Incidence, treatment, and outcomes of acute myocardial infarction following transcatheter or surgical aortic valve replacement.

OBJECTIVES: This study aimed to evaluate the incidence, treatment, and outcomes of acute myocardial infarction (AMI) following transcatheter or surgical aortic valve replacement (TAVR or SAVR). BACKGROUND: Coronary artery disease is common in patients who undergo aortic valve replacement. However, little is known about differences in clinical features of post-TAVR or post-SAVR AMI. METHODS: We retrospectively identified post-TAVR or post-SAVR (including isolated and complex SAVR) patients admitted with AMI using the Nationwide Readmissions Database 2012-2017. Incidence, invasive strategy (coronary angiography or revascularization), and in-hospital outcomes were compared between post-TAVR and post-SAVR AMIs. RESULTS: The incidence of 180-day AMI was higher post-TAVR than post-SAVR (1.59% vs. 0.72%; p < 0.001). Post-TAVR AMI patients (n = 1315), compared with post-SAVR AMI patients (n = 1344), were older, had more comorbidities and more frequent non-ST-elevation AMI (NSTEMI: 86.6% vs. 78.0%; p < 0.001). After propensity-score matching, there was no significant difference in in-hospital mortality between post-TAVR and post-SAVR AMIs (14.7% vs. 16.1%; p = 0.531), but the mortality was high in both groups, particularly in ST-elevation AMI (STEMI: 38.8% vs. 29.2%; p = 0.153). Invasive strategy was used less frequently for post-TAVR AMI than post-SAVR AMI (25.6% vs. 38.3%; p < 0.001). Invasive strategy was associated with lower mortality in both post-TAVR (adjusted odds ratio = 0.40; 95% confidence interval = [0.24-0.66]) and post-SAVR groups (0.60 [0.41-0.88]). CONCLUSIONS: AMI, albeit uncommon, was more frequent post-TAVR than post-SAVR. Patients commonly presented with NSTEMI, but the mortality of STEMI was markedly high. Further studies are needed to understand why a substantial percentage of patients do not receive invasive coronary treatment, particularly after TAVR, despite seemingly better outcomes with invasive strategy.

Successful modeling of long term outcomes in end-stage renal disease patients undergoing percutaneous coronary intervention with drug-eluting stents.

OBJECTIVES: The objective of this study is to identify and model risk factors for major adverse cardiac events (MACE) and all-cause mortality among patients with ESRD treated with PCI using DES. BACKGROUND: Patients with end-stage renal disease (ESRD) have poor long-term outcomes after percutaneous coronary intervention (PCI) compared with non-ESRD patients. However, there is a paucity of literature regarding risk factors associated with outcomes of ESRD patients after PCI with drug-eluding stents (DES). METHODS: This retrospective cohort study includes all patients with ESRD who underwent first-time PCI with DES at a single, high-volume hospital between 1/1/2005 and 12/31/2015, with follow-up through 9/1/2019. Primary outcomes were MACE (cardiac death, myocardial infarction, or unplanned revascularization) and all-cause mortality. RESULTS: Five-year MACE was 83.0% and five-year morality was 77.9% in patients with ESRD (n = 285). Among ESRD patients, factors independently associated with MACE were C-reactive peptide level, SYNTAX score, peripheral vascular occlusive disease, hemoglobin, and treatment of a restenotic lesion (c-index = 0.66). Factors independently associated with mortality in ESRD patients were age, SYNTAX score, non-use of statins at baseline, insulin-dependent diabetes, chronic obstructive pulmonary disease (COPD), peripheral vascular occlusive disease, and platelet count (c-index = 0.65). CONCLUSIONS: Despite relatively poor 1-and 5-year outcomes among ESRD patients after PCI, risk of MACE and mortality among this cohort can be successfully modelled, which meaningfully informs clinicians regarding management of ESRD patients with coronary artery disease (CAD). Further investigations are necessary to determine whether or not outcomes might be improved through risk profile modification.

End-stage renal disease as an independent risk factor for in-hospital mortality after coronary drug-eluting stenting: Understanding and modeling the risk.

