Procedural and one-year outcomes of robotic-assisted versus manual percutaneous coronary intervention.

BACKGROUND: Robotic-assisted percutaneous coronary intervention (rPCI) has proven to be feasible and safe. Comparative analyses of rPCI versus manual PCI (mPCI) are scarce. AIMS: We aimed to investigate procedural aspects and outcomes of rPCI using the second-generation CorPath GRX Vascular Robotic System compared with mPCI in patients with chronic coronary syndrome and non-ST-segment elevation myocardial infarction acute coronary syndrome. METHODS: From January to April 2021, 70 patients underwent rPCI at the University Heart & Vascular Center Hamburg-Eppendorf and were recruited into the INTERCATH study. By propensity score matching, a control cohort of 210 patients who underwent mPCI from 2015-2021 was identified. Co-primary endpoints were one-year all-cause mortality and major adverse cardiovascular events (MACE) as a composite of cardiovascular death, unplanned target lesion revascularisation, myocardial infarction, and stroke. RESULTS: The median age of the patients (n=280) was 70.7 (25th percentile-75th percentile: 62.0-78.0) years, and 24.6% were female. The Gensini score (28.5 [16.2-48.1] vs 28.0 [15.5-47.0]; p=0.78) was comparable between rPCI versus mPCI. During the PCI procedure, total contrast fluid volume did not differ, whilst longer fluoroscopy times (20.4 min [13.8-27.2] vs 14.4 min [10.4-24.3]; p=0.001) were documented in the rPCI versus mPCI cohort. After 12 months of follow-up, neither all-cause mortality (p=0.22) nor MACE (p=0.25) differed between the groups. CONCLUSIONS: rPCI was associated with longer fluoroscopy times compared with mPCI, though without increased use of contrast medium. One-year follow-up revealed no differences in all-cause mortality or MACE, supporting the safety of a robotic-assisted approach.

Platelet P2Y12 Inhibitor Monotherapy after Percutaneous Coronary Intervention: An Emerging Option for Antiplatelet Therapy De-escalation.

Antiplatelet therapy is considered essential for secondary prevention of ischemic heart disease. After percutaneous coronary intervention (PCI), temporary dual antiplatelet therapy (DAPT), a combination consisting of aspirin and an oral P2Y12 receptor blocker, is recommended. In the long term, this strategy results in more bleeding than antiplatelet therapy with aspirin alone. Therefore, to reduce bleeding, an increasing trend has been to keep DAPT as short as clinically acceptable, after which aspirin monotherapy is continued. Another option to diminish bleeding is to discontinue aspirin at the moment of DAPT cessation after PCI, and to continue on P2Y12 blocker monotherapy. This survey reviews the evidence on P2Y12 blocker monotherapy. Some clinical guidance will be provided on when and in whom P2Y12 inhibitor monotherapy may be applied after DAPT cessation following PCI.

Parenteral Antiplatelet Drugs in ST-Elevation Myocardial Infarction: Current Status and Future Directions.

Oral inhibitors of the platelet P2Y12 receptor are indispensable in the treatment of ST-elevation myocardial infarction (STEMI), improving outcomes and even reducing mortality in some studies. However, these drugs are limited by delayed absorption and suboptimal platelet inhibition at the time of primary percutaneous coronary intervention. Despite efforts to achieve faster and more sustained platelet inhibition, strategies such as prehospital administration, higher loading doses, and crushed formulations have not led to improved coronary reperfusion. Parenteral glycoprotein IIb/IIIa inhibitors act sooner and are more potent than oral P2Y12 inhibitors, but their use has been limited by the increased risk of major bleeding and thrombocytopenia. Hence, there is a clinical need to refine drugs that deliver rapid, effective, yet safe platelet inhibition in the setting of STEMI. Novel parenteral antiplatelet drugs, such as cangrelor, selatogrel, and zalunfiban, have been recently developed to achieve rapid, potent antiplatelet effects while preserving hemostasis. We provide a description of currently available parenteral antiplatelet agents and of those in clinical development for prehospital administration in STEMI patients.

Mechanical thrombectomy in ischemic stroke after cardiovascular procedures: a propensity-matched cohort analysis.

