Timing of Complete Revascularization with Multivessel PCI for Myocardial Infarction.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease, the time at which complete revascularization of nonculprit lesions should be performed remains unknown. METHODS: We performed an international, open-label, randomized, noninferiority trial at 37 sites in Europe. Patients in a hemodynamically stable condition who had STEMI and multivessel coronary artery disease were randomly assigned to undergo immediate multivessel percutaneous coronary intervention (PCI; immediate group) or PCI of the culprit lesion followed by staged multivessel PCI of nonculprit lesions within 19 to 45 days after the index procedure (staged group). The primary end point was a composite of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year after randomization. The percentages of patients with a primary or secondary end-point event are provided as Kaplan-Meier estimates at 6 months and at 1 year. RESULTS: We assigned 418 patients to undergo immediate multivessel PCI and 422 to undergo staged multivessel PCI. A primary end-point event occurred in 35 patients (8.5%) in the immediate group as compared with 68 patients (16.3%) in the staged group (risk ratio, 0.52; 95% confidence interval, 0.38 to 0.72; P<0.001 for noninferiority and P<0.001 for superiority). Nonfatal myocardial infarction and unplanned ischemia-driven revascularization occurred in 8 patients (2.0%) and 17 patients (4.1%), respectively, in the immediate group and in 22 patients (5.3%) and 39 patients (9.3%), respectively, in the staged group. The risk of death from any cause, the risk of stroke, and the risk of hospitalization for heart failure appeared to be similar in the two groups. A total of 104 patients in the immediate group and 145 patients in the staged group had a serious adverse event. CONCLUSIONS: Among patients in hemodynamically stable condition with STEMI and multivessel coronary artery disease, immediate multivessel PCI was noninferior to staged multivessel PCI with respect to the risk of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year. (Supported by Boston Scientific; MULTISTARS AMI ClinicalTrials.gov number, NCT03135275.).

Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes.

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

Combined rotational atherectomy and cutting balloon angioplasty prior to drug-eluting stent implantation in severely calcified coronary lesions: The PREPARE-CALC-COMBO study.

OBJECTIVES: To evaluate the safety and efficacy of lesion preparation using rotational atherectomy (RA) with consecutive cutting balloon angioplasty (Rota-Cut). BACKGROUND: Whether the Rota-Cut combination improves stent performance in severely calcified coronary lesions is unknown. METHODS: PREPARE-CALC-COMBO is a single-arm prospective trial in which 110 patients were treated with a Rota-Cut strategy before implantation of sirolimus-eluting stents and compared with patients treated with modified balloon (MB, scoring or cutting) or RA from a historical cohort (the randomized PREPARE-CALC trial). The study had two primary endpoints: in-stent acute lumen gain (ALG) by quantitative angiographic analysis and stent expansion (SE) on optical coherence tomography. RESULTS: In-stent ALG was significantly higher with Rota-Cut compared to RA or MB alone (1.92 ± 0.45 mm vs. 1.74 ± 0.45 mm with MB vs. 1.70 ± 0.42 mm with RA; p = 0.001 and p < 0.001, respectively). SE was comparable between groups (75.1 ± 13.8% vs. 73.5 ± 13.3 with MB vs. 73.1 ± 12.2 with RA; p = 0.19 and p = 0.39, respectively). The Rota-Cut combination resulted in higher minimal stent area (MSA) (7.1 ± 2.2mm2 vs. 6.1 ± 1.7mm2  with MB vs. 6.2 ± 1.9mm2 with RA; p = 0.003 and p = 0.004, respectively). In-hospital death occurred in one patient. Target vessel failure at 9 months was low and comparable between groups (8.2% vs. 8% with MB vs. 6% with RA; p = 1 and p = 0.79, respectively). CONCLUSION: Rota-Cut combination resulted in higher ALG and larger MSA compared with historical control of RA or MB alone, but was not associated with higher SE. Despite extensive lesion preparation, this strategy is safe, feasible, and associated with favorable clinical outcome at 9 months.

Long-Term Outcomes after Rotational Atherectomy for Calcified Chronic Total Occlusion versus Nonchronic Total Occlusion Coronary Lesions.

