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Background The relative efficacy and safety of ticagrelor and prasugrel based dual antiplatelet therapy strategies according to the platelet count (PC) in patients with acute coronary syndromes (ACS) have not been defined. Methods This is a posthoc analysis of the ISAR-REACT 5 trial, in which patients presenting with ACS were randomized to treatment with ticagrelor versus prasugrel. Patients were divided into quartiles according to PC. The primary endpoint was incidence of death, myocardial infarction, or stroke, and the safety endpoint was incidence of BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 12 months. Results A total of 3,943 patients with known PC (997 patients in quartile 1 (Q1), 1,003 in quartile 2 (Q2) [205 ± 10.3 × 109/L], 961 patients in quartile 3 (Q3) [241 ± 11.7 × 109/L], and 982 patients in quartile 4 (Q4) [317 ± 68.6 × 109/L]). There was no significant interaction between treatment arm (ticagrelor vs. prasugrel) and PC group with respect to primary endpoint (Q1: 8.8 vs. 6.3%, hazard ratio [HR] =1.41, 95% confidence interval [CI]: 0.89–2.23; p = 0.148; Q2: 9.9 vs. 5.8%, HR = 1.68, 95% CI: 1.06–2.66; p = 0.027; Q3: 7.8 vs. 5.5%, HR = 1.43, 95% CI: 0.87–2.37; p = 0.159; Q4: 10.1 vs. 10.1%, HR = 1.05, 95% CI: 0.71–1.57; p = 0.799; p for interaction [p int] = 0.482) and with respect to bleeding endpoint (Q1: 5.8 vs. 4.2%, HR = 1.41, 95% CI: 0.76–2.63; p = 0.279; Q2: 6.4 vs. 3.7%, HR = 1.62, 95% CI: 0.85–2.06; p = 0.140; Q3: 4.4 vs. 3.0%, HR = 1.53, 95% CI: 0.73–3.18; p = 0.258; Q4: 5.6 vs. 8.5%, HR = 0.67, 95% CI: 0.40–1.14; p = 0.138, p int = 0.102). Conclusions In this analysis, incidences of ischemic and bleeding events at 12 months are comparable across quartiles of platelet count.

Aims The effect of a prasugrel vs. a ticagrelor based strategy on total (including both first and recurrent) ischaemic and bleeding events in patients with acute coronary syndromes (ACS) has not been evaluated. The aim of this analysis was to investigate the treatment effect of a prasugrel vs. a ticagrelor based strategy in patients with ACS undergoing an invasive management strategy when both first and recurrent non-fatal ischaemic and bleeding events are taken into account. Methods and results This is a post-hoc analysis of the ISAR-REACT 5 randomized control trial, including all 4018 patients in the trial. The main clinical endpoints of interest included ischaemic events [myocardial infarction (MI) and stroke] and bleeding events [Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding]. An additional endpoint of interest was definite/probable stent thrombosis. The effect of the prasugrel vs. ticagrelor based strategies on these endpoints was evaluated on both time-to-first event and total events analyses. Patients in the prasugrel group had a lower risk of MI in comparison to the ticagrelor group on both time-to-first event [hazard ratio (HR) = 0.61; 95% confidence interval 0.44–0.85] and total events [HR = 0.62 (0.45–0.86)] analysis. The risk of BARC type 3 to 5 bleeding was comparable between the prasugrel and ticagrelor groups on both time-to-first event [HR = 0.96 (0.75–1.25)] and total events [HR = 0.99 (0.76–1.31)] analysis. Conclusion A prasugrel based strategy was associated with a reduction in total MI events in comparison to a ticagrelor based strategy in patients with ACS undergoing invasive assessment. Total BARC type 3 to 5 bleeding events were comparable between the two groups. Given the importance of this topic, future studies to confirm these findings would be welcome. ClinicalTrials.gov identifier: NCT01944800

Background: Whether the access site influences the comparative efficacy and safety of ticagrelor and prasugrel in patients with acute coronary syndrome (ACS) undergoing invasive treatment strategy remains unstudied. Methods: This post-hoc analysis included ACS patients undergoing invasive treatment via radial or femoral access and randomized to either ticagrelor or prasugrel in the ISAR-REACT 5 trial. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke, safety endpoint was BARC 3 to 5 bleeding. Outcomes were assessed out to 12 months after randomization. Results: Out of 4018 patients, 3984 underwent invasive treatment via radial or femoral access. 1479 had coronary angiography via radial access (ticagrelor, N = 748; prasugrel, N = 731) and 2505 via femoral access (ticagrelor, N = 1245; prasugrel, N = 1260). There was no interaction between access route and assignment to either ticagrelor or prasugrel regarding the primary efficacy or safety endpoints (P for interaction≥0.616). In the radial group, the primary efficacy endpoint (7.6% versus 5.8%, HR: 1.32 [0.88–1.97], P = 0.151) and the safety endpoint (4.3% versus 3.0%, HR: 1.36, [0.73–1.31], P = 0.300) were not statistically different in patients receiving either ticagrelor or prasugrel. In the femoral group, the primary efficacy endpoint occurred more frequently in patients assigned to ticagrelor as compared to prasugrel (10.3% versus 7.3%, HR: 1.44 [1.10–1.88], P = 0.006) without significant difference in terms of safety endpoint (6.4% versus 5.8%, HR: 1.14, [0.81–1.60], P = 0.470). Conclusions: In patients with ACS undergoing an invasive treatment strategy, the access route does not influence the comparative efficacy and safety of ticagrelor and prasugrel.

Contains fulltext : 291566.pdf (Publisher’s version ) (Open Access) BACKGROUND: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. METHODS: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March-June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. RESULTS: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825-0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24-1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05-1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic.

