Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin: The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study Martine Gilard, Bertrand Arnaud, ...Jean-Christophe Cornily, Grégoire Le Gal, Karine Lacut, Geneviève Le Calvez, Jacques Mansourati, Dominique Mottier, Jean-François Abgrall, Jacques Boschat In a previous observational study, we found the effect of clopidogrel as tested by vasodilator-stimulated phosphoprotein (VASP) phosphorylation to be diminished in patients receiving proton pump inhibitor treatment. In this double-blind placebo-controlled trial, 124 consecutive patients were randomized to receive either associated omeprazole (20 mg/day) or placebo for 7 days. The clopidogrel effect was tested on Day 1 and Day 7 in both groups by measuring platelet phosphorylated VASP. Our main end point was to compare platelet activation in the 2 groups. Omeprazole significantly decreased the antiplatelet effect of clopidogrel as assessed by a VASP phosphorylation test (p < 0.0001).
New-onset left bundle branch block (LBBB) is a specific concern of transcutaneous aortic valve implantation (TAVI) given its estimated incidence ranging from 5% to 65%. This high rate of occurrence ...is dependent on the type of device used (size and shape), implantation methods, and patient co-morbidities. The appearance of an LBBB after TAVI reflects a very proximal lesion of the left bundle branch as it exits the bundle of His. At times transient, its persistence can lead to permanent pacemaker implantation in 15% to 20% of cases, most often for high-degree atrioventricular block. The management of LBBB after TAVI is currently not defined by international societies resulting in individual centers developing their own management strategy. The potential consequences of LBBB are dysrhythmias (atrioventricular block, syncope, and sudden death) and functional (heart failure) complications. Prompt postprocedural recognition and management (permanent pacemaker implantation) of patients prevents the occurrence of potential complications and may constitute the preferred approach in this frail and elderly population despite additional costs and complications of cardiac pacing. Moreover, the expansion of future indications for TAVI necessitates better identification of the predictive factors for the development of LBBB. Indeed, long-term right ventricular pacing may potentially increase the risk of developing heart failure in this population. In conclusion, it is thus imperative to not only develop new aortic prostheses with a less-deleterious impact on the conduction system but also to prescribe appropriate pacing modes in this frail population.
Abstract Background Peripheral venous (PV) cannulation, one of the most common technical procedures in Emergency Medicine, may prove challenging, even to experienced Emergency Department (ED) staff. ...Morbid obesity (body mass index BMI ≥ 40) has been reported as a risk factor for PV access failure in the operating room. Objectives We investigated PV access difficulty in the ED, across BMI categories, focusing on patient-related predicting factors. Methods Prospective, observational study including adult patients requiring PV lines. Operators were skilled nurses and physicians. PV accessibility was clinically evaluated before all cannulation attempts, using vein visibility and palpability. Patient and PV placement characteristics were recorded. Primary outcome was failure at first attempt. Outcome frequency and comparisons between groups were examined. Predictors of difficult cannulation were explored using logistic regression. A p -value <0.05 was considered significant. Results PV lines were placed in 563 consecutive patients (53 ± 23 years, BMI: 26 ± 7 kg/m2 ), with a success rate of 98.6%, and a mean attempt of 1.3 ± 0.7 (range 1–7). Failure at the first attempt was recorded in 21% of patients (95% confidence interval CI 17.6–24.4). Independent risk factors were: a BMI ≥ 30 (odds ratio OR 1.98, 95% CI 1.09–3.60), a BMI < 18.5 (OR 2.24; 95% CI 1.07–4.66), an unfavorable (OR 1.66, 95% CI 1.02–2.69), and very unfavorable clinical assessment of PV accessibility (OR 2.38, 95% CI 1.15–4.93). Conclusion Obesity, underweight, an unfavorable, and a very unfavorable clinical evaluation of PV accessibility are independent risk factors for difficult PV access. Early recognition of patients at risk could help in planning alternative approaches for achieving rapid PV access.