Background: The role of rotational atherectomy (RA) in contemporary percutaneous coronary intervention (PCI) is expanding to include certain chronic total occlusion (CTO) lesions. However, the long-term outcome of RA in CTOs is still unclear. Objective: To investigate in-hospital and long-term outcomes after RA for CTO compared to non-CTO calcified lesions. Moreover, this report evaluates the role of the elective RA approach in calcified CTOs. Methods and Results: This study enrolled 812 patients (869 lesions; CTO, n = 80 versus non-CTO, n = 789). The mean age of the study population was 73.1 ± 8.6 years, the baseline characteristics were comparable in both groups. Balloon-resistant CTO lesions represented the main indication for RA in CTO patients (61.2%). The mean J-CTO score was 2.42 ± 0.95. The angiographic success rate was lower in CTO patients (88.8% vs 94.9%; p = 0.022). In-hospital major adverse cardiac events (MACE) rate was comparable in both groups (CTO 8.8% vs 7.0% in non-CTO;p = 0.557). At two-year follow-up, a higher target lesion failure (TLF) was observed in CTO group (25.5% vs 15.1%, log rank p = 0.041), driven by higher cardiac mortality while the clinically driven target lesion revascularisation (TLR) was comparable between the study groups. Elective RA for CTO had a shorter procedural time and lower rate of dissection (7.5% vs 25%; p = 0.030) compared to bail-out RA with similar long-term outcomes. Conclusion: Compared to non-CTO, RA for CTO can be performed with a high procedural success rate and comparable in-hospital outcomes. Apart from higher cardiac mortality in the CTO group, the long-term outcomes are comparable in both groups. Elective RA is a feasible and beneficial approach to be used in CTO intervention.

Impact of Prosthetic Valve Regurgitation Assessed by Echocardiography and Magnetic Resonance Imaging on Long-Term Clinical Outcomes after TAVR.

BACKGROUND: Prosthetic valve regurgitation (PVR) impairs early and mid-term outcomes after transcatheter aortic valve replacement (TAVR). We explored the impact of PVR assessed by transthoracic echocardiography (TTE) and magnetic resonance imaging-regurgitation fraction (MRI-RF) on long-term clinical outcomes. METHODS: PVR was assessed by TTE applying the Valve Academic Research Consortium criteria and MRI-RF (from velocity-encoded phase contrast magnetic resonance sequence) in 424 patients. RESULTS: MRI-RF correlated modestly with the echocardiographic grades of PVR (Spearman's rank correlation coefficient = 0.32, p < 0.001). Using an MRI-RF ≥20% to define ≥ moderate PVR, echocardiography and MRI-RF agreed on PVR classification in 412 patients (97.2%; kappa statistic = 0.56, p < 0.001). Five-year mortality or reintervention was higher in patients with echocardiographic ≥ moderate PVR (83.3% vs. 45.0%, log rank p value = 0.002; HR [95% CI]: 3.18 [1.48-6.84]) as well as in patients with MRI-RF ≥20% (79.3% vs. 43.2%, log rank p value <0.001; HR [95% CI]: 2.68 [1.53-4.70]), while the outcomes of patients with echocardiographic mild PVR were not significantly different from those with none-trace PVR. In the two latter groups (echocardiographic < moderate PVR), MRI-RF ≥20% was associated with a significantly higher 5-year mortality or reintervention as compared with MRI-RF <20% (79.5% vs. 42.2%, log rank p value = 0.023; HR [95% CI]: 2.26 [1.10-4.65]). CONCLUSIONS: Greater than mild PVR as defined by TTE or MRI-RF is associated with impaired long-term clinical outcomes after TAVR. MRI-RF can be used to further risk-stratify patients with echocardiographic less-than-moderate PVR.

Quality of life of patients with coronary heart disease treated with the bioresorbable vascular scaffold (ABSORB™): 2-year results from the GABI-R-registry.

BACKGROUND: Numerous studies have reported clinical endpoints following coronary revascularization using bioresorbable vascular scaffolds (BVS), while information about the impact on health-related quality of life is sparse. In this analysis of the German-Austrian ABSORB RegIstRy, the 2 year results concerning quality of life development in a large cohort of patients treated with BVS were reported. METHODS: Data were collected at baseline as well as 30 days, 6 and 24 months after coronary revascularization using BVS. The EQ-5D score, EQ visual analogue scale (VAS) and Seattle Angina Questionnaire (SAQ) were determined for each time point. Patients were categorized according to the indication for coronary revascularization [acute coronary syndrome (ACS), stable angina pectoris (SAP), silent myocardial ischemia (SMI), or other]. Binary logistic regression analysis was performed to determine factors that predict above-average scores two years after implantation. RESULTS: Data from 1317 patients in 88 centres were included. Reasons for revascularization were: ACS (n = 643), SAP (n = 443), SMI (n = 52), and other (n = 179). Mean EQ-5D was significantly increased after six months, while a value comparable to baseline was found two years after implantation. EQ VAS and four of five dimensions of SAQ were significantly improved over baseline at all follow-up surveys. Particularly strong improvements were seen in SAQ scores angina frequency and quality of life. Binary regressions showed different statistically significant predictors in the respective models. CONCLUSIONS: Following coronary revascularization with BVS strong decrease in self-reported angina frequency and increase of self-reported quality of life were observed with continuous improvements over two years of follow-up. Trial registration ClinicalTrials.gov Identifier: NCT02066623.