OBJECTIVES: We sought to compare in-hospital outcomes between patients with and without end-stage renal disease (ESRD) undergoing coronary drug-eluting stent (DES) placement and to model risk of in-hospital adverse postpercutaneous coronary intervention (PCI) events in ESRD patients. BACKGROUND: The effect of ESRD on the risk of in-hospital complications after DES PCI is relatively unclear, as is the ability to prospectively stratify risk in this population. METHODS: Consecutive patients undergoing first-time DES between April 1, 2003 and June 30, 2018 at a single tertiary care hospital were included in a prospective registry. Outcomes in those with ESRD were compared to those without ESRD. The primary endpoint was in-hospital all-cause mortality; secondary endpoints included in-hospital major adverse cardiac events (MACE)-defined as cardiac death, myocardial infarction, or unplanned revascularization-and major bleeding. Multivariate logistic regression modeling was used to identify factors associated with each outcome and to generate risk scores. RESULTS: Among 18,134 patients in the study population, 382 (2.1%) had ESRD. ESRD was associated with increased risk of in-hospital mortality (7.1 vs. 2.9%, p < .001), in-hospital MACE (6.3 vs. 2.1%, p < .001), and major bleeding (12.0 vs. 2.6%, p < .001). After multivariable risk adjustment, ESRD was independently associated with in-hospital mortality (odds ratio: 1.83, 95% confidence interval: 1.04-3.23, p = .04) but not MACE or major bleeding. Among patients with ESRD, risks of MACE and major bleeding were successfully modeled (c-statistics = .72 and .85, respectively). CONCLUSIONS: ESRD is independently associated with increased risk of in-hospital mortality after coronary DES. Future studies are necessary to validate risk models derived to identify high-risk ESRD patients.

Clinical Outcomes Before and After Complete Everolimus-Eluting Bioresorbable Scaffold Resorption: Five-Year Follow-Up From the ABSORB III Trial.

BACKGROUND: The Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) provides early drug delivery and mechanical support similar to those of metallic drug-eluting stents, followed by complete resorption in ≈3 years with recovery of vascular structure and function. The ABSORB III trial demonstrated noninferior rates of target lesion failure (cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year with BVS compared with cobalt chromium everolimus-eluting stents. Between 1 and 3 years and cumulative to 3 years, adverse event rates (particularly target vessel myocardial infarction and scaffold thrombosis) were increased after BVS. We sought to assess clinical outcomes after BVS through 5 years, including beyond the 3-year time point of complete scaffold resorption. METHODS: Clinical outcomes from ABSORB III were analyzed by randomized device (intention to treat) cumulative to 5 years and between 3 and 5 years. RESULTS: Rates of target lesion failure, target vessel myocardial infarction, and scaffold thrombosis were increased through the 5-year follow-up with BVS compared with everolimus-eluting stents. However, between 3 and 5 years, reductions in the relative hazards of the BVS compared with everolimus-eluting stents were observed, particularly for target lesion failure (hazard ratio, 0.83 [95% CI, 0.55-1.24] versus 1.35 [95% CI, 1.02-1.78]; Pint=0.052) and scaffold thrombosis (hazard ratio, 0.26 [95% CI, 0.02-2.87] versus 3.23 [95% CI, 1.25-8.30]; Pint=0.056) compared with the 0- to 3-year time period. CONCLUSIONS: In the ABSORB III trial, cumulative 5-year adverse event rates were increased after BVS compared with everolimus-eluting stents. However, the period of excess risk for BVS ended at 3 years, coincident with complete scaffold resorption. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01751906.

Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation.

BACKGROUND: Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding. METHODS: In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months) (triple-therapy group) or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and no aspirin (110-mg and 150-mg dual-therapy groups). Outside the United States, elderly patients (≥80 years of age; ≥70 years of age in Japan) were randomly assigned to the 110-mg dual-therapy group or the triple-therapy group. The primary end point was a major or clinically relevant nonmajor bleeding event during follow-up (mean follow-up, 14 months). The trial also tested for the noninferiority of dual therapy with dabigatran (both doses combined) to triple therapy with warfarin with respect to the incidence of a composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization. RESULTS: The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; P<0.001 for noninferiority; P<0.001 for superiority) and 20.2% in the 150-mg dual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; P<0.001 for noninferiority). The incidence of the composite efficacy end point was 13.7% in the two dual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups. CONCLUSIONS: Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with dabigatran and a P2Y12 inhibitor than among those who received triple therapy with warfarin, a P2Y12 inhibitor, and aspirin. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events. (Funded by Boehringer Ingelheim; RE-DUAL PCI ClinicalTrials.gov number, NCT02164864 .).

Association of adoption of transradial access for percutaneous coronary intervention in ST elevation myocardial infarction with door-to-balloon time.