BACKGROUND: Stroke after a cardiovascular procedure (CVP) is a devastating complication adversely affecting outcome. Mechanical thrombectomy (MT) has not been investigated systematically in this population. OBJECTIVE: To carry out a retrospective study in patients undergoing MT for early stroke after CVP, aiming to further characterize this cohort of patients, and to evaluate the efficacy, safety, procedural characteristics, and outcome of MT. METHODS: A single-center stroke registry of patients who received MT was analyzed. Baseline and procedural parameters, mortality, functional outcome, recanalization rates, and complications were evaluated. Propensity score matching was carried out, identifying a control cohort with non-periprocedural large vessel occlusion (LVO). RESULTS: Overall 913 patients were included (mean age 73.0 (±13.0) years, 52.5% female, median National Institutes of Health Stroke Scale score 15 (10-19)). Eleven patients with a LVO after a recent (<30 days postoperatively) CVP were identified (n=3 transcatheter aortic valve and n=1 surgical aortic valve replacements (SAVR), n=3 coronary bypass grafting (CABG) surgeries, n=2 SAVR+CABG, and n=2 aortic surgeries). After matching, 8 patients in the CVP group were compared with 16 patients in the matched cohort. Comparable rates of reperfusion were achieved. Time from symptom onset to groin puncture (171.5 min (136.3, 178.3) vs 284.0 min (215.0, 490.5); p=0.039), as well as recanalization (195.0 min (146.0, 201.0) vs 419.0 min (274.0, 613.0); p=0.028) was faster in the CVP group. However, this was not reflected by an improved outcome (modified Rankin Scale score after 90 days: 5.5 (3.3, 6.0) vs 5.0 (4.0, 6.0), mortality after 90 days 50.0% vs 37.5%). Complications did not differ between the groups. CONCLUSIONS: Use of MT for LVO stroke in patients after a recent CVP is a safe and efficient treatment in comparison with patients with a non-periprocedural LVO undergoing MT.

Association of High-Sensitivity Troponin T and I Blood Concentrations With All-Cause Mortality and Cardiovascular Outcome in Stable Patients-Results From the INTERCATH Cohort.

Background The association between high-sensitivity troponin T (hsTnT) and high-sensitivity troponin I (hsTnI) and outcome when adjusted for confounders including the angiographical severity of coronary artery disease (CAD) remains largely unknown. We therefore aimed to explore whether hsTnT and hsTnI blood levels increase with CAD severity and add independent predictive information for future major adverse cardiovascular events and all-cause mortality in stable patients. Methods and Results Patients from the INTERCATH cohort with available coronary angiography and hsTnT and hsTnI concentrations were included. Troponin concentrations were quantified via hsTnT (Roche Elecsys) and hsTnI (Abbott ARCHITECT STAT). To investigate the association of hsTnT and hsTnI with outcome, a multivariable analysis adjusting for classical cardiovascular risk factors, low-density lipoprotein cholesterol, estimated glomerular filtration rate, hs-CRP (high-sensitivity C-reactive protein), NT-proBNP (N-terminal pro-brain natriuretic peptide), and Gensini score was carried out. Of 1829 patients, 27.9% were women, and the mean age was 68.6±10.9 years. Troponin blood concentrations were higher in patients with diagnosed CAD compared with those without. Using a linear regression model current smoking, arterial hypertension, estimated glomerular filtration rate, hs-CRP, NT-proBNP, and CAD severity as graded by the Gensini and SYNTAX scores were associated with high-sensitivity troponin levels. Patients were followed for 4.4 years (25th and 75th percentiles: 4.3, 4.4). After multivariable adjustment, all-cause mortality was predicted by hsTnT (hazard ratio [HR], 1.7 [95% CI, 1.5-2.2], P<0.001) as well as hsTnI (HR, 1.5 [95% CI, 1.2-1.8], P<0.001). However, only hsTnI (HR, 1.2 [95% CI, 1.0-1.4], P=0.032) remained as an independent predictor of major adverse cardiovascular events after adjusting for most possible confounders, including CAD severity (hsTnT: HR, 1.0 [95% CI, 0.9-1.2], P=0.95). Conclusions After adjusting for classical cardiovascular risk factors, low-density lipoprotein cholesterol, estimated glomerular filtration rate, hs-CRP, NT-proBNP, and CAD severity, hsTnT and hsTnI were independently associated with all-cause mortality, but only hsTnI was associated with major adverse cardiovascular events in stable patients undergoing coronary angiography. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT04936438.

