Immediate versus staged complete revascularisation in patients presenting with acute coronary syndrome and multivessel coronary disease (BIOVASC): a prospective, open-label, non-inferiority, randomised trial.

BACKGROUND: In patients with acute coronary syndrome and multivessel coronary disease, complete revascularisation by percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. We aimed to investigate whether PCI for non-culprit lesions should be attempted during the index procedure or staged. METHODS: This prospective, open-label, non-inferiority, randomised trial was done at 29 hospitals across Belgium, Italy, the Netherlands, and Spain. We included patients aged 18-85 years presenting with ST-segment elevation myocardial infarction or non-ST-segment elevation acute coronary syndrome and multivessel (ie, two or more coronary arteries with a diameter of 2·5 mm or more and ≥70% stenosis based on visual estimation or positive coronary physiology testing) coronary artery disease with a clearly identifiable culprit lesion. A web-based randomisation module was used to randomly assign patients (1:1), with a random block size of four to eight, stratified by study centre, to undergo immediate complete revascularisation (PCI of the culprit lesion first, followed by other non-culprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularisation (PCI of only the culprit lesion during the index procedure and PCI of all non-culprit lesions deemed to be clinically significant by the operator within 6 weeks after the index procedure). The primary outcome was the composite of all-cause mortality, myocardial infarction, any unplanned ischaemia-driven revascularisation, or cerebrovascular events at 1 year after the index procedure. Secondary outcomes included all-cause mortality, myocardial infarction, and unplanned ischaemia-driven revascularisation at 1 year after the index procedure. Primary and secondary outcomes were assessed in all randomly assigned patients by intention to treat. Non-inferiority of immediate to staged complete revascularisation was considered to be met if the upper boundary of the 95% CI of the hazard ratio (HR) for the primary outcome did not exceed 1·39. This trial is registered with ClinicalTrials.gov, NCT03621501. FINDINGS: Between June 26, 2018, and Oct 21, 2021, 764 patients (median age 65·7 years [IQR 57·2-72·9] and 598 [78·3%] males) were randomly assigned to the immediate complete revascularisation group and 761 patients (median age 65·3 years [58·6-72·9] and 589 [77·4%] males) were randomly assigned to the staged complete revascularisation group, and were included in the intention-to-treat population. The primary outcome at 1 year occurred in 57 (7·6%) of 764 patients in the immediate complete revascularisation group and in 71 (9·4%) of 761 patients in the staged complete revascularisation group (HR 0·78, 95% CI 0·55-1·11, pnon-inferiority=0·0011). There was no difference in all-cause death between the immediate and staged complete revascularisation groups (14 [1·9%] vs nine [1·2%]; HR 1·56, 95% CI 0·68-3·61, p=0·30). Myocardial infarction occurred in 14 (1·9%) patients in the immediate complete revascularisation group and in 34 (4·5%) patients in the staged complete revascularisation group (HR 0·41, 95% CI 0·22-0·76, p=0·0045). More unplanned ischaemia-driven revascularisations were performed in the staged complete revascularisation group than in the immediate complete revascularisation group (50 [6·7%] patients vs 31 [4·2%] patients; HR 0·61, 95% CI 0·39-0·95, p=0·030). INTERPRETATION: In patients presenting with acute coronary syndrome and multivessel disease, immediate complete revascularisation was non-inferior to staged complete revascularisation for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischaemia-driven revascularisation. FUNDING: Erasmus University Medical Center and Biotronik.

Colchicine in Patients with Chronic Coronary Disease.

BACKGROUND: Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited. METHODS: In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke. RESULTS: A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31). CONCLUSIONS: In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).

Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. METHODS: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. RESULTS: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. CONCLUSION: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. TRIAL REGISTRATION NUMBER: NCT04412655 (2nd June 2020).

Impact of COVID-19 pandemic and diabetes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry.

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 < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78-0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. 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: NCT04412655.

Recurrent Myocardial Infarction After Primary Percutaneous Coronary Intervention in Multivessel Coronary Disease Is Primarily Related to Stent Failure: Post-Hoc Analysis of the PASSION Trial.