Contains fulltext : 290798.pdf (Publisher’s version ) (Open Access) BACKGROUND: Several reports have demonstrated the impact of the COVID-19 pandemic on the management and outcome of patients with ST-segment elevation myocardial infarction (STEMI). The aim of the current analysis is to investigate the potential gender difference in the effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI patients within the ISACS-STEMI COVID-19 Registry. METHODS: This retrospective multicenter registry was performed in high-volume primary percutaneous coronary intervention (PPCI) centers on four continents and included STEMI patients undergoing PPCIs in March-June 2019 and 2020. Patients were divided according to gender. The main outcomes were the incidence and timing of the PPCI, (ischemia time ≥ 12 h and door-to-balloon ≥ 30 min) and in-hospital or 30-day mortality. RESULTS: We included 16683 STEMI patients undergoing PPCIs in 109 centers. In 2020 during the pandemic, there was a significant reduction in PPCIs compared to 2019 (IRR 0.843 (95% CI: 0.825-0.861, p < 0.0001). We did not find a significant gender difference in the effects of the COVID-19 pandemic on the numbers of STEMI patients, which were similarly reduced from 2019 to 2020 in both groups, or in the mortality rates. Compared to prepandemia, 30-day mortality was significantly higher during the pandemic period among female (12.1% vs. 8.7%; adjusted HR [95% CI] = 1.66 [1.31-2.11], p < 0.001) but not male patients (5.8% vs. 6.7%; adjusted HR [95% CI] = 1.14 [0.96-1.34], p = 0.12). CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures similarly observed in both genders. Furthermore, we observed significantly increased in-hospital and 30-day mortality rates during the pandemic only among females. Trial registration number: NCT 04412655.

Objectives The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs). Background The outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined. Methods Patients (n = 4,012) were categorized into 3 groups: low eGFR ( Results Patients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding. Conclusions These results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800 )

Background The efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with acute coronary syndromes (ACS) are not known. We assessed the efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with ACS undergoing invasive management. Methods This pre-specified analysis of the ISAR-REACT 5 trial included 1349 smokers and 2652 nonsmokers randomized to receive ticagrelor or prasugrel. The primary endpoint was the incidence of death, myocardial infarction, or stroke; the secondary endpoint was the incidence of Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding (both endpoints assessed at 12 months). Results There was no significant treatment arm-by-smoking status interaction regarding the efficacy outcome. The primary endpoint occurred in 47 patients (7.0%) in the ticagrelor group and 41 patients (6.2%) in the prasugrel group in smokers (hazard ratio [HR] = 1.15; 95% confidence interval [CI] 0.76–1.75; P = 0.510) and in 133 patients (10.2%) in the ticagrelor group and 94 patients (7.2%) in the prasugrel group in nonsmokers (HR = 1.44 [1.10–1.87]; P = 0.007; P for interaction = 0.378). The secondary endpoint occurred in 27 patients (4.6%) in the ticagrelor group and 33 patients (5.6%) in the prasugrel group in smokers (HR = 0.81 [0.49–1.35]; P = 0.412) and in 66 patients (6.0%) in the ticagrelor group and 46 patients (4.4%) in the prasugrel group in nonsmokers (HR = 1.38 [0.94–2.01]; P = 0.097). Conclusions In patients with ACS undergoing an invasive management strategy, the smoking status did not significantly interact with the relative treatment effect of ticagrelor vs. prasugrel. Clinical trial registration NCT01944800

SARS-Cov-2 has been suggested to promote thrombotic complications and higher mortality. The aim of the present study was to evaluate the impact of SARS-CoV-2 positivity on in-hospital outcome and 30-day mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the International Survey on Acute Coronary Syndromes ST-segment elevation Myocardial Infarction (ISACS-STEMI COVID-19 registry. The 109 SARS-CoV-2 positive patients were compared with 2005 SARS-CoV-2 negative patients. Positive patients were older ( P = .002), less often active smokers ( P = .002), and hypercholesterolemic ( P = .006), they presented more often later than 12 h ( P = .037), more often to the hub and were more often in cardiogenic shock ( P = .02), or requiring rescue percutaneous coronary intervention after failed thrombolysis (P < .0001). Lower postprocedural Thrombolysis in Myocardial Infarction 3 flow ( P = .029) and more thrombectomy ( P = .046) were observed. SARS-CoV-2 was associated with a significantly higher in-hospital mortality (25.7 vs 7%, adjusted Odds Ratio (OR) [95% Confidence Interval] = 3.2 [1.71-5.99], P < .001) in-hospital definite in-stent thrombosis (6.4 vs 1.1%, adjusted Odds Ratio [95% CI] = 6.26 [2.41-16.25], P < .001) and 30-day mortality (34.4 vs 8.5%, adjusted Hazard Ratio [95% CI] = 2.16 [1.45-3.23], P < .001), confirming that SARS-CoV-2 positivity is associated with impaired reperfusion, with negative prognostic consequences.

Background: The relative efficacy and safety of more potent P2Y 12 inhibitors in patients with acute coronary syndrome and high bleeding risk (HBR) undergoing percutaneous coronary intervention remains unclear. We aimed to study the treatment effect of ticagrelor and prasugrel in percutaneous coronary intervention patients presenting with acute coronary syndrome and HBR. Methods: This post hoc analysis of the ISAR-REACT 5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5) included patients with acute coronary syndrome undergoing percutaneous coronary intervention, randomized to ticagrelor or prasugrel, in whom HBR was defined as per Academic Research Consortium criteria. The primary (efficacy) end point was the composite of all-cause death, myocardial infarction, or stroke. The secondary (safety) end point was Bleeding Academic Research Consortium type 3 to 5 bleeding. Outcomes were assessed 12 months after randomization. Results: Out of the 3239 patients included in this analysis, 486 fulfilled the criteria for Academic Research Consortium-HBR definition (HBR group; ticagrelor, n=230 and prasugrel, n=256), while 2753 did not (non-HBR group; ticagrelor, n=1375 and prasugrel, n=1378). Compared with the non-HBR group, the HBR group had a higher risk for the primary (hazard ratio [HR]=3.57 [95% CI, 2.79–4.57]; P P P for interaction=0.12) or secondary ( P for interaction=0.80) end points. Conclusions: In patients with acute coronary syndrome undergoing percutaneous coronary intervention, HBR status increased both ischemic and bleeding risk without significant impact on the relative efficacy and safety of either ticagrelor or prasugrel. These results warrant confirmation in larger cohorts. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01944800.