Abstract Since the publication of the 2012 guidelines new literature has emerged to inform decision-making. The 2016 guidelines primary panel selected a number of clinically relevant questions and ...has produced updated recommendations, on the basis of important new findings. In subjects with clinical atherosclerosis, abdominal aortic aneurysm, most subjects with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy is recommended. For all others, there is an emphasis on risk assessment linked to lipid determination to optimize decision-making. We have recommended nonfasting lipid determination as a suitable alternative to fasting levels. Risk assessment and lipid determination should be considered in individuals older than 40 years of age or in those at increased risk regardless of age. Pharmacotherapy is generally not indicated for those at low Framingham Risk Score (FRS; <10%). A wider range of patients are now eligible for statin therapy in the FRS intermediate risk category (10%-19%) and in those with a high FRS (> 20%). Despite the controversy, we continue to advocate for low-density lipoprotein cholesterol targets for subjects who start therapy. Detailed recommendations are also presented for health behaviour modification that is indicated in all subjects. Finally, recommendation for the use of nonstatin medications is provided. Shared decision-making is vital because there are many areas in which clinical trials do not fully inform practice. The guidelines are meant to be a platform for meaningful conversation between patient and care provider so that individual decisions can be made for risk screening, assessment, and treatment.
The efficacy and safety of anticoagulant treatment is not established for patients with acute symptomatic deep vein thrombosis (DVT) of the calf. We aimed to assess whether therapeutic ...anticoagulation is superior to placebo in patients with symptomatic calf DVT.
In this randomised, double-blind, placebo-controlled trial, we enrolled low-risk outpatients (without active cancer or previous venous thromboembolic disease) with a first acute symptomatic DVT in the calf from 23 university medical centres or community medical clinics in Canada, France, and Switzerland. We randomly assigned (1:1) patients to receive either the low-molecular-weight heparin nadroparin (171 UI/kg, subcutaneously, once a day) or placebo (saline 0·9%, subcutaneously, once a day) for 6 weeks (42 days). Central randomisation was done using a computer-generated randomisation list, stratified by study centre. Random allocation sequences of variable block size were centrally determined by an independent research clinical centre. Study staff, patients, and outcome assessors (central adjudication committee) were masked to group assignment. Numbered boxes of active drug or placebo were provided to pharmacies in identical packaging. All patients were prescribed compression stockings and followed up for 90 days. The primary efficacy outcome was a composite measure of extension of calf DVT to proximal veins, contralateral proximal DVT, and symptomatic pulmonary embolism at day 42 in the modified intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding at day 42. The trial was registered with ClinicalTrials.gov, number NCT00421538.
Between Feb 1, 2008, and Nov 30, 2014, we screened 746 patients, enrolling 259 patients (50% of the prespecified sample size), before the trial steering committee terminated the trial because of expiry of study drug and slow recruitment. The intention-to-treat analysis population comprised 122 patients in the nadroparin group and 130 in the placebo group. There was no significant difference between the groups in the composite primary outcome, which occurred in four patients (3%) in the nadroparin group and in seven (5%) in the placebo group (risk difference -2·1%, 95% CI -7·8 to 3·5; p=0·54). Bleeding occurred in five patients (4%) in the nadroparin group and no patients in the placebo group (risk difference 4·1, 95% CI 0·4 to 9·2; p=0·0255). In the nadroparin group one patient died from metastatic pancreatic cancer and one patient was diagnosed with heparin-induced thrombocytopenia type 2.
Nadroparin was not superior to placebo in reducing the risk of proximal extension or venous thromboembolic events in low-risk outpatients with symptomatic calf DVT, but did increase the risk of bleeding. Avoidance of systematic anticoagulation for calf DVT could have a substantial impact on individual patients and from a public health perspective.
Swiss National Science Foundation, the Programme Hospitalier de Recherche Clinique in France, and the Canadian Institutes of Health Research.
To validate the feasibility and tolerance of an intensive rehabilitation protocol initiated during the postoperative period in an intensive care unit (ICU) in liver transplant recipients.
Prospective ...randomized study.
ICU.
Liver transplant recipients over a period of 1 year (N=40).
