Coronary Angiography, Intravascular Ultrasound, and Optical Coherence Tomography for Guiding of Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Results from multiple randomized clinical trials comparing outcomes after intravascular ultrasound (IVUS)- and optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) with invasive coronary angiography (ICA)-guided PCI as well as a pivotal trial comparing the 2 intravascular imaging (IVI) techniques have provided mixed results. METHODS: Major electronic databases were searched to identify eligible trials evaluating at least 2 PCI guidance strategies among ICA, IVUS, and OCT. The 2 coprimary outcomes were target lesion revascularization and myocardial infarction. The secondary outcomes included ischemia-driven target lesion revascularization, target vessel myocardial infarction, death, cardiac death, target vessel revascularization, stent thrombosis, and major adverse cardiac events. Frequentist random-effects network meta-analyses were conducted. The results were replicated by Bayesian random-effects models. Pairwise meta-analyses of the direct components, multiple sensitivity analyses, and pairwise meta-analyses IVI versus ICA were supplemented. RESULTS: The results from 24 randomized trials (15 489 patients: IVUS versus ICA, 46.4%, 7189 patients; OCT versus ICA, 32.1%, 4976 patients; OCT versus IVUS, 21.4%, 3324 patients) were included in the network meta-analyses. IVUS was associated with reduced target lesion revascularization compared with ICA (odds ratio [OR], 0.69 [95% CI, 0.54-0.87]), whereas no significant differences were observed between OCT and ICA (OR, 0.83 [95% CI, 0.63-1.09]) and OCT and IVUS (OR, 1.21 [95% CI, 0.88-1.66]). Myocardial infarction did not significantly differ between guidance strategies (IVUS versus ICA: OR, 0.91 [95% CI, 0.70-1.19]; OCT versus ICA: OR, 0.87 [95% CI, 0.68-1.11]; OCT versus IVUS: OR, 0.96 [95% CI, 0.69-1.33]). These results were consistent with the secondary outcomes of ischemia-driven target lesion revascularization, target vessel myocardial infarction, and target vessel revascularization, and sensitivity analyses generally did not reveal inconsistency. OCT was associated with a significant reduction of stent thrombosis compared with ICA (OR, 0.49 [95% CI, 0.26-0.92]) but only in the frequentist analysis. Similarly, the results in terms of survival between IVUS or OCT and ICA were uncertain across analyses. A total of 25 randomized trials (17 128 patients) were included in the pairwise meta-analyses IVI versus ICA where IVI guidance was associated with reduced target lesion revascularization, cardiac death, and stent thrombosis. CONCLUSIONS: IVI-guided PCI was associated with a reduction in ischemia-driven target lesion revascularization compared with ICA-guided PCI, with the difference most evident for IVUS. In contrast, no significant differences in myocardial infarction were observed between guidance strategies.

Coronary artery restenosis treatment with plain balloon, drug-coated balloon, or drug-eluting stent: 10-year outcomes of the ISAR-DESIRE 3 trial.

