Impact of New-Onset Conduction Disturbances following Transcatheter Aortic Valve Replacement on Outcomes: A Single-Center Study.

Background: Transcatheter aortic valve replacement (TAVR) is known to increase the incidence of conduction disturbances compared to surgical aortic valve replacement; however, there are limited data on the impact and duration of these conduction disturbances on longer term outcomes. Objective: To determine the differential impact of persistent versus nonpersistent new-onset conduction disturbances on TAVR-related complications and outcomes. Methods: This is a single-center retrospective analysis of 927 consecutive patients with aortic stenosis who underwent TAVR at Yale New Haven Hospital from July 2012 to August 2019. Patients with new-onset conduction disturbances within 7 days following TAVR were selected for this study. Persistent and nonpersistent disturbances were, respectively, defined as persisting or not persisting on all patient ECGs for up to 1.5 years after TAVR or until death. Results: Within 7 days after TAVR, conduction disturbances occurred in 42.3% (392/927) of the patients. Conduction disturbances persisted in 150 (38%) patients and did not persist in 187 (48%) patients, and 55 (14%) patients were excluded for having mixed (both persistent and nonpersistent) disturbances. Compared with nonpersistent disturbances, patients with persistent disturbances were more likely to receive a PPM within 7 days after the TAVR procedure (46.0% versus 4.3%, p < 0.001) and had a greater unadjusted 1-year cardiac-related and all-cause mortality risk (HR 2.54, p=0.044 and HR 1.90, p=0.046, respectively). Conclusion: Persistent conduction disturbances were associated with a greater cardiac and all-cause mortality rate at one year following TAVR. Future research should investigate periprocedural factors to reduce persistent conduction disturbances and outcomes beyond one year follow-up.

Sulodexide versus Control and the Risk of Thrombotic and Hemorrhagic Events: Meta-Analysis of Randomized Trials.

Thrombotic cardiovascular disease (myocardial infarction [MI], stroke, and venous thromboembolism [VTE]) remains a major cause of death and disability. Sulodexide is an oral glycosaminoglycan containing heparan sulfate and dermatan sulfate. We conducted a systematic review and meta-analysis to determine the cardiovascular efficacy, and safety of sulodexide versus control in randomized controlled trials (RCTs). We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs reporting cardiovascular outcomes in patients receiving sulodexide versus control (placebo or no treatment). Outcomes included all-cause mortality, cardiovascular mortality, MI, stroke, deep vein thrombosis (DVT), pulmonary embolism, and bleeding. We used inverse variance random-effects models with odds ratio (OR) as the effect measure. After screening 360 records, 6 RCTs including 7,596 patients (median follow-up duration: 11.6 months) were included. Patients were enrolled for history of MI, VTE, peripheral arterial disease, or cardiovascular risk factors plus nephropathy. Use of sulodexide compared with control was associated with reduced odds of all-cause mortality (OR 0.67, 95% confidence interval [CI] 0.52-0.85, p = 0.001), cardiovascular mortality (OR 0.44, 95% CI 0.22-0.89, p = 0.02), and MI (OR 0.70, 95% CI 0.51-0.96, p = 0.03), and nonsignificantly reduced odds of stroke (OR 0.78, 95% CI 0.45-1.35, p = 0.38). Sulodexide was associated with significantly reduced odds of VTE (OR 0.44, 95% CI 0.24-0.81, p = 0.008), including DVT (OR 0.41, 95% CI 0.26-0.65, p < 0.001), but not pulmonary embolism (OR 0.92, 95% CI 0.40-2.15, p = 0.86). Bleeding events were not significantly different in the two groups (OR 1.14, 95% CI 0.47-2.74, p = 0.48). In six RCTs across a variety of clinical indications, use of sulodexide compared with placebo or no treatment was associated with reduced odds of all-cause mortality, cardiovascular mortality, MI, and DVT, without a significant increase in bleeding. Additional studies with this agent are warranted.

Angiographic predictors of 2-year stent thrombosis in patients receiving drug-eluting stents: Insights from the ADAPT-DES study.