The "usual treatment group" (n=20), which benefited from the usual treatment applied in the ICU (based on physician prescription for the physiotherapist, with one session a day), and the experimental group (n=20), which followed a protocol of early and intensive rehabilitation (based on a written protocol validated by physicians and an evaluation by physiotherapist, with 2 sessions a day), were compared.
Our primary aims were tolerance, assessed from the number of adverse events during rehabilitation sessions, and feasibility, assessed from the number of sessions discontinued.
The results revealed a small percentage of adverse events (1.5% in the usual treatment group vs 1.06% in the experimental group) that were considered to be of low intensity. Patients in the experimental group sat on the edge of their beds sooner (2.6 vs 9.7d; P=.048) and their intestinal transit resumed earlier (5.6 vs 3.7d; P=.015) than patients in the usual treatment group. There was no significant difference between the 2 arms regarding length of stay (LOS), despite a decrease in duration in the experimental group.
The introduction of an intensive early rehabilitation program for liver transplant recipients was well tolerated and feasible in the ICU. We noted that the different activities proposed were introduced sooner in the experimental group. Moreover, there is a tendency to decreased LOS in the ICU for the experimental group. These results now need to be confirmed by studies on a larger scale.
Abstract Many developments have occurred since the publication of the widely-used 2009 Canadian Cardiovascular Society (CCS) Dyslipidemia guidelines. Here, we present an updated version of the ...guidelines, incorporating new recommendations based on recent findings and harmonizing CCS guidelines with those from other Societies. The G rading of R ecommendations A ssessment, D evelopment and E valuation (GRADE) system was used, per present standards of the CCS. The total cardiovascular disease Framingham Risk Score (FRS), modified for a family history of premature coronary disease, is recommended for risk assessment. Low-density lipoprotein cholesterol remains the primary target of therapy. However, non-high density lipoprotein cholesterol has been added to apolipoprotein B as an alternate target. There is an increased emphasis on treatment of higher risk patients, including those with chronic kidney disease and high risk hypertension. The primary panel has recommended a judicious use of secondary testing for subjects in whom the need for statin therapy is unclear. Expanded information on health behaviours is presented and is the backbone of risk reduction in all subjects. Finally, a systematic approach to statin intolerance is advocated to maximize appropriate use of lipid-lowering therapy. This document presents the recommendations and principal conclusions of this process. Along with associated Supplementary Material that can be accessed online, this document will be part of a program of knowledge translation. The goal is to increase the appropriate use of evidence-based cardiovascular disease event risk assessment in the management of dyslipidemia as a fundamental means of reducing global risk in the Canadian population.
Objectives The study aimed to evaluate inclacumab for the reduction of myocardial damage during a percutaneous coronary intervention (PCI) in patients with non–ST-segment elevation myocardial ...infarction. Background P-selectin is an adhesion molecule involved in interactions between endothelial cells, platelets, and leukocytes. Inclacumab is a recombinant monoclonal antibody against P-selectin, with potential anti-inflammatory, antithrombotic, and antiatherogenic properties. Methods Patients (N = 544) with non–ST-segment elevation myocardial infarction scheduled for coronary angiography and possible ad hoc PCI were randomized to receive 1 pre-procedural infusion of inclacumab 5 or 20 mg/kg or placebo. The primary endpoint, evaluated in patients who underwent PCI, received study medication, and had available efficacy data (n = 322), was the change in troponin I from baseline at 16 and 24 h after PCI. Results There was no effect of inclacumab 5 mg/kg. Placebo-adjusted geometric mean percent changes in troponin I with inclacumab 20 mg/kg were −24.4% at 24 h (p = 0.05) and −22.4% at 16 h (p = 0.07). Peak troponin I was reduced by 23.8% (p = 0.05) and area under the curve over 24 h by 33.9% (p = 0.08). Creatine kinase-myocardial band yielded similar results, with changes of −17.4% at 24 h (p = 0.06) and −16.3% at 16 h (p = 0.09). The incidence of creatine kinase-myocardial band increases >3 times the upper limit of normal within 24 h was 18.3% and 8.9% in the placebo and inclacumab 20-mg/kg groups, respectively (p = 0.05). Placebo-adjusted changes in soluble P-selectin level were −9.5% (p = 0.25) and −22.0% (p < 0.01) with inclacumab 5 and 20 mg/kg. There was no significant difference in adverse events between groups. Conclusions Inclacumab appears to reduce myocardial damage after PCI in patients with non–ST-segment elevation myocardial infarction. (A Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction Non-STEMI Undergoing Percutaneous Coronary Intervention; NCT01327183 )
