Incidence, predictors, and prognostic impact of new permanent pacemaker implantation after TAVR with self-expanding valves

OBJECTIVES: The authors sought to evaluate the incidence, predictors, and outcomes of new permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) with contemporary self-expanding valves (SEV). BACKGROUND: Need for PPI is frequent post-TAVR, but conflicting data exist on new-generation SEV and on the prognostic impact of PPI. METHODS: This study included 3,211 patients enrolled in the multicenter NEOPRO (A Multicenter Comparison of Acurate NEO Versus Evolut PRO Transcatheter Heart Valves) and NEOPRO-2 (A Multicenter Comparison of ACURATE NEO2 Versus Evolut PRO/PRO+ Transcatheter Heart Valves 2) registries (January 2012 to December 2021) who underwent transfemoral TAVR with SEV. Implanted transcatheter heart valves (THV) were Acurate neo (n = 1,090), Acurate neo2 (n = 665), Evolut PRO (n = 1,312), and Evolut PRO+ (n = 144). Incidence and predictors of new PPI and 1-year outcomes were evaluated. RESULTS: New PPI was needed in 362 patients (11.3%) within 30 days after TAVR (8.8%, 7.7%, 15.2%, and 10.4%, respectively, after Acurate neo, Acurate neo2, Evolut PRO, and Evolut PRO+). Independent predictors of new PPI were Society of Thoracic Surgeons Predicted Risk of Mortality score, baseline right bundle branch block and depth of THV implantation, both in patients treated with Acurate neo/neo2 and in those treated with Evolut PRO/PRO+. Predischarge reduction in ejection fraction (EF) was more frequent in patients requiring PPI (P = 0.014). New PPI was associated with higher 1-year mortality (16.9% vs 10.8%; adjusted HR: 1.66; 95% CI: 1.13-2.43; P = 0.010), particularly in patients with baseline EF <40% (P for interaction = 0.049). CONCLUSIONS: New PPI was frequently needed after TAVR with SEV (11.3%) and was associated with higher 1-year mortality, particularly in patients with EF <40%. Baseline right bundle branch block and depth of THV implantation independently predicted the need of PPI.

Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen.

Haemodynamic performance and clinical outcomes of transcatheter aortic valve replacement with the self-expanding ACURATE neo2

BACKGROUND: Transcatheter aortic valve replacement (TAVR) with the ACURATE neo device has been associated with a non-negligible incidence of paravalvular aortic regurgitation (AR). The new-generation ACURATE neo2 has been designed to mitigate this limitation. AIMS: The aim of the study was to compare TAVR with the ACURATE neo and neo2 devices. METHODS: The NEOPRO and NEOPRO-2 registries retrospectively included patients undergoing transfemoral TAVR with self-expanding valves at 24 and 20 centres, respectively. Patients receiving the ACURATE neo and neo2 devices (from January 2012 to December 2021) were included in this study. Predischarge and 30-day VARC-3 defined outcomes were evaluated. The primary endpoint was predischarge moderate or severe paravalvular AR. Subgroup analyses per degree of aortic valve calcification were performed. RESULTS: A total of 2,026 patients (neo: 1,263, neo2: 763) were included. Predischarge moderate or severe paravalvular AR was less frequent for the neo2 group (2% vs 5%; p<0.001), resulting in higher VARC-3 intended valve performance (96% vs 90%; p<0.001). Furthermore, more patients receiving the neo2 had none/trace paravalvular AR (59% vs 38%; p<0.001). The reduction in paravalvular AR with neo2 was mainly observed with heavy aortic valve calcification. New pacemaker implantation and VARC-3 technical and device success rates were similar between the 2 groups; there were more frequent vascular and bleeding complications for the neo device. Similar 1-year survival was detected after TAVR (neo2: 90% vs neo: 87%; p=0.14). CONCLUSIONS: TAVR with the ACURATE neo2 device was associated with a lower prevalence of moderate or severe paravalvular AR and more patients with none/trace paravalvular AR. This difference was particularly evident with heavy aortic valve calcification.

