Quality and transparency of evidence for implantable cardiovascular medical devices assessed by the CORE-MD consortium.

BACKGROUND AND AIMS: The European Union Medical Device Regulation 2017/745 challenges key stakeholders to follow transparent and rigorous approaches to the clinical evaluation of medical devices. The purpose of this study is a systematic evaluation of published clinical evidence underlying selected high-risk cardiovascular medical devices before and after market access in the European Union (CE-marking) between 2000 and 2021. METHODS: Pre-specified strategies were applied to identify published studies of prospective design evaluating 71 high-risk cardiovascular devices in seven different classes (bioresorbable coronary scaffolds, left atrial appendage occlusion devices, transcatheter aortic valve implantation systems, transcatheter mitral valve repair/replacement systems, surgical aortic and mitral heart valves, leadless pacemakers, subcutaneous implantable cardioverter-defibrillator). The search time span covered 20 years (2000-21). Details of study design, patient population, intervention(s), and primary outcome(s) were summarized and assessed with respect to timing of the corresponding CE-mark approval. RESULTS: At least one prospective clinical trial was identified for 70% (50/71) of the pre-specified devices. Overall, 473 reports of 308 prospectively designed studies (enrolling 97 886 individuals) were deemed eligible, including 81% (251/308) prospective non-randomized clinical trials (66 186 individuals) and 19% (57/308) randomized clinical trials (31 700 individuals). Pre-registration of the study protocol was available in 49% (150/308) studies, and 16% (48/308) had a peer-reviewed publicly available protocol. Device-related adverse events were evaluated in 82% (253/308) of studies. An outcome adjudication process was reported in 39% (120/308) of the studies. Sample size was larger for randomized in comparison to non-randomized trials (median of 304 vs. 100 individuals, P < .001). No randomized clinical trial published before CE-mark approval for any of the devices was identified. Non-randomized clinical trials were predominantly published after the corresponding CE-mark approval of the device under evaluation (89%, 224/251). Sample sizes were smaller for studies published before (median of 31 individuals) than after (median of 135 individuals) CE-mark approval (P < .001). Clinical trials with larger sample sizes (>50 individuals) and those with longer recruitment periods were more likely to be published after CE-mark approval, and were more frequent during the period 2016-21. CONCLUSIONS: The quantity and quality of publicly available data from prospective clinical investigations across selected categories of cardiovascular devices, before and after CE approval during the period 2000-21, were deemed insufficient. The majority of studies was non-randomized, with increased risk of bias, and performed in small populations without provision of power calculations, and none of the reviewed devices had randomized trial results published prior to CE-mark certification.

Ultrathin-strut vs thin-strut drug-eluting stents for multi and single-stent lesions: A lesion-level subgroup analysis of 2 randomized trials.

BACKGROUND: Whether ultrathin-strut stents are particularly beneficial for lesions requiring implantation of more than 1 stent is unknown. METHODS: In a post-hoc lesion-level analysis of 2 randomized trials comparing ultrathin-strut biodegradable polymer Sirolimus-eluting stents (BP-SES) vs thin-strut durable polymer Everolimus-eluting stents (DP-EES), lesions were stratified into multistent lesions (MSL) vs single-stent lesions (SSL). The primary endpoint was target lesion failure (TLF), a composite of lesion-related unclear/cardiac death, myocardial infarction (MI), or revascularization, at 24 months. RESULTS: Among 5328 lesions in 3397 patients, 1492 (28%) were MSL (722 with BP-SES, 770 with DP-EES). At 2 years, TLF occurred in 63 lesions (8.9%) treated with BP-SES and 60 lesions (7.9%) treated with DP-EES in the MSL-group (subdistibution hazard ratio [SHR], 1.13; 95% CI, 0.77-1.64; P = .53), and in 121 (6.4%) and 136 (7.4%) lesions treated with BP-SES and DP-EES respectively (SHR, 0.86; 95% CI, 0.62-1.18; P = .35) in the SSL-group (P for interaction = .241). While the rates of lesion-related MI or revascularization were significantly lower in SSL treated with BP-SES as compared to DP-EES (3.5% vs 5.2%; SHR, 0.67; 95% CI 0.46-0.97; P = .036), no significant difference was observed in MSL (7.1% vs 5.4%; SHR, 1.31; 95% CI 0.85-2.03; P = .216) with significant interaction between groups (P for interaction = .014). CONCLUSIONS: Rates of TLF are similar between ultrathin-strut BP-SES and thin-strut DP-EES in MSL and SSL. The use of ultrathin-strut BP-SES vs thin-strut DP-EES did not prove to be particularly beneficial for the treatment of multistent lesions. TRIAL REGISTRATION: Post-hoc analysis from the BIOSCIENCE (NCT01443104) and BIOSTEMI (NCT02579031) trials.

