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.

Long-term outcomes with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in ST-segment elevation myocardial infarction: 5-year follow-up of the BIOSTEMI randomised superiority trial.

BACKGROUND: Biodegradable polymer sirolimus-eluting stents improve early stent-related clinical outcomes compared to durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The long-term advantages of biodegradable polymer sirolimus-eluting stents after complete degradation of its polymer coating in patients with STEMI remains however uncertain. METHODS: BIOSTEMI Extended Survival (BIOSTEMI ES) was an investigator-initiated, follow-up extension study of the BIOSTEMI prospective, multicentre, single-blind, randomised superiority trial that compared biodegradable polymer sirolimus-eluting stents with durable polymer everolimus-eluting stents in patients with STEMI undergoing primary percutaneous coronary intervention at ten hospitals in Switzerland. All individuals who had provided written informed consent for participation in the BIOSTEMI trial were eligible for this follow-up study. The primary endpoint was target lesion failure, defined as a composite of cardiac death, target vessel myocardial re-infarction, or clinically indicated target lesion revascularisation, at 5 years. Superiority of biodegradable polymer sirolimus-eluting stents over durable polymer everolimus-eluting stents was declared if the Bayesian posterior probability for a rate ratio (RR) of less than 1 was greater than 0·975. Analyses were performed according to the intention-to-treat principle. The study was registered with ClinicalTrials.gov, NCT05484310. FINDINGS: Between April 26, 2016, and March 9, 2018, 1300 patients with STEMI (1622 lesions) were randomly allocated in a 1:1 ratio to treatment with biodegradable polymer sirolimus-eluting stents (649 patients, 816 lesions) or durable polymer everolimus-eluting stents (651 patients, 806 lesions). At 5 years, the primary composite endpoint of target lesion failure occurred in 50 (8%) patients treated with biodegradable polymer sirolimus-eluting stents and in 72 (11%) patients treated with durable polymer everolimus-eluting stents (difference of -3%; RR 0·70, 95% Bayesian credible interval 0·51-0·95; Bayesian posterior probability for superiority 0·988). INTERPRETATION: In patients undergoing primary percutaneous coronary intervention for STEMI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 5 years of follow-up. The difference was driven by a numerically lower risk for ischaemia-driven target lesion revascularisation. FUNDING: Biotronik.

Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk.

BACKGROUND: The appropriate duration of dual antiplatelet therapy in patients at high risk for bleeding after the implantation of a drug-eluting coronary stent remains unclear. METHODS: One month after they had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent, we randomly assigned patients at high bleeding risk to discontinue dual antiplatelet therapy immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy). The three ranked primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding; cumulative incidences were assessed at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population. RESULTS: Among the 4434 patients in the per-protocol population, net adverse clinical events occurred in 165 patients (7.5%) in the abbreviated-therapy group and in 172 (7.7%) in the standard-therapy group (difference, -0.23 percentage points; 95% confidence interval [CI], -1.80 to 1.33; P<0.001 for noninferiority). A total of 133 patients (6.1%) in the abbreviated-therapy group and 132 patients (5.9%) in the standard-therapy group had a major adverse cardiac or cerebral event (difference, 0.11 percentage points; 95% CI, -1.29 to 1.51; P = 0.001 for noninferiority). Among the 4579 patients in the intention-to-treat population, major or clinically relevant nonmajor bleeding occurred in 148 patients (6.5%) in the abbreviated-therapy group and in 211 (9.4%) in the standard-therapy group (difference, -2.82 percentage points; 95% CI, -4.40 to -1.24; P<0.001 for superiority). CONCLUSIONS: One month of dual antiplatelet therapy was noninferior to the continuation of therapy for at least 2 additional months with regard to the occurrence of net adverse clinical events and major adverse cardiac or cerebral events; abbreviated therapy also resulted in a lower incidence of major or clinically relevant nonmajor bleeding. (Funded by Terumo; MASTER DAPT ClinicalTrials.gov number, NCT03023020.).

Higher 1-year mortality on rest days in patients with acute coronary syndromes and decompensated heart failure-A SPUM-ACS sub-study.