A 40-year-old Down patient without previous cardiological history was admitted to our institution for dyspnoea after COVID-19 vaccine. CT scan revealed a pulmonary thromboembolism. One week later, he developed neurological impairment and CT scan evidenced a left parietal ischaemic lesion. Concomitantly, he underwent echocardiography showing an atrioventricular septal defect typically associated to Down syndrome and never diagnosed earlier. The diagnosis of paradoxical embolisation was then supposed. Echocardiography also revealed a severe right heart section dilatation, with bidirectional shunt on the septal defects and systemic right heart pressure. Down patients affected by CHD are more prone to develop pulmonary vasculopathy than non-syndromic patients. In this case, the pulmonary vasculopathy was further exacerbated by the pulmonary embolism and by the late diagnosis of CHD. Finally, an appropriate timely diagnosis of atrioventricular septal defect could potentially avoid the neurological complication in this patient.

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.

Background: The itAlian pRospective Study on CANGrELOr (ARCANGELO) was aimed to assess the safety of using cangrelor during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) in the daily practice. Hypothesis: The safety of cangrelor after the transition to oral P2Y12 inhibitors was evaluated as the incidence of bleeding outcomes in the 30 days following PCI according to postauthorization safety study guidelines. Methods: Adults with ACS who were treated with cangrelor in one of the 28 centers involved in the study. Patients who consented to participate were followed in the 30 days following their PCI. Bleedings (Bleeding Academic Research Consortium [BARC] classification), major adverse cardiac events (MACEs), and adverse events were recorded. The interim results at two-thirds of the enrollment period are presented. Results: A total of 17 bleedings were observed in the 320 patients who completed the study at this stage. All bleedings were classified as BARC Type 1–2, except for one case of Type 3a (vessel puncture site hematoma). Four patients experienced MACEs (2 acute myocardial infarctions, 1 sudden cardiac death, 1 noncardiovascular death due to respiratory distress, and multiorgan failure). None of the bleedings was rated as related to cangrelor. Conclusions: The interim results of the ARCANGELO study provide a preliminary confirmation that the use of cangrelor on patients with ACS undergoing PCI is not associated with severe bleedings.

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. Graphical abstract

Background The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. Objectives The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of “at-risk” patient cohorts for failure to present or delays to treatment. Methods This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. Results A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p, Central Illustration

Background Current guidelines recommend intensified platelet inhibition by prasugrel or ticagrelor in patients with unstable angina (UA) or non-ST-segment elevation (NSTE) myocardial infarction (MI). Objectives This study sought to investigate the benefits and risks of ticagrelor as compared with prasugrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and planned invasive management. Methods This post hoc analysis combines the pre-specified subgroups of UA and NSTEMI of the randomized ISAR-REACT 5 trial. It included 1,179 patients assigned to ticagrelor and 1,186 assigned to prasugrel. Ticagrelor was started immediately after randomization and prasugrel after coronary angiography. The primary endpoint was a composite of death, MI, or stroke during 1-year follow-up, and the safety endpoint was Bleeding Academic Research Consortium class 3–5. Results The primary endpoint was reached in 101 (8.7%) patients in the ticagrelor and in 73 (6.3%) patients in the prasugrel group (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.04 to 1.90). The HR for all-cause death was 1.43 (95% CI: 0.93 to 2.21) and that for MI 1.43 (95% CI: 0.94 to 2.19). The safety endpoint occurred in 49 (5.2%) patients in the ticagrelor and in 41 (4.7%) patients in the prasugrel group (HR: 1.09; 95% CI: 0.72 to 1.65). Landmark analysis revealed persistence of the efficacy advantage with prasugrel after the first month. Conclusions In patients with NSTE-ACS, we found that prasugrel was superior to ticagrelor in reducing the combined 1-year risk of death, MI, and stroke without increasing the risk of bleeding. Due to the post hoc nature of the analysis, these findings need confirmation by further studies. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome; NCT01944800 )

Objectives The aim of this study was to assess the efficacy and safety of ticagrelor versus prasugrel in patients with diabetes mellitus (DM) presenting with acute coronary syndromes (ACS)...

The so-called "smoking paradox", conditioning lower mortality in smokers among STEMI patients, has seldom been addressed in the settings of modern primary PCI protocols. The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry addressing in-hospital mortality, reperfusion, and 30-day mortality among primary PCI patients in the era of the COVID-19 pandemic. Among the 16,083 STEMI patients, 6819 (42.3%) patients were active smokers, 2099 (13.1%) previous smokers, and 7165 (44.6%) non-smokers. Despite the impaired preprocedural recanalization (p < 0.001), active smokers had a significantly better postprocedural TIMI flow compared with non-smokers (p < 0.001); this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. Active smokers had a significantly lower in-hospital (p < 0.001) and 30-day (p < 0.001) mortality compared with non-smokers and previous smokers; this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. In conclusion, in our population, active smoking was significantly associated with improved epicardial recanalization and lower in-hospital and 30-day mortality compared with previous and non-smoking history.

Aims To assess whether the efficacy and safety of ticagrelor vs. prasugrel in patients with acute coronary syndromes (ACSs) are influenced by pre-admission treatment with aspirin and/or clopidogrel. Methods and results Patients (n = 4018) were categorized into two groups: pre-admission aspirin and/or clopidogrel group (n = 1455) and no pre-admission aspirin or clopidogrel group (n = 2563). The primary endpoint was the composite of all-cause death, myocardial infarction, or stroke; the secondary safety endpoint was Bleeding Academic Research Consortium (BARC) type 3–5 bleeding, both at 1 year. Patients in the pre-admission aspirin and/or clopidogrel group had a higher risk of ischaemic events, but a similar risk of bleeding to patients in the no pre-admission aspirin or clopidogrel group (cumulative incidences 10.5% vs. 6.7%, and 5.7% vs. 5.7%, respectively). The primary endpoint occurred in 81/717 patients assigned to ticagrelor and 69/738 patients assigned to prasugrel in the pre-admission aspirin and/or clopidogrel group [11.5% vs. 9.5%; hazard ratio (HR) = 1.23; 95% confidence interval (CI) 0.89–1.69], and in 103/1295 patients assigned to ticagrelor and 68/1268 patients assigned to prasugrel in the no pre-admission aspirin or clopidogrel group [8.0% vs. 5.4%; HR = 1.50 (1.10–2.03); Pint = 0.38]. BARC type 3–5 bleeding events did not differ between ticagrelor and prasugrel in patients in the pre-admission aspirin and/or clopidogrel (6.2% vs. 4.5%) or no pre-admission aspirin or clopidogrel (5.3% vs. 5.1%) group (Pint = 0.54). Conclusion In patients with ACS, pre-admission therapy with aspirin and/or clopidogrel has no influence on the relative efficacy and safety of ticagrelor and prasugrel.