OBJECTIVES: We aimed to study adoption of transradial primary percutaneous coronary intervention (TR-PPCI) for ST elevation myocardial infarction (STEMI) ("radial first" approach) and its association with door-to-balloon time (D2BT). BACKGROUND: TR-PPCI for STEMI is underutilized in the United States due to concerns about prolonging D2BT. Whether operators and hospitals adopting a radial first approach in STEMI incur prolonged D2BT is unknown. METHODS: In 1,272 consecutive cases of STEMI with PPCI at our hospital from January 1, 2011, to December 31, 2016, we studied TR-PPCI adoption and its association with D2BT including a propensity matched analysis of similar risk TR-PPCI and trans-femoral primary PCI (TF-PPCI) patients. RESULTS: With major increases in hospital-level TR-PPCI (hospital TR-PPCI rate: 2.6% in 2011 to 79.4% in 2016, p-trend<.001) and operator-level TR-PPCI (mean operator TR-PPCI rate: 2.9% in 2011 to 81.1% in 2016, p-trend = .005), median hospital level D2BT decreased from 102 min [81, 142] in 2011 to 84 min [60, 105] in 2016 (p-trend<.001). TF crossover (10.3%; n = 57) was not associated with unadjusted D2BT (TR-PPCI success 91 min [72, 112] vs. TF crossover 99 min [70, 115], p = .432) or D2BT adjusted for study year and presenting location (7.2% longer D2BT with TF crossover, 95% CI: -4.0% to +18.5%, p = .208). Among 273 propensity-matched pairs, unadjusted D2BT (TR-PPCI 98 [78, 117] min vs. TF-PPCI 101 [76, 132] min, p = .304), and D2BT adjusted for study year and presenting location (5.0% shorter D2BT with TR-PPCI, 95% CI: -12.4% to +2.4%, p = .188) were similar. CONCLUSIONS: TR-PPCI can be successfully implemented without compromising D2BT performance.

TIME Trial: Effect of Timing of Stem Cell Delivery Following ST-Elevation Myocardial Infarction on the Recovery of Global and Regional Left Ventricular Function: Final 2-Year Analysis.

RATIONALE: The TIME trial (Timing in Myocardial Infarction Evaluation) was the first cell therapy trial sufficiently powered to determine if timing of cell delivery after ST-segment-elevation myocardial infarction affects recovery of left ventricular (LV) function. OBJECTIVE: To report the 2-year clinical and cardiac magnetic resonance imaging results and their modification by microvascular obstruction. METHODS AND RESULTS: TIME was a randomized, double-blind, placebo-controlled trial comparing 150 million bone marrow mononuclear cells versus placebo in 120 patients with anterior ST-segment-elevation myocardial infarctions resulting in LV dysfunction. Primary end points included changes in global (LV ejection fraction) and regional (infarct and border zone) function. Secondary end points included changes in LV volumes, infarct size, and major adverse cardiac events. Here, we analyzed the continued trajectory of these measures out to 2 years and the influence of microvascular obstruction present at baseline on these long-term outcomes. At 2 years (n=85), LV ejection fraction was similar in the bone marrow mononuclear cells (48.7%) and placebo groups (51.6%) with no difference in regional LV function. Infarct size and LV mass decreased ≥30% in each group at 6 months and declined gradually to 2 years. LV volumes increased ≈10% at 6 months and remained stable to 2 years. Microvascular obstruction was present in 48 patients at baseline and was associated with significantly larger infarct size (56.5 versus 36.2 g), greater adverse LV remodeling, and marked reduction in LV ejection fraction recovery (0.2% versus 6.2%). CONCLUSIONS: In one of the longest serial cardiac magnetic resonance imaging analyses of patients with large anterior ST-segment-elevation myocardial infarctions, bone marrow mononuclear cells administration did not improve recovery of LV function over 2 years. Microvascular obstruction was associated with reduced recovery of LV function, greater adverse LV remodeling, and more device implantations. The use of cardiac magnetic resonance imaging leads to greater dropout of patients over time because of device implantation in patients with more severe LV dysfunction resulting in overestimation of clinical stability of the cohort. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684021.

Three-Year Outcomes With the Absorb Bioresorbable Scaffold: Individual-Patient-Data Meta-Analysis From the ABSORB Randomized Trials.