BACKGROUND: Acute coronary syndromes (ACS) occurring on rest days have been associated with higher mortality, but the current literature remains inconsistent in this regard. This study included ACS patients presenting with acute decompensated heart failure (ADHF) investigating the relationship between time of coronary catheterization and outcomes. METHODS: Analyses were performed from the prospective, multicentric Special Program University Medicine Acute Coronary Syndromes and Inflammation (SPUM-ACS) Cohort. Patients were divided into two groups according to time of coronary catheterization on either workdays (Monday, 00:00 to Friday, 23:59) or rest days (Saturday, 00:00 to Sunday, 23:59 and public holidays). ADHF was defined by Killip Class III or IV upon presentation. Patients were followed over 1 year. RESULTS: Out of 4787 ACS patients enrolled in the SPUM-ACS Cohort, 207 (4.3%) presented with ADHF. 52 (25.1%) and 155 (74.9%) patients underwent coronary angiography on rest days or workdays, respectively. Baseline characteristics were similar among these groups. ACS patients with ADHF showed increased 1-year mortality on rest days (34.6% vs. 17.4%, p-value = 0.009). After correction for baseline characteristics, including the GRACE 2.0 Score, rest day presentation remained a significant predictor for 1-year mortality (adjusted hazard ratio = 2.42 [95% confidence interval: 1.14-5.17], p-value = 0.022). CONCLUSIONS: One-year all-cause mortality was high in ACS patients with ADHF and doubled for patients admitted on rest days. The present data support the association of a rest day effect and long-term patient survival and indicate a need for further investigations.

Amulet or Watchman Device for Percutaneous Left Atrial Appendage Closure: Primary Results of the SWISS-APERO Randomized Clinical Trial.

BACKGROUND: No study has so far compared Amulet with the new Watchman FLX in terms of residual left atrial appendage (LAA) patency or clinical outcomes in patients undergoing percutaneous LAA closure. METHODS: In the investigator-initiated SWISS APERO trial (Comparison of Amulet Versus Watchman/FLX Device in Patients Undergoing Left Atrial Appendage Closure), patients undergoing LAA closure were randomly assigned (1:1) open label to receive Amulet or Watchman 2.5 or FLX (Watchman) across 8 European centers. The primary end point was the composite of justified crossover to a nonrandomized device during LAA closure procedure or residual LAA patency detected by cardiac computed tomography angiography (CCTA) at 45 days. The secondary end points included procedural complications, device-related thrombus, peridevice leak at transesophageal echocardiography, and clinical outcomes at 45 days. RESULTS: Between June 2018 and May 2021, 221 patients were randomly assigned to Amulet (111 [50.2%]) or Watchman (110 [49.8%]), of whom 25 (22.7%) patients included before October 2019 received Watchman 2.5, and 85 (77.3%) patients received Watchman FLX. The primary end point was assessable in 205 (92.8%) patients and occurred in 71 (67.6%) patients receiving Amulet and 70 (70.0%) patients receiving Watchman, respectively (risk ratio, 0.97 [95% CI, 0.80-1.16]; P=0.713). A single justified crossover occurred in a patient with Amulet who fulfilled LAA patency criteria at 45-day CCTA. Major procedure-related complications occurred more frequently in the Amulet group (9.0% versus 2.7%; P=0.047) because of more frequent bleeding (7.2% versus 1.8%). At 45 days, the peridevice leak rate at transesophageal echocardiography was higher with Watchman than with Amulet (27.5% versus 13.7%, P=0.020), albeit none was major (ie, >5 mm), whereas device-related thrombus was detected in 1 (0.9%) patient with Amulet and 3 (3.0%) patients with Watchman at CCTA and in 2 (2.1%) and 5 (5.5%) patients at transesophageal echocardiography, respectively. Clinical outcomes at 45 days did not differ between the groups. CONCLUSIONS: Amulet was not associated with a lower rate of the composite of crossover or residual LAA patency compared with Watchman at 45-day CCTA. Amulet, however, was associated with lower peridevice leak rates at transesophageal echocardiography, higher procedural complications, and similar clinical outcomes at 45 days compared with Watchman. The clinical relevance of CCTA-detected LAA patency requires further investigation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03399851.