BACKGROUND Whether there are differences in the risk profile and treatment effect in patients recruited in a low recruitment center (LRC) versus patients recruited in a high recruitment center (HRC) in a randomized multicenter trial remains unknown. METHODS AND RESULTS This study included 4018 patients with acute coronary syndrome recruited in the ISAR‐REACT 5 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5) trial. The primary end point was a composite of all‐cause death, myocardial infarction, or stroke. Overall, 3011 patients (75%) were recruited in the HRCs (7 centers recruiting 258 to 628 patients; median, 413 patients) and 1007 patients (25%) were recruited in the LRCs (16 centers recruiting 5 to 201 patients; median, 52 patients). Patients recruited in the LRCs had more favorable cardiovascular risk profiles than patients recruited in the HRCs. The primary end point occurred in 72 patients in the LRCs and 249 patients in the HRCs (cumulative incidence, 7.3% and 8.4%; P =0.267). All‐cause mortality was lower among patients recruited in the LRCs (n=29) than among patients recruited in the HRCs (n=134; cumulative incidence 2.9% versus 4.5%; P =0.031). There was no significant interaction between the treatment effect of ticagrelor versus prasugrel and patient recruitment category (LRC versus HRC) regarding the primary efficacy end point (LRC: hazard ratio [HR], 1.42 [95% CI, 0.89–2.28]; HRC: HR, 1.33 [95% CI, 1.04−1.72]; P for interaction=0.800). CONCLUSIONS Patients with acute coronary syndrome recruited in a LRC appear to have more favorable cardiovascular risk profiles and lower 1‐year mortality rates compared with patients recruited in a HRC. The recruitment volume did not interact with the treatment effect of ticagrelor versus prasugrel. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01944800.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensin-converting-enzyme (ACE)2 and patient's susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment.Methods: The ISACS-STEMI COVID-19 registry retrospectively assessed STEMI patients treated with primary percutaneous coronary intervention (PPCI) in March/June 2019 and 2020 in 109 European high-volume primary PCI centers. This subanalysis assessed the prognostic impact of chronic RASI therapy at admission on mortality and SARS-CoV2 infection among diabetic patients.Results: Our population is represented by 3812 diabetic STEMI patients undergoing mechanical reperfusion, 2038 in 2019 and 1774 in 2020. Among 3761 patients with available data on chronic RASI therapy, between those ones with and without treatment there were several differences in baseline characteristics, (similar in both periods) but no difference in the prevalence of SARS-CoV2 infection (1.6% vs 1.3%, respectively, p = 0.786). Considering in-hospital medication, RASI therapy was overall associated with a significantly lower in-hospital mortality (3.3% vs 15.8%, p < 0.0001), consistently both in 2019 and in 2010.Conclusions: This is first study to investigate the impact of RASI therapy on prognosis and SARS-CoV2 infection of diabetic patients experiencing STEMI and undergoing PPCI during the COVID-19 pandemic. Both pre-admission chronic RASI therapy and in-hospital RASI did not negatively affected patients' survival during the hospitalization, neither increased the risk of SARS-CoV2 infection.Trial registration number: NCT04412655.

Background The efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with acute coronary syndromes (ACS) are not known. Purpose The aim of this study was to assess the efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with ACS undergoing invasive evaluation. Methods This pre-specified analysis of the ISAR-REACT 5 trial included 1349 smokers and 2652 nonsmokers randomised to receive ticagrelor or prasugrel. The primary endpoint was the incidence of death, myocardial infarction, or stroke; the secondary endpoint was the incidence of Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding. Both endpoints were assessed at 12 months after randomisation. Results There was no significant treatment arm-by-smoking status interaction regarding the efficacy outcome. The primary endpoint occurred in 47 patients (7.0%) in the ticagrelor group and 41 patients (6.2%) in the prasugrel group in smokers (hazard ratio [HR]=1.15; 95% confidence interval [CI] 0.76–1.75; P=0.510) and in 133 patients (10.2%) in the ticagrelor group and 94 patients (7.2%) in the prasugrel group in nonsmokers (HR=1.44 [1.10–1.87], P=0.007; Pint=0.378). The secondary endpoint occurred in 27 patients (4.6%) in the ticagrelor group and 33 patients (5.6%) in the prasugrel group in smokers (HR=0.81 [0.49–1.35]; P=0.412) and in 66 patients (6.0%) in the ticagrelor group and 46 patients (4.4%) in the prasugrel group in nonsmokers (HR=1.38 [0.94–2.01]; P=0.097). Conlusions Although there was no significant interaction between smoking and treatment effect, the present findings suggest a greater advantage of prasugrel over ticagrelor in nonsmoker vs. smoker patients with ACS. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Centre for Cardiovascular Research;Deutsches Herzzentrum München, Germany