OBJECTIVES: Our aim was to investigate the risk of events related to non-culprit lesions after primary percutaneous coronary intervention (PCI) in patients with multivessel coronary disease (MVD). BACKGROUND: In patients undergoing primary PCI for ST-elevation myocardial infarction (STEMI) who are diagnosed with MVD, the optimal treatment strategy is currently under debate. Although observational data exposed an increased risk of multivessel PCI in the acute phase of STEMI, 2 recently published randomized controlled trials showed a reduction of death or recurrent myocardial infarction (MI) after preventive PCI of non-culprit lesions when compared with culprit-lesion PCI only. METHODS: We performed a post-hoc analysis of 279 patients with MVD included in the Paclitaxel-Eluting Stent versus Conventional Stent in Myocardial Infarction with ST-Segment Elevation (PASSION) trial. We analyzed the incidence and cause of recurrent MI. Recurrent MI due to stent failure was assumed in the event of definite or probable stent thrombosis. RESULTS: After 5 years, 14 patients (5.7%) with MVD had a recurrent MI versus 17 (5.4%) patients with 1-vessel disease (HR 1.06, 95%CI 0.52-2.15, P = 0.87). The majority of events was attributable to stent failure, while of the remaining 6 events, only 1 was proven to originate from a lesion that was judged significant at enrolment. CONCLUSIONS: In this post-hoc analysis of the PASSION trial, recurrent MI in patients with MVD was mainly related to stent failure rather than a new event originating from a significant stenosis in a non-culprit coronary artery.

Paclitaxel-eluting versus bare metal stents in primary PCI: a pooled patient-level meta-analysis of randomized trials.

Concerns have emerged regarding a higher risk of stent thrombosis after drug-eluting stent (DES) implantation, especially in the setting of ST-segment elevation myocardial infarction (STEMI). Therefore, we performed a meta-analysis based on individual patient data to evaluate long-term safety and effectiveness of paclitaxel-eluting stent (PES) as compared to bare metal stents (BMS) in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. We examined all completed randomized trials on PES for STEMI. Individual patient data were obtained from six trials. We performed survival analyses with the use of Cox-regression analysis stratified according to trial. Kaplan-Meier survival curves are presented with event rates reported as estimated probabilities. A subsequent landmark analysis was performed for patients who were event-free at 1-year follow-up in order to define outcome in terms of early (≤1 year) and late (>1 year) events. A total of six trials were finally included in the meta-analysis with 4435 patients, 2875 (64.8 %) assigned to PES and 1560 (35.2 %) to BMS. No significant differences in baseline characteristics were observed between the two groups. However, a significantly higher percentage of patients in the DES group were on dual antiplatelet therapy during 3-year follow-up, as compared to BMS. At long-term follow-up (1,095 [1,090-1,155] days), no significant difference between PES and BMS was observed in mortality (9.2 vs 11.9 %, respectively, HR [95 % CI] = 0.84 [0.67, 1.06], p = 0.15, pheterogeneity = 0.59), reinfarction (8.8 vs 7 %, respectively; HR [95 % CI] = 1.10 [0.84, 1.44], p = 0.51, pheterogeneity = 0.32), stent thrombosis (6.7 vs 4.0 % respectively, HR [95 % CI] = 1.13 [0.82, 1.55], p = 0.45, pheterogeneity = 0.99) and TVR (11.9 vs 20.0 %; HR [95 % CI] = 0.64 [0.54, 0.77], p < 0.0001, pheterogeneity = 0.25). Landmark analysis showed that PES was associated with a significantly higher rate of very late reinfarction (>1 year) (5.6 vs 3.9 %, HR [95 % CI] = 1.61 [1.05-2.47], p = 0.03, pheterogeneity = 0.51], very late ST (2.9 vs 1.1 %, HR [95 % CI] = 1.88 [1.00-3.54], p = 0.05, pheterogeneity = 0.94]. The present pooled patient-level meta-analysis demonstrates that among STEMI patients undergoing primary PCI, PES compared to BMS is associated with a significant reduction in TVR at long-term follow-up. Although there were no differences in cumulative mortality, reinfarction or stent thrombosis, the incidence of very late reinfarction and stent thrombosis was increased with PES.

Randomized Comparison of Novel Low-Dose Sirolimus-Eluting Biodegradable Polymer Stent vs Second-Generation DES: TARGET-IV NA Trial.