Incidental detection of malignancy during preprocedural workup for transcatheter aortic valve implantation: A longitudinal cohort study.

The aim of this retrospective analysis was to investigate the prevalence and prognostic importance of incidental malignancy detected during pre-TAVI computed tomography. Among 579 patients, CT-work-up for TAVI exposed previously undetected malignancy in 4.5% of patients. TAVI patients with a new malignancy had a 2.9-fold increased risk of death at 1 year, and a 16 month shorter mean survival time compared to patients with no malignancy.

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.

Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI.

BACKGROUND: Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN: The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 14 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the noninferiority between stents with respect to a device-oriented composite end point of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY: The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI.

Do quantitative levels of antispike-IgG antibodies aid in predicting protection from SARS-CoV-2 infection? Results from a longitudinal study in a police cohort.

In a COVID-19 sero-surveillance cohort study with predominantly healthy and vaccinated individuals, the objectives were (i) to investigate longitudinally the factors associated with the quantitative dynamics of antispike (anti-S1) IgG antibody levels, (ii) to evaluate whether the levels were associated with protection from SARS-CoV-2 infection, and (iii) to assess whether the association was different in the pre-Omicron compared with the Omicron period. The QuantiVac Euroimmun ELISA test was used to quantify anti-S1 IgG levels. The entire study period (16 months), the 11-month pre-Omicron period and the cross-sectional analysis before the Omicron surge included 3219, 2310, and 895 reactive serum samples from 949, 919, and 895 individuals, respectively. Mixed-effect linear, mixed-effect time-to-event, and logistic regression models were used to achieve the objectives. Age and time since infection or vaccination were the only factors associated with a decline of anti-S1 IgG levels. Higher antibody levels were significantly associated with protection from SARS-CoV-2 infection (0.89, 95% confidence interval [CI] 0.82-0.97), and the association was higher during the time period when Omicron was predominantly circulating compared with the ones when Alpha and Delta variants were predominant (adjusted hazard ratio for interaction 0.66, 95% CI 0.53-0.84). In a prediction model, it was estimated that >8000 BAU/mL anti-S1 IgG was required to reduce the risk of infection with Omicron variants by approximately 20%-30% for 90 days. Though, such high levels were only found in 1.9% of the samples before the Omicron surge, and they were not durable for 3 months. Anti-S1 IgG antibody levels are statistically associated with protection from SARS-CoV-2 infection. However, the prediction impact of the antibody level findings on infection protection is limited.

Complex primary percutaneous coronary intervention with ultrathin-strut biodegradable versus thin-strut durable polymer drug-eluting stents in patients with ST-segment elevation myocardial infarction: A subgroup analysis from the BIOSTEMI randomized trial.

BACKGROUND: Ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) are superior to thin-strut durable polymer everolimus-eluting stents (DP-EES) with respect to target lesion failure (TLF) at 2 years among patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the impact of primary percutaneous coronary intervention (pPCI) complexity on long-term clinical outcomes with BP-SES versus DP-EES in STEMI patients. METHODS: We performed a post hoc subgroup analysis from the BIOSTEMI (NCT02579031) randomized trial, which included individual data from 407 STEMI patients enrolled in the BIOSCIENCE trial (NCT01443104). STEMI patients were randomly assigned to treatment with ultrathin-strut BP-SES or thin-strut DP-EES, and further categorized into those undergoing complex versus noncomplex pPCI. Complex pPCI was defined by the presence of ≥1 of the following criteria: 3 vessel treatment, ≥3 stents implanted, ≥3 lesions treated, bifurcation lesion with ≥2 stents implanted, total stent length ≥60 mm, and/or chronic total occlusion treatment. The primary endpoint was TLF, a composite of cardiac death, target-vessel myocardial reinfarction, or clinically indicated target lesion revascularization, within 2 years. RESULTS: Among a total of 1707 STEMI patients, 421 (24.7%) underwent complex pPCI. Baseline characteristics were similar between groups. At 2 years, TLF occurred in 14 patients (7.1%) treated with BP-SES and 25 patients (11.6%) treated with DP-EES (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.32-1.19; p = 0.15) in the complex pPCI group, and in 28 patients (4.4%) treated with BP-SES and 49 patients (8.2%) treated with DP-EES (HR: 0.54; 95% CI: 0.34-0.86; p = 0.008; p for interaction = 0.74) in the noncomplex pPCI group. Individual TLF components and stent thrombosis rates did not significantly differ between groups. CONCLUSION: In a post hoc subgroup analysis from the BIOSTEMI randomized trial, ultrathin-strut BP-SES were superior to thin-strut DP-EES with respect to TLF at 2 years among STEMI patients undergoing both complex and noncomplex pPCI.

