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Background: The ISAR-REACT 5 trial compared the efficacy and safety of ticagrelor and prasugrel in patients with ACS managed invasively. The present study sought to investigate the impact of ticagrelor and prasugrel on the incidence and pattern of urgent revascularization in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI). Methods and results: This post-hoc analysis of the ISAR-REACT 5 trial included all ACS patients who underwent PCI. The primary endpoint for this analysis was the incidence of urgent revascularization at 12-month follow-up. Secondary outcome was the pattern of urgent revascularization procedures (namely, urgent target vessel/non-target vessel revascularization – TVR/NTVR). Among 3,377 ACS patients who underwent PCI, 1,676 were assigned to ticagrelor and 1,701 to prasugrel before PCI. After 12 months, the incidence of urgent revascularization was higher among patients assigned to ticagrelor as compared to prasugrel (6.8% vs. 5.2%; hazard ratio [HR] = 1.32, 95% confidence interval [CI] 1.00–1.75; p = 0.051), mostly attributable to significantly more urgent NTVR in the ticagrelor group (3.8% vs. 2.4%; HR = 1.62 [1.09–2.41]; p = 0.017). The risk of urgent TVR did not differ between treatment groups (3.3% vs. 3.0%; HR = 1.13 [0.77–1.65]; p = 0.546). Conclusions: In ACS patients treated with PCI, the cumulative rate of urgent revascularizations after 12 months is higher with ticagrelor compared to prasugrel, due to a significant increase in urgent revascularizations involving remote coronary vessels. [ABSTRACT FROM AUTHOR]

Background: The frequency and prognostic value of coronary no-reflow (CNR) was investigated in studies that have used an outdated reperfusion therapy in terms of stent technology and antithrombotic drugs. We assessed the association of CNR with adverse outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and newer antithrombotic drugs, ticagrelor or prasugrel. Methods: This study included 3100 patients with AMI who underwent PCI with current DES and third-generation P2Y12 inhibitors. CNR was defined as Thrombolysis in Myocardial Infarction (TIMI) blood flow grade ≤ 2 at the end of PCI. The primary end point was 1-year incidence of net adverse clinical and cerebral events—a composite end point of death of any cause, myocardial infarction, stroke or major bleeding. Results: CNR was diagnosed in 130 patients (4.2%). The primary end point occurred in 28 patients in the CNR group and 354 patients in the reflow group (cumulative incidence 23.2% and 12.8%; adjusted hazard ratio = 1.53, 95% confidence interval 1.01–2.33; P = 0.049). The 1-year incidences of death or myocardial infarction (14.6% vs. 7.6%; P = 0.003), myocardial infarction (8.8% vs. 3.9%; P = 0.007) and major bleeding (10.9% vs. 5.6%; P = 0.008) were significantly higher in patients with CNR than patients with reflow. The risk of adverse events in patients with CNR was highest within the first 30 days after PCI. Conclusion: In patients with AMI undergoing PCI with current DES and third generation P2Y12 receptor inhibitors, CNR was associated with a higher risk of adverse outcomes at 1 year. [ABSTRACT FROM AUTHOR]

