Summary Background Elderly patients are at high risk of ischaemic and bleeding events. Platelet function monitoring offers the possibility to individualise antiplatelet therapy to improve the ...therapeutic risk–benefit ratio. We aimed to assess the effect of platelet function monitoring with treatment adjustment in elderly patients stented for an acute coronary syndrome. Methods We did this multicentre, open-label, blinded-endpoint, randomised controlled superiority study at 35 centres in France. Patients aged 75 years or older who had undergone coronary stenting for acute coronary syndrome were randomly assigned (1:1), via a central interactive voice-response system based on a computer-generated permuted-block randomisation schedule with randomly selected block sizes, to receive oral prasugrel 5 mg daily with dose or drug adjustment in case of inadequate response (monitoring group) or oral prasugrel 5 mg daily with no monitoring or treatment adjustment (conventional group). Randomisation was stratified by centre. Platelet function testing was done 14 days after randomisation and repeated 14 days after treatment adjustment in patients in the monitoring group. Study investigators and patients were not masked to treatment allocation, but allocation was concealed from an independent clinical events committee responsible for endpoint adjudication. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularisation, and Bleeding Academic Research Consortium-defined bleeding complications (types 2, 3, or 5) at 12 months' follow-up. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT01538446. Findings Between March 27, 2012, and May 19, 2015, we randomly assigned 877 patients to the monitoring group (n=442) or the conventional group (n=435). The primary endpoint occurred in 120 (28%) patients in the monitoring group compared with 123 (28%) patients in the conventional group (hazard ratio HR, 1·003, 95% CI 0·78–1·29; p=0·98). Rates of bleeding events did not differ significantly between groups. Interpretation Platelet function monitoring with treatment adjustment did not improve the clinical outcome of elderly patients treated with coronary stenting for an acute coronary syndrome. Platelet function testing is still being used in many centres and international guidelines still recommend platelet function testing in high-risk situations. Our study does not support this practice or these recommendations. Funding Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.
The incidence, correlates, and prognostic implications of pulmonary hypertension (PH) are unclear in patients with severe aortic stenosis (AS). We studied 509 patients with severe AS evaluated for ...transcatheter aortic valve implantation (TAVI). Patients were divided into groups based on pulmonary artery systolic pressure (PASP): group I, 161 (31.6%) with PASP <40 mm Hg; group II, 175 (34.3%) with PASP 40 to 59 mm Hg; and group III, 173 (33.9%) with PASP ≥60 mm Hg. Group III patients were more symptomatic and had higher creatinine levels and higher left ventricular end-diastolic pressure. Transpulmonary gradient was >12 mm Hg in 17 patients (10.5%), 31 patients (17.7%), and 80 patients (46.2%) in groups I through III, respectively. In a median follow-up of 202 days (73 to 446) mortality rates were 35 (21.7%), 69 (39.3%), and 85 (49.1%) in groups I through III, respectively (p <0.001). Immediately after TAVI, in patients with PASP >40 mm Hg there was significant decrease in PASP (63.1 ± 16.2 to 48.8 ± 12.4 mm Hg, p <0.0001), which remained at 1 year (50.1 ± 13.1 mm Hg, p = 0.04). After surgical aortic valve replacement there was a significant immediate decrease in PASP (66.1 ± 16.3 to 44.7 ± 14.2 mm Hg, p <0.0001), which persisted at 3 to 12 months (44.8 ± 20.1 mm Hg, p <0.001). In patients who underwent balloon aortic valvuloplasty, PASP decreased immediately after the procedure (63.2 ± 14.8 to 51.8 ± 17.1 mm Hg, p <0.0001), yet at 3 to 12 months pressure returned to baseline levels (57.4 ± 17.0 mm Hg, p = 0.29). In conclusion, patients with severe AS have a high prevalence of PH, and in patients with severe AS increased PASP is associated with increased mortality. Surgical aortic valve replacement and TAVI are effective treatments for these patients and result in a significant PASP decrease.