OBJECTIVES: We sought to identify angiographic predictors of 2-year stent thrombosis (ST) in the ADAPT-DES study. BACKGROUND: A strong relationship between platelet reactivity and ST after implantation of drug-eluting stents (DES) was recently confirmed in the prospective, multicenter ADAPT-DES study. METHODS: In a pre-specified analysis of patients enrolled in ADAPT-DES, an independent angiographic core laboratory performed detailed angiographic analyses for all cases of ST. Patients with Academic Research Consortium definite/probable target-lesion ST were matched with controls in a 1:2 ratio, and multivariable Cox regression models identified angiographic predictors of 2-year ST. RESULTS: Among 8,582 patients who had successful percutaneous coronary intervention (PCI) and were included in the ADAPT-DES study, 92 (1.1%) patients had ST at 2-year follow-up. Target lesion-related ST was identified in 77 patients (82 lesions) who were clinically matched with 153 patients (196 lesions) without ST. Patients with ST were more likely to have longer target lesions, thrombus, moderate/severe calcification, American College of Cardiology/American Heart Association (ACC/AHA) type C lesions, and saphenous vein grafts. After adjustment for clinical covariates the angiographic variables that predicted ST were lesion complexity (ACC/AHA type C lesion, adjusted HR: 1.97, 95% CI: 1.19 to 3.26, P = 0.01) and presence of thrombus on index PCI (HR: 2.25, 95% CI: 1.40 to 3.59, P < 0.01). CONCLUSIONS: Anatomically complex lesions and the presence of thrombus are strong predictors of 2-year ST in the DES era. © 2016 Wiley Periodicals, Inc.

Risk stratification of patients undergoing medical therapy after coronary angiography.

AIM: We sought to investigate the prognostic impact of the SYNTAX (Synergy between PCI with TAXUS and Cardiac Surgery) score (SS) on 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) undergoing medical therapy only. METHODS AND RESULTS: Among the 13 819 patients enrolled in the ACUITY trial and undergoing coronary angiogram, 4491 patients were treated with medical therapy as the initial strategy. Of those, baseline SS and complete angiographic analysis were available in 1275 patients. Patients were divided in four groups based on the presence or absence of coronary artery disease (CAD) and subsequently, among patients with CAD, by SS. Major adverse cardiac events (MACE) and its individual components (death, myocardial infarction, and unplanned revascularization) were compared between groups. Among the 1275 patients, the mean SS was 3.5 ± 7.0 (range 0-45). SYNTAX score was 0 in 842 patients, >0 and ≤5 in 170, >5 and ≤11 in 119, and >11 in 144 patients. The 1-year rates of MACE were higher in patients with CAD and higher SS. By multivariable analysis, the SS was a strong predictor of all adverse ischaemic events, including mortality. By receiver operator characteristic analysis, an SS cut-off of 8 showed the best prognostic accuracy for death and MACE. CONCLUSION: In patients with NSTE ACS undergoing medical therapy, the SS, especially when >8, was shown to be a strong predictor of 1-year MACE, including mortality. This finding has important clinical implications for risk stratification of patients with NSTE ACS undergoing medical therapy after an initial angiogram.

Outcomes of a dedicated stent in coronary bifurcations with large side branches: A subanalysis of the randomized TRYTON bifurcation study.

