronary intervention (PCI) among patients with acute coronary syndrome (ACS) remains a matter of debate. Quantitative flow ratio (QFR) is a novel noninvasive method to assess the hemodynamic significance of coronary stenoses. We aimed to investigate whether QFR could refine the timing of staged PCI of non-target vessels (non-TVs) on top of clinical judgment for patients with ACS. METHODS AND RESULTS: For this cohort study, patients with ACS from Bern University Hospital, Switzerland, scheduled to undergo out-of-hospital non-TV staged PCI were eligible. The primary end point was the composite of non-TV myocardial infarction and urgent unplanned non-TV PCI before planned staged PCI. The association between lowest QFR per patient measured in the non-TV (from index angiogram) and the primary end point was assessed using multivariable adjusted Cox proportional hazards regressions with QFR included as linear or penalized spline (nonlinear) term. QFR was measured in 1093 of 1432 patients with ACS scheduled to undergo non-TV staged PCI. Median time to staged PCI was 28 days. The primary end point occurred in 5% of the patients. In multivariable analysis (1018 patients), there was no independent association between non-TV QFR and the primary end point (hazard ratio, 0.87 [95% CI, 0.69-1.05] per 0.1 increase; P=0.125; nonlinear P=0.648). CONCLUSIONS: In selected patients with ACS scheduled to undergo staged PCI at a median of 4 weeks after index PCI, QFR did not emerge as an independent predictor of non-TV events before planned staged PCI. Thus, this study does not provide conceptual evidence that QFR is helpful to refine the timing of staged PCI on top of clinical judgment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02241291.

Prognostic Value of a Novel Artificial Intelligence-Based Coronary Computed Tomography Angiography-Derived Ischemia Algorithm for Patients with Suspected Coronary Artery Disease.

AIMS: Coronary computed tomography angiography (CTA) imaging is used to diagnose patients with suspected coronary artery disease (CAD). A novel artificial-intelligence-guided quantitative computed tomography ischemia algorithm (AI-QCTischemia) aims to identify myocardial ischemia directly from CTA images and may be helpful to improve risk stratification. The aims were 1) the prognostic value of AI-QCTischemia among symptomatic patients with suspected CAD entering diagnostic imaging with coronary CTA, and 2) the prognostic value of AI-QCTischemia separately among patients with no/non-obstructive CAD (≤50% visual diameter stenosis) and obstructive CAD (>50% visual diameter stenosis). METHODS AND RESULTS: For this cohort study, AI-QCTischemia was calculated by blinded analysts among patients with suspected CAD undergoing coronary CTA. The primary endpoint was the composite of death, myocardial infarction (MI), or unstable angina pectoris (uAP) (median follow-up 6.9 years). 1880/2271 (83%) patients were analyzable by AI-QCTischemia. Patients with an abnormal AI-QCTischemia result (n = 509/1880) vs. patients with a normal AI-QCTischemia result (n = 1371/1880) had significantly higher crude and adjusted rates of the primary endpoint (HRadj 1.96,95% CI 1.46-2.63, p < 0.001; covariates: age/sex/hypertension/diabetes/smoking/typical angina). An abnormal AI-QCTischemia result was associated with significantly higher crude and adjusted rates of the primary endpoint among patients with no/non-obstructive CAD (n = 1373/1847) (HRadj 1.81,95% CI 1.09-3.00, p = 0.022), but not among those with obstructive CAD (n = 474/1847) (HRadj 1.26,95% CI 0.75-2.12, p = 0.386) (p-interaction = 0.032). CONCLUSION: Among patients with suspected CAD, an abnormal AI-QCTischemia result was associated with a 2-fold increased adjusted rate of long-term death, MI, or uAP. AI-QCTischemia may be useful to improve risk stratification, especially among patients with no/non-obstructive CAD on coronary CTA.

Effect of Alirocumab Added to High-Intensity Statin on Platelet Reactivity and Noncoding RNAs in Patients with AMI: A Substudy of the PACMAN-AMI Trial.