Drug-Eluting or Bare-Metal Stents for Left Anterior Descending or Left Main Coronary Artery Revascularization

BACKGROUND: New-generation drug-eluting stents (DES) reduce target-vessel revascularization compared with bare-metal stents (BMS), and recent data suggest that DES have the potential to decrease the risk of myocardial infarction and cardiovascular mortality. We evaluated the treatment effect of DES versus BMS according to the target artery (left anterior descending [LAD] and/or left main [LM] versus other territories [no-LAD/LM]). METHODS AND RESULTS: The Coronary Stent Trialist (CST) Collaboration gathered individual patient data of randomized trials of DES versus BMS for the treatment of coronary artery disease. The primary outcome was the composite of cardiac death or myocardial infarction. Hazard ratios (HRs) with 95% CIs were derived from a 1-stage individual patient data meta-analysis. We included 26 024 patients across 19 trials: 13 650 (52.4%) in the LAD/LM and 12 373 (47.6%) in the no-LAD/LM group. At 6-year follow-up, there was strong evidence that the treatment effect of DES versus BMS depended on the target vessel (P interaction=0.024). Compared with BMS, DES reduced the risk of cardiac death or myocardial infarction to a greater extent in the LAD/LM (HR, 0.76; 95% CI, 0.68­0.85) than in the no-LAD/LM territories (HR, 0.93; 95% CI, 0.83­1.05). This benefit was driven by a lower risk of cardiac death (HR, 0.83; 95% CI, 0.70­0.98) and myocardial infarction (HR, 0.74; 95% CI, 0.65­0.85) in patients with LAD/LM disease randomized to DES. An interaction (P=0.004) was also found for all-cause mortality with patients with LAD/LM disease deriving benefit from DES (HR, 0.86; 95% CI, 0.76­0.97). CONCLUSIONS: As compared with BMS, new-generation DES were associated with sustained reduction in the composite of cardiac death or myocardial infarction if used for the treatment of LAD or left main coronary stenoses.

One-month dual antiplatelet therapy after pci with resolute onyx des: final 2-year results from onyx one clear

BACKGROUND The optimal duration of dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) varies based on ischemic and high bleeding risk (HBR) factors. METHODS Onyx ONE Clear was a prospective, global, multicenter study to assess the safety and effectiveness of 1-month DAPT in patients with HBR treated with Resolute Onyx zotarolimus-eluting stents (ZES). Patients with coronary artery disease and at least 1 HBR criterion were enrolled and prescribed DAPT for 1 month post-ZES implantation, followed by single antiplatelet therapy (SAPT) thereafter. The primary endpoint was composite of cardiac death or myocardial infarction (MI) from 1 month to 1 year. The current analysis presents final 2-year results from the study. RESULTS A total of 1,507 patients were analyzed at 2 years. Mean age was 74.0 9.5 years, 32.2% female, 38.8% with type 2 diabetes, 36.0% with previous revascularization, and 48.7% presented with an acute coronary syndrome. Patients were enrolled with mean 1.6 HBR criteria and 44.6% met 2 HBR criteria. Lesion characteristics included 50.0% moderate-to-severe calcification and 78.5% B2/C lesions. At 2 years, 81.1% of patients remained on SAPT, 5.6% received DAPT, and 12.5% were prescribed oral anticoagulation only. The composite of cardiac death or MI between 1 month and 2 years was 11.7%, with rates of 5.3% for cardiac death and 7.4% for MI. Most MIs were non-Q wave (6.7%). Rates of other secondary endpoints between 1 month and 2 years included 0.9% definite or probable stent thrombosis, 13.0% targetlesion failure, 4.7% clinically driven target-lesion revascularization, 2.6% stroke, and 6.2% Bleeding Academic Research Consortium (BARC) 3 to 5 bleeding events (Table 1). CONCLUSION Among patients with HBR treated with Resolute Onyx DES and SAPT after 1 month, 2-year ischemic event rates were acceptable despite an ongoing risk of major bleeding.