OBJECTIVES: To examine the benefit of the Tryton dedicated side branch (SB) stent compared with provisional stenting in the treatment of complex bifurcation lesions involving large SBs. BACKGROUND: The TRYTON Trial was designed to evaluate the utility of a dedicated SB stent to treat true bifurcation lesions involving large (≥2.5 mm by visual estimation) SBs. Patient enrolled in the trial had smaller SB diameters than intended (59% SB ≤2.25 mm by Core Lab QCA). The TRYTON Trial did not meet its primary endpoint due to an increased rate of peri-procedural myocardial infarctions (MIs). METHODS: The TRYTON Trial randomized 704 patients to the Tryton SB stent with main vessel DES versus provisional SB treatment with main vessel DES. The rates of the primary end point of target vessel failure and the secondary powered end point of angiographic percent diameter stenosis in the SB at 9 months were assessed and compared between the two treatment strategies among patients with a SB ≥2.25 mm diameter at baseline determined by Core Lab QCA. RESULTS: Among the 704 patients enrolled in the TRYTON Trial, 289 patients (143 provisional and 146 Tryton stent; 41% of entire cohort) had a SB ≥2.25 mm. The primary end point of TVF was numerically lower in the Tryton group compared with the provisional group (11.3% vs. 15.6%, P = 0.38), and was within the non-inferiority margin. No difference among the rates of clinically driven target vessel revascularization (3.5% vs. 4.3% P = 0.77) or cardiac death (0% both groups) were seen. In-segment percent diameter stenosis of the SB was significantly lower in the Tryton group compared with the provisional group (30.4% vs. 40.6%, P = 0.004). CONCLUSIONS: Analysis of the TRYTON Trial cohort of SB ≥2.25 mm supports the safety and efficacy of the Tryton SB stent compared with a provisional stenting strategy in the treatment of bifurcation lesions involving large SBs. © 2015 Wiley Periodicals, Inc.

Impact of sex on Transcatheter aortic valve replacement outcomes: Results of a single-center study.

BACKGROUND: Early studies on transcatheter aortic valve replacement (TAVR) outcomes showed that female sex was associated with better survival. With increased use of new-generation valves, the impact of sex on contemporary TAVR outcomes is less well known. METHODS: Retrospective analysis using institutional National Cardiovascular Data Registry STS/ACC TVT data was performed on all patients undergoing TAVR at Yale New Haven Hospital from July 2012 to August 2019. New-generation valves were Evolut PRO, Evolut R, and SAPIEN 3. Old-generation valves were CoreValve, SAPIEN, and SAPIEN XT. Log-rank test and Kaplan-Meier curves were used to compare sex differences in survival up to 1 year after TAVR. Cox modeling was used to adjust for baseline and procedural characteristic differences. RESULTS: 927 consecutive patients (41.4% women) underwent TAVR. Women were older (82.8 vs 80.6 years old; p < 0.001) with higher STS mortality scores compared with men (7.6% vs 6.4%; p < 0.001) despite lower prevalence of cardiovascular comorbidities including coronary artery disease, peripheral artery disease, and smoking. Most cases used transfemoral access (90.5%) and new-generation devices (72.3%). Women received smaller valves compared with men (20-26 mm: 78.0% vs 32.9%; 29-34 mm: 22.1% vs 67.1%; overall p < 0.0001). There were no statistically significant differences between sexes in both unadjusted and adjusted 1-year mortality. CONCLUSION: Our data show no significant difference in 1-year survival between sexes using primarily new generation valves. Further studies should reassess the impact of sex on TAVR outcomes and whether newer technologies like new valve design and sizes, and CT imaging may have eliminated sex-based disparities.

Antiplatelet strategies in acute coronary syndromes: design and methodology of an international collaborative network meta-analysis of randomized controlled trials.

INTRODUCTION: The optimal choice of oral P2Y12 receptor inhibitors has the potential to significantly influence outcomes. We seek to compare the safety and efficacy of the three most commonly used oral P2Y12 receptor inhibitors (clopidogrel, prasugrel, and ticagrelor) in acute coronary syndromes (ACS) via a comprehensive systematic review and network meta-analysis. EVIDENCE ACQUISITION: In line with the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, we performed a comprehensive search for RCTs which compared cardiovascular and hemorrhagic outcomes after use of at least two of the distinct oral P2Y12 receptor inhibitors (i.e. clopidogrel, prasugrel, and ticagrelor). A search strategy has been designed to systematically search multiple databases, including MEDLINE with PubMed interface, The Cochrane Central Register of Controlled Trials, and Embase. In addition, key inclusion criteria will be trial size of at least 100 patients and at least 1 month of follow-up time. Several prespecified subgroups will be explored, including Asian patients, patients presenting with ST-elevation myocardial infarction, patients of advanced age, and others. EVIDENCE SYNTHESIS: Exploratory frequentist pairwise meta-analyses will be based primarily on a random-effects method, relying on relative risks (RR) for short-term outcomes and incidence rate ratios (IRR) for long-term outcomes. Inferential frequentist network meta-analysis will be based primarily on a random-effects method, relying on RR and IRR as specified above. Results will be reported as point summary of effect, 95% CI, and P values for effect, and graphically represented using forest plots. CONCLUSIONS: An international collaborative network meta-analysis has begun to comprehensively analyze the safety and efficacy of prasugrel, ticagrelor and clopidogrel, each on a background of aspirin, for management of patients with ACS. It is our hope that the rigor and breadth of the undertaking described herein will provide novel insights that will inform optimal patient care for patients with ACS treated conservatively, or undergoing revascularization.