AIMS: The best interventional strategy for the treatment of drug-eluting stent (DES) in-stent restenosis (ISR) is still unclear and no data from randomized trials beyond 3-year follow-up are available. We aimed to define 10-year comparative efficacy and safety of plain balloon (PB), paclitaxel-coated balloon (PCB), and paclitaxel-eluting stent (PES) for percutaneous coronary intervention (PCI) of DES-ISR. METHODS AND RESULTS: Clinical follow-up of patients randomly assigned to PB, PCB, and PES in the ISAR-DESIRE 3 trial was extended to 10 years and events were independently adjudicated. The primary endpoint was a composite of cardiac death, target vessel myocardial infarction, target lesion thrombosis, or target lesion revascularization. The major secondary safety endpoint was a composite of cardiac death, target vessel myocardial infarction, or target lesion thrombosis. The major secondary efficacy endpoint was target lesion revascularization. Incidences by the Kaplan-Meier method were compared by the log-rank test. Risk estimation was primarily performed by Cox proportional hazards regression and supplemented by weighted Cox regression accounting for non-proportional hazards and Royston-Parmar flexible parametric regression with a time-varying coefficient. Primary results were further assessed by landmark, lesion-level, per-protocol, and competing risk analyses. A total of 402 patients (500 lesions) with DES-ISR were randomly assigned to PB angioplasty (134 patients, 160 lesions), PCB angioplasty (137 patients, 172 lesions), and PES implantation (131 patients, 168 lesions). Clinical follow-up did not significantly differ among treatments [PB, 9.62 (4.50-10.02) years; PCB, 10.01 (5.72-10.02) years; PES, 9.08 (3.14-10.02) years; P = 0.300]. At 10 years, the primary composite endpoint occurred in 90 patients (72.0%) assigned to PB, 70 patients (55.9%) assigned to PCB, and 72 patients (62.4%) assigned to PES (P < 0.001). The pairwise comparison between PCB and PES resulted in a non-significant difference [multiplicity-adjusted P = 0.610; Grambsch-Therneau P = 0.004; weighted Cox: hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.80-1.51; Cox: HR 1.10, 95% CI 0.79-1.52; Royston-Parmar: HR 1.08, 95% CI 0.72-1.60]. The major secondary safety endpoint occurred in 39 patients (34.1%) assigned to PB, 39 patients (34.0%) assigned to PCB, and 42 patients (40.0%) assigned to PES (P = 0.564). Target lesion revascularization occurred in 71 patients (58.0%) assigned to PB, 55 patients (43.9%) assigned to PCB, and 42 patients (38.6%) assigned to PES (P < 0.0001). The pairwise comparison between PES and PCB resulted in a non-significant difference (multiplicity-adjusted P = 0.282; Grambsch-Therneau P = 0.002; weighted Cox: HR 0.83, 95% CI 0.56-1.22; Cox: HR 0.81, 95% CI 0.54-1.21; Royston-Parmar: HR 0.75, 95% CI 0.47-1.20). Lesion-level and per-protocol analyses were consistent. At landmark analyses, an excess of death and cardiac death associated with PES compared with PCB was observed within 5 years after PCI, though 10-year differences did not formally reach the threshold of statistical significance after adjustment for multiplicity. Competing risk regression confirmed a non-significant difference in target lesion revascularization between PCB and PES and showed an increased risk of death associated with PES compared with PCB. CONCLUSION: Ten years after PCI for DES-ISR, the primary and major secondary endpoints between PCB and PES were not significantly different. However, an excess of death and cardiac death within 5 years associated with PES and the results of the competing risk analysis are challenging to interpret and warrant further analysis. PES and PCB significantly reduced target lesion revascularization compared with PB.

Effects on Mortality and Major Bleeding of Radial Versus Femoral Artery Access for Coronary Angiography or Percutaneous Coronary Intervention: Meta-Analysis of Individual Patient Data From 7 Multicenter Randomized Clinical Trials.