Background Elderly patients are at high risk for both ischemic and bleeding events. Platelet monitoring offers the opportunity to individualized antiplatelet therapy to optimize the therapeutic ...risk/benefit ratio. Study design The ANTARCTIC study is designed to demonstrate the superiority of a strategy of platelet function monitoring with dose and drug adjustment in patients initially on prasugrel 5 mg as compared with a more conventional strategy using prasugrel 5 mg without monitoring and without adjustment (Conventional Treatment Arm) to reduce the primary end point evaluated 1 year after stent percutaneous coronary intervention in elderly patients presenting with an acute coronary syndrome (ACS). ANTARCTIC is a multicenter, prospective, open-label study with 2 parallel arms. A total of 852 elderly patients (≥75 years) undergoing stent percutaneous coronary intervention for ACS are to be enrolled. The primary end point is the time to first occurrence of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis, urgent revascularization, and bleeding complications (Bleeding Academic Research Consortium definition 2, 3, or 5). Platelet function analyses will be performed 14 days after randomization and repeated 14 days later in patients who require a change in treatment. Conclusion ANTARCTIC is a nationwide, prospective, open-label study testing a strategy of platelet function monitoring with dose and drug adjustment to reduce ischemic and bleeding complications in elderly ACS patients undergoing coronary stenting.
Abstract Background The minimalist immediate mechanical intervention (MIMI) strategy aims to restore normal anterograde flow in the culprit artery (by using manual thrombectomy or small-sized balloon ...predilation) and to defer potential stent implantation. This study evaluated the applicability and midterm clinical results of the MIMI strategy for ST-elevation myocardial infarction (STEMI) management. Methods This observational study included consecutive patients admitted for ongoing STEMI (<24 hours' evolution) at 1 institution between June 2010 and June 2013. Revascularization was performed at the physician's discretion. We compared retrospectively “intentional immediate stenting” (standard technique) and “intentional delayed stenting” (MIMI technique). Results Twenty percent of the 279 included patients were treated with the MIMI strategy. These patients were significantly younger and were more frequently men and smokers compared with patients who underwent the standard procedure. The rate of acute reocclusion of the culprit artery related to STEMI in the MIMI group was 1.8%. Drug-eluting stents were used more frequently in the MIMI group (52% vs 27% in the standard group; P < 0.001). The culprit lesion was stented less frequently in the patients treated with MIMI compared with patients in the other group (28.5% vs 9%; P < 0.001). The 1-year actuarial survival free from major adverse cardiovascular events was higher in the MIMI group than in the standard group (96.3% ± 1.8% vs 83.8% ± 2.5%; P = 0.01). Conclusions The MIMI strategy can be applied in selected patients with STEMI. In our centre, this strategy is associated with less systematic culprit lesion stenting and more implantation of drug-eluting stents. However, this needs to be evaluated further in a randomized trial.
We evaluated the safety and efficacy of dual antiplatelet therapy, in association with oral anticoagulant (OAC) therapy, in patients undergoing percutaneous coronary intervention (PCI). The use of ...this triple therapy increases the rate of adverse outcomes, as shown by retrospective studies. In this first prospective multicenter registry STENTIng and oral antiCOagulation (STENTICO), all patients with OAC therapy undergoing PCI were included and followed up at 2 and 12 months. A total of 359 patients were included from 40 French centers. In 234 (65.2%; group 1) of these 359 patients, OAC therapy was discontinued (22 ± 31 days). In 125 patients (34.8%; group 2), triple therapy was continued. The baseline characteristics were similar in the 2 groups. In group 2, a radial approach was more often used (65.6% vs 43.8%, p = 0.003), fewer drug-eluting stents were implanted (33.3% vs 24.8%, p = 0.06), and fewer anti-glycoprotein IIb/IIIa antagonists were prescribed (5.6% vs 8.5%, p = 0.02). The stroke rate did not differ significantly, at 3.0% (95% confidence interval 0.8% to 5.2%) for group 1 versus 0.8% (95% confidence interval −0.8% to 2.4%) in group 2. Severe and moderate bleeding, according to the Global Use of Strategies to Open Coronary Arteries (GUSTO) criteria, occurred in 2.1% and 6.4% of groups 1 and 2, respectively (p = 0.04). A significant difference in bleeding risk was found between the femoral and radial approaches (10.3% vs 3.8%, respectively; p = 0.01). In conclusion, adding dual antiplatelet therapy to pre-existing OAC therapy increases the post-PCI bleeding risk. Temporary discontinuation decreased this bleeding risk but tended to increase the risk of stroke. A radial approach for PCI could be a good alternative to the conventional femoral route to avoid bleeding.