Pulmonary Recovery 12 Months after Non-Severe and Severe COVID-19: The Prospective Swiss COVID-19 Lung Study.

BACKGROUND: Lung function impairment persists in some patients for months after acute coronavirus disease 2019 (COVID-19). Long-term lung function, radiological features, and their association remain to be clarified. OBJECTIVES: We aimed to prospectively investigate lung function and radiological abnormalities over 12 months after severe and non-severe COVID-19. METHODS: 584 patients were included in the Swiss COVID-19 lung study. We assessed lung function at 3, 6, and 12 months after acute COVID-19 and compared chest computed tomography (CT) imaging to lung functional abnormalities. RESULTS: At 12 months, diffusion capacity for carbon monoxide (DLCOcorr) was lower after severe COVID-19 compared to non-severe COVID-19 (74.9% vs. 85.2% predicted, p < 0.001). Similarly, minimal oxygen saturation on 6-min walk test and total lung capacity were lower after severe COVID-19 (89.6% vs. 92.2%, p = 0.004, respectively, 88.2% vs. 95.1% predicted, p = 0.011). The difference for forced vital capacity (91.6% vs. 96.3% predicted, p = 0.082) was not statistically significant. Between 3 and 12 months, lung function improved in both groups and differences in DLCO between non-severe and severe COVID-19 patients decreased. In patients with chest CT scans at 12 months, we observed a correlation between radiological abnormalities and reduced lung function. While the overall extent of radiological abnormalities diminished over time, the frequency of mosaic attenuation and curvilinear patterns increased. CONCLUSIONS: In this prospective cohort study, patients who had severe COVID-19 had diminished lung function over the first year compared to those after non-severe COVID-19, albeit with a greater extent of recovery in the severe disease group.

Duration of antiplatelet therapy after complex percutaneous coronary intervention in patients at high bleeding risk: a MASTER DAPT trial sub-analysis.

AIM: To assess the effects of 1- or ≥3-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients who received biodegradable-polymer sirolimus-eluting stents for complex percutaneous coronary intervention (PCI) and/or acute coronary syndrome (ACS). METHODS AND RESULTS: In the MASTER DAPT trial, 3383 patients underwent non-complex (abbreviated DAPT, n = 1707; standard DAPT, n = 1676) and 1196 complex (abbreviated DAPT, n = 588; standard DAPT, n = 608) PCI. Co-primary outcomes at 335 days were net adverse clinical events [NACE; composite of all-cause death, myocardial infarction, stroke, and bleeding academic research consortium (BARC) 3 or 5 bleeding events]; major adverse cardiac or cerebral events (MACCE; all-cause death, myocardial infarction, and stroke); and Types 2, 3, or 5 BARC bleeding. Net adverse clinical events and MACCE did not differ with abbreviated vs. standard DAPT among patients with complex [hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.69-1.52, and HR: 1.24, 95% CI: 0.79-1.92, respectively] and non-complex PCI (HR: 0.90, 95% CI: 0.71-1.15, and HR: 0.91, 95% CI: 0.69-1.21; Pinteraction = 0.60 and 0.26, respectively). BARC 2, 3, or 5 was reduced with abbreviated DAPT in patients with and without complex PCI (HR: 0.64; 95% CI: 0.42-0.98, and HR: 0.70; 95% CI: 0.55-0.89; Pinteraction = 0.72). Among the 2816 patients with complex PCI and/or ACS, NACE and MACCE did not differ and BARC 2, 3, or 5 was lower with abbreviated DAPT. CONCLUSION: In HBR patients free from recurrent ischaemic events at 1 month, DAPT discontinuation was associated with similar NACE and MACCE and lower bleeding rates compared with standard DAPT, regardless of PCI or patient complexity. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT03023020, and is closed to new participants, with follow-up completed.