Background: The performance of modified balloons (namely cutting or scoring balloons) to prepare severely calcified lesions in patients undergoing percutaneous coronary intervention (PCI) remains controversial. We investigated the clinical and imaging outcomes of patients undergoing PCI assigned to modified balloon therapy to prepare severely calcified coronary lesions before stent implantation. Methods: In this meta-analysis, we aggregated the study-level data from trials enrolling invasively treated patients who were randomly assigned to modified balloon or control therapy to prepare severely calcified lesions before stenting. The primary outcome was major adverse cardiac events (MACE), including death, myocardial infarction (MI), and repeat revascularization. The secondary outcomes included the individual components of the primary outcome, coronary perforation and final minimal stent area (MSA) as measured by intracoronary imaging. Results: A total of 648 participants in six trials were allocated to modified balloon therapy (n = 335) or control therapy (semi-compliant, non-compliant, or super high-pressure balloon, n = 313). The median follow-up was 11 months. Overall, MACE occurred in 8.96% of patients assigned to a modified balloon and 12.78% of patients assigned to control therapy [risk ratio = 0.70, 95% confidence interval (CI) 0.35–1.39; P = 0.24]. There was a significant treatment effect-by-modified balloon type interaction for the outcome MACE in patients assigned to cutting balloon compared with control therapy [RR = 0.40 (0.28–0.56), P for interaction (Pint) < 0.001]. Patients treated with a modified balloon compared with control therapy showed neither a significant difference for the other clinical outcomes nor for final MSA [standardized mean difference = 0.67 (− 0.71, 2.06); P = 0.26]. Conclusions: In patients treated with PCI for severely calcific coronary artery disease a strategy of lesion preparation with a modified balloon before stenting does not improve clinical or imaging outcomes compared with control therapy. The different performance of cutting and scoring balloons warrants further investigation. [ABSTRACT FROM AUTHOR]

Objectives: To assess the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome (ACS) presenting during off- and on-hours. Background: The efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to time of hospital presentation remain unknown. Methods: This post hoc analysis of the ISAR-REACT 5 trial included 1565 patients with ACS presenting off-hours and 2453 patients presenting on-hours, randomized to ticagrelor or prasugrel. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium (BARC) type 3–5 bleeding, both at 12 months. Results: The primary endpoint occurred in 80 patients (10.4%) in the ticagrelor group and 57 patients (7.3%) in the prasugrel group in patients presenting off-hours (hazard ratio [HR] = 1.45; 95% confidence interval [CI] 1.03–2.03; P = 0.033), and 104 patients (8.5%) in the ticagrelor group and 80 patients (6.7%) in the prasugrel group in patients presenting on-hours (HR = 1.29 [0.97–1.73]; P = 0.085), without significant treatment arm-by-presentation time interaction (Pint = 0.62). BARC type 3 to 5 bleeding occurred in 35 patients (5.1%) in the ticagrelor group and 37 patients (5.3%) in the prasugrel group (P = 0.84) in patients presenting off-hours, and 60 patients (5.9%) in the ticagrelor group and 43 patients (4.6%) in the prasugrel group in patients presenting on-hours (P = 0.17). Conclusions: In patients with ACS planned to undergo an invasive treatment strategy, time of presentation (off-hours vs. on-hours) does not interact significantly with the relative efficacy and safety of ticagrelor vs. prasugrel. Clinical trial registration.: NCT01944800. [ABSTRACT FROM AUTHOR]

Aims: Aim of the present study was to investigate the impact of increasing neointimal inhomogeneity and neoatherosclerosis as well as of treatment modality of in-stent restenosis (ISR) on the occurrence of periprocedural myocardial injury (PMI). Methods and results: Patients with normal or stable/falling increased baseline high-sensitivity troponin T (hs-cTnT) undergoing intravascular optical coherence tomography (OCT) and subsequent percutaneous coronary intervention (PCI) of ISR by means of drug-coated balloon (DCB) or drug-eluting stent (DES) were included. Overall, 128 patients were subdivided into low (n = 64) and high (n = 64) inhomogeneity groups, based on the median of distribution of non-homogeneous quadrants. No significant between-group differences were detected in terms of hs-cTnT changes (28.0 [12.0–65.8] vs. 25.5 [9.8–65.0] ng/L; p = 0.355), or the incidence of major PMI (31.2 vs. 31.2%; p = 1.000). Similarly, no differences were observed between DCB- and DES-treated groups in terms of hs-cTn changes (27.0 [10.0–64.0] vs. 28.0 [11.0–73.0] ng/L; p = 0.795), or the incidence of major PMI (28.9 vs. 35.6%; p = 0.566). Additionally, no significant interaction was present between optical neointimal characteristics and treatment modality in terms of changes in hs-cTnT (Pint = 0.432). No significant differences in PMI occurrence were observed between low and high neoatherosclerosis subgroups. Conclusions: In patients undergoing PCI for ISR, there was no association between increasing neointimal inhomogeneity, or increasing expression of neoatherosclerotic changes and occurrence of PMI. PMI occurrence was not influenced by the treatment modality (DCB vs. DES) of ISR lesions, a finding that supports the safety of DCB treatment for ISR. [ABSTRACT FROM AUTHOR]