Clinical outcomes in patients with high bleeding risk and bifurcations after percutaneous coronary intervention with resolute onyx and 1-month dual antiplatelet therapy

BACKGROUND The optimal duration of dual antiplatelet therapy (DAPT) in patients with high bleeding risk (HBR) undergoing percu taneous coronary intervention (PCI) varies based on individual clinical and lesion characteristics. It is unknown whether patients with HBR and bifurcation lesions can be safely treated with an abbreviated DAPT. In this analysis, we examined ischemic and bleeding outcomes at 1 year in patients with and without bifurcations who underwent PCI in the Onyx ONE Clear study. METHODS Patients meeting at least 1 HBR criterion undergoing PCI with Resolute Onyx zotarolimus-eluting stents (Medtronic) were enrolled. DAPT was required for the first month post-procedure and single antiplatelet therapy (SAPT) thereafter. In this analysis, 1-year outcomes were assessed in patients with and without treated index procedure bifurcation lesions as reported by the study investigators. RESULTS Of 1,506 patients in the Onyx ONE Clear study, 218 (14.5%) had treated index procedure bifurcation lesions. Among these, 89% were treated with a provisional stenting technique and 11% with a 2- stent technique. Patients with versus without bifurcation lesions had similar baseline clinical characteristics; however, procedure time was greater for patients with bifurcations (49.2 3 4.6 vs 40.6 28.7 minutes, P < 0.001), as was total stent length (45.3 32.5 vs 35.5 24.9 mm, P < 0.001). SAPT use after 1 month was 97% for patients both with and without bifurcations. The primary study endpoint of com posite cardiac death or myocardial infarction at 1 year was nonsig nificantly different but was numerically higher for patients with versus without bifurcations (9.8% vs 6.5%, P » 0.08), as were the rates of other ischemic events (Table 1). Conversely, major bleeding events (Bleeding Academic Research Consortium [BARC] 3-5) were less prevalent for patients with bifurcations, in part relating to differences in rates of oral anticoagulation between groups. CONCLUSION In the Onyx ONE Clear study, patients with HBR and bifurcations treated with Resolute Onyx zotarolimus-eluting stents and only 1-month DAPT tended to have nonsignificantly different but numerically slightly higher ischemic event rates and less major bleeding compared with patients without bifurcation lesions. Further studies are required to determine the optimal DAPT duration following PCI for HBR patients with coronary bifurcation lesions.

One-Month Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention With Zotarolimus-Eluting Stents in High-Bleeding-Risk Patients

BACKGROUND: Despite treatment guidance endorsing shortened dual antiplatelet therapy (DAPT) duration in high bleeding risk (HBR) patients after drug-eluting stents, limited evidence exists to support these recommendations. The present study was designed to examine the safety and effectiveness of 1-month DAPT duration following percutaneous coronary intervention with zotarolimus-eluting stents in HBR patients. METHODS: Onyx ONE Clear was a prospective, multicenter, nonrandomized study evaluating the safety and effectiveness of 1-month DAPT followed by single antiplatelet therapy in HBR patients undergoing percutaneous coronary intervention with Resolute Onyx drug-eluting stents. The primary analysis of cardiac death or myocardial infarction between 1 month and 1 year was performed in the prespecified one-month clear population of patients pooled from the Onyx ONE US/Japan study and Onyx ONE randomized controlled trial. One-month clear was defined as DAPT adherence and without major adverse events during the first month following percutaneous coronary intervention. RESULTS: Among patients enrolled in Onyx ONE US/Japan (n=752) and Onyx ONE randomized controlled trial (n=1018), 1506 patients fulfilled one-month clear criteria. Mean HBR characteristics per patient was 1.6 with 44.7% having multiple risks. By 2 months and 1 year, respectively, 96.9% and 89.3% of patients were taking single antiplatelet therapy. Between 1 month and 1 year, the rate of the primary end point was 7.0%. The 1-sided upper 97.5% CI was 8.4%, less than the performance goal of 9.7% (P<0.001). CONCLUSIONS: Among HBR patients who were event free before DAPT discontinuation at 1 month, favorable safety and effectiveness through 1 year support treatment with Resolute Onyx drug-eluting stents as part of an individualized strategy for shortened DAPT duration following percutaneous coronary intervention.

