Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial.

AIMS: The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care. METHODS AND RESULTS: After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73-1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72-1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08-0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban. CONCLUSION: After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.

Novel Supreme Drug-Eluting Stents With Early Synchronized Antiproliferative Drug Delivery to Inhibit Smooth Muscle Cell Proliferation After Drug-Eluting Stents Implantation in Coronary Artery Disease: Results of the PIONEER III Randomized Clinical Trial.

BACKGROUND: Accelerated endothelial healing after targeted antiproliferative drug delivery may limit the long-term inflammatory response of drug-eluting stents (DESs). The novel Supreme DES is designed to synchronize early drug delivery within 4 to 6 weeks of implantation, leaving behind a prohealing permanent base layer. Whether the Supreme DES is safe and effective in the short term and can improve long-term clinical outcomes is not known. METHODS: In an international, 2:1 randomized, single-blind trial, we compared treatment with Supreme DES to durable polymer everolimus-eluting stents (DP-EES) in patients with acute and chronic coronary syndromes. The primary end point was target lesion failure-a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. The trial was designed to demonstrate noninferiority (margin of 3.58%) of the Supreme DES at 12 months compared with DP-EES (URL: https://www.clinicaltrials.gov; Unique identifier: NCT03168776). RESULTS: From October 2017 to July 2019, a total of 1629 patients were randomly assigned (2:1) to the Supreme DES (N=1086) or DP-EES (N=543). At 12 months, target lesion failure occurred in 57 of 1057 patients (5.4%) in the Supreme DES group and in 27 of 532 patients (5.1%) in the DP-EES group (absolute risk difference, 0.32% [95% CI, -1.87 to 2.5]; Pnoninferiority=0.002]. There were no significant differences in rates of device success, clinically driven target lesion revascularization, or stent thrombosis at 12 months, and the safety composite of cardiovascular death and target vessel myocardial infarction was 3.5% versus 4.6% (hazard ratio, 0.76 [95% CI, 0.46-1.25]) with Supreme DES compared with DP-EES, although rates of combined clinically and non-clinically driven target lesion revascularization at 12 months were higher with Supreme DES. CONCLUSIONS: Among patients with acute and chronic coronary syndromes undergoing percutaneous coronary intervention, the Supreme DES proved to be noninferior to the standard DP-EES. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03168776.

Peripheral artery disease and clinical outcomes in patients with atrial fibrillation: A report from the FANTASIIA registry.

BACKGROUND: Atrial fibrillation (AF) and peripheral artery disease (PAD) are common conditions that increase cardiovascular risk. We determined the association between PAD and prognosis in a cohort of real-world patients receiving oral anticoagulant therapy for nonvalvular AF. METHODS: We prospectively included 1956 patients (mean age 73.8 ± 9.5 years, 44.0% women) receiving oral anticoagulant therapy for AF. Clinical characteristics were collected at baseline. Patients were followed for a period of 3 years. Survival analysis and multivariable regression analyses were performed to assess variables related to death, stroke, bleeding, myocardial infarction and major adverse cardiovascular events (MACE). RESULTS: Patients with PAD (n = 118; 6%) exhibited higher rates of cardiovascular risk factors and cardiovascular diseases. After 3 years of follow-up, there were a total of 255 deaths (no PAD 233, vs PAD 22), 45 strokes (43 vs 2), 146 major bleedings (136 vs 10) and 168 MACE (148 vs 20). On univariate analysis, there was a higher risk of cardiovascular mortality (2.02%/year no PAD vs 4.08%/year PAD, P = .02), myocardial infarction (0.99%/year no PAD vs 2.43%/year PAD, P = .02) and MACE (3.18%/year no PAD vs 6.99%/year PAD, P < .01). There was no statistically significant association with these events after multivariable adjustment. CONCLUSIONS: In a large cohort of anticoagulated patients with AF, the presence of PAD represents a higher risk subgroup and is associated with worse crude outcomes. The exact contribution of the PAD independently of other cardiovascular diseases or risk factors requires further investigation.

Revascularization of coronary chronic total occlusions in an infarct-related artery and recurrence of ventricular arrhythmias among patients with secondary prevention implantable cardioverter defibrillator.