BACKGROUND: The Absorb bioresorbable vascular scaffold (BVS) completely resorbs within 3 years after coronary artery implantation. The safety and effectiveness of BVS through this critical 3-year period have not been characterized. METHODS: We performed an individual-patient-data pooled meta-analysis of the 4 randomized ABSORB trials in which 3389 patients with coronary artery disease were randomly assigned to everolimus-eluting Absorb BVS (n=2164) or cobalt-chromium everolimus-eluting stents (n=1225). The primary efficacy outcome measure was target lesion failure (cardiac mortality, target vessel myocardial infarction, or ischemia-driven target lesion revascularization), and the primary safety outcome measure was device thrombosis. RESULTS: BVS compared with cobalt-chromium everolimus-eluting stents resulted in higher 3-year rates of target lesion failure (11.7% versus 8.1%; risk ratio [RR], 1.38; 95% confidence interval [CI], 1.10-1.73; P=0.006), driven by greater target vessel myocardial infarction (7.8% versus 4.2%; RR, 1.72; 95% CI, 1.26-2.35; P=0.0006) and ischemia-driven target lesion revascularization (6.6% versus 4.4%; RR, 1.44; 95% CI, 1.05-1.98; P=0.02), with comparable cardiac mortality (1.1% versus 1.1%; RR, 0.93; 95% CI, 0.47-1.88; P=0.85). Device thrombosis rates through 3 years were also higher with BVS (2.4% versus 0.6%; RR, 3.71; 95% CI, 1.70-8.11; P=0.001). Between 1 and 3 years, target lesion failure rates (6.1% versus 3.9%; P=0.02) and device thrombosis rates (1.1% versus 0.0%; P<0.0001) were higher with BVS than cobalt-chromium everolimus-eluting stents. CONCLUSIONS: In the present individual-patient-data pooled meta-analysis of the ABSORB trials, BVS was associated with increased rates of target lesion failure and device thrombosis between 1 and 3 years and cumulatively through 3 years of follow-up compared with everolimus-eluting stents. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifiers: NCT01751906, NCT01844284, NCT01923740, and NCT01425281.

Blinded outcomes and angina assessment of coronary bioresorbable scaffolds: 30-day and 1-year results from the ABSORB IV randomised trial.

BACKGROUND: Previous studies showed more adverse events with coronary bioresorbable vascular scaffolds (BVS) than with metallic drug-eluting stents (DES), although in one randomised trial angina was reduced with BVS. However, these early studies were unmasked, lesions smaller than intended for the scaffold were frequently enrolled, implantation technique was suboptimal, and patients with myocardial infarction, in whom BVS might be well suited, were excluded. METHODS: In the active-controlled, blinded, multicentre, randomised ABSORB IV trial, patients with stable coronary artery disease or acute coronary syndromes aged 18 years or older were recruited from 147 hospitals in five countries (the USA, Germany, Australia, Singapore, and Canada). Enrolled patients were randomly assigned (1:1) to receive polymeric everolimus-eluting BVS (Absorb; Abbott Vascular, Santa Clara, CA, USA) with optimised implantation technique or cobalt-chromium everolimus-eluting stents (EES; Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetic status, whether patients would have been eligible for enrolment in the previous ABSORB III trial, and site. Patients and clinical assessors were masked to randomisation. The primary endpoint was target lesion failure (cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation) at 30 days, tested for non-inferiority with a 2·9% margin for the risk difference. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02173379, and is closed to accrual. FINDINGS: Between Aug 15, 2014, and March 31, 2017, we screened 18 722 patients for eligibility, 2604 of whom were enrolled. 1296 patients were assigned to BVS, and 1308 patients were assigned to EES. Follow-up data at 30 days and 1 year, respectively, were available for 1288 and 1254 patients with BVS and for 1303 and 1272 patients with EES. Biomarker-positive acute coronary syndromes were present in 622 (24%) of 2602 patients, and, by angiographic core laboratory analysis, 78 (3%) of 2893 of lesions were in very small vessels. Target lesion failure at 30 days occurred in 64 (5·0%) patients assigned to BVS and 48 (3·7%) patients assigned to EES (difference 1·3%, upper 97·5% confidence limit 2·89; one-sided pnon-inferiority=0·0244). Target lesion failure at 1 year occurred in 98 (7·8%) patients assigned to BVS and 82 (6·4%) patients assigned to EES (difference 1·4%, upper 97·5% confidence limit 3·4; one-sided pnon-inferiority=0·0006). Angina, adjudicated by a central events committee at 1 year, occurred in 270 (20·3%) patients assigned to BVS and 274 (20·5%) patients assigned to EES (difference -0·3%, 95% CI -3·4% to 2·9%; one-sided pnon-inferiority=0·0008; two-sided psuperiority=0·8603). Device thrombosis within 1 year occurred in nine (0·7%) patients assigned to BVS and four (0·3%) patients assigned to EES (p=0·1586). INTERPRETATION: Polymeric BVS implanted with optimised technique in an expanded patient population resulted in non-inferior 30-day and 1-year rates of target lesion failure and angina compared with metallic DES. FUNDING: Abbott Vascular.

Angiographic predictors of adverse outcomes after percutaneous coronary intervention in patients with radiation associated coronary artery disease.