Aims: To define the incidence of events related to the stented vessel (target vessel related events: TVRE) and events related to non-stented vessels (non-target vessel related events: NTVRE) through to 10-year follow-up in patients post-PCI with newer generation drug eluting stents (DES). Methods and results: The current study is a post-hoc analysis of patient level data from two randomised controlled trials in Germany. Patients older than 18 years with ischemic symptoms or evidence of myocardial ischemia in the presence of ≥ 50% de novo stenosis located in the native coronary vessels were considered eligible. The endpoints of interest were TVRE (a composite of first target vessel myocardial infarction or target vessel revascularization) and NTVRE (a composite of first non-target vessel MI or non-target vessel revascularization) through to 10 years post PCI. We included 4953 patients in this analysis. Through to 10-years post-PCI, TVRE occurred in 1238 of 4953 patients (cumulative incidence: 25.8%) and NTVRE occurred in 1442 of 4953 patients (cumulative incidence: 30.3%). The majority of TVRE and NTVRE were revascularization events. From 0 to 1 years, the cumulative incidence of TVRE was 15.9% and of NTVRE was 12.3%. From 1 to 10 years, the cumulative incidences of TVRE and NTVRE were 11.2% and 22.4%, respectively. Conclusion: At 10-year post-PCI with new generation drug eluting stents, events related to remote vessel disease progression account for a higher proportion of events than events related to the stented vessel. Trial registration: ISAR TEST 4 ClinicalTrials.gov Identifier: NCT00598676. ISAR TEST 5 ClinicalTrials.gov Identifier: NCT00598533. [ABSTRACT FROM AUTHOR]

Aims: To investigate the clinical outcomes associated with an antithrombotic therapy with or without clopidogrel after transcatheter aortic valve replacement (TAVR). Methods and results: This is a study-level meta-analysis including all randomized trials investigating antithrombotic regimens after TAVR. The protocol was registered with PROSPERO (CRD42020191036). We searched electronic scientific databases for eligible studies. The primary outcome was all-cause death. Main secondary outcome was major bleeding. Other outcomes were life-threatening (or disabling) bleeding, myocardial infarction (MI) and stroke. Six eligible trials randomly allocated 3056 TAVR patients to aspirin or oral anticoagulation (OAC) with clopidogrel (n = 1525) versus aspirin and/or OAC without clopidogrel (n = 1531). In the overall estimates, an antithrombotic therapy with clopidogrel versus without displayed a comparable risk of all-cause death [Risk Ratio—RR = 0.83, 95% Confidence intervals—CI (0.57–1.20); P = 0.25] and major bleeding [RR = 1.33, 95% CI (0.61–2.92); P = 0.39]. However, the combination of aspirin or OAC with clopidogrel doubled the risk of major bleeding as compared to aspirin or OAC without clopidogrel [RR = 2.08, 95% CI (1.27–3.42); P = 0.015, P for interaction = 0.021]. Treatment strategies did not differ with respect to the risk of life-threatening bleeding, MI and stroke. Conclusions: In patients receiving TAVR, a therapeutic strategy of aspirin or OAC with clopidogrel significantly increases the risk of major bleeding without impact on mortality and ischemic outcomes compared to aspirin or OAC without clopidogrel. The performance of different antithrombotic regimens in terms of long-term clinical outcomes and bioprosthesis valve function requires further investigation. Forest plots from pairwise and network meta-analyses associated with an antithrombotic therapy with or without clopidogrel Risk ratio for all outcomes of interest calculated with the pairwise meta-analysis (left side) and for main outcomes calculated with the network meta-analysis (right side) in patients allocated to an antithrombotic therapy with clopidogrel or without. The diamonds indicate the point estimate and the left and the right ends of the lines the [95% CI]. CI: Confidence intervals; OAC; oral anticoagulation. [ABSTRACT FROM AUTHOR]