Abbreviated Antiplatelet Therapy in Patients at High Bleeding Risk With or Without Oral Anticoagulant Therapy After Coronary Stenting: An Open-Label, Randomized, Controlled Trial.

BACKGROUND: The optimal duration of antiplatelet therapy (APT) in patients at high bleeding risk with or without oral anticoagulation (OAC) after coronary stenting remains unclear. METHODS: In the investigator-initiated, randomize, open-label MASTER DAPT trial (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Standard DAPT Regimen), 4579 patients at high bleeding risk were randomized after 1-month dual APT to abbreviated or nonabbreviated APT strategies. Randomization was stratified by concomitant OAC indication. In this subgroup analysis, we report outcomes of populations with or without an OAC indication. In the population with an OAC indication, patients changed immediately to single APT for 5 months (abbreviated regimen) or continued ≥2 months of dual APT and single APT thereafter (nonabbreviated regimen). Patients without an OAC indication changed to single APT for 11 months (abbreviated regimen) or continued ≥5 months of dual APT and single APT thereafter (nonabbreviated regimen). Coprimary outcomes at 335 days after randomization were net adverse clinical outcomes (composite of all-cause death, myocardial infarction, stroke, and Bleeding Academic Research Consortium 3 or 5 bleeding events); major adverse cardiac and cerebral events (all-cause death, myocardial infarction, and stroke); and type 2, 3, or 5 Bleeding Academic Research Consortium bleeding. RESULTS: Net adverse clinical outcomes or major adverse cardiac and cerebral events did not differ with abbreviated versus nonabbreviated APT regimens in patients with OAC indication (n=1666; hazard ratio [HR], 0.83 [95% CI, 0.60-1.15]; and HR, 0.88 [95% CI, 0.60-1.30], respectively) or without OAC indication (n=2913; HR, 1.01 [95% CI, 0.77-1.33]; or HR, 1.06 [95% CI, 0.79-1.44]; Pinteraction=0.35 and 0.45, respectively). Bleeding Academic Research Consortium 2, 3, or 5 bleeding did not significantly differ in patients with OAC indication (HR, 0.83 [95% CI, 0.62-1.12]) but was lower with abbreviated APT in patients without OAC indication (HR, 0.55 [95% CI, 0.41-0.74]; Pinteraction=0.057). The difference in bleeding in patients without OAC indication was driven mainly by a reduction in Bleeding Academic Research Consortium 2 bleedings (HR, 0.48 [95% CI, 0.33-0.69]; Pinteraction=0.021). CONCLUSIONS: Rates of net adverse clinical outcomes and major adverse cardiac and cerebral events did not differ with abbreviated APT in patients with high bleeding risk with or without an OAC indication and resulted in lower bleeding rates in patients without an OAC indication. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03023020.

Sinus of Valsalva Dimension and Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: Ascending aortic root anatomy is routinely evaluated on pre-procedural multi-detector computed tomography (MDCT). However, its clinical significance has not been adequately studied. We aimed to investigate the impact of the sinus of Valsalva (SOV) dimension on clinical outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: In a prospective TAVI registry, we retrospectively assessed SOV dimensions by pre-procedural MDCT. Patients were stratified according to tertiles of SOV diameter indexed to body surface area (SOVi). The primary endpoint was all-cause mortality at 1 year. RESULTS: Among 2066 consecutive patients undergoing TAVI between August 2007 and June 2018, 1554 patients were eligible for the present analysis. Patients in the large SOVi group were older (83 ± 6 vs 82 ± 6 vs 81 ± 6; P < .001) and had a higher Society of Thoracic Surgeons Predicted Risk of Mortality (6.3 ± 3.8 vs 5.1 ± 3.1 vs 4.9 ± 3.5; P < .001) than those in the other groups. Patients in the large SOVi group had a higher incidence of moderate or severe paravalvular regurgitation (11.9% vs 4.5% vs 3.5%; P < .001). At 1 year, a large SOVi was independently associated with an increased risk of mortality (HR: 1.62; 95% CI: 1.19-2.21; P = .002) and major or life-threatening bleeding (HR: 1.30; 95% CI: 1.02-1.65; P = .035). CONCLUSIONS: Dilatation of the aortic root at the SOV was associated with adverse outcomes after TAVI. The assessment of the aortic root should be integrated into the risk stratification system in patients undergoing TAVI.

Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS) - A phase II, randomized, double-blind, multi-center, placebo-controlled trial.

BACKGROUND: Activation of inflammatory pathways during acute myocardial infarction contributes to infarct size and left ventricular (LV) remodeling. The present prospective randomized clinical trial was designed to test the efficacy and safety of broad-spectrum anti-inflammatory therapy with a mammalian target of rapamycin (mTOR) inhibitor to reduce infarct size. DESIGN: Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS, clinicaltrials.gov NCT01529554) is a phase II randomized, double-blind, multi-center, placebo-controlled trial on the effects of a 5-day course of oral everolimus on infarct size, LV remodeling, and inflammation in patients with acute ST-elevation myocardial infarction (STEMI). Within 5 days of successful primary percutaneous coronary intervention (pPCI), patients are randomly assigned to everolimus (first 3 days: 7.5 mg every day; days 4 and 5: 5.0 mg every day) or placebo, respectively. The primary efficacy outcome is the change from baseline (defined as 12 hours to 5 days after pPCI) to 30-day follow-up in myocardial infarct size as measured by cardiac magnetic resonance imaging (CMRI). Secondary endpoints comprise corresponding changes in cardiac and inflammatory biomarkers as well as microvascular obstruction and LV volumes assessed by CMRI. Clinical events, laboratory parameters, and blood cell counts are reported as safety endpoints at 30 days. CONCLUSION: The CLEVER-ACS trial tests the hypothesis whether mTOR inhibition using everolimus at the time of an acute STEMI affects LV infarct size following successful pPCI.

Cardiovascular outcomes in patients with left atrial enlargement undergoing transcatheter aortic valve implantation.

BACKGROUND: Increased left ventricular afterload resulting from severe aortic stenosis (AS) leads to progressive cardiac remodeling. Left atrial enlargement (LAE) is an early manifestation in a series of maladaptive changes and may affect clinical outcomes after valvular replacement therapy. The aim of this study is to determine the impact of LAE on clinical outcomes in symptomatic patients with severe AS undergoing transcatheter aortic valve implantation (TAVI). METHODS: In a prospective single-center TAVI registry, we analyzed LA dimensions measured by echocardiography before intervention. Patients with atrial fibrillation or concomitant mitral valve disease were excluded. LAE was defined as indexed LA volume >34 ml/m2 . The primary endpoint was cardiovascular death (CVD) at 1 year. RESULTS: Among 1663 patients undergoing TAVI between August 2007 and December 2016, 768 (46.2%) were eligible for the present analysis and 486 patients had LAE. The prevalence of LAE was higher in males (68.3%) as compared to females (58.8%). Patients with LAE were older (82.3 ± 6.7 years vs. 80.0 ± 6.4 years) and had a higher STS-PROM score (6.1 ± 4.7% vs. 4.7 ± 2.9%). After adjustment, patients with LAE had an increased risk of CVD at 1-year compared to patients with normal LA dimensions (49 [10.4%] vs. 8 [2.9%]; HRadj , 3.52; 95% CI, 1.66-7.44)]. In multivariable analysis, LAE was independently associated with an increased risk of CVD at 1-year (HRadj , 3.52; 95% CI, 1.66-7.44). CONCLUSIONS: LAE secondary to AS was documented in a significant proportion of patients undergoing TAVI and was associated with a more than threefold increased risk of CVD at 1-year.

Watchman FLX vs. Watchman 2.5 in a Dual-Center Left Atrial Appendage Closure Cohort: the WATCH-DUAL study.