OBJECTIVES: To evaluate whether the revascularization of a coronary chronic total occlusion in an infarct-related artery (IRACTO) may be associated with lower recurrence of ventricular arrhythmias (VA) among patients with a secondary prevention implantable cardioverter defibrillator (ICD). BACKGROUND: IRACTO is increasingly recognized as an independent predictor of VA. It is unknown whether IRACTO revascularization can reduce the burden of VA. METHODS: Multicenter observational cohort study that included consecutive patients with prior myocardial infarction and secondary prevention ICD. The primary endpoint was any appropriate ICD therapy. RESULTS: Among the 460 patients included, 269 (58%) had at least one IRACTO at the coronary angiogram performed before ICD implantation; of these, 20 (7%) had their IRACTO successfully revascularized (IRACTO-R) afterwards. During a median follow-up of 48 months, 229 patients (49%) had at least one appropriate ICD therapy. Patients with IRACTO not revascularized (IRACTO-NR) had the highest incidence of ICD therapies (65%) while patients with IRACTO-R had the lowest (10%, p < .001). In the entire cohort, IRACTO-NR was an independent predictor of appropriate ICD therapies (HR 2.85, p < .001) and appropriate ICD shocks (HR 2.94, p < .001). Among patients with IRACTO at baseline, IRACTO-R was independently associated with a marked reduction of appropriate ICD therapies (HR 0.12, p = .002) and appropriate ICD shocks (HR 0.21, p = .03). CONCLUSIONS: In patients with prior myocardial infarction and secondary prevention ICD, IRACTO revascularization was independently associated with a markedly lower incidence of appropriate ICD therapies and shocks. These results should be corroborated by larger prospective studies.

Imaging and 2-year clinical outcomes of thin strut sirolimus-eluting bioresorbable vascular scaffold: The MeRes-1 extend trial.

OBJECTIVES: This study explores the safety and efficacy of thin strut MeRes100 sirolimus-eluting bioresorbable vascular scaffold (BRS) in patients with de novo coronary artery lesions. BACKGROUND: In interventional cardiology, the emergence of BRS technology is catalyzing the next paradigm shift. METHODS: The MeRes-1 Extend was a multicenter, prospective, single-arm, open-label study enrolling 64 patients in Spain, Macedonia, Brazil, South Africa, Malaysia, and Indonesia. The safety endpoint was major adverse cardiac events (MACE) which composed of cardiac death, myocardial infarction (MI), and ischemia-driven target lesion revascularization (ID-TLR). The imaging efficacy endpoint was mean in-scaffold late lumen loss (LLL) evaluated by quantitative coronary angiography (QCA). Optical coherence tomography (OCT) imaging was performed at baseline and 6-month follow-up. RESULTS: A total of 69 target lesions were identified in 64 enrolled patients (mean age 58.30 ± 9.02 years). Of the treated lesions, 49 (71.01%) lesions were of type B2/C. Procedural and device success was achieved in 64 and 62 patients, respectively. At 2-year follow-up, MACE was reported in one patient (1.61%) in the form of ID-TLR. There was no case of MI, cardiac death or scaffold thrombosis through 2-year. In a subset of 32 patients, paired QCA showed mean in-scaffold LLL of 0.18 ± 0.31 mm at 6-month follow-up. In a subset of 21 patients, OCT revealed 97.95 ± 3.69% strut coverage with mean scaffold area of 7.56 ± 1.79 mm2 and no evidence of strut malapposition. CONCLUSIONS: The clinical and imaging outcomes of MeRes-1 Extend trial demonstrated favorable safety and efficacy of MeRes100 sirolimus-eluting BRS in patients with de novo coronary artery lesions.

Magnesium-Based Resorbable Scaffold Versus Permanent Metallic Sirolimus-Eluting Stent in Patients With ST-Segment Elevation Myocardial Infarction: The MAGSTEMI Randomized Clinical Trial.