BACKGROUND: In some randomized clinical trials, transradial access (TRA) compared with transfemoral access (TFA) was associated with lower mortality in patients with coronary artery disease undergoing invasive management. We analyzed the effects of TRA versus TFA across multicenter randomized clinical trials and whether these associations are modified by patient or procedural characteristics. METHODS: We performed an individual patient data meta-analysis of multicenter randomized clinical trials comparing TRA with TFA among patients undergoing coronary angiography with or without percutaneous coronary intervention. The primary outcome was all-cause mortality and the co-primary outcome was major bleeding at 30 days. The primary analysis was conducted by 1-stage mixed-effects models on the basis of the intention-to-treat cohort. The effect of access site on mortality and major bleeding was assessed further by multivariable analysis. The relationship among access site, bleeding, and mortality was investigated by natural effect model mediation analysis with multivariable adjustment. RESULTS: A total of 21 600 patients (10 775 TRA, 10 825 TFA) from 7 randomized clinical trials were included. The median age was 63.9 years, 31.9% were women, 95% presented with acute coronary syndrome, and 75.2% underwent percutaneous coronary intervention. All-cause mortality (1.6% versus 2.1%; hazard ratio, 0.77 [95% CI, 0.63-0.95]; P=0.012) and major bleeding (1.5% versus 2.7%; odds ratio, 0.55 [95% CI, 0.45-0.67]; P<0.001) were lower with TRA. Subgroup analyses for mortality showed consistent results, except for baseline hemoglobin level (Pinteraction=0.003), indicating that the benefit of TRA was substantial in patients with moderate or severe anemia, whereas it was not significant in patients with milder or no baseline anemia. After adjustment, TRA remained associated with 24% and 51% relative risk reduction of all-cause mortality and major bleeding, respectively. A mediation analysis showed that the benefit of TRA on mortality was only partially driven by major bleeding prevention and ancillary mechanisms are required to fully explain the causal association. CONCLUSIONS: TRA is associated with lower all-cause mortality and major bleeding at 30 days compared with TFA. The effect on mortality was driven by patients with anemia. The reduction in major bleeding only partially explains the mortality benefit. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42018109664.

Short dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy vs. prolonged dual antiplatelet therapy after percutaneous coronary intervention with second-generation drug-eluting stents: a systematic review and meta-analysis of randomized clinical trials.

AIMS: After percutaneous coronary intervention (PCI) with second-generation drug-eluting stent (DES), whether short dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with a P2Y12 receptor inhibitor confers benefits compared with prolonged DAPT is unclear. METHODS AND RESULTS: Multiple electronic databases, including PubMed, Scopus, Web of Sciences, Ovid, and ScienceDirect, were searched to identify randomized clinical trials comparing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT after PCI with second-generation DES implantation. The primary and co-primary outcomes of interest were major bleeding and stent thrombosis 1 year after randomization. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fixed-effect and random-effects models. Multiple sensitivity analyses including random-effects models 95% CI adjustment were applied. A sensitivity analysis comparing trials using P2Y12 inhibitor SAPT with those using aspirin SAPT was performed. A total of five randomized clinical trials (32 145 patients) were available. Major bleeding was significantly lower in the patients assigned to short DAPT followed by P2Y12 inhibitor SAPT compared with those assigned to 12-month DAPT (random-effects model: HR 0.63, 95% 0.45-0.86). No significant differences between groups were observed in terms of stent thrombosis (random-effects model: HR 1.19, 95% CI 0.86-1.65) and the secondary endpoints of all-cause death (random-effects model: HR 0.85, 95% CI 0.70-1.03), myocardial infarction (random-effects model: HR 1.05, 95% CI 0.89-1.23), and stroke (random-effects model: HR 1.08, 95% CI 0.68-1.74). Sensitivity analyses showed overall consistent results. By comparing trials testing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT with trials testing ≤3 months of DAPT followed by aspirin SAPT vs. 12-month of DAPT, there was no treatment-by-subgroup interaction for each endpoint. By combining all these trials, regardless of the type of SAPT, short DAPT was associated with lower major bleeding (random-effects model: HR 0.63, 95% CI 0.48-0.83) and no differences in stent thrombosis, all-cause death, myocardial infarction, and stroke were observed between regimens. CONCLUSION: After second-generation DES implantation, 1-3 months of DAPT followed by P2Y12 inhibitor SAPT is associated with lower major bleeding and similar stent thrombosis, all-cause death, myocardial infarction, and stroke compared with prolonged DAPT. Whether P2Y12 inhibitor SAPT is preferable to aspirin SAPT needs further investigation.

Association between surgical risk and 30-day stroke after transcatheter versus surgical aortic valve replacement: a systematic review and meta-analysis.