Clinical outcomes according to lesion complexity in patients with high bleeding risk treated with 1-month dual antiplatelet therapy following pci: analysis from the onyx one clear study

BACKGROUND Safety and effectiveness outcomes were examined at 1 year among high bleeding risk (HBR) patients treated with 1 month of dual antiplatelet therapy (DAPT) following PCI with zotarolimus eluting stents (ZES) (Resolute Onyx, Medtronic, Santa Rosa, Califor nia) according to lesion complexity (Table). METHODS The 1-year clinical outcomes were evaluated in HBR pa tients treated with ZES who were event-free following 1-month DAPT post-procedure with planned single antiplatelet therapy thereafter. Propensity score adjustment was performed to account for baseline differences (Table). RESULTS A total of 1,506 patients were stratified by complex (n » 395) or noncomplex (n » 1,111) PCI criteria (Table). Complex patients were more frequently men (72.2% vs. 66.1%; p » 0.03) and had higher rates of prior myocardial infarction (MI) (34.4% vs. 23.4%), prior CABG (24.1% vs. 8.9%), multivessel disease (78.2% vs. 39.8%), and B2/C lesion classification (84.2% vs. 75.6%), all p < 0.001. Complex patients had more lesions treated (1.7 vs. 1.2), longer stent length per patient (65.1 mm vs. 26.9 mm), and longer procedure time (58.8 min vs. 35.3 min), all p < 0.001. Procedural success was higher among noncomplex patients (90.8% vs. 82.0%; p < 0.001). In unadjusted analysis, the rate of MI was higher in patients with complex lesions (p » 0.04). How ever, no significant differences in any outcomes between patients with and without complex lesions were present after propensity score adjustment (Table). CONCLUSION Despite greater anatomic and procedural complexity, similar safety and effectiveness were observed in complex and noncomplex patients treated with 1-month DAPT following PCI with Resolute Onyx ZES after propensity score adjustment. These findings support 1-month DAPT among selected HBR patients undergoing PCI with Resolute Onyx ZES irrespective of lesion and procedural complexity.

Ischemic and bleeding outcomes in patients with versus without atrial fibrillation: analysis from the onyx one month dapt program

BACKGROUND The Onyx ONE and Onyx ONE CLEAR studies demonstrated favorable safety and effectiveness in patients at high bleeding risk (HBR) who were event-free 1 month following Resolute Onyx zotarolimus-eluting stent (ZES) implantation and were then treated with single antiplatelet therapy (SAPT) through to 1 year. The present analysis assessed outcomes in patients with versus without history of atrial fibrillation (AF) in whom oral anticoagulant (OAC) use is common. METHODS HBR patients who were event-free at 1 month were sepa rated into 2 groups according to history of AF. Clinical outcomes be tween 1 and 12 months were assessed. RESULTS Among 1,506 patients who were event-free at 1 month in whom treatment with SAPT was intended, 536 (35.6%) had a history of AF and 970 (64.4%) did not. The mean number of HBR criteria at enrollment was 1.7 for AF compared with 1.5 for non-AF patients (p < 0.001). AF patients were more likely to be men (73% vs. 65%; p » 0.001), were more likely to have had prior PCI (34% vs. 28%; p » 0.03) or CABG (16% vs. 11%; p » 0.003), and were more likely taking OACs (80.6% vs. 10.6%; p < 0.001). At 1 year, 89% of AF and non-AF patients were taking SAPT (p » 1.00), although 85.8% of AF patients and 12.4% of non-AF patients were taking OAC (p < 0.001). Ischemic event rates were similar between AF and non-AF groups: target lesion failure (8.5% vs. 7.9%), cardiac death (2.8% vs. 2.5%), myocardial infarction (4.7% vs. 4.9%), target lesion revascularization (2.8% vs. 3.6%), and definite/probable stent thrombosis (0.4% vs. 0.8%), all p > 0.05. BARC 2 to 5 (16.0% vs. 9.4%) bleeding events were higher for AF compared with non-AF patients (p < 0.001) driven by BARC 2 bleeding; BARC 3 to 5 events were similar (4.5% vs. 3.7%; p » 0.49). CONCLUSION After Resolute Onyx ZES implantation in HBR patients and intended treatment of SAPT after 1 month, despite differences in baseline characteristics, ischemic events were similar but moderate bleeding events were higher in patients with versus without a history of AF. Further studies are warranted to optimize management of AF patients post-stenting to minimize the bleeding.