BACKGROUND: Drug-eluting stents (DESs) with controlled antiproliferative drug release reduce restenosis risk, but durable polymers can delay healing and inhibit reendothelialization. The Firehawk biodegradable polymer sirolimus-eluting stent (BP-SES) has a fully biodegradable sirolimus-containing polymer coating localized to recessed abluminal grooves on the stent surface and delivers roughly one-third the drug dose of other DESs. OBJECTIVES: We report the primary results of the TARGET-IV NA (Firehawk Rapamycin Target Eluting Coronary Stent North American Trial) randomized controlled trial comparing clinical outcomes with BP-SES vs currently used second-generation DESs. METHODS: The TARGET-IV NA study was a prospective, multicenter, single-blind, 1:1 randomized noninferiority trial comparing the BP-SES with control in North America and Europe among patients undergoing percutaneous coronary intervention for chronic or acute coronary syndromes. The primary endpoint was target lesion failure (TLF) at 12 months (composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization). The primary analysis (intention-to-treat) tested noninferiority of BP-SES vs control using an absolute margin of 3.85% and 1-sided α of 0.025. Noninferiority-powered secondary endpoints were tested in an optical coherence tomography substudy (endpoint: mean neointimal hyperplasia thickness) and an angiography substudy (endpoint: in-stent late lumen loss). RESULTS: A total of 1,720 patients (mean age 66 years; 74% male) with 2,159 lesions were randomly allocated to receive either BP-SES (860 patients, 1,057 lesions) or control second-generation DES (860 patients, 1,084 lesions). A total of 61% of patients presented with stable coronary disease, 32% had unstable angina, and 7% had non-ST-segment elevation myocardial infarction (NSTEMI) or recent ST-segment elevation myocardial infarction. The rate of TLF with BP-SES was noninferior to control at 12 months (3.4% vs 3.3%, absolute risk difference 0.13%, upper bound 97.5% CI: 2.03, Pnoninferiority < 0.0001). Cardiac death, myocardial infarction, and stent thrombosis rates were similar between groups. Angiographic follow-up was available in 104 patients (97.2% of those enrolled in the angiographic substudy) and 128 (94.1%) lesions. At 13 months, the powered secondary endpoint of mean in-stent late lumen loss was 0.149 ± 0.263 mm for BP-SES and 0.327 ± 0.463 mm for control (least squares mean difference: -0.178; 90% CI: -0.2943 to -0.0632; Pnoninferiority < 0.0001). The optical coherence tomography substudy included 37 patients (42 lesions) with no difference in mean neointimal hyperplasia thickness between groups at 13 months (Pnoninferiority = 0.01). CONCLUSIONS: The biodegradable polymer sirolimus-eluting stent was noninferior to currently used second-generation DES with regard to TLF at 1 year. (Firehawk® Rapamycin Target Eluting Coronary Stent North American Trial; NCT04562532).

Timing of Complete Multivessel Revascularization in Patients Presenting With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Complete revascularization of the culprit and all significant nonculprit lesions in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD) reduces major adverse cardiac events, but optimal timing of revascularization remains unclear. OBJECTIVES: This study aims to compare immediate complete revascularization (ICR) and staged complete revascularization (SCR) in patients presenting with NSTE-ACS and MVD. METHODS: This prespecified substudy of the BIOVASC (Percutaneous Complete Revascularization Strategies Using Sirolimus Eluting Biodegradable Polymer Coated Stents in Patients Presenting With Acute Coronary Syndrome and Multivessel Disease) trial included patients with NSTE-ACS and MVD. Risk differences of the primary composite outcome of all-cause mortality, myocardial infarction (MI), unplanned ischemia-driven revascularization (UIDR), or cerebrovascular events and its individual components were compared between ICR and SCR at 1 year. RESULTS: The BIOVASC trial enrolled 1,525 patients; 917 patients presented with NSTE-ACS, of whom 459 were allocated to ICR and 458 to SCR. Incidences of the primary composite outcome were similar in the 2 groups (7.9% vs 10.1%; risk difference 2.2%; 95% CI: -1.5 to 6.0; P = 0.15). ICR was associated with a significant reduction of MIs (2.0% vs 5.3%; risk difference 3.3%; 95% CI: 0.9 to 5.7; P = 0.006), which was maintained after exclusion of procedure-related MIs occurring during the index or staged procedure (2.0% vs 4.4%; risk difference 2.4%; 95% CI: 0.1 to 4.7; P = 0.032). UIDRs were also reduced in the ICR group (4.2% vs 7.8%; risk difference 3.5%; 95% CI: 0.4 to 6.6; P = 0.018). CONCLUSIONS: ICR is safe in patients with NSTE-ACS and MVD and was associated with a reduction in MIs and UIDRs at 1 year.

Impact of hypertension on mortality in patients with ST-elevation myocardial infarction undergoing primary angioplasty: insights from the international multicenter ISACS-STEMI registry.