BACKGROUND: Stroke is a feared complication of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). OBJECTIVES: With this meta-analysis we aimed to evaluate the incidence of 30-day stroke with TAVR and SAVR focusing on its possible correlation with surgical risk. METHODS: Major electronic databases were searched for studies published between January 2002 and October 2019 reporting the rates of 30-day stroke after TAVR and SAVR. Data were pooled using fixed- and random-effects models. The primary outcome of the study was stroke rate within 30-day from TAVR or SAVR. Results were stratified according to surgical risk score (high, intermediate and low). RESULTS: A total of 23 studies were identified (TAVR: 14,589 patients; SAVR: 11,681 patients). Regardless of the model used, in the overall population TAVR was associated with a significant reduction in the risk of stroke compared with SAVR (fixed effect: OR 0.78, 95% CI 0.66-0.92, p = .003; random-effects: OR 0.80, 95% CI 0.64-1.00, p = .045). Rates of 30-day stroke after TAVR and SAVR were not significantly different in the high- (OR 1.01, 95% CI 0.44-1.98, p = .105) and intermediate-risk groups (OR 0.92, 95% CI 0.63-1.36, p = .319), while low-risk patients had a lower rate of 30-day stroke after TAVR than SAVR (OR 0.65, 95% CI 0.50-0.83, p < .001). Meta-regression showed a significant association between surgical risk score and 30-day stroke rate (p = .007). CONCLUSIONS: TAVR is associated with a lower risk of 30-day stroke compared with SAVR, mainly as a result of the significant advantage observed in patients at low surgical risk.

Transcatheter versus surgical aortic valve replacement in the digital era: Meta-analysis based on the reconstruction of time-to-event individual patient data.

Clinical benefits of transcatheter aortic valve replacement (TAVR) over surgery emerge soon after intervention and show durable, consistent trends within 1 year. TAVR by transfemoral access is associated with improved outcomes compared with TAVR by transthoracic access. Reconstructing time-to-event individual patient data is advantageous and allows higher flexibility in terms of meta-analysis design and modeling of data.

Radial artery access among mainstays of contemporary percutaneous coronary intervention: Is it time to forget how to puncture a femoral artery?

Radial artery access should be the default approach for coronary angiography and percutaneous coronary intervention regardless of the clinical presentation. Benefits of radial access are strongly depending on the volume of transradial procedures performed. Currently, a significant proportion of procedures continues to be performed by femoral access despite validated advantages associated with the transradial approach.

Five-year follow-up of polymer-free sirolimus- and probucol-eluting stents versus new generation zotarolimus-eluting stents in patients presenting with st-elevation myocardial infarction.

BACKGROUND: Patients with ST-segment elevation myocardial infarction (STEMI) undergoing drug-eluting stent (DES) implantation are at increased risk of late adverse events, partly explained by an exaggerated inflammatory reaction to durable-polymer stent coatings. OBJECTIVES: We sought to investigate whether implantation of polymer-free DES would reduce this risk. METHODS: In the ISAR-TEST 5 (the Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol- and Zotarolimus-Eluting Stents) trial, patients were randomly allocated to receive a polymer-free sirolimus- and probucol-eluting stent or a new generation durable-polymer zotarolimus-eluting stent. We analyzed late clinical outcomes in the subgroup of patients presenting with STEMI. The primary endpoint was the combined incidence of cardiac death, target vessel-related myocardial infarction or target lesion revascularization at 5 years. RESULTS: 311 patients with STEMI were randomized to receive sirolimus- and probucol-eluting stents (n = 215) or zotarolimus-eluting stents (n = 96). At 5 years, there was no difference in the incidence of the primary endpoint in patients treated with sirolimus- and probucol-eluting stents versus zotarolimus-eluting stents (18.3% versus 20.1% respectively, hazard ratio = 0.87, 95% CI, 0.50-1.51; P = 0.62). Rates of the individual components of the primary endpoint were also comparable in both groups. The incidence of definite/probable stent thrombosis was 1.4% versus 1.0% respectively (hazard ratio = 1.35, 95% CI, 0.14-12.94, P = 0.80). CONCLUSIONS: Long-term outcomes of patients with STEMI treated with polymer-free sirolimus- and probucol-eluting stents versus durable-polymer zotarolimus-eluting stents were similar. Stent thrombosis rates were low and comparable in both treatment groups, with no events beyond 12 months. CLINICAL TRIAL REGISTRATION: Registered at ClinicalTrials.gov (Identifier NCT 00598533) © 2016 Wiley Periodicals, Inc.