Impact of predilatation prior to transcatheter aortic valve implantation with the self-expanding acurate neo device (From the Multicenter NEOPRO Registry)

Safety and feasibility of transfemoral Acurate neo implantation without systematic predilatation are not fully investigated. Our aim was to evaluate the use and impact of pre-implantation balloon aortic valvuloplasty (pre-BAV) before transcatheter aortic valve implantation (TAVI) with Acurate neo. The NEOPRO Registry retrospectively included 1,263 patients who underwent transfemoral TAVI with Acurate neo at 18 centers between January 2012 and March 2018. Information on preBAV was available for 1,262 patients (99.9%). Primary endpoints were pre-discharge moderate-tosevere paravalvular aortic regurgitation (PAR II+), 30-day new permanent pacemaker implantation (PPI), and 30-day all-cause mortality or stroke. A total of 1,262 patients who underwent TAVI with (n=1,051) or without predilatation (n=211) were included. A reduction in the pre-BAV rate was observed during the study period (from 95.7% in the first date quintile to 78.4% in the last date quintile). Patients who underwent pre-BAV had higher degrees of aortic valve (AV) and left ventricular outflow tract (LVOT) calcification. Primary endpoints were similar between pre-BAV and no pre-BAV groups (PAR II+ 5.5% vs. 3.4%, p=0.214; 30-day PPI 9.0% vs. 8.0%, p=0.660; 30-day death or stroke 4.9% vs. 4.4%, p=0.743). The need for postdilatation and other procedural outcomes were comparable between groups. Predilatation did not have a significant impact on primary endpoints across AV and LVOT calcification subgroups (subgroup analyses) and was not independently associated with primary endpoints (multivariate analyses). In conclusion, transfemoral Acurate neo implantation without predilatation appears to be feasible and safe, especially in patients with milder degrees of AV and LVOT calcification. (AU)

Association of pulse pressure with clinical outcomes in patients under different antiplatelet strategies after percutaneous coronary intervention: analysis of GLOBAL LEADERS

BACKGROUND: We evaluated the association of pulse pressure (PP) and different antiplatelet regimes with clinical and safety outcomes in an all-comers percutaneous coronary intervention (PCI) population. METHODS: In this analysis of GLOBAL LEADERS (n = 15,936) we compared the experimental therapy of 23 months of ticagrelor after 1 month of dual-antiplatelet therapy (DAPT) vs standard DAPT for 12 months followed by aspirin monotherapy in subjects who underwent PCI and were divided into 2 groups according to the median PP (60 mm Hg). The primary end point (all-cause death or new Q-wave myocardial infarction) and the composite end points: patient-oriented composite end points (POCE), Bleeding Academic Research Consortium (BARC) 3 or 5, and net adverse clinical events (NACE) were evaluated. RESULTS: At 2 years, subjects in the high-PP group (n = 7971) had similar rates of the primary end point (4.3% vs 3.9%; P = 0.058), POCE (14.9% vs 12.7%; P = 0.051), and BARC 3 or 5 (2.5% vs 1.7%; P = 0.355) and higher rates of NACE (16.4% vs 13.7%; P = 0.037) compared with the low-PP group (n = 7965). Among patients with PP < 60 mm Hg, the primary end point (3.4% vs 4.4%, adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.96), POCE (11.8% vs 13.5%, aHR 0.86, 95% CI 0.76-0.98), NACE (12.8% vs 14.7%, aHR 0.85, 95% CI 0.76-0.96), and BARC 3 or 5 (1.4% vs 2.1%, aHR 0.69, 95% CI 0.49-0.97) were lower with ticagrelor monotherapy compared with DAPT. The only significant interaction was for BARC 3 or 5 (P = 0.008). CONCLUSIONS: After contemporary PCI, subjects with high PP levels experienced high rates of NACE at 2 years. In those with low PP, ticagrelor monotherapy led to a lower risk of bleeding events compared with standard DAPT.