OBJECTIVE: The effect of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. We aimed to explore the effect of alirocumab added to high-intensity statin therapy on P2Y12 reaction unit (PRU) among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). In addition, we assessed circulating platelet-derived noncoding RNAs (microRNAs and YRNAs). METHODS: This was a prespecified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Patients recruited at Bern University Hospital, receiving DAPT with a potent P2Y12 inhibitor, and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The primary endpoint was PRU at 4 weeks after study drug initiation as assessed by VerifyNow P2Y12 point-of-care assays. RESULTS: Among 139 randomized patients, the majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] in the alirocumab group vs. 69 [94.5%] in the placebo group, p = 0.14). There were no significant differences in the primary endpoint PRU at 4 weeks between groups (12.5 [interquartile range, IQR: 27.0] vs. 19.0 [IQR: 30.0], p = 0.26). Consistent results were observed in 126 patients treated with ticagrelor (13.0 [IQR: 20.0] vs. 18.0 [IQR: 27.0], p = 0.28). Similarly, platelet-derived noncoding RNAs did not significantly differ between groups. CONCLUSION: Among AMI patients receiving DAPT with a potent P2Y12 inhibitor, alirocumab had no significant effect on platelet reactivity as assessed by PRU and platelet-derived noncoding RNAs.

Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy.

BACKGROUND: The frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown. OBJECTIVES: This study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy. METHODS: The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed. RESULTS: Overall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: -27.1 mg/dL; 95% CI: -37.7 to -16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04). CONCLUSIONS: Triple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844).

Impact of alirocumab on plaque regression and haemodynamics of non-culprit arteries in patients with acute myocardial infarction: a prespecified substudy of the PACMAN-AMI trial.

BACKGROUND: Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on top of statins leads to plaque regression and stabilisation. The effects of PCSK9 inhibitors on coronary physiology and angiographic diameter stenosis (DS%) are unknown. AIMS: This study aimed to investigate the effects of the PCSK9 inhibitor alirocumab on coronary haemodynamics as assessed by quantitative flow ratio (QFR) and DS% by three-dimensional quantitative coronary angiography (3D-QCA) in non-infarct-related arteries (non-IRA) among acute myocardial infarction (AMI) patients. METHODS: This was a prespecified substudy of the randomised controlled PACMAN-AMI trial, comparing alirocumab versus placebo on top of rosuvastatin. QFR and 3D-QCA were assessed at baseline and 1 year in any non-IRA ≥2.0 mm and 3D-QCA DS% >25%. The prespecified primary endpoint was the number of patients with a mean QFR increase at 1 year, and the secondary endpoint was the change in 3D-QCA DS%. RESULTS: Of 300 enrolled patients, 265 had serial follow-up, of which 193 underwent serial QFR/3D-QCA analysis in 282 non-IRA. At 1 year, QFR increased in 50/94 (53.2%) patients with alirocumab versus 40/99 (40.4%) with placebo (Δ12.8%; odds ratio 1.7, 95% confidence interval [CI]: 0.9 to 3.0; p=0.076). DS% decreased by 1.03±7.28% with alirocumab and increased by 1.70±8.27% with placebo (Δ-2.50%, 95% CI: -4.43 to -0.57; p=0.011). CONCLUSIONS: Treatment of AMI patients with alirocumab versus placebo for 1 year resulted in a significant regression in angiographic DS%, whereas no overall improvement of coronary haemodynamics was observed. CLINICALTRIALS: gov: NCT03067844.

Clinical outcomes in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary interventions later than 48 h after symptom onset.