Background The efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unknown. Purpose To assess the efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to BMI. Methods This post-hoc analysis of the ISAR-REACT 5 trial included 3987 patients with BMI data available. BMI was grouped in 3 categories: low (BMI Results There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (Pint=0.578). However, the primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the low BMI group (11.7% vs. 7.5%; hazard ratio [HR]=1.62; 95% confidence interval [CI], 1.09–2.42; P=0.018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the intermediate BMI group (8.3% vs. 6.2%; HR=1.36 [0.97–1.91]; P=0.076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the high BMI group (8.6% vs. 7.3%; HR=1.18 [0.76–1.84]; P=0.451). BARC type 3 to 5 bleeding events did not differ between ticagrelor and prasugrel in patients with low (6.5% vs. 6.6%), intermediate (5.6% vs. 5.0%), or high (4.4% vs. 2.8%) BMI. Conclusions BMI of patients with ACS did not impact significantly on the treatment effect of ticagrelor vs. prasugrel in terms of both efficacy and safety. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Center for Cardiovascular Research;Deutsches Herzzentrum München, Germany

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)

Background and aims SARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Methods We selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1st until April 30th, in 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure. Results Our population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or the modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p, Graphical abstract Image 1

The efficacy and safety of ticagrelor vs prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unstudied. We assessed the efficacy and safety of ticagrelor vs prasugrel in patients with ACS according to BMI.Patients (n=3987) were grouped into 3 categories: normal weight (BMI 25kg/mThe primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the normal weight group (11.7% vs 7.5%; HR, 1.62; 95%CI, 1.09-2.42; P=.018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the overweight group (8.3% vs 6.2%; HR, 1.36; 95%CI, 0.97-1.91; P=.076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the obesity group (8.6% vs 7.3%; HR, 1.18; 95%CI, 0.76-1.84; P=.451). The 1-year incidence of bleeding events did not differ between ticagrelor and prasugrel in patients with normal weight (6.5% vs 6.6%; P=.990), overweight (5.6% vs 5.0%; P=.566) or obesity (4.4% vs 2.8%; P=.219). There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (PIn patients with ACS, BMI did not significantly impact the treatment effect of ticagrelor vs prasugrel in terms of efficacy or safety.NCT01944800.

Importance It is unclear whether ticagrelor or prasugrel hydrochloride is superior for patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Objective To assess the safety and efficacy of ticagrelor vs prasugrel for patients with ACS treated with PCI. Design, Setting, and Participants A prespecified analysis was performed of a postrandomization subgroup of 3377 patients who presented with ACS and were treated with PCI in the investigator-initiated, multicenter, phase 4, open-label Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5 randomized clinical trial, conducted from September 1, 2013, to February 28, 2018. Statistical analysis was performed from September 1, 2020, to January 30, 2021. Analysis was performed according to the intention-to-treat principle. Interventions Patients were randomly assigned to a ticagrelor-based or prasugrel-based strategy. This analysis focuses on the subgroup of patients who underwent PCI that was formed after randomization. Main Outcomes and Measures The primary end point was a composite consisting of all-cause death, myocardial infarction, or stroke at 12 months. The safety end point was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding. Results The ticagrelor group comprised 1676 patients (1323 men [78.9%]; mean [SD] age, 64.4 [12.0] years), and the prasugrel group comprised 1701 patients (1341 men [78.8%]; mean [SD] age, 64.7 [12.0] years). The primary end point occurred for 162 patients (9.8%) in the ticagrelor group and 120 patients (7.1%) in the prasugrel group (hazard ratio [HR], 1.41; 95% CI, 1.11-1.78;P = .005). Myocardial infarction occurred in 88 patients (5.3%) in the ticagrelor group compared with 55 patients (3.8%) in the prasugrel group (HR, 1.67; 95% CI, 1.19-2.34;P = .003). The safety end point, BARC type 3 to 5 bleeding, occurred in 84 of 1672 patients (5.3%) in the ticagrelor group and 78 of 1680 patients (4.9%) in the prasugrel group (HR; 1.10; 95% CI, 0.81-1.50;P = .54). Conclusions and Relevance Among patients presenting with ACS who were treated with PCI, the incidence of the primary composite end point occurred less frequently for patients who received prasugrel compared with those who received ticagrelor. The incidence of bleeding events was comparable between the 2 groups. These results suggest that, for patients presenting with ACS who undergo PCI, a prasugrel-based strategy is superior to a ticagrelor-based strategy. However, because these observations are based on a postrandomization subgroup, these findings should be regarded as hypothesis generating and dedicated randomized clinical trials may be warranted to confirm these findings. Trial Registration ClinicalTrials.gov Identifier:NCT01944800

Background: The comparative efficacy and safety of ticagrelor and prasugrel in patients with acute coronary syndrome undergoing complex percutaneous coronary intervention (PCI) has not been defined. Methods: This post hoc analysis included all patients with acute coronary syndrome treated with PCI and randomized to either ticagrelor or prasugrel in the ISAR-REACT 5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment). Complex PCI was defined as at least one of the following: multivessel PCI, ≥3 stents implanted, ≥3 lesions treated, and total stented length >60 mm. The primary efficacy end point was the composite of all-cause death, myocardial infarction, or stroke; the safety end point was Bleeding Academic Research Consortium types 3 to 5 bleeding. Outcomes were assessed out to 12 months after randomization. Results: Among the 3377 patients treated with PCI in the ISAR-REACT 5 trial, 1429 underwent complex PCI (ticagrelor, N=696 and prasugrel, N=733) and 1948 underwent noncomplex PCI (ticagrelor, N=980 and prasugrel, N=968). There was no interaction between PCI complexity, assignment to either ticagrelor or prasugrel, and the primary efficacy or safety end points ( P for interaction: ≥0.13). In the complex PCI group, the primary efficacy end point (11.0% versus 9.2%, hazard ratio: 1.19 [0.85–1.66], P =0.303) and the safety end point (5.2% versus 6.1%, hazard ratio: 0.83 [0.53–1.31], P =0.419) were not statistically different in patients receiving either ticagrelor or prasugrel. In the noncomplex PCI group, the primary efficacy end point occurred more frequently in patients assigned to ticagrelor as compared to prasugrel (8.9% versus 5.5%, hazard ratio: 1.66 [1.18–2.34], P =0.004) without significant difference in terms of the safety end point (5.4% versus 4.1%, hazard ratio: 1.41 [0.92–2.17], P =0.110). Conclusions: In patients with acute coronary syndrome, PCI complexity does not influence the comparative efficacy and safety of ticagrelor and prasugrel. The observed comparable performance of ticagrelor and prasugrel in patients with acute coronary syndrome undergoing complex PCI requires further confirmation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01944800.