Incidence and impact of acute kidney injury in patients with acute coronary syndromes treated with coronary artery bypass grafting: Insights from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) and Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trials.

BACKGROUND: Acute kidney injury (AKI) is a well-recognized predictor of morbidity and mortality after percutaneous coronary intervention. However, the impact of AKI on the outcome of patients with acute coronary syndromes (ACS) in relation to coronary artery bypass grafting (CABG) has not been established. METHODS: Of the 17,421 patients who presented with non-ST-segment elevation ACS or ST-segment elevation myocardial infarction enrolled in the ACUITY and HORIZONS-AMI trials, 1,406 (8.0%) underwent CABG as principal treatment after coronary angiography. End points were measured at 1 month and 1 year and included death, myocardial infarction, and ischemia-driven target vessel revascularization. Acute kidney injury was defined as a rise in creatinine of ≥ 0.5 mg/dL, or > 25%, from baseline at initial angiography. RESULTS: Acute kidney injury occurred during hospital admission in 449 (31.9%) of the 1,406 patients treated with CABG. One-month and 1-year mortality was 6.7% vs 2.2% (P < .0001) and 10.4% vs 4.3% (P < .0001) for patients with vs without AKI, respectively. Analogously, the 1-month and 1-year incidence of composite major adverse cardiac events (MACEs; death, MI, or target vessel revascularization) was 17.6% vs 12.4% (P = .003) and 22.0% vs 15.3% (P = .002) for patients with vs without AKI, respectively. After adjustment for age, sex, race, diabetes, hypertension, and baseline creatinine clearance, AKI was an independent predictor of mortality (overall and cardiac-related) and MACE at both 1 month and 1 year in patients treated with CABG. CONCLUSIONS: Acute kidney injury occurred in approximately 1 of every 3 patients with ACS treated with CABG and is a powerful independent predictor of death and MACE. These data highlight the need for AKI prevention strategies in patients undergoing CABG.

Five-year clinical outcomes in patients with diabetes mellitus treated with polymer-free sirolimus- and probucol-eluting stents versus second-generation zotarolimus-eluting stents: a subgroup analysis of a randomized controlled trial.

BACKGROUND: Improved outcomes in patients with diabetes mellitus undergoing percutaneous coronary intervention remain an unmet clinical need. We assessed the long-term efficacy and safety of novel polymer-free sirolimus- and probucol-eluting stent in diabetic patients enrolled in intracoronary stenting and angiographic results: test efficacy of sirolimus- and probucol-eluting versus zotarolimus-eluting stents 5 trial. METHODS: In a pre-specified subgroup analysis, outcomes of diabetic patients treated with a sirolimus- and probucol-eluting stent or a second-generation zotarolimus-eluting stent were compared. The primary endpoint was a device-oriented composite outcome comprising cardiac death, target vessel-related myocardial infarction (MI), or target lesion revascularization (TLR) at 5-year follow-up. Event-free survival was assessed using the Kaplan-Meier method. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated from univariate Cox proportional hazards models. RESULTS: A total of 870 patients with diabetes mellitus were treated with either a sirolimus- and probucol-eluting stent (n = 575) or a second-generation zotarolimus-eluting stent (n = 295). At 5 years, the rate of device-oriented composite endpoint was comparable between the sirolimus- and probucol-eluting stent and the second-generation zotarolimus-eluting stent (32.9 versus 33.4 %, HR 0.88, 95 % CI 0.76-1.26). No significant differences were observed between the sirolimus- and probucol-eluting stent and the second-generation zotarolimus-eluting stent groups in the incidence of cardiac death (15.6 versus 16.7 % HR 0.92, 95 % CI 0.63-1.32), target-vessel MI (4.6 versus 6.6 %, HR 0.73, 95 % CI 0.40-1.34), and TLR (18.6 versus 18.8 %, HR 1.00, 95 % CI, 0.72-1.41). The rate of definite or probable stent thrombosis was low and similar in both groups (2.5 versus 2.6 %, HR 1.02, 95 % CI, 0.41-2.52). CONCLUSIONS: In patients with diabetes the long-term efficacy and safety of a polymer-free sirolimus- and probucol-eluting stent were comparable to a second-generation durable polymer zotarolimus-eluting stent. Trial registration ClinicalTrials.gov NCT00598533. Registered 10 January 2008.