Individual Patient Data Pooled Analysis of Randomized Trials of Bivalirudin versus Heparin in Acute Myocardial Infarction: Rationale and Methodology.

BACKGROUND: Individual randomized controlled trials (RCTs) of periprocedural anticoagulation with bivalirudin versus heparin during percutaneous coronary intervention (PCI) have reported conflicting results. Study-level meta-analyses lack granularity to adjust for confounders, explore heterogeneity, or identify subgroups that may particularly benefit or be harmed. OBJECTIVE: To overcome these limitations, we sought to develop an individual patient-data pooled database of RCTs comparing bivalirudin versus heparin. METHODS: We conducted a systematic review to identify RCTs in which ≥1,000 patients with acute myocardial infarction (AMI) undergoing PCI were randomized to bivalirudin versus heparin. RESULTS: From 738 identified studies, 8 RCTs met the prespecified criteria. The principal investigators of each study agreed to provide patient-level data. The data were pooled and checked for accuracy against trial publications, with discrepancies addressed by consulting with the trialists. Consensus-based definitions were created to resolve differing antithrombotic, procedural, and outcome definitions. The project required 3.5 years to complete, and the final database includes 27,409 patients (13,346 randomized to bivalirudin and 14,063 randomized to heparin). CONCLUSION: We have created a large individual patient database of bivalirudin versus heparin RCTs in patients with AMI undergoing PCI. This endeavor may help identify the optimal periprocedural anticoagulation regimen for patient groups with different relative risks of adverse ischemic versus bleeding events, including those with ST-segment and non-ST-segment elevation MI, radial versus femoral access, use of a prolonged bivalirudin infusion or glycoprotein inhibitors, and others. Adherence to standardized techniques and rigorous validation processes should increase confidence in the accuracy and robustness of the results.

Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research.

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

Mortality, Length of Stay, and Cost Implications of Procedural Bleeding After Percutaneous Interventions Using Large-Bore Catheters.

Importance: Bleeding complications after percutaneous transcatheter interventions that used large-bore catheters are frequent and associated with high mortality and morbidity. Objective: To describe the incidence of bleeding complications among patients undergoing contemporary endovascular interventions involving large-bore catheters and its association with in-hospital mortality, length of stay, and health care cost. Design, Setting, and Participants: This retrospective cohort study analyzed all 17 672 patients from the Healthcare Cost and Utilization Project's National Inpatient Sample database who were recorded as having undergone a transcatheter aortic valve replacement (n = 3223), an endovascular aneurysm repair (n = 12 633), or a percutaneous left ventricular assist device implant (n = 1816) between January 1, 2012, and December 31, 2013. Bleeding complication was defined as any transfusion, any hemorrhage or hematoma, or the need for percutaneous or surgical intervention to control the bleeding event. Health care costs were determined by multiplying the total charge for each visit by the cost to charge ratios reported for each hospital code in the database. Data were collected from the database on April 29, 2016. Main Outcomes and Measures: Adjusted association between bleeding complications and mortality was determined by multivariable logistic regression. Length of stay and total health care costs were compared using multivariable linear regression between patients who did and patients who did not have bleeding complications. Results: Bleeding complications occurred in 3128 patients (17.7%) (1984 men and 1144 women, with a mean [SD] age of 75.6 [11.9] years). Bleeding was associated with higher mortality (adjusted odds ratio, 2.70; 95% CI, 2.27-3.22; P < .001) and longer hospital stay (adjusted multiplicative difference, 2.14; 95% CI, 2.06-2.16; P < .001). Median (interquartile range) total health care costs were $48 663 ($32 620-$71 547) for patients with bleeding complications compared with $29 968 ($21 924-$43 287) for patients without a bleeding complication (adjusted multiplicative difference, 1.55; 95% CI, 1.52-1.59; P < .001). Conclusions and Relevance: Periprocedural bleeding was common among patients who underwent transcatheter intervention using large-bore catheters and was associated with a statistically significant increase in mortality, length of stay, and cost.