BACKGROUND: The use of poly-l-lactide acid-based bioresorbable scaffolds is limited in daily clinical practice because of safety concerns and lack of physiological benefit. Magnesium-based bioresorbable scaffold (MgBRS) presents a short resorption period (<1 year) and have the potential of being thromboresistant and exhibiting early restoration of vasomotor function. To date, however, no randomized clinical trial has investigated the performance of MgBRS. Therefore, this study aimed to compare the in-stent/scaffold vasomotion between MgBRS and permanent metallic sirolimus-eluting stent (SES) at 12-month follow-up in ST-segment-elevation myocardial infarction patients. METHODS: This investigator-driven, multicenter, randomized, single-blind, controlled trial randomized ST-segment-elevation myocardial infarction patients 1:1 to SES or MgBRS at 11 academic centers. The primary end point was the rate of increase (≥3%) after nitroglycerin in mean lumen diameter of the in-stent/scaffold segment at 12 months with superiority of MgBRS over SES in the as-treated population. The main secondary end points included angiographic parameters of restenosis, device-oriented composite end point, their individual components, and device thrombosis rate. Besides, endothelial-dependent vasomotor response to acetylcholine (ie, endothelial function) was also assessed in a subgroup of patients (n=69). RESULTS: Between June 2017 and June 2018, 150 ST-segment-elevation myocardial infarction patients were randomized (MgBRS, n=74; SES, n=76). At 1 year, the primary end point was significantly higher in the MgBRS arm (56.5% versus 33.8%; P=0.010). Conversely, late lumen loss was significantly lower in the SES group (in-segment: 0.39±0.49mm versus 0.02±0.27mm, P<0.001; in-device: 0.61±0.55mm versus 0.06±0.21mm; P<0.001). The device-oriented composite end point was higher in the MgBRS arm driven by an increase in ischemia-driven target lesion revascularization rate (12[16.2%] versus 4[5.2%], P=0.030). Definite thrombosis rate was similar between groups (1[1.4%] in the MgBRS arm versus 2[2.6%] in the SES group; P=1.0). Endothelial function assessment at device segment evidenced a more pronounced vasoconstrictive response to maximal dose of acetylcholine in the MgBRS arm (-8.3±3.5% versus -2.4±1.3% in the SES group, P=0.003). CONCLUSIONS: When compared to SES, MgBRS demonstrated a higher capacity of vasomotor response to pharmacological agents (either endothelium-independent or endothelium-dependent) at 1 year. However, MgBRS was associated with a lower angiographic efficacy, a higher rate of target lesion revascularization, without thrombotic safety concerns. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03234348.

Safety and efficacy of a sirolimus-eluting coronary stent with ultra-thin strut for treatment of atherosclerotic lesions (TALENT): a prospective multicentre randomised controlled trial.

BACKGROUND: Supraflex is a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts. We aimed to compare Supraflex with the standard of care, Xience, an everolimus-eluting stent with a durable polymer coating, regarding clinical outcomes with a randomised trial in an all-comer population. METHODS: We did a prospective, randomised, single-blind, multicentre study (TALENT) across 23 centres in Europe (the Netherlands, Poland, the UK, Spain, Bulgaria, Hungary, and Italy). Eligible participants were aged 18 years or older, had one or more coronary artery stenosis of 50% or greater in a native coronary artery, saphenous venous graft, or arterial bypass conduit, and had a reference vessel diameter of 2·25-4·50 mm. Patients underwent percutaneous coronary intervention in an all-comer manner. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts (Supraflex) or an everolimus-eluting stent with a durable polymer coating (Xience). Randomisation was done by local investigators by use of a web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint-cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation-between groups at 12 months after the procedure, assessed in an intention-to-treat population. On assumption of 1-year composite endpoint prevalence of 8·3%, a margin of 4·0% was defined for non-inferiority of the Supraflex group compared with the Xience group. This trial is registered with ClinicalTrials.gov, number NCT02870140. FINDINGS: Between Oct 21, 2016, and July 3, 2017, 1435 patients with 1046 lesions were randomly assigned to Supraflex, of whom 720 received the index procedure, and 715 patients with 1030 lesions were assigned to Xience, all receiving the index procedure. At 12 months, the primary endpoint had occurred in 35 patients (4·9 %) in the Supraflex group and in 37 patients (5·3%) in the Xience group (absolute difference -0·3% [one-sided 95% upper confidence bound 1·6%], pnon-inferiority<0·0001). Definite or probable stent thrombosis prevalence, a safety indicator, was low in both groups and did not differ between them. INTERPRETATION: The Supraflex stent was non-inferior to the Xience stent for a device-oriented composite clinical endpoint at 12 months in an all-comer population. Supraflex seems a safe and effective alternative drug-eluting stent to other stents in clinical practice. FUNDING: European Cardiovascular Research Institute.