Background: Very long-term outcomes according to diabetic status of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES) are scant. Both, the durable polymer zotarolimus-eluting stent (DP-ZES), the first DES to gain FDA-approval for specific use in patients with diabetes mellitus, and the polymer-free sirolimus- and probucol-eluting stent (PF-SES), with a unique design that enables effective drug release without the need of a polymer offer the potential to enhance clinical long-term outcomes especially in patients with diabetes mellitus. Methods: We investigate 10-year clinical outcomes of the prespecified subgroups of patients with and without diabetes mellitus, randomly assigned to treatment with PF-SES versus DP-ZES in the ISAR-TEST 5 trial. The primary endpoint of interest was major adverse cardiac events (MACE), defined as the composite of all-cause death, any myocardial infarction or any revascularization. Further endpoints of interest were cardiac death, myocardial infarction related to the target vessel and target lesion revascularization as well as the individual components of the primary composite endpoint and the incidence of definite or probable stent thrombosis at 10 years. Results: This analysis includes a total of 3002 patients randomly assigned to PF-SES (n = 2002) or DP-ZES (n = 1000). Prevalence of diabetes mellitus was high and comparable, 575 Patients (28.7%) in PF-SES group and 295 patients (29.5%) in DP-ZES group (P = 0.66). At 10 years 53.5% of patients with diabetes mellitus and 68.5% of patients without diabetes mellitus were alive. Regarding major adverse cardiac events, PF-SES as compared to DP-ZES showed comparable event rates in patients with diabetes mellitus (74.8% vs. 79.6%; hazard ratio 0.86; 95% CI 0.73–1.02; P = 0.08) and in patients without diabetes (PF-SES 62.5% vs. DP-ZES 62.2%; hazard ratio 0.99; 95% CI 0.88–1.11; P = 0.88). Conclusion: At 10 years, both new-generation DES show comparable clinical outcome irrespective of diabetic status or polymer strategy. Event rates after PCI in patients with diabetes mellitus are considerable higher than in patients without diabetes mellitus and continue to accrue over time. Trial registration: ClinicalTrials.gov, NCT00598533, Registered 10 January 2008, https://clinicaltrials.gov/ct2/show/NCT00598533?term=NCT00598533 Kaplan-Meier estimates of endpoints of interest for patients with vs. without diabetes mellitus treated with PF-SES vs. DP-ZES. Bar graphs: Kaplan-Meier estimates as percentages. PF-SES: polymer-free sirolimus-eluting stent; DP-ZES: durable polymer zotarolimus-eluting stent; DM: diabetes mellitus. Comparison of event rates of individual endpoints in patients with and without diabetes mellitus treated with PF-SES vs. DP-ZES all without statistically significant differences. Comparison of event rates of individual endpoints in overall patients with vs. without diabetes mellitus significantly different (P ≤ 0.01 for all comparisons). [ABSTRACT FROM AUTHOR]