Background: Concerns have been raised on a potential interaction between renin-angiotensin system inhibitors (RASI) and the susceptibility to coronavirus disease 2019 (COVID-19). No data have been so far reported on the prognostic impact of RASI in patients suffering from ST-elevation myocardial infarction (STEMI) during COVID-19 pandemic, which was the aim of the present study. Methods: STEMI patients treated with primary percutaneous coronary intervention (PPCI) and enrolled in the ISACS-STEMI COVID-19 registry were included in the present sub-analysis and divided according to RASI therapy at admission. Results: Our population is represented by 6095 patients, of whom 3654 admitted in 2019 and 2441 in 2020. No difference in the prevalence of SARSCoV2 infection was observed according to RASI therapy at admission (2.5% vs 2.1%, p = 0.5), which was associated with a significantly lower mortality (adjusted OR [95% CI]=0.68 [0.51 & ndash;0.90], P = 0.006), confirmed in the analysis restricted to 2020 (adjusted OR [95% CI]=0.5[0.33 & ndash;0.74], P = 0.001). Among the 5388 patients in whom data on in-hospital medication were available, in-hospital RASI therapy was associated with a significantly lower mortality (2.1% vs 16.7%, OR [95% CI]=0.11 [0.084 & ndash;0.14], p < 0.0001), confirmed after adjustment in both periods. Among the 62 SARSCoV-2 positive patients, RASI therapy, both at admission or in-hospital, showed no prognostic effect. Conclusions: This is the first study to investigate the impact of RASI therapy on the prognosis and SARSCoV2 infection of STEMI patients undergoing PPCI during the COVID-19 pandemic. Both pre-admission and in-hospital RASI were associated with lower mortality. Among SARSCoV2-positive patients, both chronic and in-hospital RASI therapy showed no impact on survival.

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 mul...

AIM Sex-specific analyses of direct head-to-head comparisons between newer P2Y12 inhibitors are limited. This study was conducted to assess the efficacy and safety of ticagrelor versus prasugrel in women and men with acute coronary syndromes (ACS) planned for an invasive strategy. METHODS This pre-specified analysis of the ISAR-REACT 5 trial included 956 women and 3,062 men with ACS randomly assigned to either ticagrelor or prasugrel. The primary endpoint was the 12-month incidence of death, myocardial infarction, or stroke; the safety endpoint was the 12-month incidence of bleeding (type 3-5 according to the Bleeding Academic Research Consortium [BARC]). RESULTS The primary endpoint occurred in 42 women (8.9%) in the ticagrelor group and 39 women (8.3%) in the prasugrel group (hazard ratio [HR]=1.10, 95% confidence interval [CI] 0.71-1.70, P=0.657) and in 142 men (9.4%) in the ticagrelor group and 98 men (6.5%) in the prasugrel group (HR=1.47 [1.13-1.90], P=0.004; P for interaction [Pint]=0.275). BARC type 3-5 bleeding occurred in 36 women (9.7%) in the ticagrelor group and 34 women (9.7%) in the prasugrel group (HR=1.04 [0.65-1.67], P=0.856) and in 59 men in the ticagrelor group (4.4%) and 46 men (3.6%) in the prasugrel group (HR=1.24 [0.85-1.83], P=0.266; Pint=0.571). CONCLUSIONS Although there was no significant interaction between sex and treatment effect of study drugs, the superior efficacy of prasugrel was more evident among men. No difference in bleeding between the two study groups was seen for both women and men.

Background It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes–ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. Methods The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. Results A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73–0.85, p p p Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients. Conclusions The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic. Trial registration number: NCT 04412655.

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 Munchen.

Objectives The aim of this study was to identify independent correlates of very late scaffold thrombosis (VLST) from an analysis of consecutively treated patients from 15 multicenter studies. Background Recent analyses suggest an increased risk for VLST with the Absorb Bioresorbable Vascular Scaffold compared with drug-eluting stents, but insights as to correlates of risk are limited. Methods A total of 55 patients were identified with scaffold thrombosis. They were matched 2:1 with control subjects selected randomly from patients without thrombosis from the same study. Quantitative coronary angiography was available for 96.4% of patients. Multiple logistic and Cox regression analysis were used to identify significant independent outcome correlates from 6 pre-specified characteristics. Results Patients had scaffold thrombosis at a median of 20 months (interquartile range: 17 to 27 months). Control subjects were followed for 36 months (interquartile range: 24 to 38 months). For the combined groups, reference vessel diameter (RVD) was 2.84 ± 0.50 mm, scaffold length was 26 ± 16 mm, and post-dilatation was performed in 56%. Univariate correlates of thrombosis were smaller nominal scaffold/RVD ratio (linear p = 0.001; ratio 2.72 mm; odds ratio: 3.4; p = 0.001). Post-dilatation at ≥16 atm, post-dilatation balloon/scaffold ratio, final percentage stenosis, and dual antiplatelet therapy were not correlated with VLST. Only scaffold/RVD ratio remained a significant independent correlate of VLST (p = 0.001), as smaller ratio was correlated with RVD (p Conclusions In the present analysis, the largest to date of its type, relative scaffold undersizing was the strongest determinant of VLST. Given current understanding of “scaffold dismantling,” this finding likely has ramifications for all bioresorbable scaffolds.