Impact of preprocedural TIMI flow on clinical outcome in low-risk patients with ST-elevation myocardial infarction: Results from the ATLANTIC study.

OBJECTIVES: This study sought to analyze the impact of the preprocedural thrombolysis in myocardial infarction (TIMI) flow on clinical outcome in patients with ST-elevation myocardial infarction (STEMI). BACKGROUND: Previous studies have shown that the TIMI flow 0/1 prior to primary percutaneous coronary intervention (PCI) is associated with a poor clinical outcome. However, it is unclear whether the same is true in patients with ongoing STEMI of less than 6 hr duration, rapid reperfusion, and modern guideline-adherent therapy. METHODS: The ATLANTIC study compared prehospital versus inhospital treatment with ticagrelor in patients with acute STEMI. For this analysis, patients were divided into three groups according to the preprocedural TIMI flow grade of the infarct vessel: TIMI 0/1, TIMI 2, and TIMI 3. RESULTS: From a total of 1,680 patients, 1,113 had TIMI 0/1, 279 TIMI 2, and 288 TIMI 3 flow before primary PCI. At 30 days, the composite ischemic endpoint (5.5, 2.9, and 2.1%, p < .05) and all-cause death (3.0, 1.4, and 2.1%, p = .30) were highest in patients with TIMI flow 0/1. After adjustment, preprocedural TIMI flow <3 (versus 3) was not an independent predictor of major adverse ischemic events within 30 days (odds ratio 1.89, 95% confidence interval 0.74-4.85). However, definite stent thrombosis occurred only in patients with initial TIMI flow 0/1 (1.0%). Among these patients, those with prehospital administration of ticagrelor were less often affected (0.3% vs. 1.3%, p < .05). CONCLUSION: In this post-hoc analysis, preprocedural TIMI flow was not independently associated with a higher rate of adverse ischemic events.

Thrombocytopenia after transcatheter aortic valve implantation. A comparison between balloon-expandable and self-expanding valves.

BACKGROUND: Thrombocytopenia after transcatheter aortic valve implantation (TAVI) is common and has been related to higher mortality and major complications. No comparison between balloon-expandable (BEV) and self-expanding valves (SEV) regarding drop platelet count (DPC) has been reported to date. The objectives of this study were to analyze the differences in DPC between BEVs or SEVs and their prognostic implications in clinical outcomes. METHODS: We retrospectively analyzed patients undergoing TAVI. Platelet counts after TAVI were collected. Two groups were created: DPC ≤ 30% and DPC > 30%. VARC-2 criteria were used to define outcomes. RESULTS: Study population was composed of 195 patients (age 77.5 ± 6.7, 57.4% males). All of them but one experienced DPC (mean DPC 31.9 ± 15.3%). DPC was significantly higher among the patients treated with BEV compared to those treated with SEV (36.3 ± 15.1% vs 27.7 ± 14.4, P < 0.001). After multivariate analysis, the use of BEV was independently associated with a higher rate of DPC > 30% (67.4% vs 36.0%; OR 3.4; 95% CI, 1.42-8.16). At 30 days, the DPC > 30% was associated with a higher rate of life-threatening/major bleeding, major vascular complications, in-hospital sepsis and mortality. At one year, there were no statistically significant differences in the mortality rate between groups (6.35% vs 10.0%, HR 1.54; 95% CI, 0.56-4.25). CONCLUSIONS: In this study, the use of BEV was associated with a higher risk of DPC after TAVI. A DPC rate > 30% was associated with an increased risk of major complications at 30 days.

MAGnesium-based bioresorbable scaffold and vasomotor function in patients with acute ST segment elevation myocardial infarction: The MAGSTEMI trial: Rationale and design.