Background: In patients with acute myocardial infarction (MI) receiving percutaneous coronary intervention (PCI), the role of systemic therapeutic hypothermia remains controversial. We sought to investigate the role of systemic therapeutic hypothermia versus standard of care in patients with acute MI treated with PCI. Methods: This is a study-level meta-analysis of randomized trials. The primary outcome was all-cause death. The main secondary outcome was infarct size. Other secondary outcomes were recurrent MI, ischemia-driven target vessel revascularization (TVR), major adverse cardiovascular events, and bleeding. Results: A total of 1012 patients with acute MI receiving a PCI in nine trials (503 randomly assigned to hypothermia and 509 to control) were available for the quantitative synthesis. The weighted median follow-up was 30 days. As compared to controls, patients assigned to hypothermia had similar risk of all-cause death (risk ratio, [95% confidence intervals], 1.25 [0.80; 1.95], p = 0.32), with a trend toward higher risk of ischemia-driven TVR (3.55 [0.80; 15.87], p = 0.09) mostly due to acute or subacute stent thrombosis. Although in the overall cohort, infarct size was comparable between groups (standardized mean difference [95% Confidence intervals], 0.06 [− 0.92; 1.04], p = 0.92), patients effectively achieving the protocol-defined target temperature in the hypothermia group had smaller infarct size as compared to controls (p for interaction = 0.016). Treatment strategies did not differ with respect to the other outcomes. Conclusions: As compared to standard of care, systemic therapeutic hypothermia in acute MI patients treated with PCI provided similar mortality with a signal toward more frequent repeat revascularization. Among patients assigned to hypothermia, those effectively achieving the protocol-defined target temperature displayed smaller infarct size. Trial Registration: PROSPERO, CRD42019138754. [ABSTRACT FROM AUTHOR]

Aims: To describe optical coherence tomography (OCT) findings in patients with in-stent restenosis (ISR) and determine predictors of neointimal patterns and neoatherosclerosis. Methods and results: Patients undergoing OCT prior to PCI for ISR in three European centres were included. Analyses were performed in a core laboratory. Qualitative and quantitative [gray-scale signal intensity (GSI)] neointima analyses were performed on a per quadrant basis. A total of 107 patients were included. Predominantly homogeneous lesions included 4.5% (0.0–14.3) non-homogeneous quadrants, while predominantly non-homogeneous ones included 28.1% (20.3–37.5) homogeneous quadrants. Mean GSI values differed significantly between homogeneous [108.4 (92.5–123.6)], non-homogeneous [79.9 (61.2–95.9)], and neoatherosclerosis [88.3 (72.8–104.9)] quadrants (p < 0.001 for all comparisons). Stent underexpansion was observed in 48.5% and 61.1% of lesions, respectively (p = 0.225). Female sex and maximal neointimal thickness independently correlate with a non-homogeneous pattern, while angiographic pattern and diabetes mellitus inversely correlate with such pattern. Time from index stenting procedure was the only independent predictor of neoatherosclerosis. Conclusions: Different neointimal patterns coexist in a significant proportion of ISR lesions. GSI values differ significantly between neointimal categories. Neoatherosclerosis is a time-dependent phenomenon, displaying different time courses in DES compared to BMS, with earlier appearance in the former group. Stent underexpansion is a frequent finding in patients with ISR. [ABSTRACT FROM AUTHOR]

The relationship between central pulse pressure (CPP) measured at the time of primary percutaneous coronary intervention (PPCI) and long-term prognosis after ST-segment elevation myocardial infarction (STEMI) has not been investigated. CPP measurements were performed in 1348 patients with STEMI (327 women; mean age 62.5 ± 12.1 years) undergoing PPCI. Aortic systolic and diastolic blood pressure was measured before intervention. The primary outcome was 8-year all-cause mortality. The median [25–75th percentile] CPP value was 55.0 [43.0–70.0] mmHg. CPP correlated negatively with heart rate (P < 0.001), body mass index (P = 0.007), Killip class (P < 0.001) and initial area at risk (P < 0.001) and positively with age (P < 0.001), female sex (P < 0.001), diabetes (P = 0.012), arterial hypertension (P < 0.001) and glomerular filtration rate (P = 0.004). There were 181 deaths over the follow-up. In patients with CPP within the 1st, 2nd and 3rd tertiles, the Kaplan–Meier estimates of mortality were 17.3%, 10.8% and 24.2%, respectively; univariable hazard ratio [HR] =1.52, 95% confidence interval [CI] 0.99 to 2.32; P = 0.055 for tertile 1 vs. tertile 2 and HR =2.09 [1.36–3.21]; P < 0.001 for tertile 3 vs. tertile 2. For CPP values lower than 35 mmHg and higher than 71 mmHg, the association between CPP and all-cause mortality was significant (HR =1.276 [1.004–1.621] for the 35 mmHg value and HR =1.289 [1.003–1.657] for the 71 mmHg value) compared with the CPP reference value (54 mmHg). After adjustment, the association between CPP and all-cause mortality was attenuated (P = 0.304). In patients with STEMI undergoing PPCI there is a U-shaped association between CPP and mortality up to 8 years after PPCI. [ABSTRACT FROM AUTHOR]