AIMS: No studies have compared Watchman 2.5 (W2.5) with Watchman FLX (FLX) devices to date. We aimed at comparing the FLX with W2.5 devices with respect to clinical outcomes, left atrial appendage (LAA) sealing properties and device-related thrombus (DRT). METHODS AND RESULTS: All consecutive left atrial appendage closure (LAAC) procedures performed at two European centres between November 2017 and February 2021 were included. Procedure-related complications and net adverse cardiovascular events (NACE) at 6 months after LAAC were recorded. At 45-day computed tomography (CT) follow-up, intra- (IDL) and peri- (PDL) device leak, residual patent neck area (RPNA), and DRT were assessed by a Corelab. Out of 144 LAAC consecutive procedures, 71 and 73 interventions were performed using W2.5 and FLX devices, respectively. There were no differences in terms of procedure-related complications (4.2% vs. 2.7%, P = 0.626). At 45-day CT, the FLX was associated with lower frequency of IDL [21.3% vs. 40.0%; P = 0.032; odds ratio (OR): 0.375; 95% confidence interval (CI): 0.160-0.876; P = 0.024], similar rate of PDL (29.5% vs. 42.0%; P = 0.170), and smaller RPNA [6 (0-36) vs. 40 (6-115) mm2; P = 0.001; OR: 0.240; 95% CI: 0.100-0.577; P = 0.001] compared with the W2.5 group. At 45 days, rate of DRT as detected by CT and/or transoesophageal echocardiography (TOE), was higher with W2.5 (6.0% vs. 0%, P = 0.045). At 6-month follow-up, NACE did not differ between groups. CONCLUSIONS: In this cohort of consecutive LAACs, FLX as compared to W2.5, was associated with similar procedure-related complications and 6-month NACE, but with improved LAA neck coverage, and lower IDL and DRT.

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.

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment-Elevation Myocardial Infarction: Primary Results of the FABOLUS-FASTER Trial.

BACKGROUND: Standard administration of newer oral P2Y12 inhibitors, including prasugrel or ticagrelor, provides suboptimal early inhibition of platelet aggregation (IPA) in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. We aimed to investigate the effects of cangrelor, tirofiban, and prasugrel, administered as chewed or integral loading dose, on IPA in patients undergoing primary percutaneous coronary intervention. METHODS: The FABOLUS-FASTER trial (Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over Prasugrel: A Multicenter Randomized Open-Label Trial in Patients with ST-Elevation Myocardial Infarction Referred for Primary Percutaneous Intervention) is an investigator-initiated, multicenter, open-label, randomized study. A total of 122 P2Y12-naive patients with ST-segment-elevation myocardial infarction were randomly allocated (1:1:1) to cangrelor (n=40), tirofiban (n=40) (both administered as bolus and 2-hour infusion followed by 60 mg of prasugrel), or 60-mg loading dose of prasugrel (n=42). The latter group underwent an immediate 1:1 subrandomization to chewed (n=21) or integral (n=21) tablets administration. The trial was powered to test 3 hypotheses (noninferiority of cangrelor compared with tirofiban using a noninferiority margin of 9%, superiority of both tirofiban and cangrelor compared with chewed prasugrel, and superiority of chewed prasugrel as compared with integral prasugrel, each with α=0.016 for the primary end point, which was 30-minute IPA at light transmittance aggregometry in response to 20 µmol/L adenosine diphosphate. RESULTS: At 30 minutes, cangrelor did not satisfy noninferiority compared with tirofiban, which yielded superior IPA over cangrelor (95.0±8.9 versus 34.1±22.5; P<0.001). Cangrelor or tirofiban were both superior to chewed prasugrel (IPA, 10.5±11.0; P<0.001 for both comparisons), which did not provide higher IPA over integral prasugrel (6.3±11.4; P=0.47), despite yielding higher prasugrel active metabolite concentration (ng/mL; 62.3±82.6 versus 17.1±43.5; P=0.016). CONCLUSIONS: Cangrelor provided inferior IPA compared with tirofiban; both treatments yielded greater IPA compared with chewed prasugrel, which led to higher active metabolite concentration but not greater IPA compared with integral prasugrel. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02978040; URL: https://www.clinicaltrialsregister.eu; EudraCT 2017-001065-24.

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.