AIM: Use of a Bioresorbable Scaffolds (BRS) either in clinical practice or in the setting of an acute myocardial infarction (MI) is controversial. Despite an overall high rate of thrombosis, vascular healing response following BRS implantation tend to superiority as compared to metallic drug-eluting stent in ST-segment elevation myocardial infarction (STEMI) patients. We sought to compare the in-stent/scaffold vasomotion between metallic BRS and sirolimus eluting stent (SES) at 12-month angiographic follow-up in the setting of patients with STEMI treated by primary PCI. STUDY DESIGN: This is an investigator-driven, prospective, multicenter, randomized, single blind, two-arm, controlled trial (ClinicalTrials.gov number: NCT03234348). This trial will randomize ~148 patients 1:1 to SES or BRS. Primary end-point is the in-stent/scaffold change in mean lumen diameter after nitroglycerin administration at 12-month angiographic follow-up. Besides, patient-oriented combined endpoint of all-cause death, any MI, and any revascularization, together with scaffold/stent thrombosis rate and device-oriented endpoint of cardiac death, target vessel (TV)-MI and TVR at 1 year will be also evaluated. Clinical follow-up will be scheduled yearly up to 5 years. CONCLUSION: This trial will shed light on the vascular vasomotion following BRS implantation in the complex scenario of STEMI.

Long-term impact of diabetes in patients with ST-segment elevation myocardial infarction: Insights from the EXAMINATION randomized trial.

BACKGROUND: Long-term outcomes of diabetic patients suffering from ST-segment elevation myocardial infarction (STEMI) and treated with second-generation drug-eluting stent have been scarcely evaluated. The aim of this posthoc subanalysis of the EXAMINATION trial was to compare 5-year outcomes according to the presence of diabetes mellitus. METHODS: From a total of 1,497 patients included in the trial, 258 were diabetics (n = 137, received everolimus-eluting stent (EES) and n = 121 bare-metal stent (BMS); whereas 1,239 were nondiabetics (n = 613 treated with EES and n = 626 with BMS). Patient-oriented combined endpoint (POCE) defined as all-cause death, any MI or any revascularization, and other clinical parameters were collected up to 5-years. All results were adjusted for various potential confounders. RESULTS: At 5-years, patients with diabetes showed similar rates of POCE between diabetics treated with EES and those treated with BMS (32.8% vs. 32.2%; p = 0.88). However, rates of TLR were significantly lower in the EES group (4.4% vs. 9.9%; HR 0.52 (0.29-0.94); P = 0.03). In non-diabetics, the use of EES was associated with a significant improvement in all-clinical parameters except for MI rate: POCE: [10.0% vs. 12.6%; HR 0.78(0.62-0.98); P = 0.038], all cause death: [7.0% vs. 12.1%; HR 0.62(0.42-0.90); P = 0.014], and [TLR: 4.2 vs. 6.7; HR 0.60 (0.37-0.98); P = 0.04]. Overall, diabetics showed higher rate of POCE at 5-years (32.6% vs. 21.5% in nondiabetics HR1.45[1.03-2.04];p = 0.03) driven by increased rates of MI and the need for revascularization that occurred in coronary segments remote from target lesions [2.7% vs. 1.1%; HR: 2.27 (1.12-5.23); P = 0.02 and 14% vs. 6.2%; HR: 2.11 (1.38-3.22); P = 0.001, respectively]. CONCLUSIONS: Diabetics had worse clinical outcomes than nondiabetics after STEMI mainly due to atherosclerosis progression. At 5-years, the treatment with EES did not reduce the rate of POCE in diabetics but reduced the need for revascularization compared with BMS.

Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: A sub-analysis of the ATLANTIC trial.

OBJECTIVE: We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM. BACKGROUND: DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population. METHODS: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested. RESULTS: A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution (≥70%) after PCI (OR 0.59, 95% CI 0.43-0.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62-4.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08-5.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54-28.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding. CONCLUSIONS: DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.

Diabetes mellitus, frailty and prognosis in very elderly patients with acute coronary syndromes.

BACKGROUND: The magnitude of the association between diabetes (DM) and outcomes in elderly patients with acute coronary syndromes (ACS) is controversial. No study assessed the prognostic impact of DM according to frailty status in these patients. METHODS: The LONGEVO-SCA registry included unselected ACS patients aged ≥ 80 years. Frailty was assessed by the FRAIL scale. We evaluated the impact of previous known DM on the incidence of death or readmission at 6 months according to status frailty by the Cox regression method. RESULTS: A total of 532 patients were included. Mean age was 84.3 years, and 212 patients (39.8%) had previous DM diagnosis. Patients with DM had more comorbidities and higher prevalence of frailty (33% vs 21.9%, p = 0.002). The incidence of death or readmission at 6 months was higher in patients with DM (HR 1.52, 95% CI 1.12-2.05, p 0.007), but after adjusting for potential confounders this association was not significant. The association between DM and outcomes was not significant in robust patients, but it was especially significant in patients with frailty [HR 1.72 (1.05-2.81), p = 0.030, p value for interaction = 0.049]. CONCLUSIONS: About 40% of elderly patients with ACS had previous known DM diagnosis. The association between DM and outcomes was different according to frailty status.