Impact of Chronic Total Occlusions on Revascularization Scores and Outcome Prediction.

OBJECTIVES: To evaluate the contribution of chronic total occlusion (CTO)-related SYNTAX score (SS) to the overall SS for patients with CTO and compare the traditional SS to a simplified variant. The SS algorithm assigns CTO lesions a greater weight (5× points) than non-CTO lesions (50% to <100% diameter stenosis; 2× points). METHODS: We calculated the SS and the simplified SS (2× points also to CTO lesions) for 4356 patients from the angiographic substudy of the Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY) trial. We compared the association between SS and 1-year mortality and major adverse cardiac events for patients with and without a CTO. We also compared the simplified SS with the traditional SS. RESULTS: The median SS was 20 (interquartile range, 13-27.5) for patients with a CTO and 8 (interquartile range, 2-16) for patients without a CTO. For patients with a CTO, the CTO lesion(s) contributed 67 ± 26% of the total SS. The simplified SS reclassified 187/603 (31.0%) of patients with a SS >22 to a SS ≤22. The traditional SS did not improve discrimination indices for predicting outcomes compared with the simplified SS. CONCLUSIONS: CTO lesions contribute considerably to the total SS in patients with a CTO. A simplified SS that does not differentiate between CTO and non-CTO lesions appeared equivalent to the traditional SS for risk prediction, but reclassified a substantial proportion of patients to a SS ≤22 and may impact choice of revascularization strategy for patients with complex coronary artery disease involving a CTO lesion.

Two-year outcomes after percutaneous coronary intervention of calcified lesions with drug-eluting stents.

BACKGROUND: Percutaneous coronary intervention (PCI) of lesions with coronary arterial calcification (CAC) is common and has been historically associated with an increased risk of adverse events. Whether the association between target lesion calcification (CAC) and outcomes differ across drug-eluting stent generation or between patients with high vs. low residual platelet reactivity (PR) remains unknown. We assessed the association of CAC with adverse ischemic and bleeding events among patients undergoing contemporary PCI with drug-eluting stents (DES). METHODS: We included all 8582 patients who underwent successful PCI with DES in the prospective ADAPT-DES study. Patients were grouped according to whether or not they had CAC. We used a multivariable logistic regression analysis to determine independent predictors of CAC. We assessed the 2-year risk of major adverse cardiac events (MACE: Death, myocardial infarction, or stent thrombosis) and bleeding by constructing Kaplan-Meier curves and fitting unadjusted and adjusted Cox proportional hazards models. We assessed the influence of DES generation and PR on the effect of CAC on outcomes by including interaction terms in the models. RESULTS: CAC was present in 2644 (30.8%) patients. Age, smoking, hypertension, hyperlipidemia, insulin-treated diabetes, hemodialysis, and peripheral artery disease were independent predictors of CAC. Having a CAC was associated with increased unadjusted and adjusted hazards for 2-year MACE and bleeding. The association between CAC and ischemic outcomes was consistent across DES generations and PR (pinteraction>0.05). CONCLUSION: Contemporary DES PCI of calcified lesions is common and is associated with an increased risk of ischemic and bleeding complications.

Safety and Efficacy of Bivalirudin in Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention: From the REPLACE-2, ACUITY and HORIZONS-AMI Trials.