Ticagrelor or Prasugrel in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: In this prespecified subgroup analysis, we included 1653 patients with ST-segment-elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization. RESULTS: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95-1.82]; P=0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P=0.83), stroke (1.3% versus 1.0%; P=0.46), and definite stent thrombosis (1.8% versus 1.0%; P=0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18-3.23]; P=0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80-1.87]; P=0.36). CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Prognostic value of haemoglobin drop in patients with acute coronary syndromes.

BACKGROUND: The prognostic value of in-hospital haemoglobin drop in patients with acute coronary syndrome (ACS) undergoing invasive therapy remains insufficiently investigated. MATERIALS AND METHODS: This observational study included 3838 patients with ACS with admission and in-hospital nadir haemoglobin values available. Haemoglobin drop was defined as a positive difference between admission and nadir haemoglobin values. The primary endpoint was one-year all-cause mortality. RESULTS: In-hospital haemoglobin drop occurred in 3142 patients (82%). Patients were categorized into 4 groups: no haemoglobin drop (n = 696 patients), <3 g/dl haemoglobin drop (n = 2703 patients), 3 to <5 g/dl haemoglobin drop (n = 344 patients) and ≥5 g/dl haemoglobin drop (n = 95 patients). The primary endpoint occurred in 156 patients: 17 patients (2.5%) in the group with no haemoglobin drop, 81 patients (3.0%) in the group with <3g/dl haemoglobin drop, 37 patients (10.9%) in the group with 3 to <5 g/dl haemoglobin drop and 21 patients (22.2%) in the group with ≥5 g/dl haemoglobin (adjusted hazard ratio [HR] = 1.30, 95% confidence interval 1.17 to 1.45; p < .001 for one g/dl haemoglobin drop). The association of haemoglobin drop with one-year mortality remained significant after exclusion of patients with in-hospital overt bleeding (adjusted HR = 1.27 [1.11-1.46]; p < .001 for one g/dl haemoglobin drop). The lowest haemoglobin drop associated with mortality was 1.23 g/dl in all patients (HR = 1.03 [1.02-1.04]) and 1.13 g/dl in patients without overt bleeding (HR = 1.03 [1.01-1.04]). CONCLUSIONS: In patients with ACS, in-hospital haemoglobin drop was associated with higher risk of one-year mortality even in the absence of overt bleeding.

Individual patient data analysis of the BIOFLOW study program comparing safety and efficacy of a bioresorbable polymer sirolimus eluting stent to a durable polymer everolimus eluting stent.

OBJECTIVES: This analysis of pooled individual patient data (IPD) aimed to evaluate the safety and efficacy of a bioresorbable polymer sirolimus eluting stent system (BP-SES; Orsiro) compared to a durable polymer everolimus eluting stent system (DP-EES; Xience) in the pooled population as well as in subgroups. METHODS: IPD with up to 12 months follow-up of the randomized controlled trials BIOFLOW-II (NCT01356888), -IV (NCT01939249), and -V (NCT02389946) as well as the all comers registry BIOFLOW-III (NCT01553526) were pooled. A total of 3,717 subjects (2,923 in BP-SES and 794 in DP-EES) with 5,328 lesions (4,225 lesions in BP-SES and 1,103 in DP-EES) were included in the IPD. The primary endpoint was target lesion failure (TLF) at 12 months follow-up. Subgroups analyzed included diabetes, age (≥65 years), gender, complex lesions (B2/C), small vessels (reference vessel diameter ≤2.75 mm), multivessel treatment, renal disease, and patients with acute coronary syndrome. RESULTS: Overall, TLF at 12 months was significantly lower with 5.2%in the BP-SES group versus 7.6% in the DP-EES group (p = .0098). Similarly, target vessel myocardial infarction (TV-MI) was 3.1 versus 5.7% (p = .0005). The rate of stent thrombosis was similar in both groups (0.004%). By regression analysis, an independent stent effect in favor of BP-SES was observed for TLF (p = .0043) and TV-MI (p = .0364) in small vessels. CONCLUSION: Results of this IPD analysis suggest that the BP-SES with ultrathin struts is as safe as and more efficacious than DP-EES in the overall cohort and especially in small vessels.