Oral anti-Xa anticoagulation after trans-aortic valve implantation for aortic stenosis: The randomized ATLANTIS trial.

BACKGROUND: Antithrombotic treatment regimen following transcatheter aortic valve replacement (TAVR) is not evidence-based. Apixaban, a non-vitamin K direct anticoagulant (NOAC) was shown to be superior to VKA and superior to aspirin to prevent cardioembolic stroke in non-valvular atrial fibrillation. It may have the potential to reduce TAVR-related thrombotic complications including subclinical valve thrombosis along with a better safety than the standard of care. DESIGN: ATLANTIS is a multicenter, randomized, phase IIIb, prospective, open-label, superiority study comparing standard of care (SOC Group) versus an apixaban-based strategy (Anti-Xa Group) after successful TAVR (ClinicalTrials.gov NCT 02664649). Randomization is stratified according to the need for chronic anticoagulation therapy for a reason other than the TAVR procedure. In the experimental arm, patients receive 5 mg bid of apixaban or a reduced dose of 2.5 mg bid according to the drug label or when apixaban is combined with antiplatelet therapy. In the control arm, patients receive VKA therapy if there is an indication for oral anticoagulation or antiplatelet therapy alone (single or dual) or the combination of both if needed. The primary study end point is the composite of all-cause death, TIA/stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep venous thrombosis, systemic embolism, life-threatening, disabling or major bleeding, according to the Valve Academic Research Consortium definitions. CONCLUSIONS: ATLANTIS tests the superiority of an apixaban-based strategy versus the recommended standard of care strategy to reduce the risk of post-TAVR thromboembolic and bleeding complications in an all comer population.

Ticagrelor versus clopidogrel for recovery of vascular function immediately after successful chronic coronary total occlusion recanalization: A randomized clinical trial.

Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor. We sought if ticagrelor may augment adenosine-induced coronary blood flow vs. clopidogrel immediately after successful CTO percutaneous coronary intervention (PCI).

Duration of ischemia and treatment effects of pre- versus in-hospital ticagrelor in patients with ST-segment elevation myocardial infarction: Insights from the ATLANTIC study.

BACKGROUND: Among patients with STEMI in the ATLANTIC study, pre-hospital administration of ticagrelor improved post-PCI ST-segment resolution and 30-day stent thrombosis. We investigated whether this clinical benefit with pre-hospital ticagrelor differs by ischemic duration. METHODS: In a post hoc analysis we compared absence of ST-segment resolution post-PCI and stent thrombosis at 30 days between randomized treatment groups (pre- versus in-hospital ticagrelor) stratified by symptom onset to first medical contact (FMC) duration [≤1 hour (n = 773), >1 to ≤3 hours (n = 772), and >3 hours (n = 311)], examining the interaction between randomized treatment strategy and duration of symptom onset to FMC for each outcome. RESULTS: Patients presenting later after symptom onset were older, more likely to be female, and have higher baseline risk. Patients with symptom onset to FMC >3 hours had the greatest improvement in post-PCI ST-segment elevation resolution with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 2.9% vs. >1 to ≤3 hours, 3.6% vs. >3 hours, 12.2%; adjusted p for interaction = 0.13), while patients with shorter duration of ischemia had greater improvement in stent thrombosis at 30 days with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 1.3% vs. >1 hour to ≤3 hours, 0.7% vs. >3 hours, 0.4%; adjusted p for interaction = 0.55). Symptom onset to active ticagrelor administration was independently associated with stent thrombosis at 30 days (adjusted OR 1.89 per 100 minute delay, 95%CI 1.20-2.97, P < .01), but not post-PCI ST-segment resolution (P = .41). CONCLUSIONS: The effect of pre-hospital ticagrelor to reduce stent thrombosis was most evident when given early within 3 hours after symptom onset, with delay in ticagrelor administration after symptom onset associated with higher rate of stent thrombosis. These findings re-emphasize the need for early ticagrelor administration in primary PCI treated STEMI patients.