AIMS: Routine revascularization in patients with ST-segment elevation myocardial infarction (STEMI) presenting >48 h after symptom onset is not recommended. METHODS AND RESULTS: We compared outcomes of STEMI patients undergoing percutaneous coronary intervention (PCI) according to total ischaemic time. Patients included in the Bern-PCI registry and the Multicenter Special Program University Medicine ACS (SPUM-ACS) between 2009 and 2019 were analysed. Based on symptom-to-balloon-time, patients were categorized as early (<12 h), late (12-48 h), or very late presenters (>48 h). Co-primary endpoints were all-cause mortality and target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization at 1 year. Of 6589 STEMI patients undergoing PCI, 73.9% were early, 17.2% late, and 8.9% very late presenters. The mean age was 63.4 years, and 22% were female. At 1 year, all-cause mortality occurred more frequently in late vs. early [5.8 vs. 4.4%, hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.01-1.78, P = 0.04] and very late (6.8%) vs. early presenters (HR 1.59, 95% CI 1.12-2.25, P < 0.01). There was no excess in mortality comparing very late and late presenters (HR 1.18, 95% CI 0.79-1.77, P = 0.42). Target lesion failure was more frequent in late vs. early (8.3 vs. 6.5%, HR 1.29, 95% CI 1.02-1.63, P = 0.04) and very late (9.4%) vs. early presenters (HR 1.47, 95% CI 1.09-1.97, P = 0.01), and similar between very late and late presenters (HR 1.14, 95% CI 0.81-1.60, P = 0.46). Following adjustment, heart failure, impaired renal function, and previous gastrointestinal bleeding, but not treatment delay, were the main drivers of outcomes. CONCLUSION: PCI >12 h after symptom onset was associated with less favourable outcomes, but very late vs. late presenters did not have an excess in events. While benefits seem uncertain, (very) late PCI appeared safe.

Acute Coronary Occlusion in Patients With Non-ST-Segment Elevation Out-of-Hospital Cardiac Arrest.

BACKGROUND: According to current guidelines, hemodynamic status should guide the decision between immediate and delayed coronary angiography (CAG) in out-of-hospital cardiac arrest (OHCA) patients without ST-segment elevation. A delayed strategy is advised in hemodynamically stable patients, and an immediate approach is recommended in unstable patients. OBJECTIVES: This study sought to assess the frequency, predictors, and clinical impact of acute coronary occlusion in hemodynamically stable and unstable OHCA patients without ST-segment elevation. METHODS: Consecutive unconscious OHCA patients without ST-segment elevation who were undergoing CAG at Bern University Hospital (Bern, Switzerland) between 2011 and 2019 were included. Frequency and predictors of acute coronary artery occlusions and their impact on all-cause and cardiovascular mortality at 1 year were assessed. RESULTS: Among the 386 patients, 169 (43.8%) were hemodynamically stable. Acute coronary occlusions were found in 19.5% of stable and 24.0% of unstable OHCA patients (P = 0.407), and the presence of these occlusions was predicted by initial chest pain and shockable rhythm, but not by hemodynamic status. Acute coronary occlusion was associated with an increased risk of cardiovascular death (adjusted HR: 2.74; 95% CI: 1.22-6.15) but not of all-cause death (adjusted HR: 0.72; 95% CI: 0.44-1.18). Hemodynamic instability was not predictive of fatal outcomes. CONCLUSIONS: Acute coronary artery occlusions were found in 1 in 5 OHCA patients without ST-segment elevation. The frequency of these occlusions did not differ between stable and unstable patients, and the occlusions were associated with a higher risk of cardiovascular death. In OHCA patients without ST-segment elevation, chest pain or shockable rhythm rather than hemodynamic status identifies patients with acute coronary occlusion.

Sex Differences in 10-Year Outcomes After Percutaneous Coronary Intervention With Drug-Eluting Stents: Insights From the DECADE Cooperation.