Optimal antithrombotic pharmacotherapy in patients affected by diabetes mellitus (DM) undergoing percutaneous coronary intervention is unclear. We sought to evaluate the safety and efficacy of bivalirudin compared with heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with DM undergoing percutaneous coronary intervention. We pooled patient-level data from the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events-2, Acute Catheterization and Urgent Intervention Triage strategy, and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trials. The primary efficacy end point was the incidence of major adverse cardiac events, defined as the composite of death, myocardial infarction, or unplanned revascularization at 30 days. The primary safety end point was the incidence of 30-day non-coronary artery bypass graft-related major bleeding. All-cause mortality was reported at 30 days and 1 year. Of the 14,737 patients included in the pooled database, 3,641 (24.7%) had DM. Patients with DM had higher rates of 30-day major bleeding and 30-day and 1-year all-cause mortality. There were no differences in 30-day major adverse cardiac events between bivalirudin versus heparin plus GPI in patients with DM (6.9% vs 7.8%; relative risk [RR] 0.89, 95% CI 0.71 to 1.12) or without DM (7.5% vs 6.7%; RR 1.11, 95% CI 0.97 to 1.27; pinteraction = 0.10). Bivalirudin treatment was associated with reduced risk of major bleeding in similar magnitude in patients with DM (4.3% vs 6.6% RR 0.68, 95% CI 0.51 to 0.89) or without DM (3.2% vs 6.1%; RR 0.51, 95% CI 0.43 to 0.61; pinteraction = 0.15). The hemorrhagic benefit of bivalirudin was noted for both access site- and non-access site-related bleeding. Overall, bivalirudin treatment was associated with a significant 1-year mortality benefit (2.7% vs 3.3%; RR 0.82, 95% CI 0.68 to 0.98; p = 0.03), which was consistent between patients with or without DM (pinteraction = 0.30). In conclusion, compared with heparin plus GPI, bivalirudin was associated with similar 30-day antithrombotic efficacy and better 30-day freedom from bleeding and 1-year mortality, irrespective of diabetic status.

Dedicated Bifurcation Stent for the Treatment of Bifurcation Lesions Involving Large Side Branches: Outcomes From the Tryton Confirmatory Study.

OBJECTIVES: The aim of this study was to prospectively study and confirm the safety and efficacy of the Tryton Side Branch Stent in the treatment of coronary artery bifurcations involving large side branches (SBs). BACKGROUND: The TRYTON Pivotal randomized controlled trial (RCT) was designed to compare the Tryton stent with standard provisional SB stenting in large vessels. The trial inadvertently enrolled patients with too small SBs (<2.25 mm). The overall trial did not meet its primary endpoint, because of an increased rate of periprocedural myocardial infarction in the Tryton stent arm. A post hoc analysis restricted to the intended population showed that the trial would have met its endpoint if only patients with SBs ≥2.25 mm in diameter (by core laboratory quantitative coronary angiography) had been enrolled. METHODS: The Tryton Confirmatory Study was a prospective, single-arm extension of the TRYTON Pivotal RCT that enrolled an additional 133 patients treated with the Tryton Side Branch Stent. It was designed to confirm the results of the post hoc analysis and emphasized the inclusion of appropriately sized SBs. The primary endpoint was noninferiority with regard to periprocedural myocardial infarction (creatine kinase myocardial band 3 times the upper limit of normal) compared with a performance goal based on the TRYTON Pivotal RCT. RESULTS: Among the 133 enrolled patients, 132 (99.2%) had SBs ≥2.25 mm. Baseline clinical and angiographic parameters were similar in this study and the RCT. Periprocedural myocardial infarction occurred in 10.5% of patients, which was numerically lower than the provisional group in the TRYTON Pivotal RCT (11.9%). The 95% confidence bounds did not extend beyond the pre-defined performance goal of 17.9%, meeting the noninferiority primary endpoint. CONCLUSIONS: The Tryton Confirmatory Study, in conjunction with the post hoc analysis of the intended population in the TRYTON Pivotal RCT, supports the safety and efficacy of the Tryton Side Branch Stent for treatment of bifurcation lesions involving large SBs.

Relation Between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.