BACKGROUND: Hypertension is the most prevalent cardiovascular risk factor, with several detrimental effects on the cardiovascular system. Contrasting results have been reported so far on its prognostic role in patients admitted for ST-segment elevation myocardial infarction (STEMI). Therefore, we investigated the impact of hypertension on short-term mortality in a large multicenter contemporary registry of STEMI patients, including patients treated during COVID-19 pandemic. METHODS: The ISACS-STEMI COVID-19 was a retrospective registry that included STEMI patients treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 in 109 high-volume primary PCI centers from 4 continents. We collected data on baseline, clinical and procedural characteristics, in-hospital outcome and 30-day mortality. For this analysis patients were grouped according to history of hypertension at admission. RESULTS: A total of 16083 patients were assessed, including 8813 (54.8%) with history of hypertension. These patients were more often elderly, with a worse cardiovascular risk profile, but were less frequently active smoker. Some procedural differences were observed between the two groups, including lower rate of thrombectomy and use of glycoprotein IIb/IIIa inhibitors or cangrelor but more extensive coronary disease in patients with hypertension. Between patients with and without hypertension, there was no significant difference in SARS-CoV-2 positivity. Hypertensive patients had a significantly higher in-hospital and 30-day mortality, similarly observed in both pre-COVID-19 and COVID-19 era, and confirmed after adjustment for main baseline differences and propensity score (in-hospital mortality: adjusted odds ratio (OR) [95% confidence interval (CI)] =1.673 [1.389-2.014], P < 0.001; 30-day mortality: adjusted hazard ratio (HR) [95% CI] = 1.418 [1.230-1.636], P < 0.001). CONCLUSION: This is one of the largest and contemporary study assessing the impact of hypertension in STEMI patients undergoing primary angioplasty, including also the COVID-19 pandemic period. Hypertension was independently associated with significantly higher rates of in-hospital and 30-day mortality.

Age-Related Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry.

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.

Gender Difference in the Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry.

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.

SARS-CoV-2 Positivity, Stent Thrombosis, and 30-day Mortality in STEMI Patients Undergoing Mechanical Reperfusion.

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.

Lack of long-term clinical benefit of thrombus aspiration during primary percutaneous coronary intervention with paclitaxel-eluting stents or bare-metal stents: post-hoc analysis of the PASSION-trial.

BACKGROUND: Although current clinical guidelines recommend the use of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI), previous studies evaluating TA demonstrated contradictory results. The aim of this study was to evaluate long-term clinical outcome after TA in adjunct to PPCI for acute ST-segment myocardial infarction (STEMI), as compared with conventional treatment, with the use of paclitaxel-eluting stents or bare-metal stents. METHODS: We analyzed data of the PASSION trial, in which 619 patients with STEMI were randomly assigned to a paclitaxel-eluting stent or a bare-metal stent. TA was performed in 311 patients (50.2%). Clinical endpoints at 2 years were compared between patients who received TA during PPCI with patients who underwent conventional PPCI. The primary outcome of interest was a composite of cardiac death, recurrent myocardial infarction (MI), or target-lesion revascularization (TLR). A propensity score model was made to account for baseline differences that could have affected the probability of performing TA. RESULTS: Complete follow-up was available for 598 patients (96.6%). The cumulative incidence of the combined outcome measure of cardiac death, recurrent MI, or TLR was 40 (13.0%) in the TA group and 41 (13.5%) in the conventional PPCI group (HR 0.96; 95% CI 0.62-1.47; P = 0.84). Also after adjusting for propensity score, no significant difference in event rate was observed between both treatment groups. CONCLUSIONS: In this post-hoc analysis of the PASSION trial, TA in adjunct to PPCI did not affect rates of major adverse cardiac events at 2 years follow-up, as compared with conventional PPCI.

Primary percutaneous coronary intervention by magnetic navigation compared with conventional wire technique.