Background Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of ...subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. Methods CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow ≤1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1:1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in the minutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. Results Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. Conclusions The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.
With femoral access, bivalirudin decreases risks of major bleeding after percutaneous coronary intervention (PCI) and provides better net clinical benefit compared to unfractionated heparin (UFH) ...plus planned glycoprotein IIb/IIIa inhibitors. Whether this benefit exists compared to UFH monotherapy is less clear. We performed a systematic review and meta-analysis to compare outcomes in patients undergoing transfemoral PCI with UFH or bivalirudin. Randomized trials (n = 3) and observational studies (n = 13) comparing bivalirudin to UFH monotherapy were reviewed. Primary outcomes were 30-day rates of major adverse cardiovascular events (MACEs) including death, myocardial infarction (MI), urgent revascularization, as well as all-cause mortality, MI, major bleeding, and blood transfusion. We collected data from 16 studies involving 32,492 patients undergoing PCI. Most observational studies were performed in the United States, whereas all randomized trials were done in Europe. Compared to UFH monotherapy, bivalirudin was associated with similar risk of MACEs (odds ratios OR 0.92, 95% confidence interval CI 0.75 to 1.12), a substantial 45% relative decrease in major bleeding (OR 0.55, 95% CI 0.43 to 0.72), and a trend in the decrease of transfusion (OR 0.87, 95% CI 0.70 to 1.08). A decrease in mortality was seen in observational studies (OR 0.62, 95% CI 0.45 to 0.85) but remained inconclusive in randomized trials (OR 0.63, 95% CI 0.20 to 2.01). MI rate was similar with the 2 anticoagulants. In conclusion, in patients undergoing transfemoral PCI, the benefit of bivalirudin over UFH monotherapy is driven by a significant decrease in major bleeding with similar rates of MACE. As PCI practice moves toward other bleeding-avoidance strategies such as the radial approach, future studies should focus on the interaction between anticoagulant strategy and access-site choice.
Early Aldosterone Blockade in Acute Myocardial Infarction Beygui, Farzin, MD, PhD; Cayla, Guillaume, MD, PhD; Roule, Vincent, MD ...
Journal of the American College of Cardiology,
04/2016, Letnik:
67, Številka:
16
Journal Article
Recenzirano
Odprti dostop
Abstract Background Mineralocorticoid receptor antagonists (MRA) improve outcome in the setting of post–myocardial infarction (MI) heart failure (HF). Objectives The study sought to assess the ...benefit of an early MRA regimen in acute MI irrespective of the presence of HF or left ventricular (LV) dysfunction. Methods We randomized 1,603 patients to receive an MRA regimen with a single intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) for 6 months in addition to standard therapy or standard therapy alone. The primary outcome of the study was the composite of death, resuscitated cardiac arrest, significant ventricular arrhythmia, indication for implantable defibrillator, or new or worsening HF at 6-month follow-up. Key secondary/safety outcomes included death and other individual components of the primary outcome and rates of hyperkalemia at 6 months. Results The primary outcome occurred in 95 (11.8%) and 98 (12.2%) patients in the treatment and control groups, respectively (hazard ratio HR: 0.97; 95% confidence interval CI: 0.73 to 1.28). Death occurred in 11 (1.4%) and 17 (2.1%) patients in the treatment and control groups, respectively (HR: 0.65; 95% CI: 0.30 to 1.38). In a non–pre-specified exploratory analysis, the odds of death were reduced in the treatment group (3 0.5% vs. 15 2.4%; HR: 0.20; 95% CI: 0.06 to 0.70) in the subgroup of ST-segment elevation MI (n = 1,229), but not in non–ST-segment elevation MI (p for interaction = 0.01). Hyperkalemia >5.5 mmol/l–1 occurred in 3% and 0.2% of patients in the treatment and standard therapy groups, respectively (p < 0.0001). Conclusions The study failed to show the benefit of early MRA use in addition to standard therapy in patients admitted for MI. (Aldosterone Lethal effects Blockade in Acute myocardial infarction Treated with or without Reperfusion to improve Outcome and Survival at Six months follow-up; NCT01059136 ).