Whether the association between platelet count (PC) and thrombotic and bleeding risk is independent of or varies by residual platelet reactivity to antiplatelet therapies is unclear. We sought to investigate the independent and combined effects of PC and platelet reactivity on thrombotic and bleeding risk after coronary artery implantation of drug-eluting stents (DES). Patients enrolled in the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents study were stratified by PC tertiles. The study cohort comprised 8,402 patients. By linear regression analysis, lower PC was strongly and independently associated with higher platelet reactive units (PRUs) on clopidogrel. After multivariable adjustment (including PRU and aspirin reactive units), high, but not low, PC tertile was independently associated with higher risk of thrombotic complications, including spontaneous myocardial infarction and stent thrombosis. Although no independent association was observed between PC tertiles and hemorrhagic risk, both high and low PC tertiles were associated with increased risk for all-cause mortality. After stratification of PC tertiles by tertiles of PRUs, the crude risk of thrombotic complications was highest in patients in the high PC and high PRU tertiles. By multivariable adjustment, PRU increases were uniformly associated with higher risk of thrombotic events across PC tertiles, without evidence of interaction. In conclusion, higher PCs and higher PRUs act independently and synergistically in determining thrombotic risk. Alongside PRU, PCs could be a simple hematological parameter to consider for risk stratification and in tailoring duration and potency of pharmacologic platelet inhibition after DES implantation.

Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.

Anemic patients remain at increased risk of ischemic and bleeding events. Whether the effects of hemoglobin levels on thrombotic and bleeding risk are independent of platelet reactivity on clopidogrel, however, remains unknown. Patients from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents study were categorized by the presence of anemia at baseline, defined according the World Health Organization criteria. Platelet reactivity was measured with VerifyNow assay; high platelet reactivity (HPR) on clopidogrel was defined as platelet reactive units value >208. Of 8,413 patients included in the study cohort, 1,816 (21.6%) had anemia. HPR was more prevalent in patients with anemia (58.3% vs 38.4%; p <0.001), an association that persisted after multivariate adjustment (adjusted odds ratio: 2.04; 95% confidence interval [CI]: 1.82 to 2.29; p <0.0001). Patients with anemia had higher 2-year rates of major adverse cardiac events (9.5% vs 5.6%; p <0.0001), major bleeding (11.8% vs 7.7%; p <0.0001), and all-cause mortality (4.0% vs 1.4%; p <0.0001); however, after adjustment for baseline clinical confounders, including HPR, anemia was no longer significantly associated with major adverse cardiac events but was still independently associated with all-cause mortality (adjusted HR 1.61, 95% CI 1.23 to 2.12; p <0.0001) and major bleeding (adjusted HR 1.42, 95% CI 1.20 to 1.68; p <0.0001). The effect of HPR on clinical outcomes was uniform according to anemia status, without evidence of interaction. In conclusion, anemia independently correlated with HPR. After percutaneous coronary intervention with drug-eluting stents, anemia at baseline was significantly associated with higher 2-year hemorrhagic and mortality risk; conversely, its association with ischemic risk was attenuated after multivariate adjustment, including HPR.

The association between the extent of coronary artery disease and major bleeding events after percutaneous coronary intervention: from the ACUITY trial.

OBJECTIVE: We sought to evaluate the relation between the extent of coronary artery disease (CAD) and bleeding risk in patients undergoing percutaneous coronary intervention (PCI) for non-ST segment elevation acute coronary syndrome (NSTEACS). BACKGROUND: Patients with severe CAD undergoing PCI for NSTEACS are at high risk for recurrent adverse events. Hemorrhagic events after PCI are associated with high rates of morbidity and mortality. Despite sharing many common risk factors, the relationship between the extent of CAD and bleeding after PCI remains understudied. METHODS: The SYNTAX score (SS) was used to quantify the extent and severity of CAD. We stratified 2627 patients from the ACUITY PCI cohort into SS groups based on score tertiles from the ACUITY trial (<7, 7-12, and >12). Thirty-day major bleeding rates were determined for each group. RESULTS: When stratified by ACUITY tertiles, 30-day major bleeding rates were significantly greater in the highest SS tertile (>12) than in the intermediate and lowest tertiles (P<.01). By multivariable analysis, the SS (by augmentation of 1 point) remained independently associated with 30-day major bleeding (hazard ratio = 1.03; 95% confidence interval, 1.01-1.04; P<.01). CONCLUSION: The results of this large-scale study suggest that in addition to its previously described association with adverse ischemic events, the extent of CAD, as assessed by the SS, was independently associated with major bleeding after PCI for NSTEACS.