BACKGROUND: Although some studies have investigated sex-related outcomes up to 5 years after percutaneous coronary intervention (PCI), analyses at longer follow-up (ie, to 10 years) in large cohorts treated exclusively with drug-eluting stent (DES) platforms are lacking. Therefore, this study aimed to define whether sex-related differences in long-term outcomes after PCI persist both in the DES era and at longer-term follow-up. METHODS: Individual data of patients treated with DES in 5 randomized controlled trials with 10-year follow-up were pooled. Patients were divided into 2 groups by sex. The analysis of individual participant data was performed using a 1-stage approach by entering a clustering effect by parent study in all univariable and multivariable models focusing on sex. The main outcomes of interest for this analysis included cardiovascular death, myocardial infarction, repeat revascularization, and definite stent thrombosis to 10 years after PCI. Survival was analyzed by the Kaplan-Meier method to estimate the time to first event, and differences between the 2 groups were tested with the log-rank test. Hazard ratios (HRs) and 95% CIs were calculated with a Cox proportional hazards model. Conventional multivariable analyses with adjustment for relevant variables were performed. RESULTS: Among 9700 patients undergoing PCI with DES implantation included in the present analysis, 2296 were women and 7404 were men. Through to 10 years, cardiovascular death occurred in 407 of the 2296 female patients and 1012 of the 7404 male patients (adjusted HR [HRadj], 0.94 [95% CI, 0.80-1.11]). Female sex was associated with a lower risk of repeat revascularization of the target lesion (HRadj, 0.80 [95% CI, 0.74-0.87]), target vessel (HRadj, 0.81 [95% CI, 0.76-0.87]), and nontarget vessels (HRadj, 0.69 [95% CI, 0.62-0.77]). Compared with male patients, female patients displayed an increased risk of myocardial infarction in the first 30 days after PCI with DES (HRadj, 1.65 [95% CI, 1.24-2.19]) but a comparable risk of myocardial infarction thereafter. The risk of definite stent thrombosis was not significantly different between female and male patients (HRadj, 1.14 [95% CI, 0.89-1.47]). CONCLUSIONS: Through to 10-year follow-up after PCI with DES, female patients are at increased risk of early myocardial infarction, receive fewer repeat revascularizations, and have no difference in cardiovascular mortality compared with male patients.

Transient injection site reaction to alirocumab during immune system activation: a case series.

Background: Injection site reactions (ISRs) are known side effects of the proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor alirocumab. Transient ISR to alirocumab after a long phase of good tolerability have not been reported previously. Case summary: A 55-year-old woman (Patient 1) and a 77-year-old man (Patient 2) were treated with alirocumab for the management of dyslipidaemia. Both patients tolerated the treatment without side effects for 7 and 2 months, respectively. After an upper respiratory tract infection in Patient 1 and a first COVID-19 vaccination in Patient 2, both patients suddenly developed ISR with erythema, calor, and itching upon 2 (Patient 1) and 1 (Patient 2) subsequent injection(s), respectively. Symptoms resolved with local steroids, oral antihistamines, and cooling. After termination of the presumed immune system activated state, alirocumab was well tolerated again in both patients without recurrence of any ISR upon repeated applications. Discussion: These are the first cases to report transient ISR to a PCSK9 inhibitor, possibly triggered by activation of the immune system, after prolonged good tolerability. Based on the transient and benign nature of the reaction, such patients should be encouraged to continue supervised treatment, as tolerability may return after resolution of the pro-inflammatory state.

Ten-year patterns of stent thrombosis after percutaneous coronary intervention with new- versus early-generation drug-eluting stents: insights from the DECADE cooperation.

INTRODUCTION AND OBJECTIVES: The DECADE cooperation is a pooled analysis of individual patient data from drug-eluting stent (DES) trials with a 10-year follow-up. This analysis reports the risk of definite stent thrombosis (ST) through to 10 years after percutaneous coronary intervention (PCI) in patients treated with early- and new-generation DES. METHODS: Individual patient data from 5 DES trials with a 10-year follow-up were pooled. The primary endpoint was definite ST up to 10 years after PCI. Patients were divided into 2 groups as per the generation of DES implanted (early and new DES). Individual participant data were analyzed using a 1-stage approach. RESULTS: We included 9700 patients, 6866 in the new DES group and 2834 in the early DES group. Through to 10 years, definite ST occurred in 69 of 6866 patients treated with new DES and in 91 of 2834 patients treated with early DES (1.0% vs 3.5%, adjusted hazard ratio, 0.32; 95%CI, 0.23-0.45). The rate of definite ST was lower in the new DES group than in the early DES group from 1 to 5 years (rate ratio, 0.14; 95%CI, 0.08-0.26) and from 5 to 10 years (rate ratio, 0.23; 95%CI, 0.08-0.61) after PCI. CONCLUSIONS: The incidence of definite ST through to 10 years after PCI with new-generation DES was 1%. New-generation DES are associated with a lower 10-year incidence of definite ST than early-generation DES, particularly beyond 1 year after PCI.