OBJECTIVES: To determine procedural predictors of long-term outcomes for patients with radiation associated coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI). BACKGROUND: Patients who develop CAD after external beam radiation therapy (XRT) for cancer are at high-risk for adverse events following PCI. It is unknown if specific angiographic features can predict outcomes in this population. METHODS: This is an observational study of 157 patients with malignancy who received XRT prior to PCI. Rates of major adverse cardiovascular and cerebrovascular events (MACCEs; all-cause mortality, myocardial infarction, repeat revascularization, or stroke) were compared across patient characteristics over time with the Cox proportional hazards and Kaplan-Meier's analyses. RESULTS: During follow-up of 5.4 ± 4.5 years, 91 (58%) patients had MACCE. On Kaplan-Meier's analysis of angiographic characteristics, MACCE was more frequent in patients with at least moderate target vessel calcification (P = 0.023), ostial stenosis (P = 0.049), target vessel diameter ≥ 3.0 mm (P = 0.018), a SYNTAX score ≥ the median of 11 (P = 0.014), or bare metal stenting (BMS)/balloon angioplasty (BA) compared to drug-eluting stenting (DES) (P = 0.006). Cardiac death was more frequent in patients with SYNTAX score ≥ 11 (P = 0.028) or BMS (P = 0.043). After multivariable adjustment for both angiographic and clinical characteristics, independent predictors of MACCE were BMS placement (P = 0.013), chronic kidney disease ≥ stage 3 (P = 0.019), New York Heart Association (NYHA) heart failure class ≥3 (P = 0.034), and SYNTAX score ≥ 11 (P = 0.041). CONCLUSIONS: In patients previously exposed to XRT treated with PCI, independent angiographic predictors of MACCE include SYNTAX score ≥ 11 and BMS placement, suggestive that DES should be preferred in this population.

Safety and efficacy of dual vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials.

Aims: Of patients with atrial fibrillation (AF), approximately 10% undergo percutaneous coronary intervention (PCI). We studied the safety and efficacy of dual vs. triple antithrombotic therapy (DAT vs. TAT) in this population. Methods and results: A systematic review and meta-analysis was conducted using PubMed, Embase, EBSCO, Cochrane database of systematic reviews, Web of Science, and relevant meeting abstracts for Phase 3, randomized trials that compared DAT vs. TAT in patients with AF following PCI. Four trials including 5317 patients were included, of whom 3039 (57%) received DAT. Compared with the TAT arm, Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding showed a reduction by 47% in the DAT arm [4.3% vs. 9.0%; hazard ratio (HR) 0.53, 95% credible interval (CrI) 0.36-0.85, I2 = 42.9%]. In addition, there was no difference in the trial-defined major adverse cardiac events (MACE) (10.4% vs. 10.0%, HR 0.85, 95% CrI 0.48-1.29, I2 = 58.4%), or in individual outcomes of all-cause mortality, cardiac death, myocardial infarction, stent thrombosis, or stroke between the two arms. Conclusion: Compared with TAT, DAT shows a reduction in TIMI major or minor bleeding by 47% with comparable outcomes of MACE. Our findings support the concept that DAT may be a better option than TAT in many patients with AF following PCI.

2-year outcomes with the Absorb bioresorbable scaffold for treatment of coronary artery disease: a systematic review and meta-analysis of seven randomised trials with an individual patient data substudy.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) offer the potential to improve long-term outcomes of percutaneous coronary intervention after their complete bioresorption. Randomised trials have shown non-inferiority between BVS and metallic drug-eluting stents at 1 year in composite safety and effectiveness outcomes, although some increases in rates of target vessel-related myocardial infarction and device thrombosis were identified. Outcomes of BVS following the first year after implantation are unknown. We sought to ascertain whether BVS are as safe and effective as drug-eluting stents within 2 years after implantation and between 1 and 2 years. METHODS: We did a systematic review and meta-analysis of randomised trials in which patients were randomly assigned to everolimus-eluting Absorb BVS or metallic everolimus-eluting stents (EES) and followed up for at least 2 years. We searched MEDLINE, the Cochrane database, TCTMD, ClinicalTrials.gov, Clinical Trial Results, CardioSource, and abstracts and presentations from major cardiovascular meetings up to April 1, 2017, to identify relevant studies. The primary efficacy outcome measure was the device-oriented composite endpoint (cardiac mortality, target vessel-related myocardial infarction, or ischaemia-driven target lesion revascularisation) and the primary safety outcome measure was definite or probable device thrombosis. Individual patient data from the four ABSORB trials were used for landmark and subgroup analysis and multivariable modelling. FINDINGS: We identified seven randomised trials in which 5583 patients were randomly assigned to Absorb BVS (n=3261) or metallic EES (n=2322) and followed up for 2 years. BVS had higher 2-year relative risks of the device-oriented composite endpoint than did EES (9·4% [304 of 3217] vs 7·4% [169 of 2299]; relative risk [RR] 1·29 [95% CI 1·08-1·56], p=0·0059). These differences were driven by increased rates of target vessel-related myocardial infarction (5·8% [187 of 3218] vs 3·2% [74 of 2299]; RR 1·68 [95% CI 1·29-2·19], p=0·0003) and ischaemia-driven target lesion revascularisation (5·3% [169 of 3217] vs 3·9% [90 of 2300]; 1·40 [1·09-1·80], p=0·0090) with BVS, with non-significant differences in cardiac mortality. The cumulative 2-year incidence of device thrombosis was higher with BVS than with EES (2·3% [73 of 3187] vs 0·7% [16 of 2281]; RR 3·35 [95% CI 1·96-5·72], p<0·0001). Landmark analysis between 1 and 2 years also showed higher rates of the device-oriented composite endpoint (3·3% [69 of 2100] vs 1·9% [23 of 1193]; RR 1·64 [95% CI 1·03-2·61], p=0·0376) and device thrombosis (0·5% [11 of 2085] vs none [0 of 1183], p<0·0001) in BVS-treated patients than in EES-treated patients. INTERPRETATION: BVS was associated with increased rates of composite device-oriented adverse events and device thrombosis cumulatively at 2 years and between 1 and 2 years of follow-up compared with EES. FUNDING: Abbott Vascular.

Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease.

BACKGROUND: In patients with coronary artery disease who receive metallic drug-eluting coronary stents, adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall. Bioresorbable vascular scaffolds have been developed to attempt to improve long-term outcomes. METHODS: In this large, multicenter, randomized trial, 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular (Absorb) scaffold (1322 patients) or an everolimus-eluting cobalt-chromium (Xience) stent (686 patients). The primary end point, which was tested for both noninferiority (margin, 4.5 percentage points for the risk difference) and superiority, was target-lesion failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) at 1 year. RESULTS: Target-lesion failure at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7 percentage points; 95% confidence interval, -0.5 to 3.9; P=0.007 for noninferiority and P=0.16 for superiority). There was no significant difference between the Absorb group and the Xience group in rates of cardiac death (0.6% and 0.1%, respectively; P=0.29), target-vessel myocardial infarction (6.0% and 4.6%, respectively; P=0.18), or ischemia-driven target-lesion revascularization (3.0% and 2.5%, respectively; P=0.50). Device thrombosis within 1 year occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13). CONCLUSIONS: In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting cobalt-chromium stent, was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. (Funded by Abbott Vascular; ABSORB III ClinicalTrials.gov number, NCT01751906.).

Fractional flow reserve guided percutaneous coronary intervention results in reduced ischemic myocardium and improved outcomes.

OBJECTIVES: To determine if fractional flow reserve guided percutaneous coronary intervention (FFR-guided PCI) is associated with reduced ischemic myocardium compared with angiography-guided PCI. BACKGROUND: Although FFR-guided PCI has been shown to improve outcomes, it remains unclear if it reduces the extent of ischemic myocardium at risk compared with angiography-guided PCI. METHODS: We evaluated 380 patients (190 FFR-guided PCI cases and 190 propensity-matched controls) who underwent PCI from 2009 to 2014. Clinical, laboratory, angiographic, stress testing, and major adverse cardiac events [MACE] (all-cause mortality, recurrence of MI requiring PCI, stroke) data were collected. RESULTS: Mean age was 63 ± 11 years; the majority of patients were males (76%) and Caucasian (77%). Median duration of follow up was 3.4 [Range: 1.9, 5.0] years. Procedural complications including coronary dissection (2% vs. 0%, P = .12) and perforation (0% vs. 0%, P = 1.00) were similar between FFR-guided and angiography-guided PCI patients. FFR-guided PCI patients had lower unadjusted (14.7% vs. 23.2%, P = .04) and adjusted [OR = 0.58 (95% CI: 0.34-0.98)] risk of repeat revascularization at one year. FFR-guided PCI patients were less likely (23% vs. 32%, P = .02) to have ischemia and had lower (5.9% vs. 21.1%, P < .001) ischemic burden (moderate-severe ischemia) on post-PCI stress testing. Presence of ischemia post-PCI remained a strong predictor of MACE [OR = 2.14 (95%CI: 1.28-3.60)] with worse survival compared to those without ischemia (HR = 1.63 (95% CI: 1.06-2.51). CONCLUSION: Compared with angiography-guided PCI, FFR-guided PCI results in less repeat revascularization and a lower incidence of post PCI ischemia translating into improved survival, without an increase in complications.