Everolimus eluting bioresorbable vascular scaffolds in patients with acute coronary syndromes: Two-year results from the German-Austrian ABSORB registry.

OBJECTIVES: To identify potential differences in 2-year outcome between patients who underwent coronary revascularization using bioresorbable vascular scafffolds (BVS) in stable coronary artery disease (CAD) and acute coronary syndromes (ACS). BACKGROUND: Data from randomized trials suggest a significantly higher event rate following coronary revascularization using everolimus-eluting BVS as compared to new generation drug eluting stents. Whether particular patient subgroups are at increased risk for scaffold thrombosis and target lesion failure (TLF) has not clearly been demonstrated. METHODS: German-Austrian ABSORB RegIstRy is a prospective all-comer multi-center observational study of consecutive patients who were considered for coronary revascularization with BVS. We compared 1499 patients with stable CAD to 1594 patients with ACS. Endpoints were major adverse cardiac events (MACE), TLF, and scaffold thrombosis. RESULTS: While single vessel disease was more prevalent in ACS (46% vs. 37%, p < 0.0001), lesion complexity (B2/C stenosis 37% vs. 36%, bifurcation 2.4% vs. 3.4%, p < 0.05), number of implanted scaffolds/patient (1.34 vs. 1.43), scaffold length (18 vs. 18 mm) or the rate of high pressure postdilatation (68% vs. 70%) did not differ between ACS and stable CAD. Two-year MACE rates were 11.6% in ACS and 11.4% in stable CAD, TLF occurred in 7.0% versus 7.4% and target vessel revascularization in 8.8 versus 10.2% (n.s. for all). Definite scaffold thrombosis rates were not significantly different (ACS 1.9% vs. stable CAD 2.1%). CONCLUSION: Real-world 2-year event rates after coronary revascularization with BVS are not significantly different between individuals with ACS as compared to stable CAD.

Predictors of scaffold failure and impact of optimized scaffold implantation technique on outcome: Results from the German-Austrian ABSORB RegIstRy.

AIMS: We aimed to investigate predictors of scaffold failure and the potential impact of an optimized scaffold implantation technique by means of a learning curve on long-term clinical outcome after bioresorbable scaffold (BRS) implantation and to evaluate predictors of scaffold failure. METHODS AND RESULTS: A total of 3326 patients were included in this prospective, observational, multi-center study (ClinicalTrials.gov NCT02066623) of consecutive patients undergoing BRS implantation between November 2013 and January 2016. The 3144 patients completed follow-up after 24 months, 3265 patients were eligible for time-to-event-analysis. Clinical endpoints were major adverse cardiac events-a composite endpoint of death, target vessel revascularization and myocardial infarction, and scaffold thrombosis (ScT). Patients were grouped according to treatment before or since 2015. During follow-up MACE rate improved from 2.52% after 30 days, 5.45% after 6 months and 12.67% after 24 months to 1.52%, 3.44%, and 10.52%, respectively. A total of 75 ScT occurred. In multiple regression analysis, treatment of bifurcations, long lesions, and procedures performed earlier than 2014 were identified as predictors for the occurrence of ScT. CONCLUSION: Treatment of bifurcation lesions is the strongest predictor of ScT following BRS implantation. A significantly lower incidence of ScT and 24-month target lesion revascularization in patients recruited after 2014 into our observational registry suggests the influence of a learning curve.

Typical atrial flutter but not fibrillation predicts coronary artery disease in formerly healthy patients.