Frequency and Outcomes of Periprocedural MI in Patients With Chronic Coronary Syndromes Undergoing PCI.

BACKGROUND: Definitions of periprocedural myocardial infarction (MI) differ with respect to biomarker threshold as well as ancillary criteria for myocardial ischemia and are limited in terms of validation. OBJECTIVES: This study evaluated the frequency and impact of periprocedural MI by using various MI definitions among patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI). METHODS: Between 2010 and 2018, periprocedural MIs were assessed according to the third and fourth Universal Definition of Myocardial Infarction (UDMI), Academic Research Consortium-2 (ARC-2), and Society for Cardiovascular Angiography and Interventions (SCAI) criteria based on high-sensitivity troponin in patients with CCS undergoing PCI enrolled into the Bern PCI registry. The primary endpoint was cardiac death at 1 year. RESULTS: Among 4,404 patients with CCS, periprocedural MI defined by the third UDMI, fourth UDMI, ARC-2, and SCAI were observed in 18.0%, 14.9%, 2.0%, and 2.0% of patients, respectively. Among patients with periprocedural MI defined by the third UDMI, fourth UDMI, ARC-2, and SCAI, cardiac mortality at 1 year was 2.9%, 3.0%, 5.8%, and 10.0%. The ARC-2 (HR: 3.90; 95% CI: 1.54-9.93) and SCAI (HR: 7.66; 95% CI: 3.64-16.11) were more relevant compared with the third UDMI (HR: 1.76; 95% CI: 1.04-3.00) and fourth UDMI (HR: 1.93; 95% CI: 1.11-3.37) for cardiac death at 1 year. CONCLUSIONS: Among patients with CCS undergoing PCI, periprocedural MI defined according to the ARC-2 and SCAI criteria was 7 to 9 times less frequent compared with the third and fourth UDMI. Periprocedural MI defined by using the ARC-2 and SCAI were more prognostic for cardiac death at 1 year compared with the third and fourth UDMI. (CARDIOBASE Bern PCI Registry; NCT02241291).

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.

Impact of Intracoronary Optical Coherence Tomography in Routine Clinical Practice: A Contemporary Cohort Study.

BACKGROUND/PURPOSE: Guidelines recommend intracoronary optical coherence tomography (OCT) to assess stent failure and guide percutaneous coronary intervention (PCI) but OCT may be useful for other indications in routine clinical practice. METHODS/MATERIALS: We conducted an international registry of OCT cases at two large tertiary care centers to assess clinical indications and the potential impact on decision making of OCT in clinical routine. Clinical indications, OCT findings, and their impact on interventional or medical treatment strategy were retrospectively assessed. RESULTS: OCT was performed in 810 coronary angiography cases (1928 OCT-pullbacks). OCT was used for diagnostic purposes in 67% (N = 542) and OCT-guided percutaneous coronary intervention in 50% (N = 404, 136 cases with prior diagnostic indication). Most frequent indications for diagnostic OCT were culprit lesion identification in suspected ACS (29%) and stent failure assessment (28%). OCT findings in the diagnostic setting influenced patient management in 74%. OCT-guided PCIs concerned ACS patients in 45%. Among the 55% with chronic coronary syndrome, long lesions >28 mm (19%), left main PCI (16%), and bifurcation PCI with side-branch-stenting (5%) were the leading indications for PCI-guidance. Post-procedural OCT findings led to corrective measures in 52% (26% malapposition, 14% underexpansion, 6% edge dissection, 3% intrastent mass, 3% geographic plaque miss). CONCLUSIONS: OCT was most frequently performed to identify culprit lesions in suspected ACS, for stent failure assessment, and PCI-guidance. OCT may impact subsequent treatment strategies in two out of three patients.

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.