Ascertainment of silent myocardial infarction in patients undergoing percutaneous coronary intervention (from the GLOBAL LEADERS Trial)

Abstract: Q-wave myocardial infarction (QWMI) comprises 2 entities. First, a clinically evident MI, which can occur spontaneously or be related to a coronary procedure. Second, silent MI which is incidentally detected on serial electrocardiographic (ECG) assessment. The prevalence of silent MI after percutaneous coronary intervention (PCI) in the drug-eluting stent era has not been fully investigated. The GLOBAL LEADERS is an all-comers multicenter trial which randomized 15,991 patients who underwent PCI to 2 antiplatelet treatment strategies. The primary end point was a composite of all-cause death or nonfatal new QWMI at 2-years follow-up. ECGs were collected at discharge, 3-month and 2-year visits, and analyzed by an independent ECG core laboratory following the Minnesota code. All new QWMI were further reviewed by a blinded independent cardiologist to identify a potential clinical correlate by reviewing clinical information. Of 15,968 participants, ECG information was complete in 14,829 (92.9%) at 2 years. A new QWMI was confirmed in 186 (1.16%) patients. Transient new Q-waves were observed in 28.5% (53 of 186) of them during the follow-up. The majority of new QWMI (78%, 146 of 186) were classified as silent MI due to the absence of a clinical correlate. Silent MI accounted for 22.1% (146 of 660) of all MI events. The prevalence of silent MI did not differ significantly between treatment strategies (experimental vs reference: 0.88% vs 0.98%, p = 0.5027). In conclusion, we document the prevalence of silent MI in an all-comers population undergoing PCI in this large-scale randomized trial. (AU)

Current generation balloon-expandable transcatheter valve positioning strategies during aortic valve-in-valve procedures and clinical outcomes

OBJECTIVES: This study sought to evaluate SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, California) positioning using different strategies. BACKGROUND: Aortic valve-in-valve (ViV) is associated with high risk of elevated gradients. METHODS: S3 aortic ViV procedures in stented bioprostheses were studied. Transcatheter heart valve (THV) positioning was analyzed in a centralized core lab blinded to clinical outcomes. A combined endpoint of severely elevated mean gradient ($30 mm Hg) or pacemaker need was established. Two positioning strategies were compared: central marker method and top of S3 method. Optimal final depth was defined as S3 depth #20%. RESULTS: A total of 113 patients met inclusion criteria and were analyzed (76.5 _ 9.7 years of age, 65.8% male, STS score 8 _ 7.6%). THVs had incomplete shortening in comparison to fully expanded valves (92 _ 3.4%), and expansion was more complete in optimal positioning cases compared with others (93.2 _ 2.7% vs. 91.5 _ 3.5%; p » 0.027). The central marker method demonstrated greater correlation with final implantation depth than the top of S3 method (R2 of 0.48 and 0.14; p < 0.001 and p » 0.001, respectively). The combined endpoint rate was 4.3% in the optimal (higher than 3 mm) implantation group, 12% in the intermediate group, and 50% in the low group (p < 0.001). There were no cases of THV embolization. In cases with central marker higher than 3 mm, 72.4% had optimal final depth. In those with central marker higher than 6 mm, 90% had optimal final depth. CONCLUSIONS: Optimal S3 positioning in aortic ViV is associated with better outcomes. Central marker positioning is more reliable than top of S3 positioning. Central marker bottom position should be 3 mm to 6 mm above the ring. (AU)

Comparison of clinical outcomes between Magmaris and Orsiro drug eluting stent at 12 months: Pooled patient level analysis from BIOSOLVE II-III and BIOFLOW II trials

Background The aim of this study was to compare the 12-month clinical outcomes of patients treated with Magmaris or Orsiro. Second generation drug-eluting absorbable metal scaffold Magmaris (Dreams 2G) has proved to be safe and effective in the BIOSOLVE-II study. Similarly, biodegradable polymer sirolimus-eluting stent, Orsiro has shown notable clinical results even in all-comer populations. Methods Magmaris group patients were taken from the BIOSOLVE-II and BIOSOLVE-III trials, while the patients from Orsiro group were enrolled in BIOFLOW-II trial. The primary outcome was explored using a time-to-event assessment of the unadjusted clinical outcomes for target lesion failure (TLF) at 12 months, followed by a multivariate analysis adjusting for all the significantly different covariates between the groups. Results The study population consisted of 482 patients (521 lesions), 184 patients (189 lesions) in Magmaris group and 298 patients (332 lesions) in Orsiro group. The mean age was 65.5 ±â€¯10.8 and 62.7 ±â€¯10.4 years in Magmaris and Orsiro groups, respectively ( p = 0.005). Magmaris and Orsiro unadjusted TLF rates were 6.0 and 6.4% with no significant difference between the groups ( p = 0.869). In the multivariate analysis, there were no meaningful differences between Magmaris and Orsiro groups. Finally, none of the groups presented device thrombosis cases at 12 months. Conclusion At 12 months there were no significant differences between Magmaris and Orsiro groups neither in the unadjusted assessment nor in the multivariate analysis for target lesion failure. These results should be taken as hypothesis generating and may warrant a head to head comparison on a randomized fashion.

