Giuseppe Andò

Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial

BACKGROUND It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. METHODS We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. FINDINGS We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). INTERPRETATION In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. FUNDING The Medicines Company and Terumo.

Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes

BACKGROUND Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome. METHODS We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events. RESULTS The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34). CONCLUSIONS In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.).

Scientific Foundation and Possible Implications for Practice of the Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX (MATRIX) Trial

Early invasive management and the use of combined antithrombotic therapies have decreased the risk of recurrent ischaemia in patients with acute coronary syndrome (ACS) but have also increased the bleeding risk. Transradial intervention (TRI) and bivalirudin infusion compared to transfemoral intervention (TFI) or unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPI) decrease bleeding complications in patients with ACS. To what extent, a bleeding preventive strategy incorporating at least one of these two treatment options translates into improved outcomes is a matter of debate. The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX study is a large-scale, multicenter, prospective, open-label trial, conducted at approximately 100 sites in Europe aiming to primarily assess whether TRI and bivalirudin infusion, as compared to TFI and UFH plus provisional GPI, decrease the 30-day incidence of death, myocardial infarction or stroke across the whole spectrum of ACS patients.

Age, glomerular filtration rate, ejection fraction, and the AGEF score predict contrast-induced nephropathy in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

In patients undergoing primary percutaneous coronary interventions (PCI) for ST‐segment elevation myocardial infarction (STEMI), the occurrence of Contrast‐Induced Nephropathy (CIN) has a pronounced impact both on morbidity and mortality. We investigated the variables associated with CIN development in 481 consecutive patients with STEMI undergoing primary PCI and evaluated the predictive value of a 3‐variable clinical risk score (the AGEF score) based on age, left ventricular ejection fraction (EF), and estimated glomerular filtration rate (eGFR).

Radial Access Reduces Mortality in Patients With Acute Coronary Syndromes: Results From an Updated Trial Sequential Analysis of Randomized Trials.

OBJECTIVES The authors sought to investigate whether the cumulative evidence coming from randomized studies has reached the necessary power to consider radial access as a bleeding avoidance strategy that reduces mortality and ischemic endpoints in patients with acute coronary syndromes (ACS). BACKGROUND Studies in ACS patients have reached conflicting conclusions about the impact of radial access in improving ischemic outcomes in addition to the established bleeding benefit. METHODS English-language publications and abstracts of major cardiovascular meetings until October 2015 were scrutinized. Study quality, patient characteristics, procedural data, and outcomes were extracted. Data were pooled in random effects meta-analyses with classic and trial sequential techniques. Trial sequential analysis combines the a priori information size calculation needed to allow for clinically meaningful statistical inference with the adjustment of thresholds for which results are considered significant. RESULTS Seventeen studies, encompassing data from 19,328 patients, were pooled. Radial access was found to reduce mortality (relative risk [RR]: 0.73; 95% confidence interval [CI]: 0.60 to 0.88; p = 0.001), major adverse cardiovascular events (RR: 0.86; 95% CI: 0.77 to 0.95; p = 0.005), and major bleeding (RR: 0.60; 95% CI: 0.48 to 0.76; p < 0.001). Multiple sensitivity analyses showed consistent results, and trial sequential analysis suggested firm evidence for a meaningful reduction in mortality with radial access. CONCLUSIONS Radial access reduces mortality compared with femoral access in ACS patients undergoing invasive management. This benefit is paralleled by consistent reductions in major adverse cardiovascular events and major bleeding, supporting radial access as the default strategy for cardiac catheterization in patients with ACS.