Background The association between obesity and bleeding after percutaneous coronary intervention (PCI) is not well defined. We investigated the impact of body mass index (BMI) on PCI-related ...bleeding, and whether bivalirudin, compared to heparin, used as PCI anticoagulant modifies this relationship. Methods From 2000 to 2009, 16,783 patients who underwent PCI were grouped according to 6 BMI groups: underweight (<18.5 kg/m2 ), “normal” weight (18.5-24.9 kg/m2 ), overweight (25-29.9 kg/m2 ), class I (30-34.9 kg/m2 ), class II (35-39.9 kg/m2 ), and class III obesity (≥40 kg/m2 ). Bivalirudin was used in 11,433 patients and heparin in 5,350. In-hospital major bleeding (hematocrit drop ≥15% or gastrointestinal bleeding) and need for transfusion rates were collected. Results The incidence of major bleeding varied significantly throughout the BMI spectrum (5.6% vs 2.5% vs 1.9% vs 1.6% vs 2.1% vs 1.9%, respectively, from underweight to class III obese patients, P < .001). The incidence of transfusion across BMI followed the same reverse J-shape curve (10.9% vs 6.6% vs 3.6% vs 3.4% vs 3.8% vs 5.6%, P < .001). After adjustment for potential confounding factors, underweight patients had neither an increased risk for major bleeding nor an increased risk for transfusion compared with “normal” weight patients. Class I obese patients had a lower risk of major bleeding (odds ratio OR 0.68 95% CI 0.48-0.97). Overweight, class I, and II obese patients had a lower risk of transfusion (respectively, OR 0.68 0.55-0.84, 0.68 0.53-0.87, and 0.66 0.48-0.92). The highest BMI patients had neither an increased risk for major bleeding (class II and III obesity) nor an increased risk for transfusion (class III obesity). The same reverse J-shaped relationship to BMI seen in the overall population for the raw incidence of major bleeding was found when the population was divided according to type of anticoagulant used as follows: bivalirudin or heparin. Likewise, the “need for transfusion” relationship to BMI is not altered by bivalirudin use. Conclusion The better outcome for bleeding seen in patients in the middle of the BMI spectrum suggests the existence of a “bleeding obesity paradox,” which persists after adjustment by confounding factors and exists irrespective of the anticoagulant used.
Abstract Background Whether academic hospitals provide better quality of care for patients with acute myocardial infarction is widely debated. The aim of this study was to compare processes of care ...and mortality between academic and nonacademic hospitals in the contemporary era of acute myocardial infarction management. Methods We analyzed the original data from a prospective cohort study of 3059 patients, including 1714 with ST-segment elevation and 1345 with non-ST-segment elevation myocardial infarction, enrolled at 39 and 183 academic and nonacademic hospitals, respectively, in France. Results Unadjusted 1-year mortality for academic and nonacademic hospitals was 10% versus 15% for patients with ST-segment elevation myocardial infarction ( P = .01) and 13% versus 14% for patients with non-ST-segment elevation myocardial infarction ( P = .75). Patients treated in academic or nonacademic hospitals with percutaneous coronary intervention capability were more likely to receive reperfusion and recommended drug therapies than those treated in nonacademic hospitals without percutaneous coronary intervention capability. After adjusting for baseline characteristics, the hazards of death associated with admission to nonacademic hospitals with and without percutaneous coronary intervention capability relative to academic hospitals were 1.13 (95% confidence interval CI, 0.79-1.62) and 1.65 (95% CI, 1.09-2.49) for those with ST-segment elevation myocardial infarction and 0.95 (95% CI, 0.66-1.36) and 1.06 (95% CI, 0.72-1.58) for those with non-ST-segment elevation myocardial infarction, respectively. Further adjustment for receipt of acute reperfusion and recommended drug therapies eliminated all differences in mortality between the study groups. Conclusion Admission to academic hospitals was associated with a more frequent use of recommended therapies, conveying a survival advantage for patients with ST-segment elevation myocardial infarction.
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