Monitoring respiratory rate (RR) is recommended at the time of hospital presentation for acute decompensation in heart failure (HF). Device-based continuous monitoring of RR may be helpful for diagnostic and prognostic stratification after implantable cardioverter-defibrillator (ICD) implantation. This study was undertaken to analyze short- and long-term changes in ICD-measured RR and to relate RR with the patient's clinical status and the occurrence of HF events.One hundred twenty-four consecutive HF patients who received ICD endowed with this diagnostic capability (Boston Scientific Inc., Natick, MA, USA) were prospectively enrolled. Patients were followed up for 12 months.At the baseline, the proportion of New York Heart Association (NYHA) class III-IV was higher among patients with daily maximum RR27 breaths/min (third tertile) than those with24 breaths/min (first tertile) (43 vs. 23%, p 0.05). Moreover, the ejection fraction was lower (27 ± 7 vs. 34 ± 8%, p 0.05). In patients with HF hospitalizations (33 events) and urgent visits for HF (15 events), the weekly average of RR calculated over the 7 days preceding hospital accesses did not differ from values recorded at the baseline and before scheduled follow-up visits. However, the weekly variation in RR (i.e., the difference between maximum and minimum values collected over the week) was significantly higher prior to hospitalization (p 0.05). A weekly variation3 breaths/min in maximum RR predicted an impending hospital admission for HF with sensitivity of 73 % and specificity of 57%.In this study, elevated values of ICD-monitored RR identified patients with worse functional status and lower systolic function. The weekly variation in RR increased before HF exacerbation. This monitoring technology may represent a useful tool in the clinical management of patients with HF.

The aim of this study was to identify independent correlates of very late scaffold thrombosis (VLST) from an analysis of consecutively treated patients from 15 multicenter studies.Recent analyses suggest an increased risk for VLST with the Absorb Bioresorbable Vascular Scaffold compared with drug-eluting stents, but insights as to correlates of risk are limited.A total of 55 patients were identified with scaffold thrombosis. They were matched 2:1 with control subjects selected randomly from patients without thrombosis from the same study. Quantitative coronary angiography was available for 96.4% of patients. Multiple logistic and Cox regression analysis were used to identify significant independent outcome correlates from 6 pre-specified characteristics.Patients had scaffold thrombosis at a median of 20 months (interquartile range: 17 to 27 months). Control subjects were followed for 36 months (interquartile range: 24 to 38 months). For the combined groups, reference vessel diameter (RVD) was 2.84 ± 0.50 mm, scaffold length was 26 ± 16 mm, and post-dilatation was performed in 56%. Univariate correlates of thrombosis were smaller nominal scaffold/RVD ratio (linear p = 0.001; ratio 1.18:1; odds ratio: 7.5; p = 0.002) and larger RVD (linear p = 0.001;2.72 mm; odds ratio: 3.4; p = 0.001). Post-dilatation at ≥16 atm, post-dilatation balloon/scaffold ratio, final percentage stenosis, and dual antiplatelet therapy were not correlated with VLST. Only scaffold/RVD ratio remained a significant independent correlate of VLST (p = 0.001), as smaller ratio was correlated with RVD (p 0.001). Post hoc analysis of 8 other potential covariates revealed no other correlates of outcome.In the present analysis, the largest to date of its type, relative scaffold undersizing was the strongest determinant of VLST. Given current understanding of "scaffold dismantling," this finding likely has ramifications for all bioresorbable scaffolds.

Aims To compare the efficacy and safety of drug-eluting stents vs. bare-metal stents in patients with acute ST-segment elevation myocardial infarction. Methods and results We performed a meta-analysis of eight randomized trials comparing drug-eluting stents (sirolimus-eluting or paclitaxel-eluting stents) with bare-metal stents in 2786 patients with acute ST-segment elevation myocardial infarction. All patients were followed up for a mean of 12.0–24.2 months. Individual data were available for seven trials with 2476 patients. The primary efficacy endpoint was the need for reintervention (target lesion revascularization). The primary safety endpoint was stent thrombosis. Other outcomes of interest were death and recurrent myocardial infarction. Drug-eluting stents significantly reduced the risk of reintervention, hazard ratio of 0.38 (95% CI, 0.29–0.50), P < 0.001. The overall risk of stent thrombosis: hazard ratio of 0.80 (95% CI, 0.46–1.39), P = 0.43; death: hazard ratio of 0.76 (95% CI, 0.53–1.10), P = 0.14; and recurrent myocardial infarction: hazard ratio of 0.72 (95% CI, 0.48–1.08, P = 0.11) was not significantly different for patients receiving drug-eluting stents vs. bare-metal stents. Conclusion The use of drug-eluting stents in patients with acute ST-segment elevation myocardial infarction is safe and improves clinical outcomes by reducing the risk of reintervention compared with bare-metal stents.

Item does not contain fulltext OBJECTIVES: The authors sought to identify and verify independent correlates of device thrombosis from an analysis of multicenter trials and registries. BACKGROUND: Recent analyses suggest an increased risk of device thrombosis with Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, California) implantation compared with metallic drug-eluting stents, and data from moderate size studies suggest a risk relationship to vessel size and technique. METHODS: From 8,771 consecutively treated patients, 105 patients (1.2%) were identified with scaffold thrombosis within 1 year of implantation. They were matched 2:1 with controls selected randomly from nonthrombosis patients. Data-restricted multiple logistic analysis was used to identify significant independent covariates of the outcome. RESULTS: Early (within 1 month) scaffold thrombosis occurred in 69 patients and late (1 to 12 months) thrombosis occurred in 36 patients. Modelling found significant correlations of thrombosis to be final minimal lumen diameter 1.1:1 balloon/scaffold ratio (OR: 2.3; p = 0.022), and reference vessel diameter

Aims The OPTI-MIND study aims to collect 2-year clinical outcomes of pacemaker patients in real-world clinical practice, overall and according to patient characteristics and pacemaker settings. Methods and results The present analysis of the OPTI-MIND study describes the programmed device settings after discharge from the pacemaker implant. The objective was to determine whether these settings fit recent guidelines for device-programmed physiological pacing based on the preservation of atrioventricular synchrony, avoiding unnecessary pacing, ensuring rate increase during exercise or preventing neurally mediated symptoms. A total of 1740 patients were enroled at 68 centres worldwide. Baseline patient characteristics and device programming settings are available in 1674 of 1740 patients (96%). Guidelines to ensure physiological pacing were followed in 41% of patients: in patients with sinus node disease (SND), and without atrioventricular block (AVB), device programming could have led to unnecessary right ventricular pacing in 38% of patients. In SND patients with chronotropic incompetence, assisted rate increase during exercise was not programmed in 42% of patients. In 11% of patients with AVB, atrioventricular (AV) synchrony was not pursued; the main drivers being advanced age and history of atrial fibrillation. Patients with both SND and AVB were generally programmed physiologically (87%). Conclusion The present analysis showed that frequent deviations occurred when comparing the device settings at discharge from the pacemaker implant in clinical practice to the available guidelines on pacing mode selection. Analysis of 2-year outcomes in the OPTI-MIND study will provide an insight into whether specific physiological settings could improve the quality of pacing with a positive effect on patient outcome.