Impact of clinical presentation on ischaemic and bleeding outcomes in patients receiving 6- or 24-month duration of dual-antiplatelet therapy after stent implantation: a pre-specified analysis from the PRODIGY (Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia) trial

AIMS We investigated if acute coronary syndrome (ACS) rather than stable coronary artery disease (SCAD) presentation is an outcome modifier with respect to the duration of dual-antiplatelet therapy (DAPT) in patients undergoing coronary stenting. METHODS AND RESULTS In the Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia (PRODIGY) trial, a total of 1465 (74.3%) patients presented ACS whereas 505 (25.7%) had SCAD and were randomized to 6- or 24-month DAPT. At 24 months, the composite of death, myocardial infarction (MI), or cerebrovascular accident (CVA) did not differ between the long- and short-term DAPT arms in both ACS (11.1 vs. 11.7%; P = 0.67) and SCAD (7.5 vs. 4.8%; P = 0.21) patients, respectively. Long-term DAPT was associated with a 75% increase of Bleeding Academic Research Consortium (BARC)-class 2, 3, or 5 bleeding in ACS [7.1 vs. 4.1%; hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.11-2.74, P = 0.015; number needed to treat for harm (NNTH): 33.3] and a five-fold increase in SCAD (8.2 vs. 1.6%; HR 5.37, 95% CI 1.84-15.74, P = 0.002; NNTH: 15.1) patients, with a borderline quantitative interaction (PINT = 0.056). As a result, net adverse cardiovascular events (death, MI, CVA, BARC class 2, 3, or 5 bleeding) were more than doubled in SCAD patients receiving 24-month DAPT, whereas they did not differ in ACS patients (PINT = 0.024). CONCLUSIONS This analysis suggests that clinical presentation may be a treatment modifier with respect to DAPT duration after stenting consistent with the hypothesis that SCAD-but not ACS-patients are exposed to a significant increase in bleeding and net adverse clinical events when treated with 24-month compared with 6-month therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00611286. http://clinicaltrials.gov/ct2/show/NCT00611286?term=prodigy&rank=2.

Renal Function–Adjusted Contrast Volume Redefines the Baseline Estimation of Contrast-Induced Acute Kidney Injury Risk in Patients Undergoing Primary Percutaneous Coronary Intervention

Background—Age, estimated glomerular renal function (eGFR), and ejection fraction are preprocedural predictors of contrast-induced acute kidney injury (CI-AKI) after primary percutaneous coronary intervention. The effect of renal function–adjusted contrast volume (CV) remains not totally explored, and a threshold has not yet been established. Methods and Results—Logistic regression and receiver-operating characteristic curve analyses were used to assess whether CV/eGFR was an independent predictor of CI-AKI. The increased discriminative value of CV/eGFR over the preprocedural model based on age, eGFR, and ejection fraction was examined using the net reclassification improvement analysis. Of 470 patients enrolled, we observed 25 (5.3%) cases of CI-AKI. Patients with CI-AKI had received a higher renal function–adjusted CV (CV/eGFR 3.62 versus 1.96; P<0.001), and CI-AKI incidence was higher (15%; P<0.001) in patients in the highest quartile of CV/eGFR, corresponding to the cutoff indicated by the receiver-operating characteristic curve (>2.5; area under the curve, 0.77). At multivariable analysis, CV/eGFR above the cutoff (odds ratio, 5.57; P=0.002) remained an independent predictor of CI-AKI. The model with CV/eGFR demonstrated a statistically significantly net reclassification improvement of 0.23 (P=0.021) over the baseline preprocedural model, largely driven by a correct decrease in risk estimates for patients not experiencing CI-AKI, with a likelihood ratio &khgr;2 of 5.973 (P=0.029). Conclusions—CV remains a key risk factor for CI-AKI after primary percutaneous coronary intervention and our study supports the need for minimizing CV, independently from baseline preprocedural risk. A CV restricted to no more than twice and a half the baseline eGFR might be valuable in reducing the risk of CI-AKI.

Incremental Value of the CRUSADE, ACUITY, and HAS-BLED Risk Scores for the Prediction of Hemorrhagic Events After Coronary Stent Implantation in Patients Undergoing Long or Short Duration of Dual Antiplatelet Therapy