AIMS: Long-term mortality after ablation of typical atrial flutter has been found to be increased two-fold in comparison to atrial fibrillation ablations through a period of 5 years with unclear mechanism. METHODS AND RESULTS: We analysed 189 consecutive patients who underwent ablation for typical atrial flutter (AFL), in which the incidence of AF was the first manifestation of cardiac disease. According to the clinical standards of our centre, the routine recommendation was to evaluate for coronary artery disease (CAD) by invasive angiogram or computed tomography scan. We compared the AFL patients to 141 patients with paroxysmal atrial fibrillation (AFIB) without known structural heart disease who underwent ablation in the same period and who had routine coronary angiograms performed. Out of 189 patients who presented with AFL, coronary status was available in 152 patients (80.4%). Both groups were balanced for mean age (64.9 years in AFL vs. 63.2 years in AFIB; P = 0.15), body mass index (BMI; 28.8 vs. 28.5 kg/m2; P = 0.15), CHA2DS2-VASc-Score (2.20 vs. 2.04; P = 0.35), smoking status (22.2% smokers vs. 28.4%; P = 0.23), and renal function (GFR >60 mL/min in 96.7% of all patients vs. 95.7%; P = 0.76). There were significantly lower values for left ventricular ejection fraction (52.5% vs. 59.7%; P < 0.001), female sex (17.0% vs. 47.5%; P < 0.001), hyperlipidaemia (37.9% vs. 58.9%; P < 0.001), and family history of cardiovascular disease (CVD) (15.0 vs. 31.9%; P = 0.001) in the AFL vs. AFIB cohorts. Coronary artery disease with stenoses >50% was found in 26.3% of all patients with available coronary status in AFL and in 7.0% in AFIB (P < 0.001). Coronary artery disease with stenoses >75% in 16.4% in AFL whereas only in 1.4% in AFIB (P < 0.001). Multivessel disease was detected in 10.5% in AFL and 0.7% in AFIB (P < 0.001). After correction for age, left ventricular ejection fraction, BMI, CHA2DS2-VASc-Score and its individual components, smoking status, hyperlipidaemia, and family history of CVD, there was a more than five-fold increase in the likelihood of CAD with stenosis >50% in AFL as compared to AFIB [odds ratio (OR 5.26)]. A multivariate analysis was performed in the AFL group. Patients with clinically relevant stenoses (>75%) were older (70.6 years vs. 63.8 years; P = 0.001), had a higher number of risk factors (3.08 vs. 2.24; P ≤ 0.0016) and a higher CHA2DS2-VASc-Score (3.20 vs. 2.00; P < 0.0001). With logistic regression, significant CAD could be predicted by higher values for CHA2DS2-VASc-Score with an exponential rise to a pretest-probability of 42.1% at a value of 4 points. CONCLUSION: These data suggest that typical atrial flutter constitutes a manifestation of previously asymptomatic CAD. Due to the inclusion criteria, CAD has to be considered silent and chronic in most of the patients. Therefore, the presence of typical atrial flutter in formerly healthy patients should raise suspicion of otherwise silent CAD and initiate further investigations and risk stratification with particular emphasis on the individual CHA2DS2-VASc-Scores.

Age- and Weight-Adapted Dose of Prasugrel Versus Standard Dose of Ticagrelor in Patients With Acute Coronary Syndromes : Results From a Randomized Trial.

BACKGROUND: The efficacy and safety of a reduced dose of prasugrel versus a standard dose of ticagrelor in elderly patients or those with a low body weight presenting with an acute coronary syndrome (ACS) are unknown. OBJECTIVE: To investigate the effect of an age- and weight-adapted dose of prasugrel versus a standard dose of ticagrelor in patients with ACS. (ClinicalTrials.gov: NCT01944800). DESIGN: Prespecified analysis of the multicenter, randomized ISAR-REACT 5 trial. SETTING: 23 centers in Germany and Italy. PATIENTS: 3997 patients with ACS planned for invasive management. INTERVENTION: Participants were randomly assigned to receive a standard dose of ticagrelor or prasugrel (reduced dose in the elderly or low-weight group and standard dose in the neither elderly nor low-weight group). MEASUREMENTS: The efficacy end point was a composite of death, myocardial infarction, or stroke, and the safety end point was bleeding, both at 12 months. RESULTS: In the elderly or low-weight group, the efficacy end point occurred in 12.7% of patients assigned to receive prasugrel and 14.6% of those assigned to receive ticagrelor (hazard ratio [HR], 0.82 [95% CI, 0.60 to 1.14]); in the neither elderly nor low-weight group, the efficacy end point occurred in 4.8% of patients assigned to receive prasugrel and 7.3% of those assigned to receive ticagrelor (HR, 0.65 [CI, 0.48 to 0.88]; P for interaction > 0.2). In the elderly or low-weight group, Bleeding Academic Research Consortium type 3 to 5 bleeding occurred in 8.1% of patients assigned to receive prasugrel and 10.6% of those assigned to receive ticagrelor (HR, 0.72 [0.46 to 1.12]), and in 3.7% and 3.8%, respectively, of patients in the neither elderly nor low-weight group (HR, 0.98 [CI, 0.65 to 1.47]; P for interaction > 0.2). LIMITATION: The study is a subgroup analysis. CONCLUSION: In elderly or low-weight patients with ACS, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting these patients against the excess risk for bleeding. PRIMARY FUNDING SOURCE: German Center for Cardiovascular Research and Deutsches Herzzentrum München.

Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), the use of percutaneous coronary intervention (PCI) to restore blood flow in an infarct-related coronary artery improves outcomes. The use of PCI in non-infarct-related coronary arteries remains controversial. METHODS: We randomly assigned 885 patients with STEMI and multivessel disease who had undergone primary PCI of an infarct-related coronary artery in a 1:2 ratio to undergo complete revascularization of non-infarct-related coronary arteries guided by fractional flow reserve (FFR) (295 patients) or to undergo no revascularization of non-infarct-related coronary arteries (590 patients). The FFR procedure was performed in both groups, but in the latter group, both the patients and their cardiologist were unaware of the findings on FFR. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, revascularization, and cerebrovascular events at 12 months. Clinically indicated elective revascularizations performed within 45 days after primary PCI were not counted as events in the group receiving PCI for an infarct-related coronary artery only. RESULTS: The primary outcome occurred in 23 patients in the complete-revascularization group and in 121 patients in the infarct-artery-only group that did not receive complete revascularization, a finding that translates to 8 and 21 events per 100 patients, respectively (hazard ratio, 0.35; 95% confidence interval [CI], 0.22 to 0.55; P<0.001). Death occurred in 4 patients in the complete-revascularization group and in 10 patients in the infarct-artery-only group (1.4% vs. 1.7%) (hazard ratio, 0.80; 95% CI, 0.25 to 2.56), myocardial infarction in 7 and 28 patients, respectively (2.4% vs. 4.7%) (hazard ratio, 0.50; 95% CI, 0.22 to 1.13), revascularization in 18 and 103 patients (6.1% vs. 17.5%) (hazard ratio, 0.32; 95% CI, 0.20 to 0.54), and cerebrovascular events in 0 and 4 patients (0 vs. 0.7%). An FFR-related serious adverse event occurred in 2 patients (both in the group receiving infarct-related treatment only). CONCLUSIONS: In patients with STEMI and multivessel disease who underwent primary PCI of an infarct-related artery, the addition of FFR-guided complete revascularization of non-infarct-related arteries in the acute setting resulted in a risk of a composite cardiovascular outcome that was lower than the risk among those who were treated for the infarct-related artery only. This finding was mainly supported by a reduction in subsequent revascularizations. (Funded by Maasstad Cardiovascular Research and others; Compare-Acute ClinicalTrials.gov number, NCT01399736 .).

Rationale and design of the MULTISTARS AMI Trial: A randomized comparison of immediate versus staged complete revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease.

About half of patients with acute ST-segment elevation myocardial infarction (STEMI) present with multivessel coronary artery disease (MVD). Recent evidence supports complete revascularization in these patients. However, optimal timing of non-culprit lesion revascularization in STEMI patients is unknown because dedicated randomized trials on this topic are lacking. STUDY DESIGN: The MULTISTARS AMI trial is a prospective, international, multicenter, randomized, two-arm, open-label study planning to enroll at least 840 patients. It is designed to investigate whether immediate complete revascularization is non-inferior to staged (within 19-45 days) complete revascularization in patients in stable hemodynamic conditions presenting with STEMI and MVD and undergoing primary percutaneous coronary intervention (PCI). After successful primary PCI of the culprit artery, patients are randomized in a 1:1 ratio to immediate or staged complete revascularization. The primary endpoint is a composite of all-cause death, non-fatal myocardial infarction, ischemia-driven revascularization, hospitalization for heart failure, and stroke at 1 year. CONCLUSIONS: The MULTISTARS AMI trial tests the hypothesis that immediate complete revascularization is non-inferior to staged complete revascularization in stable patients with STEMI and MVD.

Comparison of long-term clinical outcomes in multivessel coronary artery disease patients treated either with bioresoarbable polymer sirolimus-eluting stent or permanent polymer everolimus-eluting stent: 5-year results of the CENTURY II randomized clinical trial.