TIcaGrEloR and Absorb bioresorbable vascular scaffold implantation for recovery of vascular function after successful chronic total occlusion recanalization (TIGER-BVS trial): Rationale and study design.

OBJECTIVES: To explore the role of ticagrelor versus clopidogrel in coronary blood flow normalization immediately after chronic coronary total occlusion (CTO) recanalization. BACKGROUND: Coronary vascular function of a CTO immediately after recanalization is demonstrated to be poor. METHODS: The TIGER BVS is a prospective, double-randomized, open-label, two parallel-group controlled clinical trial to evaluate efficacy of ticagrelor versus clopidogrel in improving vascular function of coronary segment distal to CTO immediately after CTO recanalization. A total of 50 patients who receive CTO PCI will be randomized 1:1 to receive ticagrelor versus clopidogrel at least 3 days before the procedure. Immediately after CTO recanalization with Absorb BVS implantation, a specific study of vascular function under adenosine infusion will be performed. Patients will be therefore randomized 1:1 to receive angiographic follow-up with vascular function and optical coherence tomography analyses at 1- or 3-year follow-up. This study is registered on ClinicalTrials.gov with number NCT02211066. CONCLUSIONS: The TIGER BVS trial will provide the first randomized comparison between ticagrelor versus clopidogrel in recovering vascular function in CTO patients. It will also provide important data on vascular restoration therapy of Absorb BVS in this scenario.

Inappropriate doses of direct oral anticoagulants in real-world clinical practice: prevalence and associated factors. A subanalysis of the FANTASIIA Registry.

Aims: To describe the prevalence and associated factors of inappropriate doses of direct oral anticoagulants (DOAC) in a national registry of patients of real clinical practice. Methods and results: Five hundred and thirty outpatients with atrial fibrillation treated with DOAC were included in a prospective, national, multicentre study. The appropriateness of the doses of DOAC was defined according to the recommendations of the European Heart Rhythm Association. Mean age was 73 ± 9 years, with a 46% of women. Two hundred and sixty-seven patients were prescribed dabigatran, 190 rivaroxaban, and 73 apixaban. A total of 172 patients (32%) did not receive the appropriate dose: 93 patients received a lower dose (18%) and 79 patients a higher dose (15%). In the comparisons among the subgroups of inappropriately low, appropriate, and inappropriately high dose, we observed significant trends to older age (69 ± 8 years vs. 73 ± 10 years vs. 77 ± 6 years), more frequent female sex (37% vs. 46% vs. 59%), antiplatelet drugs (5% vs. 8% vs. 25%), rivaroxaban (14% vs. 38% vs. 53%), and apixaban use (5% vs. 15% vs. 19%), higher CHAD2DS2-VASc (3.00 ± 1.38 vs. 3.58 ± 1.67 vs. 4.59 ± 1.44) and HAS-BLED scores (1.83 ± 0.87 vs. 1.92 ± 1.07 vs. 2.47 ± 1.13), lower body mass index (30 ± 6 kg/m2 vs. 29 ± 4 kg/m2 vs. 28 ± 4 kg/m2) and glomerular filtration rate (74 ± 27 mL/min vs. 70 ± 22 mL/min vs. 63 ± 16 mL/min), and lower frequency of dabigatran use (81% vs. 47% vs. 28%) (all comparisons P ≤ 0.01). Conclusion: In this real-life study, 32% of patients received an inappropriate dose of DOAC. Several clinical factors can identify patients at risk of this situation.

Quality of oral anticoagulation with vitamin K antagonists in 'real-world' patients with atrial fibrillation: a report from the prospective multicentre FANTASIIA registry.