Establishing a robotic-assisted PCI program: experiences at a large tertiary referral center.

Robotic-assisted percutaneous coronary interventions (rPCI) have proven feasible and safe while reducing radiation exposure for the operator. Recently, rPCI systems have been refined to facilitate the treatment of complex lesions. The aim of the current study was to evaluate challenges and opportunities of establishing an rPCI program at a tertiary referral center. rPCI was performed using the CorPath GRX Vascular Robotic System (Corindus Inc., a Siemens Healthineers Company, Waltham, USA). Baseline, procedural, and in-hospital follow-up data were prospectively assessed. rPCI success was defined as completion of the PCI without or with partial manual assistance. The safety endpoint was the composite of missing angiographic success or procedure-related adverse events during hospital stay. Overall, 86 coronary lesions were treated in 71 patients (28.2% female) from January to April 2021. Median age was 71.0 years (IQR 60.3; 79.8). Indications for rPCI were stable angina pectoris (71.8%), unstable angina (12.7%) and non-ST elevation myocardial infarction (15.5%). Most lesions were complex (type B2/C: 88.4%) and included 7 cases of rPCI for chronic total occlusions. Angiographic and rPCI success were achieved in 100.0% and 94.2%, respectively. Partial manual assistance was used in 25.6%. Conversion to manual PCI was required in 5.8%. The safety endpoint occurred in 7.0% of patients. rPCI when applied as clinical routine for complex coronary lesions is effective with good immediate angiographic and clinical results. Future investigations should focus on the identification of patients that particularly benefit from robotic-assisted vs. manual PCI despite higher resource utilization.

Completeness of revascularisation in acute coronary syndrome patients with multivessel disease.

A significant proportion of patients presenting with acute coronary syndromes (ACS) have multivessel disease (MVD). Despite the abundance of clinical trials in this area, several questions regarding the procedure of complete coronary revascularisation remain unanswered. This state-of-the-art review summarises the latest evidence on complete revascularisation (CR) in this subset of patients and critically appraises clinical decision making based on non-culprit lesion (NCL) assessment. Future areas of research are put into perspective.

Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke. CONCLUSIONS: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

Using proximity extension proteomics assay to identify biomarkers associated with infarct size and ejection fraction after ST-elevation myocardial infarction.

Plasma concentrations of many cardiovascular and inflammatory proteins are altered after ST-elevation myocardial infarction (STEMI) and may provide prognostic information. We conducted a large-scale proteomic analysis in patients with STEMI, correlating protein levels to infarct size and left ventricular ejection fraction (LVEF) determined with cardiac magnetic resonance imaging. We analysed 131 cardiovascular and inflammatory proteins using a multiplex proximity extension assay and blood samples obtained at baseline, 6, 24, and 96 h from the randomised clinical trial CHILL-MI. Cardiac magnetic resonance imaging data at 4 ± 2 days and 6 months were available as per trial protocol. Using a linear regression model with bootstrap resampling and false discovery rate adjustment we identified five proteins (ST2, interleukin-6, pentraxin-3, interleukin-10, renin, and myoglobin) with elevated values corresponding to larger infarct size or worse LVEF and four proteins (TNF-related apoptosis-inducing ligand, TNF-related activation induced cytokine, interleukin-16, and cystatin B) with values inversely related to LVEF and infarct size, concluding that among 131 circulating inflammatory and cardiovascular proteins in the acute and sub-acute phase of STEMI, nine showed a relationship with infarct size and LVEF post-STEMI, with IL-6 and ST2 exhibiting the strongest association.

Relation of Bleeding Events to Mortality in Patients With ST-Segment Elevation Myocardial Infarction Treated by Percutaneous Coronary Intervention (a DANAMI-3 Substudy).