Aims Comparison of magnetic guidewire navigation in percutaneous coronary intervention (MPCI) vs. conventional percutaneous coronary intervention (CPCI) for the treatment of acute myocardial infarction. Methods and results We compared 65 sequential patients (mean age 61 ± 15 years) undergoing primary MPCI with those of 405 patients undergoing CPCI (mean age 61 ± 13 years). The major endpoint was contrast media use. Technical success and procedural outcomes were evaluated. Clinical demographics and angiographic characteristics of the two groups were similar, except for fewer patients with previous coronary artery bypass grafting (CABG) and hypertension in the CPCI group and fewer patients with diabetes in the MPCI group. The technical success rate was high in both the MPCI and CPCI groups (95.4 vs. 98%). There was significantly less contrast media usage in the MPCI compared with the CPCI group, median reduction of contrast media of 30 mL with an OR = 0.41 (0.21-0.81). Fluoroscopy times were significantly reduced for MPCI compared with CPCI, median reduction of 7.2 min with an OR = 0.42 (0.20-0.79). Conclusion This comparison indicates the feasibility and non-inferiority of magnetic navigation in performing primary PCI and suggests the possibility of reductions in contrast media use and fluoroscopy time compared with CPCI.

Extremity Dysfunction After Large-Bore Radial and Femoral Arterial Access.

Background The use of large-bore (LB) arterial access and guiding catheters has been advocated for complex percutaneous coronary intervention. However, the impact of LB transradial access (TRA) and transfemoral access (TFA) on extremity dysfunction is currently unknown. Methods and Results The predefined substudy of the COLOR (Complex Large-Bore Radial PCI) trial aimed to assess upper and lower-extremity dysfunction after LB radial and femoral access. Upper-extremity function was assessed in LB TRA-treated patients by the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire and lower-extremity function in LB TFA-treated patients by the Lower Extremity Functional Scale questionnaire. Extremity pain and effect of access site complications and risk factors on extremity dysfunction was also analyzed. There were 343 patients who completed analyzable questionnaires. Overall, upper and lower-extremity function did not decrease over time when LB TRA and TFA were used for complex percutaneous coronary intervention, as represented by the median Quick Disabilities of the Arm, Shoulder, and Hand score (6.8 at baseline and 2.1 at follow-up, higher is worse) and Lower Extremity Functional Scale score (56 at baseline and 58 at follow-up, lower is worse). Clinically relevant extremity dysfunction occurred in 6% after TRA and 9% after TFA. A trend for more pronounced upper-limb dysfunction was present in female patients after LB TRA (P=0.05). Lower-extremity pain at discharge was significantly higher in patients with femoral access site complications (P=0.02). Conclusions Following LB TRA and TFA, self-reported upper and lower-limb function did not decrease over time in the majority of patients. Clinically relevant limb dysfunction occurs in a small minority of patients regardless of radial or femoral access. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03846752.

Impact of Smoking Status on Mortality in STEMI Patients Undergoing Mechanical Reperfusion for STEMI: Insights from the ISACS-STEMI COVID-19 Registry.

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.

COVID-19 pandemic, mechanical reperfusion and 30-day mortality in ST elevation myocardial infarction.

OBJECTIVE: The initial data of the International Study on Acute Coronary Syndromes - ST Elevation Myocardial Infarction COVID-19 showed in Europe a remarkable reduction in primary percutaneous coronary intervention procedures and higher in-hospital mortality during the initial phase of the pandemic as compared with the prepandemic period. The aim of the current study was to provide the final results of the registry, subsequently extended outside Europe with a larger inclusion period (up to June 2020) and longer follow-up (up to 30 days). METHODS: This is a retrospective multicentre registry in 109 high-volume primary percutaneous coronary intervention (PPCI) centres from Europe, Latin America, South-East Asia and North Africa, enrolling 16 674 patients with ST segment elevation myocardial infarction (STEMI) undergoing PPPCI in March/June 2019 and 2020. The main study outcomes were the incidence of PPCI, delayed treatment (ischaemia time >12 hours and door-to-balloon >30 min), in-hospital and 30-day mortality. RESULTS: In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio 0.843, 95% CI 0.825 to 0.861, p<0.0001). This reduction was significantly associated with age, being higher in older adults (>75 years) (p=0.015), and was not related to the peak of cases or deaths due to COVID-19. The heterogeneity among centres was high (p<0.001). Furthermore, the pandemic was associated with a significant increase in door-to-balloon time (40 (25-70) min vs 40 (25-64) min, p=0.01) and total ischaemia time (225 (135-410) min vs 196 (120-355) min, p<0.001), which may have contributed to the higher in-hospital (6.5% vs 5.3%, p<0.001) and 30-day (8% vs 6.5%, p=0.001) mortality observed during the pandemic. CONCLUSION: Percutaneous revascularisation for STEMI was significantly affected by the COVID-19 pandemic, with a 16% reduction in PPCI procedures, especially among older patients (about 20%), and longer delays to treatment, which may have contributed to the increased in-hospital and 30-day mortality during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.