Recent analyses suggest an increased risk of very late scaffold thrombosis (VLST) beyond 1 year after implantation of Absorb BVS compared to metallic DES, but insights as to correlates of risk emanate from a limited number of patients. We sought to identify and verify independent correlates of

INTRODUCTION AND OBJECTIVES: The performance of drug-eluting stents (DESs) in high-risk patients with diabetes and acute ST-elevation myocardial infarction (STEMI) who have undergone primary angioplasty has not been previously studied. The objective was to evaluate the efficacy and safety of DESs in diabetic patients with STEMI. METHODS: We performed a pooled analysis of individual patient data from seven randomized trials that compared DESs (i.e., sirolimus- or paclitaxel-eluting stents) with bare-metal stents (BMSs) in patients with STEMI. The analysis involved 389 patients with diabetes mellitus from a total of 2476 patients. The outcomes of interest were target-lesion revascularization, stent thrombosis, death and the composite endpoint of death or recurrent myocardial infarction during a follow-up of 12-24 months. RESULTS: Overall, 206 diabetic patients received a DES and 183, a BMS. The risk of target-lesion revascularization was significantly lower in patients treated with a DES compared to those treated with a BMS (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.23-0.88; P=.02). There was no significant difference in the risk of stent thrombosis between those treated with a DES or a BMS (HR 0.33, 95% CI 0.09-1.13; P=.08). Similarly, the risk of the combined endpoint of death or myocardial infarction was not significantly different between patients treated with a DES or a BMS (HR 0.64, 95% CI 0.36-1.13; P=.12). CONCLUSIONS: Compared with BMSs, DES use improved clinical outcomes in diabetic patients undergoing primary angioplasty for STEMI: the need for reintervention was reduced, with no increase in mortality or myocardial infarction.

Introduccion y objetivos. Los resultados obtenidos con los stents liberadores de farmacos (SLF) en el grupo de pacientes de alto riesgo formado por los pacientes diabeticos con infarto agudo de miocardio con elevacion del segmento ST (IAMCEST) tratados con angioplastia primaria no se han estudiado con anterioridad. Nuestro objetivo fue evaluar la eficacia y la seguridad de los SLF en pacientes diabeticos con IAMCEST. Metodos. Llevamos a cabo un analisis combinado de los datos de pacientes individuales de siete ensayos aleatorizados en los que se comparo el empleo de stents liberadores de sirolimus o de paclitaxel (SLF) con el de stents convencionales (SC) en el contexto de un IAMCEST. Se incluyo en este analisis a 389 pacientes con diabetes mellitus de un grupo total de 2.476. Los objetivos del estudio fueron la revascularizacion de la lesion diana, la trombosis del stent, la muerte y la variable combinada de muerte o infarto de miocardio recurrente durante un periodo de seguimiento de 12-24 meses. Resultados. Hubo 206 pacientes diabeticos tratados con SLF y 183 tratados con SC. El riesgo de que se practicara una revascularizacion de la lesion diana fue significativamente inferior en los pacientes tratados con SLF en comparacion con los pacientes tratados con SC (razon de riesgos [HR] = 0,44; intervalo de confianza [IC] del 95%, 0,23-0,88; p = 0,02). El riesgo de trombosis del stent no presento diferencias significativas entre los pacientes tratados con SLF y los tratados con SC (HR = 0,33; IC del 95%, 0,09-1,13; p = 0,08). De forma analoga, el riesgo de la variable de valoracion combinada formada por la muerte y el infarto de miocardio no presento diferencias significativas entre los pacientes tratados con SLF y los tratados con SC (HR = 0,64; IC del 95%, 0,36-1,13; p = 0,12). Conclusiones. En comparacion con los SC, los SLF mejoran los resultados clinicos en los pacientes diabeticos a los que se practica una angioplastia primaria por un IAMCEST, al reducir la necesidad de reintervencion sin incrementar la tasa de mortalidad o infarto de miocardio.

Recent concerns have emerged on the potential higher risk of stent thrombosis after DES implantation, that might be even more pronounced among STEMI patients. Thus, the aim of the current study was to perform a meta-analysis to evaluate the benefits and safety of DES as compared to BMS in patients undergoing primary angioplasty for STEMI.The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of DES for STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher, paclitaxel-eluting stent (PES), Taxus. Information on study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were extracted by two investigators. Disagreements were resolved by consensus.A total of 11 trials were included in the meta-analysis, involving 3605 patients (1888 or 52.3% randomized to DES and 1719 or 47.7% randomized to BMS). At 12 months follow-up, no significant difference was observed in mortality (4.1% vs 4.4%, OR [95% CI]=0.91 [0.66-1.27], p=0.59, reinfarction (3.1% vs 3.4%, OR [95% CI]=0.85 [0.58, 1.23], p=0.38 or stent thrombosis (1.6% vs 2.2%, OR [95% CI]=0.76 [0.47, 1.23], p=0.22), whereas DES were associated with a significant reduction in TVR (5.0% vs 12.6%, OR [95% CI]=0.36 [0.28, 0.47], p0.0001). Safety and efficacy of DES were confirmed at 18 to 24 months follow-up (data available from 4 trials including 1178 patients).This meta-analysis shows that among selected STEMI patients undergoing primary angioplasty, SES and PES, as compared to BMS, are safe and associated with a significant reduction in TVR at 1 and 2 years follow-up.