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.

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.

Amplatzer left atrial appendage closure: Single versus combined procedures.

OBJECTIVES: This study compares procedural and late clinical outcomes of left atrial appendage closure (LAAC) with Amplatzer devices as a single versus a combined procedure with other structural or coronary interventions. BACKGROUND: Multiple cardiac conditions are frequent among elderly patients and invite simultaneous treatment to ensure a favorable patient outcomes. METHODS: 559 consecutive patients (73.3 ± 11.1 years) underwent LAAC with Amplatzer devices at two centres (Bern and Zurich university hospitals, Switzerland) either as a single procedure or combined with other interventions. The primary safety endpoint was a composite of major peri-procedural complications and major bleeding at follow-up, the primary efficacy endpoint included stroke, systemic embolism, and cardiovascular/unexplained death. All event rates are reported per 100 patient-years. RESULTS: In 263 single and 296 combined procedures with percutaneous coronary interventions (47.6%), closure of an atrial septal defect (8.4%) or a patent foramen ovale (36.5%), transcatheter aortic valve implantation (10.1%), mitral clipping (4.1%), atrial fibrillation ablation (8.8%), or another procedure (3.0%) were analyzed. Device success (96.6% [single] vs. 99.0% [combined], p = .08) did not differ between the groups. After a mean follow-up of 2.6 ± 1.5 vs. 2.5 ± 1.5 years and a total of 1,422 patient-years, the primary efficacy (40/677, 5.9% [single] vs. 37/745, 5.0% [combined]; HR, 1.2, 95% CI, 0.8-1.9, p = .44), as well as the primary safety endpoint (25/677, 3.7% vs 28/745, 3.8%; HR, 1.0, 95% CI, 0.6-1.8, p = .89) were comparable. CONCLUSIONS: LAAC with Amplatzer devices combined with structural, coronary, and electrophysiological procedures offers procedural feasibility and safety, as well as long-term efficacy.

Impact of individual stroke risk on outcome after Amplatzer left atrial appendage closure in patients with atrial fibrillation.

OBJECTIVES: To investigate periprocedural and long-term outcome of left atrial appendage closure (LAAC) using Amplatzer occluders with respect to individual pre-procedural stroke risk. BACKGROUND: LAAC is a proven strategy for prevention from stroke and bleeding in patients with nonvalvular atrial fibrillation not amenable to oral anticoagulation. Whether individual pre-procedural stroke risk may affect procedural and long-term clinical outcome after LAAC is unclear. METHODS: Multicenter study of consecutive patients who underwent Amplatzer-LAAC. Using pre-procedural CHADS2 score, outcomes were compared between a low (0-2 points) and a high stroke risk group (3-6 points). RESULTS: Five hundred consecutive patients (73.9 ± 10.1 years) who underwent Amplatzer-LAAC. Two hundred and forty eight had preprocedural CHADS2 score ≤ 2 points (low-risk group) and the remaining 252 patients had 3-6 points (high-risk group). Periprocedural complication rates (6.0% vs. 5.6%, p = .85), procedural success (LAAC without major periprocedural or device-related complications or major para-device leaks: 89.4% vs. 87.9%, p = .74), and 30-day-mortality (2.4% vs. 2.6%, p = .77) were comparable. After 1,346 patient-years (PY), the long-term composite efficacy endpoint (stroke, systemic embolism, cardiovascular, and unexplained death) was reached in 23/653 (3.5/100 PY) versus 52/693 (7.5/100 PY); HR = 2.13; 95%-CI, 1.28-3.65, p = .002) with stroke rates 67% and 68% lower than anticipated by preprocedural CHADS2 score. Combined safety endpoint (major periprocedural complications and major, life-threatening or fatal bleedings) occurred in 22/653 (3.4/100 PY) versus 28/693 (4.0/100 PY); HR = 1.20; 95%-CI, 0.66-2.20, p = .52). CONCLUSIONS: Compared with patients at low risk of stroke, LAAC with Amplatzer devices is associated with similar safety and efficacy in high-risk patients in our study.