1-year outcomes with the Absorb bioresorbable scaffold in patients with coronary artery disease: a patient-level, pooled meta-analysis.

BACKGROUND: Compared with metallic drug-eluting stents, bioresorbable vascular scaffolds (BVS) offer the potential to improve long-term outcomes of percutaneous coronary intervention. Whether or not these devices are as safe and effective as drug-eluting stents within the first year after implantation is unknown. METHODS: We did a patient-level, pooled meta-analysis of four randomised trials in which 3389 patients with stable coronary artery disease or a stabilised acute coronary syndrome were enrolled at 301 academic and medical centres in North America, Europe, and the Asia-Pacific region. These patients were randomly assigned to the everolimus-eluting Absorb BVS (n=2164) or the Xience cobalt-chromium everolimus-eluting stent (CoCr-EES; n=1225). The primary endpoints were the 1-year relative rates of the patient-oriented composite endpoint (all-cause mortality, all myocardial infarction, or all revascularisation) and the device-oriented composite endpoint of target lesion failure (cardiac mortality, target vessel-related myocardial infarction, or ischaemia-driven target lesion revascularisation). All analyses were by intention to treat. The four randomised trials included in our meta-analysis are all registered with ClinicalTrials.gov, numbers NCT01751906, NCT01844284, NCT01923740, and NCT01425281. FINDINGS: The summary treatment effect for the 1-year relative rates of the patient-oriented composite endpoint did not differ significantly different between BVS and CoCr-EES (relative risk [RR] 1·09 [0·89-1·34], p=0·38). Similarly, the 1-year relative rates of the device-oriented composite endpoint did not differ between the groups (RR 1·22 [95% CI 0·91-1·64], p=0·17). Target vessel-related myocardial infarction was increased with BVS compared with CoCr-EES (RR 1·45 [95% CI 1·02-2·07], p=0·04), due in part to non-significant increases in peri-procedural myocardial infarction and device thrombosis with BVS (RR 2·09 [0·92-4·75], p=0·08). The relative rates of all-cause and cardiac mortality, all myocardial infarction, ischaemia-driven target lesion revascularisation, and all revascularisation did not differ between BVS and CoCr-EES. Results were similar after multivariable adjustment for baseline imbalances, and were consistent across most subgroups and in sensitivity analysis when two additional randomised trials with less than 1 year of follow-up were included. INTERPRETATION: In this meta-analysis, BVS did not lead to different rates of composite patient-oriented and device-oriented adverse events at 1-year follow-up compared with CoCr-EES. FUNDING: Abbott Vascular.

Bleeding complications of triple antithrombotic therapy after percutaneous coronary interventions.

BACKGROUND: 5% of patients undergoing coronary stenting have an indication for anticoagulation. The aim of our study was to determine the bleeding rates and complications in patients on triple oral antithrombotic therapy (TOAT) after coronary stenting. METHODS: We studied patients who underwent coronary stenting in our institution between 2003-2013 and were started on TOAT. Bleeding was the primary outcome. RESULTS: Totally, 999 patients were treated with TOAT with a median follow up of 127 days. All patients were treated with warfarin as an anticoagulant. 267 patients (26.7%) developed a total of 331 bleeding events. 100 patients had bleeding during the first 30 days of therapy. Major bleeding, minor bleeding, bleeding requiring medical attention, and minimal bleeding developed in 2.9%, 3.3%, 17.2%, and 3.3% of the patients respectively as their most significant bleeding event. Patients with anticoagulation initiated at time of stenting had a significantly higher bleeding rate compared to those already on chronic anticoagulation [adjusted HR (95% CI): 1.37 (1.03-1.79), P = 0.03]. The bleeding likelihood was significantly higher for patients with drug-eluted stents (DES) compared to bare-metal stents (BMS) [adjusted OR (95% CI): 1.52 (1.14 - 2.04), P < 0.05]. Patients with atrial fibrillation had an increased rate of bleeding after 6 month of initiation of TOAT with significantly worse outcomes. CONCLUSIONS: TOAT after coronary stenting is associated with high bleeding rates. Patients with AF had worse outcomes. Patients with newly initiated anticoagulation at time of stenting bleed significantly more than people already on chronic anticoagulation prior to stenting. © 2016 Wiley Periodicals, Inc.

Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial.