Abstract Objectives The purpose of this study was to assess whether the benefits conferred by radial access (RA) at an individual level are offset by a proportionally greater incidence of vascular ...access site complications (VASC) at a population level when femoral access (FA) is performed. Background The recent widespread adoption of RA for cardiac catheterization has been associated with increased rates of VASCs when FA is attempted. Methods Logistic regression was used to calculate the adjusted VASC rate in a contemporary cohort of consecutive patients (2006 to 2008) where both RA and FA were used, and compared it with the adjusted VASC rate observed in a historical control cohort (1996 to 1998) where only FA was used. We calculated the adjusted attributable risk to estimate the proportion of VASC attributable to the introduction of RA in FA patients of the contemporary cohort. Results A total of 17,059 patients were included. At a population level, the VASC rate was higher in the overall contemporary cohort compared with the historical cohort (adjusted rates: 2.91% vs. 1.98%; odds ratio OR: 1.48, 95% confidence interval CI: 1.17 to 1.89; p = 0.001). In the contemporary cohort, RA patients experienced fewer VASC than FA patients (adjusted rates: 1.44% vs. 4.19%; OR: 0.33, 95% CI: 0.23 to 0.48; p < 0.001). We observed a higher VASC rate in FA patients in the contemporary cohort compared with the historical cohort (adjusted rates: 4.19% vs. 1.98%; OR: 2.16, 95% CI: 1.67 to 2.81; p < 0.001). This finding was consistent for both diagnostic and therapeutic catheterizations separately. The proportion of VASCs attributable to RA in the contemporary FA patients was estimated at 52.7%. Conclusions In a contemporary population where both RA and FA were used, the safety benefit associated with RA is offset by a paradoxical increase in VASCs among FA patients. The existence of this radial paradox should be taken into consideration, especially among trainees and default radial operators.
Objective To describe, from the point of view of anesthesia and intensive care specialists, the perioperative management of high-risk patients with aortic stenosis who underwent transcatheter ...(transfemoral and transapical) aortic valve implantation (TAVI). The authors specifically focused on immediate postoperative complications. Design Retrospective review of collected data. Setting Academic hospital. Participants Ninety consecutive patients with severe aortic stenosis who underwent TAVI. Interventions General anesthesia followed by postoperative care. Complications were defined by pre-established criteria. Measurements and Main Results Of 184 patients referred between October 2006 and February 2009, 90 were consecutively treated with TAVI because of a high surgical risk or contraindications to surgery. The transfemoral approach was used as the first option (n = 62), and the transapical approach when contraindications to the former were present (n = 28). Results are presented as mean ± standard deviation or median (25-75 percentiles) as appropriate. Patients were 81 ± 8 years old, in New York Heart Association classes II (9%), III (54 %), or IV (37%); left ventricular ejection fraction was below 0.5 in 38% of patients. The predicted surgical mortality was 24% (16-32) and 15% (11-23) with the logistic EuroSCORE and STS-Predicted Risk of Mortality, respectively. The valve was implanted in 92% of the cases. The duration of anesthesia and (intra- and postoperative) mechanical ventilation was 190 (160-230) minutes and 245 (180-420) minutes, respectively. Hospital mortality was 11%. The most frequent cardiac complications were heart failure (20%) and atrioventricular block (16%), with 6% requiring a pacemaker. Vascular complications (major and minor) occurred in 29% of the patients. Conclusions Despite their severe comorbidities, the mortality of the patients in this cohort was below that predicted by cardiac surgery risk scores. Monitoring, hemodynamic instability, and the frequency of complications require management and follow-up of these patients in similar ways as for open cardiac surgery. The frequency of complications in this cohort was comparable to that published by other groups.
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