Simultaneous large bi-atrial device-related thrombi.

Simultaneous appearance of a pacemaker-lead associated thrombus and a left atrial appendage closure device related thrombus in a patient with urothelial carcinoma shown in a transesophageal echocardiography.

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.

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.

Robotic-assisted percutaneous coronary intervention: experience in Switzerland.

Aims of the study: Percutaneous coronary intervention (PCI) exposes operators to ionizing radiation. Robotic-assisted PCI (RA-PCI) is a novel technology that enables interventional cardiologists to operate coronary devices remotely from a radiation-shed cockpit. The aim of this study is to describe the experience and challenges during the initiation of a RA-PCI program and to report outcomes of the first 21 patients undergoing RA-PCI in Switzerland. Methods: All patients undergoing RA-PCI using the CorPath GRX Vascular Robotic System between 06/2021 and 12/2021 at Inselspital, Bern University Hospital were included in this retrospective registry study. Baseline, procedural and clinical follow-up data were prospectively assessed as part of the Cardiobase Bern PCI registry (NCT02241291). The two endpoints of interest were clinical success [defined as <30% residual diameter stenosis in the absence of in-hospital major adverse cardiovascular events (MACE: composite of death, periprocedural myocardial infarction, target-vessel revascularization, and stroke)] and robotic success (defined as clinical success and completion of RA-PCI without or with partial manual assistance). Additional outcome measures include clinical long-term outcomes at one year. Results: Twenty-five lesions in 21 patients were treated with RA-PCI (age 62.4 ± 9.1 years, 24% female). Clinical success was achieved in 100%, and robotic success in 81% (17/21 procedures, including 4 procedures requiring partial manual assistance). Manual conversion (e.g. manual completion of the procedure) occurred in 19% (4 procedures). Reasons for manual assistance or conversion were poor guiding-catheter back-up or platform limitations (4), adverse events (2x transient slow-flow that was solved manually), safety decision (1x vasovagal reaction not related to robotic approach), and software error (1). No in-hospital MACE occurred. During 12 months of follow-up, one patient suffered a non-target-vessel myocardial infarction requiring repeat PCI. Conclusions: RA-PCI can safely be performed without clinically relevant robot-associated complications in selected patients with approximately 80% of procedures conducted without or with partial manual assistance.

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.

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.

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).

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

AIMS: The Non-adherence Academic Research Consortium (NARC) has recently developed a consensus-based standardized classification for medication non-adherence in cardiovascular clinical trials. We aimed to assess the prevalence of NARC-defined self-reported non-adherence to P2Y12 inhibitors and its impact on clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: Using a standardized questionnaire administered at 1 year after PCI, we assessed the 4 NARC-defined non-adherence levels including type, decision-maker, reasons, and timing within the Bern PCI registry. The primary endpoint was the patient-oriented composite endpoint (POCE) defined as a composite of death, myocardial infarction, stroke, and any revascularization at 1 year. The recommended P2Y12 inhibitor duration was 12 months. Among 3,896 patients, P2Y12 inhibitor non-adherence was observed in 647 (17%) patients. Discontinuation was permanent in the majority of patients (84%). The decision was mainly driven by a physician (94%), and rarely by patients (6%). The most frequent reason was risk profile change (43%), followed by unlisted reasons (25%), surgery (17%), and adverse events (14%). Non-adherence occurred early (<30 days) in 21%, late (30-180 days) in 45%, and very late (>180 days) in 33%. The majority of POCE events (n = 421/502, 84%) occurred during adherence to the prescribed P2Y12 inhibitor. Permanent discontinuation, doctor-driven non-adherence, and risk profile change emerged as independent predictors for POCE. CONCLUSIONS: In real-world PCI population treated with 1-year DAPT, non-adherence was observed in nearly one-fifth of patients. Non-adherence to P2Y12 inhibitors was associated with worse clinical outcomes, while the risk was related to underlying contexts. CLINICALTRIALS.GOV IDENTIFIER: NCT02241291.

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.