Background Multiple scores have been proposed to stratify bleeding risk, but their value to guide dual antiplatelet therapy duration has never been appraised. We compared the performance of the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HAS‐BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) scores in 1946 patients recruited in the Prolonging Dual Antiplatelet Treatment After Grading Stent‐Induced Intimal Hyperplasia Study (PRODIGY) and assessed hemorrhagic and ischemic events in the 24‐ and 6‐month dual antiplatelet therapy groups. Methods and Results Bleeding score performance was assessed with a Cox regression model and C statistics. Discriminative and reclassification power was assessed with net reclassification improvement and integrated discrimination improvement. The C statistic was similar between the CRUSADE score (area under the curve 0.71) and ACUITY (area under the curve 0.68), and higher than HAS−BLED (area under the curve 0.63). CRUSADE, but not ACUITY, improved reclassification (net reclassification index 0.39, P=0.005) and discrimination (integrated discrimination improvement index 0.0083, P=0.021) of major bleeding compared with HAS‐BLED. Major bleeding and transfusions were higher in the 24‐ versus 6‐month dual antiplatelet therapy groups in patients with a CRUSADE score >40 (hazard ratio for bleeding 2.69, P=0.035; hazard ratio for transfusions 4.65, P=0.009) but not in those with CRUSADE score ≤40 (hazard ratio for bleeding 1.50, P=0.25; hazard ratio for transfusions 1.37, P=0.44), with positive interaction (P int=0.05 and P int=0.01, respectively). The number of patients with high CRUSADE scores needed to treat for harm for major bleeding and transfusion were 17 and 15, respectively, with 24‐month rather than 6‐month dual antiplatelet therapy; corresponding figures in the overall population were 67 and 71, respectively. Conclusions Our analysis suggests that the CRUSADE score predicts major bleeding similarly to ACUITY and better than HAS BLED in an all‐comer population with percutaneous coronary intervention and potentially identifies patients at higher risk of hemorrhagic complications when treated with a long‐term dual antiplatelet therapy regimen. Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT00611286.

Endothelial Functions in Pathophysiology of Thrombosis and Fibrinolysis: Late Spontaneous Recanalization of an Occluded Internal Carotid Artery: A Case Report

The use of oral contraceptives is a potential cause of ischemic stroke in young women. The risk of stroke is higher when contraceptives contain high levels of estrogens. A thrombotic occlusion of the right internal carotid artery, seen on ultrasound, developed in a patient who was taking high-dose estrogen contraception. Recanalization occurred several months later by spontaneous thrombolysis and was confirmed by cerebral angiography. This case suggests that the activation of endothelial spontaneous antithrombotic mechanisms may allow the dissolution of a thrombus, once the cause of the thrombosis has been identified and removed and when the endothelium has maintained its functional integrity.

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with chronic kidney disease: A systematic review and network meta-analysis

BACKGROUND Currently there is lack of head-to-head comparisons between different Non-Vitamin K Antagonist Oral Anticoagulants (NOACs), especially in more risky subgroups, as those with chronic kidney disease (CKD). METHODS We assessed the relative efficacy and safety of the four NOACs on the market in a systematic review and network meta-analysis of patients with atrial fibrillation (AF) and moderate CKD enrolled in the phase 3 randomized trials. A Bayesian framework was used to perform the network meta-analysis. Treatment hierarchy was assessed by surface under the cumulative ranking (SUCRA) curves. RESULTS Five randomized trials including 13,878 AF patients with moderate CKD were identified. Full/Single dose NOACs were associated with significant reductions in the odds of stroke/systemic embolism (odd ratio [OR] 0.79, 95% credible intervals [CrI] 0.67-0.94) and major bleeding (OR 0.74, 95% CrI 0.65-0.86) compared with Warfarin. Dabigatran 150 had the highest probability of being ranked first with respect to efficacy (SUCRA 0.96), whereas Apixaban had the second highest (SUCRA 0.67); Dabigatran 110, Rivaroxaban and Edoxaban High-Dose showed similar probabilities of being ranked first for efficacy (SUCRA 0.54, 0.53, 0.51, respectively); with respect to safety, only Apixaban and Edoxaban High Dose had a probability >50% of being ranked first (SUCRA 0.84 and 0.61, respectively). CONCLUSIONS Indirect comparisons generated the hypothesis that Apixaban and Edoxaban High-Dose might be more likely associated with a better net clinical profile in AF patients with moderate CKD. These findings may potentially guide physicians in selecting the most appropriate NOAC for each patient, while waiting for dedicated evidences.