Current Management of In-Stent Restenosis.

In-stent restenosis (ISR) remains the primary cause of target lesion failure following percutaneous coronary intervention (PCI), resulting in 10-year incidences of target lesion revascularization at a rate of approximately 20%. The treatment of ISR is challenging due to its inherent propensity for recurrence and varying susceptibility to available strategies, influenced by a complex interplay between clinical and lesion-specific conditions. Given the multiple mechanisms contributing to the development of ISR, proper identification of the underlying substrate, especially by using intravascular imaging, becomes pivotal as it can indicate distinct therapeutic requirements. Among standalone treatments, drug-coated balloon (DCB) angioplasty and drug-eluting stent (DES) implantation have been the most effective. The main advantage of a DCB-based approach is the avoidance of an additional metallic layer, which may otherwise enhance neointimal hyperplasia, provide the substratum for developing neoatherosclerosis, and expose the patient to a persistently higher risk of coronary ischemic events. On the other hand, target vessel scaffolding by DES implantation confers relevant mechanical advantages over DCB angioplasty, generally resulting in larger luminal gain, while drug elution from the stent surface ensures the inhibition of neointimal hyperplasia. Nevertheless, repeat stenting with DES also implies an additional permanent metallic layer that may reiterate and promote the mechanisms leading to ISR. Against this background, the selection of either DCB or DES on a patient- and lesion-specific basis as well as the implementation of adjuvant treatments, including cutting/scoring balloons, intravascular lithotripsy, and rotational atherectomy, hold the potential to improve the effectiveness of ISR treatment over time. In this review, we comprehensively assessed the available evidence from randomized trials to define contemporary interventional treatment of ISR and provide insights for future directions.

Trends in transcatheter aortic valve implantation practice and clinical outcomes at an Irish tertiary referral centre.

OBJECTIVE: A paucity of data exists on how transcatheter aortic valve implantation (TAVI) practice has evolved in Ireland. This study sought to analyse temporal trends in patient demographics, procedural characteristics, and clinical outcomes at an Irish tertiary referral centre. METHODS: The prospective Mater TAVI database was divided into time tertiles based on when TAVI was performed: Group A, November 2008-April 2013; Group B, April 2013-September 2017; and Group C, September 2017-February 2022. Patient and procedural characteristics and clinical outcomes were compared across groups. RESULTS: A total of 1063 (Group A, 59; Group B, 268; and Group C:, 736) patients were treated with TAVI during the study period (mean age 81.1±7.4, mean Society of Thoracic Surgeons score 5.9±5.1).Conscious sedation (Group A, 0%; Group B, 59.9%; and Group C, 90.2%, p<0.001) and femoral artery access (Group A, 76.3%; Group B, 90.7%; and Group C, 96.6%, p<0.001) were used more frequently over time. The median length of hospital stay reduced from 9 days (IQR 7, 18) in Group A to 2 days (IQR 2, 3) in Group C. In-hospital death was numerically higher in Group A compared with Group C (6.8% vs 1.9%, p=0.078). At 1-year follow-up, the rate of death and/or stroke was similar in Group A and Group C (20.3% vs 12.0%, adjusted HR 1.49, 95% CI (0.59 to 3.74)). CONCLUSION: There was exponential growth in TAVI procedural volume during the study period. A minimalist approach to TAVI emerged, and this was associated with significantly shorter procedure duration and hospital stay. Clinical outcomes at 1-year follow-up did not change significantly over time.