A randomized comparison of manual versus mechanical thrombus removal in primary percutaneous coronary intervention in the treatment of ST-segment elevation myocardial infarction (TREAT-MI).

OBJECTIVES: The objective of this study was to compare the efficacy and long-term clinical outcome of manual thrombus aspiration with the Export catheter (Medtronic, Minneapolis, MN) versus mechanical thrombus cutting/aspiration with the X-sizer system (eV3, White Bear Lake, MN) in primary percutaneous coronary intervention (PPCI). BACKGROUND: In PPCI for acute ST-segment elevation myocardial infarction (STEMI), markers of myocardial reperfusion are improved with adjunctive thrombectomy. Previous studies of different devices showed a variability in performance, suitability, and short-term clinical outcome. In current literature, no direct comparison is available. METHODS: We prospectively randomized 201 patients admitted for PPCI for STEMI to either the Export catheter or the X-sizer prior to stent deployment. Technical success in advancing to and across the lesion, improvement of flow, reduction of thrombus, and the effect on ST-segment resolution were examined. The primary endpoint of the follow-up study was the combined endpoint of cardiac death, recurrent myocardial infarction (MI), or target-vessel revascularization (TVR) at 3 years. RESULTS: Although the Export catheter was more successfully deployed, other procedural parameters were similar with a trend toward better ST-segment resolution (56.6% vs. 44%; P = 0.06) as compared to the X-sizer system. The occurrence of the primary clinical endpoint at 3 years was 22.2% and 18.6%, respectively (HR 1.20; 95% CI 0.65-2.22; P = 0.35). CONCLUSION: Despite shorter procedural times, better lesion crossing, and fewer complications, both surrogate endpoints as well as 3-year clinical follow-up were similar with the use of the Export catheter as compared to the X-sizer system.

Randomized Comparison Between Radial and Femoral Large-Bore Access for Complex Percutaneous Coronary Intervention.

OBJECTIVES: The aim of this study was to investigate whether transradial (TR) percutaneous coronary intervention (PCI) is superior to transfemoral (TF) PCI in complex coronary lesions with large-bore guiding catheters with respect to clinically relevant access site-related bleeding or vascular complications. BACKGROUND: The femoral artery is currently the most applied access site for PCI of complex coronary lesions, especially when large-bore guiding catheters are required. With downsizing of TR equipment, TR PCI may be increasingly applied in these patients and might be a safer alternative compared with the TF approach. METHODS: An international prospective multicenter trial was conducted, randomizing 388 patients with planned PCI for complex coronary lesions, including chronic total occlusion, left main, heavy calcification, or complex bifurcation, to either 7-F TR access (TRA) or 7-F TF access (TFA). The primary endpoint was defined as access site-related clinically significant bleeding or vascular complications requiring intervention at discharge. The secondary endpoint was procedural success. RESULTS: The primary endpoint event rate was 3.6% for TRA and 19.1% for TFA (p < 0.001). The crossover rate from radial to femoral access was 3.6% and from femoral to radial access was 2.6% (p = 0.558). The procedural success rate was 89.2% for TFA and 86.0% for TRA (p = 0.285). There was no difference between TFA and TRA with regard to procedural duration, contrast volume, or radiation dose. CONCLUSIONS: In patients undergoing PCI of complex coronary lesions with large-bore access, radial compared with femoral access is associated with a significant reduction in clinically relevant access-site bleeding or vascular complications, without affecting procedural success. (Complex Large-Bore Radial Percutaneous Coronary Intervention [PCI] Trial [Color]; NCT03846752).

Impact of SARS-CoV-2 positivity on clinical outcome among STEMI patients undergoing mechanical reperfusion: Insights from the ISACS STEMI COVID 19 registry.

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 < 0.001). Despite similar pre and postprocedural TIMI flow, we observed a trend in higher use of GP IIb-IIIa inhibitors and a significantly higher use of thrombectomy in the SARS-CoV-2 positive patients. SARS-CoV-2 positivity was associated with a remarkably higher in hospital mortality (29% vs 5.5%, p < 0.001), definite in-stent thrombosis (8.1% vs 1.6%, p = 0.004) and heart failure (22.6% vs 10.6%, p = 0.001) that was confirmed after adjustment for confounding factors. CONCLUSIONS: Our study showed that among STEMI patients, SARS-CoV-2 positivity is associated with larger thrombus burden, a remarkably higher mortality but also higher rates of in-stent thrombosis and heart failure.