OBJECTIVES: To assess the long-term safety and efficacy of a sirolimus-eluting stent with bioresorbable polymer (BP-SES; Ultimaster), in comparison to a benchmark everolimus-eluting, permanent polymer stent (PP-EES; Xience), in a prespecified subgroup of patients with multivessel coronary artery disease (MVD) enrolled in the CENTURY II trial. BACKGROUND: The use of coronary stenting in high-risk subgroups, like MVD patients, is rising. The clinical evidence, including long-term comparative analysis of the efficacy and safety benefits of different new-generation drug eluting stents, however, remains insufficient. METHODS: Among 1,119 patients (intention-to-treat) enrolled in the CENTURY II prospective, randomized, single-blind, multicenter trial, a prespecified subgroup of 456 MVD patients were allocated by stratified randomization to treatment with BP-SES (n = 225) or PP-EES (n = 231). The previously reported primary endpoint of this study was freedom from target lesion failure (TLF: a composite of cardiac death, target vessel-related myocardial infarction [MI] and clinically-indicated target lesion revascularization) at 9 months. RESULTS: In this MVD substudy, baseline patient, lesion and procedure characteristics were similar between the treatment arms. At 1 and 5 years, both BP-SES and PP-EES displayed low and comparable rates of TLF (5.3 vs. 7.8%; p = .29 and 10.2 vs. 13.4%; p = .29), and definite or probable stent thrombosis (0.4 vs. 1.3%; p = .33 and 0.9 vs. 1.7%; p = .43), respectively. Composite endpoint of cardiac death and MI, and patient-oriented composite endpoint of any death, MI, and coronary revascularizations were also similar. CONCLUSIONS: These results confirm good long-term safety and efficacy of the studied bioresorbable polymer stent in this high-risk patient population.

Impact of Lesion Preparation Technique on Side Branch Compromise in Calcified Coronary Bifurcations: A Subgroup Analysis of the PREPARE-CALC Trial.

OBJECTIVES: To analyze the impact of different techniques of lesion preparation of severely calcified coronary bifurcation lesions. BACKGROUND: The impact of different techniques of lesion preparation of severely calcified coronary bifurcation lesions is poorly investigated. METHODS: We performed an as-treated analysis on 47 calcified bifurcation lesions treated with scoring/cutting balloons (SCB) and 68 lesions treated with rotational atherectomy (RA) in the PREPARE-CALC trial. Compromised side branch (SB) as assessed in the final angiogram was the primary outcome measure and was defined as any significant stenosis, dissection, or thrombolysis in myocardial infarction flow <3. RESULTS: True bifurcation lesions were present in 49% vs. 43% of cases in the SCB and RA groups, respectively. After stent implantation, SB balloon dilatation was necessary in around one-third of cases (36% vs. 38%; p = 0.82), and a two-stent technique was performed in 21.3% vs. 25% (p = 0.75). At the end of the procedure, the SB remained compromised in 15 lesions (32%) in the SCB group and 5 lesions (7%) in the RA group (p = 0.001). Large coronary dissections were more frequently observed in the SCB group (13% vs. 2%; p = 0.02). Postprocedural levels of cardiac biomarkers were significantly higher in patients with a compromised SB at the end of the procedure. CONCLUSIONS: In the PREPARE-CALC trial, side branch compromise was more frequently observed after lesion preparation with SCB as compared with RA. Consequently, in calcified bifurcation lesions, an upfront debulking with an RA-based strategy might optimize the result in the side branch.

Feasibility and clinical outcome of rotational atherectomy in patients presenting with an acute coronary syndrome.

OBJECTIVES: We aimed to investigate the feasibility, safety, and outcome of rotational atherectomy (RA) in the setting of acute coronary syndrome (ACS). BACKGROUND: Limited data are available on the use of RA in patients presenting with ACS. METHODS: This analysis is from an observational registry, which enrolled all consecutive patients undergoing RA in a tertiary center. Between 2002 and 2015, 433 patients with stable coronary artery disease (SCAD) were treated with RA. Within the same period, 108 patients with ACS (8 STEMI and 100 NSTE-ACS) were treated with RA. Procedural success was similar between the ACS and the SCAD groups (96.6% vs. 96.4%, P = 0.90), and no significant difference was observed in procedural complications (slow-flow: 0.8% vs. 2.8%, P = 0.32; coronary dissection: 6.8% vs. 7.2%, P = 1.00; coronary perforation: 0.8% vs. 1.7%, P = 0.69). In-hospital MACE rates were comparable (3.7% vs. 3.2%, P = 0.77). The risk of MACE within 24 months was higher in ACS patients (39.9% vs. 22.4%, log-rank P = 0.002; HR: 1.39; 95% CI: 1.12-1.73; P = 0.003). Multivariable Cox regression analysis identified left ventricular ejection fraction (HR 0.97; 95% CI: 0.85-0.99; P = 0.001), treatment with a BMS (HR 2.22, 95% CI: 1.15-4.25, P = 0.02) or early generation drug eluting stent (HR 1.99; 95% CI 1.09-3.64; P = 0.03), as well as ACS presentation (HR 1.53; 95% CI: 1.02-2.29; P = 0.04) as predictors of MACE at two years. CONCLUSIONS: RA is technically feasible and safe in high risk patients presenting with ACS. However, successful application of RA did not mitigate the higher rate of long term cardiovascular events.