The frequency and pattern of progression or regression of coronary atherosclerosis in contemporary patients with diabetes remain unknown. This study included 605 patients with coronary artery disease (CAD). Two coronary angiographic examinations at baseline and after 2 years were performed. The analysis focused on non-stented segments with diameter stenosis ≥25 %. Atherosclerosis progression (or regression) was defined as a decrease (or increase) in the mean minimal lumen diameter (MLD) in the 2-year angiogram compared to mean MLD in the baseline angiogram of >0.2 mm. Statins were prescribed in 576 patients (95.2 %). The primary outcome was atherosclerosis progression or regression in the 2-year angiogram. One hundred sixty-nine patients (28 %) had diabetes. Diabetic patients had greater reduction of mean MLD in the 24 angiogram compared to baseline angiogram than nondiabetic patients (0.11 ± 0.18 vs. −0.08 ± 0.15 mm, P < 0.001). Atherosclerosis progression was observed in 37 patients with diabetes and 16 nondiabetic patients (21.9 vs. 3.7 %; P < 0.001). Atherosclerosis regression was observed in two diabetic patients and 78 nondiabetic patients (1.2 vs. 17.9 %; P < 0.001). A progression pattern across all coronary segments was observed in 70 patients (41.4 %) with diabetes and 60 patients (13.8 %) without diabetes ( P < 0.001). Diabetic patients with a low-density lipoprotein cholesterol ≥70 mg/dl showed more atherosclerosis progression than diabetic patients with LDL cholesterol <70 mg/dl (delta-MLD: 0.12 ± 0.19 vs. 0.08 ± 0.16 mm; P = 0.04). In conclusion, in contemporary patients with CAD treated with moderate-intensity statin therapy, diabetes is associated with the increased risk of progression and decreased probability of regression of coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: In percutaneous coronary intervention (PCI) patients new-generation drug-eluting stent (DES) has reduced adverse events in comparison to early-generation DES. The aim of the current study was to investigate the long-term clinical efficacy and safety of new-generation DES versus early-generation DES for PCI of unprotected left main coronary artery (uLMCA) disease. Methods: The patient-level data from the ISAR-LEFT MAIN and ISAR-LEFT MAIN 2 randomized trials were pooled. The clinical outcomes of PCI patients assigned to new-generation DES (everolimus- or zotarolimus-eluting stent) versus early-generation DES (paclitaxel- or sirolimus-eluting stent) were studied. The primary endpoint was the composite of death, myocardial infarction (MI), target lesion revascularization and stroke (MACCE, major adverse cardiac and cerebrovascular event). Results: In total, 1257 patients were available. At 3 years, the risk of MACCE was comparable between patients assigned to new-generation DES or early-generation DES (28.2 versus 27.5 %, hazard ratio-HR 1.03, 95 % confidence intervals-CI 0.83-1.26; P = 0.86). Definite/probable stent thrombosis was low and comparable between new-generation DES and early-generation DES (0.8 versus 1.6 %, HR 0.52, 95 % CI 0.18-1.57; P = 0.25); in patients treated with new-generation DES no cases occurred beyond 30 days. Diabetes increased the risk of MACCE in patients treated with new-generation DES but not with early-generation DES ( P = 0.004). Conclusions: At 3-year follow-up, a PCI with new-generation DES for uLMCA disease shows comparable efficacy to early-generation DES. Rates of stent thrombosis were low in both groups. Diabetes significantly impacts the risk of MACCE at 3 years in patients treated with new-generation DES for uLMCA disease. ClinicalTrials.gov Identifiers: NCT00133237; NCT00598637. [ABSTRACT FROM AUTHOR]