RATIONALE: Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear. OBJECTIVE: The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size after ST-segment-elevation-myocardial infarction. METHODS AND RESULTS: This prospective study comprised patients consecutively enrolled in the CCTRN TIME (Cardiovascular Cell Therapy Research Network Timing in Myocardial Infarction Evaluation) trial who agreed to have their BMCs stored and analyzed at the CCTRN Biorepository. Change in infarct size between baseline (3 days after percutaneous coronary intervention) and 6-month follow-up was measured by cardiac MRI. Infarct-size measurements and BMC phenotype and function data were obtained for 101 patients (mean age, 56.5 years; mean screening ejection fraction, 37%; mean baseline cardiac MRI ejection fraction, 45%). At 6 months, 75 patients (74.3%) showed a reduction in infarct size (mean change, -21.0±17.6%). Multiple regression analysis indicated that infarct size reduction was greater in patients who had a larger percentage of CD31(+) BMCs (P=0.046) and in those with faster BMC growth rates in colony-forming unit Hill and endothelial-colony forming cell functional assays (P=0.033 and P=0.032, respectively). CONCLUSIONS: This study identified BMC characteristics associated with a better clinical outcome in patients with segment-elevation-myocardial infarction and highlighted the importance of endothelial precursor activity in regenerating infarcted myocardium. Furthermore, it suggests that for these patients with segment-elevation-myocardial infarction, myocardial repair was more dependent on baseline BMC characteristics than on whether the patient underwent intracoronary BMC transplantation. CLINICAL TRIAL REGISTRATION INFORMATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684021.

Bone marrow cell characteristics associated with patient profile and cardiac performance outcomes in the LateTIME-Cardiovascular Cell Therapy Research Network (CCTRN) trial.

BACKGROUND: Although several preclinical studies have shown that bone marrow cell (BMC) transplantation promotes cardiac recovery after myocardial infarction, clinical trials with unfractionated bone marrow have shown variable improvements in cardiac function. METHODS: To determine whether in a population of post-myocardial infarction patients, functional recovery after BM transplant is associated with specific BMC subpopulation, we examined the association between BMCs with left ventricular (LV) function in the LateTIME-CCTRN trial. RESULTS: In this population, we found that older individuals had higher numbers of BM CD133(+) and CD3(+) cells. Bone marrow from individuals with high body mass index had lower CD45(dim)/CD11b(dim) levels, whereas those with hypertension and higher C-reactive protein levels had higher numbers of CD133(+) cells. Smoking was associated with higher levels of CD133(+)/CD34(+)/VEGFR2(+) cells and lower levels of CD3(+) cells. Adjusted multivariate analysis indicated that CD11b(dim) cells were negatively associated with changes in LV ejection fraction and wall motion in both the infarct and border zones. Change in LV ejection fraction was positively associated with CD133(+), CD34(+), and CD45(+)/CXCR4(dim) cells as well as faster BMC growth rates in endothelial colony forming assays. CONCLUSIONS: In the LateTIME population, BM composition varied with patient characteristics and treatment. Irrespective of cell therapy, recovery of LV function was greater in patients with greater BM abundance of CD133(+) and CD34(+) cells and worse in those with higher levels of CD11b(dim) cells. Bone marrow phenotype might predict clinical response before BMC therapy and administration of selected BM constituents could potentially improve outcomes of other future clinical trials.

Management of drug eluting stent in-stent restenosis: A systematic review and meta-analysis.

BACKGROUND: The optimal management for coronary drug eluting stent in-stent restenosis (DES ISR) is unclear. We performed a meta-analysis of observational and randomized studies to compare the outcomes of management of DES ISR using DES, drug eluting balloon (DEB), or balloon angioplasty (BA). METHODS: Eligible studies (25 single arm and 13 comparative, including 4 randomized studies with a total of 7,474 patients with DES ISR) were identified using MEDLINE search and proceedings of international meetings. Outcomes studied include major adverse cardiac events (MACE), target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis (ST), and mortality. Follow-up ranged from 0.5 to 3.5 years (mean 1.4 years). RESULTS: The rate of TLR was significantly lower in the DES (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.36-0.69) and DEB (OR 0.31, 95% CI 0.18-0.55) groups compared to BA. Similarly, TVR rate was significantly lower in the DES (OR 0.55, 95% CI 0.39-0.77) and DEB (OR 0.32, 95% CI 0.18-0.58) groups compared to BA. All other outcomes were similar between the DES/BA and DEB/BA comparisons. TLR was significantly lower in the DES group compared to BA for vessels < or > 2.75 mm. CONCLUSION: Treatment of coronary DES ISR with DES or DEB is associated with a reduction in the risk of TLR and TVR compared to BA alone. The relative risk reduction for TLR with DES is similar to DEB. DEBs have a potential role in the treatment of DES ISR by avoiding placement of another layer of stent. © 2015 Wiley Periodicals, Inc.