Impact of prosthesis-iteration evolution and sizing practice on the incidence of prosthesis-patient mismatch after transcatheter aortic valve replacement.

OBJECTIVES: To investigate the impact of the introduction of the next generation self-expanding (SE) and balloon-expandable (BE) transcatheter heart valves (THVs) on the incidence of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR). BACKGROUND: PPM is a risk factor for accelerated degeneration of bioprosthetic aortic valves. Data on PPM after TAVR are derived mainly from studies of older generation THVs. METHODS: PPM was assessed at 30 days post-TAVR with the older generation (Medtronic CoreValve, n = 120 and Edwards Sapien XT, n = 121) and the next generation THVs (Medtronic Evolut R/Pro, n = 136 and Edwards Sapien 3, n = 363). RESULTS: The incidence of any and severe PPM was 15.1% and 0.0% for the older generation THVs, and 42.8% and 12.1% for the next generation THVs. The incidence of moderate and severe PPM was 23.3% and 3.5% in patients who received an Evolut R/Pro vs. 33.1% and 14.7% in those who received a Sapien 3 (P < 0.001). On multivariable analysis, TAVR with the Sapien 3 THV was not associated with PPM, while left ventricular ejection fraction (0.97 [0.95-0.99], P = 0.002), history of myocardial infarction (2.09 [1.00-4.34], P = 0.049), annulus maximum diameter (0.84 [0.77-0.92], P < 0.001), and THV oversizing (0.90 [0.87-0.94], P < 0.001) were independently associated with PPM. In Sapien 3, the risk of any and severe PPM was higher in those with no oversizing (odds ratio: 3.25 [1.23-8.53], P = 0.017 and 5.79[2.33-14.36], P < 0.001). CONCLUSIONS: The incidence of PPM in contemporary TAVR is significant, especially with the next generation BE THV without adequate oversizing.

Clinical outcomes in unselected patients treated with the PROMUS Element platinum-chromium, everolimus-eluting stent: Final five-year results from the PE PROVE Study.

OBJECTIVES: The goal of this analysis was to evaluate the final 5-year safety and effectiveness of the PROMUS Element platinum-chromium everolimus-eluting stent in unselected patients treated in routine clinical practice. BACKGROUND: The prospective, open-label PROMUS Element™ European Post-Approval Surveillance Study (PE-PROVE) enrolled 1,010 "real-world" patients who received the PROMUS Element stent. Adverse event rates were low at 1-year, and the incidence of stent thrombosis was 0.6%. METHODS: The primary endpoint was target vessel failure (TVF; overall and PE stent-related), a composite of cardiac death, myocardial infarction (MI) related to the target vessel, or target vessel revascularization (TVR) at 1-year post-implantation. Five-year clinical outcomes were evaluated in overall as well as high-risk patient subgroups. RESULTS: The overall 5-year TVF rate was 14.9%, with 7.0% being related to the study stent. Cardiac death, MI and TVR related to the study stent occurred in 0.5%, 3.2%, and 5.7%, respectively. Stent thrombosis through 5-year follow-up was 1.0%. The rates of overall and study stent related TVF were numerically higher in patients with medically treated diabetes, long lesions (≥28 mm), and small diameter vessels (≤2.5 mm) compared to the overall study population. Additionally, favorable stent thrombosis rates through 5 years were reported for the PROMUS Element stent in these high-risk subgroups. CONCLUSIONS: The final 5-year data from the PE-PROVE study demonstrate favorable outcomes and low rates of adverse events with the PE stent when used in "real-world" patients with coronary artery disease.