PCSK9 inhibitors: current status and emerging frontiers in lipid control.

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of global mortality, imposing substantial healthcare economic burdens. Among the modifiable risk factors, hypercholesterolemia, especially elevated low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in ASCVD development. Novel therapies such as PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors are emerging to address this concern. These inhibitors offer the potential to reduce ASCVD risk by directly targeting LDL-C levels. AREAS COVERED: The article reviews the structural and functional aspects of PCSK9, highlighting its role in LDL receptor regulation. The pharmacological strategies for PCSK9 inhibition, including monoclonal antibodies, binding peptides, gene silencing, and active immunization, are explored. Clinical evidence from various trials underscores the safety and efficacy of PCSK9 inhibitors in reducing LDL-C levels and potentially improving cardiovascular outcomes. Despite these promising results, challenges such as cost-effectiveness and long-term safety considerations are addressed. EXPERT OPINION: Among PCSK9 inhibitors, monoclonal antibodies represent a cornerstone. Many trials have showed their efficacy in reducing LDL-C and the risk for major adverse clinical events, revealing long-lasting effects, with special benefits particularly for statin-intolerant and familial hypercholesterolemia patients. However, long-term impacts, high costs, and patient selection necessitate further research.

Pharmacological and clinical appraisal of factor XI inhibitor drugs.

The evolution of anticoagulation therapy, from vitamin K antagonists to the advent of direct oral anticoagulants (DOACs) almost two decades ago, marks significant progress. Despite improved safety demonstrated in pivotal trials and post-marketing observations, persistent concerns exist, particularly regarding bleeding risk and the absence of therapeutic indications in specific subgroups or clinical contexts. Factor XI (FXI) has recently emerged as a pivotal contributor to intraluminal thrombus formation and growth, playing a limited role in sealing vessel wall injuries. Inhibiting FXI presents an opportunity to decouple thrombosis from haemostasis, addressing concerns related to bleeding events while safeguarding against thromboembolic events. Notably, FXI inhibition holds promise for patients with end-stage renal disease or cancer, where clear indications for DOACs are currently lacking. Various compounds have undergone design, testing, and progression to phase 2 clinical trials, demonstrating a generally favourable safety and tolerability profile. However, validation through large-scale phase 3 trials with sufficient power to assess both safety and efficacy outcomes is needed. This review comprehensively examines FXI inhibitors, delving into individual classes, exploring their pharmacological properties, evaluating the latest evidence from randomized trials, and offering insights into future perspectives.

[Drug-eluting stents in contemporary interventional practice: the STENT PANORAMA project (Part I)]. / Gli stent coronarici a rilascio di farmaco nella pratica interventistica contemporanea: progetto STENT PANORAMA (Parte I).

STENT PANORAMA is a project carried out by the Young Interventional Cardiologists of Triveneto coordinated by the Italian Society of Interventional Cardiology (GISE) Veneto delegation. The project includes two parts: the first, here reported, is aimed at describing in a standardized and easily usable way the main technological characteristics of the latest generation of the drug eluting stents (DES) that are most widely used in the Italian cath-labs. The second, to follow, will aim to summarize the main scientific evidence regarding the performance of individual devices with particular reference to subgroups of clinical interest. The ambitious goal of the STENT PANORAMA working group is to provide the interventional cardiologist with a thorough, practical, and functional knowledge of the DES currently available in the modern therapeutic armamentarium to promote a therapeutic strategy tailored to the patient.