Rationale and design of the Onyx ONE global randomized trial: a randomized controlled trial of high-bleeding risk patients after stent placement with 1month of dual antiplatelet therapy

BACKGROUND AND RATIONALE: Polymer-free drug-eluting stent (DES) implantation in combination with 1-month dual antiplatelet therapy (DAPT) has shown superior safety and efficacy outcomes compared with bare-metal stents among patients with high-bleeding risk (HBR) treated with 1-month DAPT. The safety and efficacy of the newer-generation durable-polymer DES Resolute Onyx compared with polymer-free DES among HBR patients treated with 1-month DAPT is unknown. TRIAL DESIGN: The Onyx ONE global randomized trial is an international, prospective, randomized, blinded, controlled study enrolling HBR patients undergoing percutaneous coronary intervention. The trial will randomize up to 2,000 patients in a 1:1 fashion to receive either the durable-polymer Resolute Onyx DES or the polymer-free Biosensors BioFreedom DES. After index procedure, patients in both arms will be treated with 1month of DAPT (aspirin and oral P2Y12 inhibitor), followed by single antiplatelet therapy thereafter. The primary end end point of cardiac death, myocardial infarction, or stent thrombosis at 1-year follow-up. The powered secondary end point is target lesion failure (defined as the composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization) at 1year. Patient follow-up is planned for 1, 2, and 6months and 1 and 2years after the procedure. CONCLUSIONS: The Onyx ONE global randomized trial is the first study to directly compare the safety and efficacy of a durable polymer DES (Resolute Onyx) with a polymer-free DES (BioFreedom) in HBR patients treated with 1month of DAPT.

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC)

Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.(AU)

Drug-eluting or bare-metal stents for percutaneous coronary intervention: a systematic review and individual patient data meta-analysis of randomised clinical trials

Background New-generation drug-eluting stents (DES) have mostly been investigated in head-to-head non-inferiority trials against early-generation DES and have typically shown similar efficacy and superior safety. How the safety profile of new-generation DES compares with that of bare-metal stents (BMS) is less clear.Methods We did an individual patient data meta-analysis of randomized clinical trials to compare outcomes after implantation of new-generation DES or BMS among patients undergoing percutaneous coronary intervention. The primary outcome was the composite of cardiac death or myocardial infarction. Data were pooled in a one-stage random-effects meta-analysis and examined at maximum follow-up and a 1-year landmark. Risk estimates are reported as hazard ratios (HRs) with 95% CIs. This study is registered in PROSPERO, number CRD42017060520.Findings We obtained individual data for 26 616 patients in 20 randomized trials. Mean follow-up was 3·2 (SD 1·8) years. The risk of the primary outcome was reduced in DES recipients compared with BMS recipients (HR 0·84, 95% CI 0·78­0·90, p<0·001) owing to a reduced risk of myocardial infarction (0·79, 0·71­0·88, p<0·001) and a possible slight but non-significant cardiac mortality benefit (0·89, 0·78­1·01, p=0·075). All-cause death was unaffected (HR with DES 0·96, 95% CI 0·88­1·05, p=0·358), but risk was lowered for definite stent thrombosis (0·63, 0·50­0·80, p<0·001) and target-vessel revascularization (0·55, 0·50­0·60, p<0·001). We saw a time-dependent treatment effect, with DES being associated with lower risk of the primary outcome than BMS up to 1 year after placement. While the effect was maintained in the longer term, there was no further divergence from BMS after 1 year. Interpretation The performance of new-generation DES in the first year after implantation means that BMS should no longer be considered the gold standard for safety. Further development of DES technology should target improvements in clinical outcomes beyond 1 year. (AU)