Bleeding events in relation to treatment of ST-segment elevation myocardial infarction (STEMI) have previously been associated with mortality. In this study, we investigated the incidence and prognosis of, and variables associated with serious bleedings within 30 days after primary percutaneous coronary intervention in patients from The Third Danish Study of Optimal Acute Treatment of Patients with ST-Segment Elevation Myocardial Infarction (DANAMI-3) (n = 2,217). Hospital charts were read within 30 days postadmission to assess bleeding events using thrombolysis in myocardial infarction (TIMI) and Bleeding Academic Research Consortium criteria. TIMI minor/major bleeding (TMMB) occurred in 59 patients (2.7%). Variables associated with TMMB were female gender (hazard ratio [HR] 3.9, 95% confidence interval [CI] 2.2 to 6.7, p <0.0001), symptom-to-catheterization time >3 hours (HR 1.9, 95% CI 1.1 to 3.3, p = 0.02), use of glycoprotein IIb/IIIa inhibitor (HR 2.1, 95% CI 1.2 to 3.7, p = 0.01), and increasing S-creatinine (HR 1.1, 95% CI 1.0 to 1.2, p = 0.001). Undergoing 2 in-hospital procedures were not associated with increased risk of TMMB. TMMB was strongly associated with 30-day mortality in multivariable analysis (HR 4.8, 95% CI 2.2 to 10.4, p <0.0001) but not with mortality days 31 to 365. When excluding fatal bleedings from the analysis, a TMMB was no longer associated with 30-day mortality. In conclusion, we found that in a contemporary STEMI-population, the incidence of 30-day TMMB was low. A TMMB was strongly associated with 30-day mortality but not with mortality days 31 to 365. If patients survived a serious bleeding, their short- and long-term prognoses were not affected.

Adverse events while awaiting myocardial revascularization: a systematic review and meta-analysis.

OBJECTIVES: The aim of the current study was to estimate adverse event rates while awaiting myocardial revascularization and review criteria for prioritizing patients. METHODS: A PubMed search was performed on 19 January 2015, to identify English-language, original, observational studies reporting adverse events while awaiting coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Rates of death, non-fatal myocardial infarction (MI) and emergency revascularization were calculated as occurrence rates per 1000 patient-weeks and pooled using random-effects models. RESULTS: The search yielded 1323 articles, of which 22 were included with 66 410 patients and 607 675 patient-weeks on the wait list. When awaiting CABG, rates per 1000 patient-weeks were 1.1 [95% confidence interval 0.9-1.3] for death, 1.0 [0.6-1.6] for non-fatal MI and 1.8 [0.8-4.1] for emergency revascularization. Subgroup analyses demonstrated consistent outcomes, and sensitivity analyses demonstrated comparable event rates with low heterogeneity. Higher urgency of revascularization was based primarily on angiographic complexity, angina severity, left ventricular dysfunction and symptoms on stress testing, and such patients with a semi-urgent status had a higher risk of death than patients awaiting elective revascularization (risk ratio at least 2.8). Individual studies identified angina severity and left ventricular dysfunction as most important predictors of death when awaiting CABG. Adverse rates per 1000 patient-weeks for patients awaiting PCI were 0.1 [95% confidence interval 0.0-0.4] for death, 0.4 [0.1-1.2] for non-fatal MI and 0.7 [0.4-1.4] for emergency revascularization but were based on only a few old studies. CONCLUSIONS: Rates of death, non-fatal MI and emergency revascularization when awaiting myocardial revascularization are infrequent but higher in specific patients. Countries that not yet have treatment recommendations related to waiting times should consider introducing a maximum to limit adverse events, particularly when awaiting CABG.

Potent P2Y12 Inhibitors in Men Versus Women: A Collaborative Meta-Analysis of Randomized Trials.