Aims: The efficacy and safety of oral anticoagulation (OAC) using the vitamin K antagonists (VKA) are closely associated with the quality of anticoagulation, reflected by time in therapeutic range (TTR). The SAMe-TT2R2 is a risk score developed to predict the quality of anticoagulation control among VKA users. To analyse the quality of anticoagulation and its clinical determinants based on different methods in a prospective cohort of atrial fibrillation patients on VKA treatment participating in the multicentre Spanish observational registry FANTASIIA. Methods and results: Estimated TTR was calculated from Rosendaal, direct method, international normalized ratio variability, and NICE criteria. Time in therapeutic range values were compared for those patients with a SAMe-TT2R2 score 0-2 and >2. One thousand four hundred and seventy patients were analysed (56.4% male, mean age 74.1 ± 9.5 years). Mean TTR was 61.5 ± 25.1 with Rosendaal and 64.7 ± 24.2 with direct method. There was a high correlation between both methods (ρ = 0.805). The prevalence of poor anticoagulation control was 55%. Diabetes mellitus [odds ratio (OR) 1.38; P = 0.008], peripheral artery disease (PAD, OR 1.62; P = 0.048), and HAS-BLED (OR 1.13; P = 0.022) were independently associated with TTR < 70%. SAMe-TT2R2 score 0-2 had a higher mean TTR than patients with SAMe-TT2R2 >2 (P = 0.044), with a specificity of > 90% for predicting TTR < 70%. Patients with TTR < 70% had higher risk of events (21.7 vs. 16.8%; P = 0.021). Conclusion: In a multicentre prospective registry, 55% of AF patients had poor anticoagulation control with diabetes mellitus, PAD, and HAS-BLED being independently associated with TTR < 70%. A high SAMe-TT2R2 scores had a high specificity for predicting a TTR < 70% as an indicator of poor quality anticoagulation.

Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial.

BACKGROUND: No medium-term data are available on the random comparison between everolimus-eluting bioresorbable vascular scaffolds and everolimus-eluting metallic stents. The study aims to demonstrate two mechanistic properties of the bioresorbable scaffold: increase in luminal dimensions as a result of recovered vasomotion of the scaffolded vessel. METHODS: The ABSORB II trial is a prospective, randomised, active-controlled, single-blind, parallel two-group, multicentre clinical trial. We enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients (2:1) to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb; Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. At 3 year follow-up, the primary endpoint was superiority of the Absorb bioresorbable scaffold versus the Xience metallic stent in angiographic vasomotor reactivity after administration of intracoronary nitrate. The co-primary endpoint is the non-inferiority of angiographic late luminal loss. For the endpoint of vasomotion, the comparison was tested using a two-sided t test. For the endpoint of late luminal loss, non-inferiority was tested using a one-sided asymptotic test, against a non-inferiority margin of 0·14 mm. The trial is registered at ClinicalTrials.gov, number NCT01425281. FINDINGS: Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the Absorb group (335 patients, 364 lesions) or the Xience group (166 patients, 182 lesions). The vasomotor reactivity at 3 years was not statistically different (Absorb group 0·047 mm [SD 0·109] vs Xience group 0·056 mm [0·117]; psuperiority=0·49), whereas the late luminal loss was larger in the Absorb group than in the Xience group (0·37 mm [0·45] vs 0·25 mm [0·25]; pnon-inferiority=0·78). This difference in luminal dimension was confirmed by intravascular ultrasound assessment of the minimum lumen area (4·32 mm2 [SD 1·48] vs 5·38 mm2 [1·51]; p<0·0001). The secondary endpoints of patient-oriented composite endpoint, Seattle Angina Questionnaire score, and exercise testing were not statistically different in both groups. However, a device-oriented composite endpoint was significantly different between the Absorb group and the Xience group (10% vs 5%, hazard ratio 2·17 [95% CI 1·01-4·70]; log-rank test p=0·0425), mainly driven by target vessel myocardial infarction (6% vs 1%; p=0·0108), including peri-procedural myocardial infarction (4% vs 1%; p=0·16). INTERPRETATION: The trial did not meet its co-primary endpoints of superior vasomotor reactivity and non-inferior late luminal loss for the Absorb bioresorbable scaffold with respect to the metallic stent, which was found to have significantly lower late luminal loss than the Absorb scaffold. A higher rate of device-oriented composite endpoint due to target vessel myocardial infarction, including peri-procedural myocardial infarction, was observed in the Absorb group. The patient-oriented composite endpoint, anginal status, and exercise testing, were not statistically different between both devices at 3 years. Future studies should investigate the clinical impact of accurate intravascular imaging in sizing the device and in optimising the scaffold implantation. The benefit and need for prolonged dual antiplatelet therapy after bioresorbable scaffold implantation could also become a topic for future clinical research. FUNDING: Abbott Vascular.