Dual antiplatelet therapy duration based on ischemic and bleeding risks after coronary stenting

Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)

Transcatheter aortic valve replacement with next-generation self-expanding devices: a multicenter, retrospective, propensity-matched comparison of evolut pro versus acurate neo transcatheter heart valves

Abstract OBJECTIVES: The aim of this study was to compare transcatheter aortic valve replacement (TAVR) with the Acurate neo (NEO) and Evolut PRO (PRO) devices. BACKGROUND: The NEO and PRO bioprostheses are 2 next-generation self-expanding devices developed for TAVR. METHODS: The NEOPRO (A Multicenter Comparison of Acurate NEO Versus Evolut PRO Transcatheter Heart Valves) registry retrospectively included patients who underwent transfemoral TAVR with either NEO or PRO valves at 24 centers between January 2012 and March 2018. One-to-one propensity score matching resulted in 251 pairs. Pre-discharge and 30-day Valve Academic Research Consortium (VARC)-2 defined outcomes were evaluated. Binary logistic regression was performed to adjust the treatment effect for propensity score quintiles. RESULTS: A total of 1,551 patients (n = 1,263 NEO; n = 288 PRO) were included. The mean age was 82 years, and the mean Society of Thoracic Surgeons score was 5.1%. After propensity score matching (n = 502), VARC-2 device success (90.6% vs. 91.6%; p = 0.751) and pre-discharge moderate to severe (II+) paravalvular aortic regurgitation (7.3% vs. 5.7%; p = 0.584) were comparable between the NEO and PRO groups. Furthermore, there were no significant differences in any 30-day clinical outcome between matched NEO and PRO pairs, including all-cause mortality (3.2% vs. 1.2%; p = 0.221), stroke (2.4% vs. 2.8%; p = 1.000), new permanent pacemaker implantation (11.0% vs. 12.8%; p = 0.565), and VARC-2 early safety endpoint (10.6% vs. 10.4%; p = 1.000). Logistic regression on the unmatched cohort confirmed a similar risk of VARC-2 device success, paravalvular aortic regurgitation II+, and 30-day clinical outcomes after NEO and PRO implantation. CONCLUSIONS: (AU)

Risk of Early Adverse Events After Clopidogrel Discontinuation in Patients Undergoing Short-Term Dual Antiplatelet Therapy: An Individual Participant Data Analysis

OBJECTIVES: The study sought to evaluate the presence of a clinically relevant rebound phenomenon after dual antiplatelet therapy (DAPT) discontinuation in randomized trials. BACKGROUND: It is currently unknown whether clopidogrel discontinuation after short-term DAPT is associated with an early hazard of ischemic events. METHODS: The authors performed an individual participant data analysis and aggregate meta-analysis. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of cardiac death, myocardial infarction (MI), or stroke. RESULTS: The study included 11,473 PCI patients with individual participant data from 6 randomized trials comparing short-term DAPT (3 or 6 months) versus long-term DAPT (12 months or more). During the first 90 days following clopidogrel discontinuation, there was no significant increase in the risk of MACCE between patients randomized to short-term DAPT compared with long-term DAPT (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.71 to 1.98; p»0.52; absolute risk difference 0.10%; 95% CI: 0.16% to 0.36%). The risk of MI or stent thrombosis was similar among patients randomized to short-term DAPT versus long-term DAPT (HR: 0.93; 95% CI: 0.46 to 1.90; p»0.85). In the aggregate data meta-analysis of 11 trials including 38,919 patients, a higher risk of early MACCE was observed after long-term ($12 months) DAPT duration (HR: 2.28; 95% CI: 1.69 to 3.09; p<0.001) but not short-term (<12 months) DAPT duration (HR: 1.08; 95% CI: 0.67 to 1.74; p for interaction»0.036).CONCLUSIONS: Among patients undergoing PCI with predominantly new-generation DES, discontinuation of clopidogrel after 3 or 6 months DAPT duration was not associated with an early increase in adverse clinical events. An early increase in MACCE was observed after long-term ($12 months) DAPT exposure.