BACKGROUND: Sex-specific differences in response to antiplatelet therapies have been described. Whether women and men derive comparable benefit from intensification of antiplatelet therapy remains uncertain. OBJECTIVES: The study investigated the efficacy and safety of the potent P2Y12 inhibitors in patients with coronary artery disease. METHODS: A collaborative sex-specific meta-analysis was conducted of phase III or IV randomized trials of potent P2Y12 inhibitors, including prasugrel, ticagrelor, and intravenous cangrelor. Seven trials were included that enrolled a total of 24,494 women and 63,346 men. Major adverse cardiovascular events (MACE) were defined as the primary endpoint for each trial. RESULTS: Potent P2Y12 inhibitors significantly reduced the risk of MACE by 14% in women (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.78 to 0.94) and by 15% in men (HR: 0.85; 95% CI: 0.80 to 0.90; p interaction = 0.93). Treatment reduced the risk of myocardial infarction by 13% in women (HR: 0.87; 95% CI: 0.78 to 0.96) and 16% in men (HR: 0.84; 95% CI: 0.77 to 0.91; p interaction = 0.65), and the risk of stent thrombosis by 51% in women (HR: 0.49; 95% CI: 0.37 to 0.65) and 41% in men (HR: 0.59; 95% CI: 0.42 to 0.84; p interaction = 0.85). Directional consistency was seen for cardiovascular death in women (HR: 0.87; 95% CI: 0.76 to 1.01) and men (HR: 0.85; 95% CI: 0.77 to 0.95; p interaction = 0.86). The potent P2Y12 inhibitors increased major bleeding in women (HR: 1.28; 95% CI: 0.87 to 1.88) and men (HR: 1.52; 95% CI: 1.12 to 2.07; p interaction = 0.62). CONCLUSIONS: In randomized trials, the efficacy and safety of the potent P2Y12 inhibitors were comparable between men and women. Given these data, sex should not influence patient selection for the administration of potent P2Y12 inhibitors.

Gender Differences in Associations Between Intraprocedural Thrombotic Events During Percutaneous Coronary Intervention and Adverse Outcomes.

Women are frequently reported to have increased morbidity after presentation with acute coronary syndromes and myocardial infarction; however, whether a greater thrombotic tendency contributes to gender differences in clinical outcomes of urgent percutaneous coronary intervention is unknown. Intraprocedural Thrombotic Events (IPTEs) are defined as new or increasing thrombus, abrupt vessel closure, no reflow or slow reflow, or distal embolization at any time during percutaneous coronary intervention. IPTEs were evaluated in this pooled analysis of 6,591 patients with stent implantation and blinded quantitative coronary angiography (QCA) analysis, from the ACUITY and HORIZONS-AMI trials. We compared major adverse cardiac events (MACE) at in-hospital, 30-day, and 1-year follow-up and major bleeding at 30 days according to gender and the presence or absence of IPTE. IPTE was identified in 507 patients (7.7%), with 119 of 1,744 (6.8%) occurring in women and 388 of 4,847 (8.0%) in men (p = 0.12). IPTE, but not gender, was independently associated with MACE at in-hospital and 30-day follow-up. At 1-year follow-up, the adjusted hazard of MACE was higher in women and in patients with IPTE; however, the risk of MACE associated with IPTE was similar among women and men. There was no significant interaction between IPTE and gender for 1-year MACE or 30-day bleeding. IPTE predicted major bleeding only in women. In conclusion, in acute coronary syndromes, women have increased risk of adverse outcome at 1 year. IPTEs are common, occur at similar frequency, and are associated with similar degree of increased MACE in both genders at short- and long-term follow-up. Higher thrombotic propensity does not offer a mechanistic explanation for the worse outcomes noted in women.

A post hoc analysis of long-term prognosis after exenatide treatment in patients with ST-segment elevation myocardial infarction.

AIMS: We aimed to assess the effect of exenatide treatment as an adjunct to primary percutaneous coronary intervention (PCI) on long-term clinical outcome. METHODS AND RESULTS: We performed a post hoc analysis in 334 patients with a first STEMI included in a previous study randomised to exenatide (n=175) or placebo (n=159) as an adjunct to primary PCI. The primary endpoint was a composite of all-cause mortality and admission for heart failure during a median follow-up of 5.2 years (interquartile range: 5.0-5.5). Secondary endpoints were all-cause mortality and admission for heart failure, individually. The primary composite endpoint occurred in 24% in the exenatide group versus 27% in the placebo group, p=0.44 (HR 0.80, p=0.35). Admission for heart failure was lower in the exenatide (11%) compared to the placebo group (20%) (HR 0.53, p=0.042). All-cause mortality occurred in 14% in the exenatide group versus 9% in the placebo group (HR 1.45, p=0.20). CONCLUSIONS: In this post hoc analysis of patients with a STEMI, treatment with exenatide at the time of primary PCI did not reduce the primary composite endpoint or the secondary endpoint of all-cause -mortality. However, exenatide treatment reduced the incidence of admission for heart failure.

Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised controlled trial.

BACKGROUND: Despite successful treatment of the culprit artery lesion by primary percutaneous coronary intervention (PCI) with stent implantation, thrombotic embolisation occurs in some cases, which impairs the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the clinical outcomes of deferred stent implantation versus standard PCI in patients with STEMI. METHODS: We did this open-label, randomised controlled trial at four primary PCI centres in Denmark. Eligible patients (aged >18 years) had acute onset symptoms lasting 12 h or less, and ST-segment elevation of 0·1 mV or more in at least two or more contiguous electrocardiographic leads or newly developed left bundle branch block. Patients were randomly assigned (1:1), via an electronic web-based system with permuted block sizes of two to six, to receive either standard primary PCI with immediate stent implantation or deferred stent implantation 48 h after the index procedure if a stabilised flow could be obtained in the infarct-related artery. The primary endpoint was a composite of all-cause mortality, hospital admission for heart failure, recurrent infarction, and any unplanned revascularisation of the target vessel within 2 years' follow-up. Patients, investigators, and treating clinicians were not masked to treatment allocation. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01435408. FINDINGS: Between March 1, 2011, and Feb 28, 2014, we randomly assigned 1215 patients to receive either standard PCI (n=612) or deferred stent implantation (n=603). Median follow-up time was 42 months (IQR 33-49). Events comprising the primary endpoint occurred in 109 (18%) patients who had standard PCI and in 105 (17%) patients who had deferred stent implantation (hazard ratio 0·99, 95% CI 0·76-1·29; p=0·92). Procedure-related myocardial infarction, bleeding requiring transfusion or surgery, contrast-induced nephopathy, or stroke occurred in 28 (5%) patients in the conventional PCI group versus 27 (4%) patients in the deferred stent implantation group, with no significant differences between groups. INTERPRETATION: In patients with STEMI, routine deferred stent implantation did not reduce the occurrence of death, heart failure, myocardial infarction, or repeat revascularisation compared with conventional PCI. Results from ongoing randomised trials might shed further light on the concept of deferred stenting in this patient population. FUNDING: Danish Agency for Science, Technology and Innovation, and Danish Council for Strategic Research.

Optimal timing of initiation of oral P2Y12-receptor antagonist therapy in patients with non-ST elevation acute coronary syndromes. Lessons learnt from the ACCOAST-trial.

The optimal time-point of the initiation of P2Y12 antagonist therapy in patients with non-ST elevation acute coronary syndromes (NTSE-ACS) is still a matter of debate. European guidelines recommend P2Y12 as soon as possible after first medical contact. However, the only trial which compared the two strategies did not demonstrate any benefit of pre-treatment with prasugrel before angiography compared to starting therapy after angiography and just prior to percutaneous coronary intervention (PCI). This paper summarizes the results of pharmacodynamic and previous studies, and gives recommendations for the initiation of P2Y12 antagonist therapy in NSTE-ACS in different clinical situations.

Long-term outcomes for women versus men with unstable angina/non-ST-segment elevation myocardial infarction managed medically without revascularization: insights from the TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes trial.

BACKGROUND: Women with acute coronary syndromes (ACS) are less likely to undergo invasive revascularization than men, but sex-specific differences in long-term outcomes and platelet reactivity among medically managed ACS patients remain uncertain. We examined sex-specific differences in long-term ischemic and bleeding outcomes and platelet reactivity for medically managed ACS patients randomized to prasugrel versus clopidogrel plus aspirin. METHODS: Data from 9,326 patients enrolled in TRILOGY ACS were analyzed to determine differences in long-term ischemic and bleeding outcomes between women (n = 3,650 [39%]) and men (n = 5,676 [61%]) randomized to prasugrel 10 mg/d (5 mg/d for patients ≥75 years and/or <60 kg) versus clopidogrel 75 mg/d. Sex-specific differences in 30-day platelet reactivity were analyzed in 2,564 (27%) patients participating in a platelet function substudy. RESULTS: Compared with men, women were older, weighed less, were less likely to have prior myocardial infarction or revascularization, and had lower baseline creatinine clearance and hemoglobin level values. Rates of the composite of cardiovascular death/myocardial infarction/stroke (20.2% vs 19.1%; P = .56), all-cause mortality (12.2% vs 11.7%; P = .88), and Global Use of Strategies to Open Occluded Arteries severe/life-threatening/moderate bleeding (3.8% vs 2.8%; P = .74) through 30 months were similar in women versus men. After adjustment, women had significantly lower risk for ischemic outcomes and all-cause mortality. There were no sex-specific, treatment-related differences in 30-day platelet reactivity. CONCLUSIONS: Long-term ischemic and bleeding outcomes in medically managed ACS patients were similar for women versus men, as was treatment-related platelet reactivity. Women had a higher baseline risk profile and, after adjustment, significantly lower risk of the primary composite end point and all-cause death through 30 months.

Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3­PRIMULTI): an open-label, randomised controlled trial.

BACKGROUND: Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only. METHODS: We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularization of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01960933. FINDINGS: From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularization guided by FFR values. Median follow-up was 27 months (range 12­44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0∙56, 95% CI 0∙38­0∙83; p=0∙004). INTERPRETATION: In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularization should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints. FUNDING: Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research.

Prehospital administration of P2Y12 inhibitors and early coronary reperfusion in primary PCI: an observational comparative study.

The newer oral P2Y12 inhibitors prasugrel and ticagrelor have been reported to be more potent and faster-acting antiplatelet agents than clopidogrel. This study aimed to investigate whether prehospital loading with prasugrel or ticagrelor improves early coronary reperfusion as compared to prehospital loading with clopidogrel in a real-world ST-elevation myocardial infarction (STEMI) setting. Over a 70-month period, 3497 patients with on-going STEMI of less than 6 hours and without cardiac arrest or cardiogenic shock underwent primary percutaneous coronary intervention (PPCI) at our centre. The primary endpoint of this study was the proportion of patients who did not meet the criteria for TIMI (Thrombolysis In Myocardial Infarction) flow grade 3 in the infarct-related artery at initial angiography before PPCI. Prehospital loading with prasugrel (n = 883) or ticagrelor (n = 491) did not significantly improve coronary reperfusion as compared to prehospital loading with clopidogrel (n = 1,532) - a TIMI-flow 3 at initial angiography was absent in 71.7 %, 69.0 % and 71.5 % of patients, respectively. Major adverse cardiac event (MACE) rates were low at 30 days (3.4 % to 4.0 %) and did not significantly differ between the different P2Y12 inhibitor regimens. In conclusion, this large observational, non-randomised study is the first to show that prehospital loading with the newer P2Y12 inhibitors does not improve early coronary reperfusion as compared to prehospital loading with clopidogrel in a PPCI cohort excluding cardiac arrest and cardiogenic shock.

Cerebral lesions in patients undergoing coronary artery bypass grafting in relation to asymptomatic carotid and vertebral artery stenosis.

OBJECTIVES: Carotid artery stenosis (CAS) and vertebral artery stenosis (VAS) are associated with cerebral infarction after coronary artery bypass graft surgery (CABG). It remains unclear whether this association is causal. We investigated the associations between neurologically asymptomatic CAS and VAS and the occurrence of subclinical cerebral lesions after CABG verified by magnetic resonance imaging. METHODS: CABG patients were included and CAS and VAS were identified by magnetic resonance angiography. Cerebral magnetic resonance imaging was performed to identify new post-operative subclinical cerebral lesions. The associations between CAS/VAS post-operative cerebral lesions were investigated. RESULTS: Forty-six patients were included in the study. 13% had significant CAS and 11% had significant VAS. Thirty-five percent had new cerebral infarction postoperatively. We found a significant association between the presence of cerebral vessel stenosis and acute cerebral infarction (67% vs. 27%, p = 0.047). However none of the patients with stenosis had isolated cerebral lesions in the ipsilateral vascular territory. CONCLUSION: Asymptomatic CAS and VAS is common in CABG patients and is associated with an increased risk of postoperative cerebral infarction. Our study suggests that asymptomatic CAS and VAS primarily are risk markers rather than causal factors for cerebral infarction after CABG.