Reasonable incomplete revascularisation after percutaneous coronary intervention: the SYNTAX Revascularisation Index.

AIMS: Incomplete revascularisation is common after percutaneous coronary intervention (PCI). While the absolute amount of residual coronary artery disease (CAD) after PCI has been shown to be associated with worse outcomes, whether the proportion of treated CAD is prognostically important remains to be determined. We sought to quantify the proportion of CAD burden treated by PCI and to evaluate its impact on outcomes using a new prognostic instrument - the SYNTAX Revascularisation Index (SRI). METHODS AND RESULTS: The baseline SYNTAX score (bSS) and residual SYNTAX score (rSS) were determined from 2,618 angiograms of patients enrolled in the prospective ACUITY trial. The SRI was then calculated for each patient using the following formula: SRI=(1-[rSS/bSS])×100. Outcomes were examined according to three SRI groups (SRI=100% [complete revascularisation], 50-99%, and <50%). The median bSS was nine (IQR 5, 16), and after PCI the median rSS was one (IQR 0, 6). The median SRI was 85% (IQR 50, 100), and was 100% in 1,079 patients (41.2%), 50-99% in 907 patients (34.6%), and <50% in 632 patients (24.1%). One-year adverse outcomes, including death, were inversely proportional to the SRI. An SRI cut-off of <80% (present in 1,189 [45.4%] patients after PCI) had the best prognostic accuracy for prediction of death (area under the curve 0.60, 95% confidence interval [CI]: 0.53-0.67, p<0.0001). By multivariable analysis, SRI was an independent predictor of one-year mortality (hazard ratio [HR] 2.17, 95% CI: 1.05-4.35, p=0.03). However, when compared to other scores, the rSS showed superior accuracy and predictive capability for one-year mortality. CONCLUSIONS: The SRI is a newly described method for quantifying the proportion of CAD burden treated by PCI. Given its correlation with mortality, and pending external validation, the SRI may be useful in assessing the degree of revascularisation after PCI, with SRI ≥80% representing a reasonable goal. However, the rSS showed superior predictive capability for one-year mortality.

Incidence, Predictors, and Impact of Post-Discharge Bleeding After Percutaneous Coronary Intervention.

BACKGROUND: The incidence, predictors, and prognostic impact of post-discharge bleeding (PDB) after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation are unclear. OBJECTIVES: This study sought to characterize the determinants and consequences of PDB after PCI. METHODS: The prospective ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) study was used to determine the incidence and predictors of clinically relevant bleeding events occurring within 2 years after hospital discharge. The effect of PDB on subsequent 2-year all-cause mortality was estimated by time-adjusted Cox proportional hazards regression. RESULTS: Among 8,582 "all-comers" who underwent successful PCI with DES in the ADAPT-DES study, PDB occurred in 535 of 8,577 hospital survivors (6.2%) at a median time of 300 days (interquartile range: 130 to 509 days) post-discharge. Gastrointestinal bleeding (61.7%) was the most frequent source of PDB. Predictors of PDB included older age, lower baseline hemoglobin, lower platelet reactivity on clopidogrel, and use of chronic oral anticoagulation therapy. PDB was associated with higher crude rates of all-cause mortality (13.0% vs. 3.2%; p < 0.0001). Following multivariable adjustment, PDB was strongly associated with 2-year mortality (hazard ratio [HR]: 5.03; p < 0.0001), with an effect size greater than that of post-discharge myocardial infarction (PDMI) (HR: 1.92; p = 0.009). CONCLUSIONS: After successful PCI with DES in an unrestricted patient population, PDB is not uncommon and has a strong relationship with subsequent all-cause mortality, greater that that associated with PDMI. Efforts to reduce PDB may further improve prognosis after successful DES implantation. (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794).