Objectifying the impact of incomplete revascularization by repeat angiographic risk assessment with the residual SYNTAX score after left main coronary artery percutaneous coronary intervention.

OBJECTIVES: We investigated the prognostic accuracy of a standardized quantification of incomplete revascularization after percutaneous coronary intervention (PCI) of the unprotected left main coronary artery (ULMCA) named residual SYNTAX score (rSS). BACKGROUND: Prognostic implications of coronary lesions left untreated after ULMCA PCI are confounded by the lack of a uniform definition of incomplete revascularization. METHODS: Baseline SYNTAX score (bSS), rSS, and the difference between bSS and rSS (ΔSS ) were assessed in predicting the risk of 2-year cardiac mortality of 400 patients undergoing ULMCA PCI. RESULTS: The rSS and bSS showed comparable discrimination (rSS area under the curve [AUC] 0.72, 95% confidence interval [95% CI] 0.61-0.83; bSS AUC 0.73, 95% CI 0.62-0.84). Hosmer-Lemeshow statistics were 0.60 for rSS (P = 0.44) and 2.45 (P = 0.12) for bSS, reflecting better calibration ability of the rSS. The ΔSS provided the worst discrimination and calibration characteristics (AUC 0.55; 95% CI 0.44-0.66; Hosmer-Lemeshow statistic 3.13, P = 0.08). The rSS was independently associated with the 2-year adjusted-risk of cardiac mortality (hazard ratio 1.07, 95% CI 1.03-1.12, P = 0.001). The risk information from both the rSS and bSS slightly improved the discrimination ability compared with risk information from each single risk assessment (AUC 0.74, 95% CI 0.62-0.86) with a net reclassification improvement of +14.2% and +13.6% over rSS and bSS alone, respectively. CONCLUSIONS: The rSS carries a prognostic value as independent predictor of 2-year cardiac mortality. Compared with a single assessment of the SYNTAX score, information coming from repeat assessment of the angiographic risk may improve the ability to discriminate and reclassify patients undergoing ULMCA PCI.

Usefulness of the logistic clinical SYNTAX score for predicting 1-year mortality in patients undergoing percutaneous coronary intervention of the left main coronary artery.

OBJECTIVES: To externally validate the logistic clinical SYNTAX in patients undergoing percutaneous coronary intervention (PCI) of the left main coronary artery (LMCA). BACKGROUND: A novel version of the clinical SYNTAX score (CSS) has been recently introduced to overcome the limitations of categorical risk scores for PCI by the incorporation of clinical variables and the SYNTAX score (SXscore) into a logistic formula for predicting 1-year mortality. METHODS: Core and extended models of the logistic CSS (logCSS(core) and logCSS(ext)) were applied to 400 patients undergoing LMCA PCI, and their performance was compared with those of the standard CSS, SXscore, and age, creatinine, and ejection fraction (ACEF) score by different measures of discrimination and calibration. RESULTS: A significant gradient in the distribution of 1-year mortality was noted with all the models (P < 0.001), with the SYNTAX and ACEF scores showing the lowest (0.64) and the highest (0.75) c-statistic, respectively. Based on Somers' D(xy) rank correlation, discrimination of both the logCSS(core) and the logCSS(ext) was numerically lower than that of the ACEF score. The logCSS(core) was miscalibrated toward underpredicting all-cause mortality in low-predicted probabilities, while the logCSS(ext) tended to underpredict in low-predicted probabilities and overpredict in high-predicted probabilities. Slope and intercept values reflected a better calibration ability of the logCSS(core) compared with the logCSS(ext). The global accuracy of the logCSS(core) was superior to that of the logCSS(ext) (Brier score 0.087 vs. 0.095). CONCLUSIONS: A personalized approach to risk stratification of LMCA PCI with the logistic CSS is feasible and of potential clinical utility. However, in this study, the logistic CSS did not achieve superior discrimination compared with other categorical models, and suffered from mild to moderate miscalibration.