The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for ...low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied.
In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes.
A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups.
After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).
Patients' responses to oral antiplatelet therapy are subject to variation. Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy.
We ...randomly assigned 2440 patients scheduled for coronary stenting at 38 centers to a strategy of platelet-function monitoring, with drug adjustment in patients who had a poor response to antiplatelet therapy, or to a conventional strategy without monitoring and drug adjustment. The primary end point was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation. For patients in the monitoring group, the VerifyNow P2Y12 and aspirin point-of-care assays were used in the catheterization laboratory before stent implantation and in the outpatient clinic 2 to 4 weeks later.
In the monitoring group, high platelet reactivity in patients taking clopidogrel (34.5% of patients) or aspirin (7.6%) led to the administration of an additional bolus of clopidogrel, prasugrel, or aspirin along with glycoprotein IIb/IIIa inhibitors during the procedure. The primary end point occurred in 34.6% of the patients in the monitoring group, as compared with 31.1% of those in the conventional-treatment group (hazard ratio, 1.13; 95% confidence interval CI, 0.98 to 1.29; P=0.10). The main secondary end point, stent thrombosis or any urgent revascularization, occurred in 4.9% of the patients in the monitoring group and 4.6% of those in the conventional-treatment group (hazard ratio, 1.06; 95% CI, 0.74 to 1.52; P=0.77). The rate of major bleeding events did not differ significantly between groups.
This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring. (Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others; ARCTIC ClinicalTrials.gov number, NCT00827411.).
Summary Background Optimum duration of dual antiplatelet treatment (DAPT) after coronary stenting remains uncertain, with an unknown efficacy to safety ratio of extended treatment leading to ...discrepancies between international guidelines and clinical practice. We assessed whether DAPT continuation beyond 1 year after coronary stenting is beneficial. Methods This analysis was a planned extension of the previously published ARCTIC-Monitoring trial, in which we randomly allocated 2440 patients to a strategy of platelet function testing with antiplatelet treatment adjustment or a conventional strategy after coronary stenting with drug-eluting stent (DES). We recruited patients (aged 18 years or older) scheduled for planned DES implantation at 38 centres in France. After 1 year of follow-up, patients without contraindication to interruption of DAPT were eligible for a second randomisation to this second phase of the study (ARCTIC-Interruption). Using a computer-generated randomisation sequence (1:1; stratified by centre), we allocated patients to a strategy of interruption of DAPT where the thienopyridine was interrupted and single aspirin antiplatelet treatment was maintained (interruption group) or a strategy of DAPT continuation for 6–18 months (continuation group). The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularisation, analysed by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00827411. Findings Between Jan 4, 2011, and March 3, 2012, 1259 eligible patients were randomly allocated to treatment in ARCTIC-Interruption: 624 to the interruption group and 635 to the continuation group. After a median follow-up of 17 months (IQR 15–18), the primary endpoint occurred in 27 (4%) patients in the interruption group and 24 (4%) patients in the continuation group (hazard ratio HR 1·17 95% CI 0·68–2·03; p=0·58). STEEPLE major bleeding events occurred more often in the continuation group (seven 1% patients) compared with the interruption group (one <0·5% patient; HR 0·15 0·02–1·20; p=0·073). Major or minor bleedings were also more common in the continuation group compared with the interruption group (12 2% patients vs three 1% patients; HR 0·26 0·07–0·91; p=0·04). Interpretation Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after stenting with DES when no event has occurred within the first year after stenting. No conclusion can be drawn for high-risk patients who could not be randomised. The consistency between findings from all trials of such interruption suggests the need for a reappraisal of guidelines for DAPT after coronary stenting towards shorter duration of treatment. Funding Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION Study Group), Fondation de France, Sanofi-Aventis, Cordis, Medtronic, Boston Scientific, Fondation SGAM.
Abstract
Aims
The aims of the present study were to describe the proportion of patients eligible for the COMPASS trial within the Reduction of Atherothrombosis for Continued Health (REACH) registry, ...the reasons for ineligibility, and to put in perspective the characteristics and outcomes of trial-eligible patients from the REACH registry compared with those of patients enrolled in the reference aspirin arm of the COMPASS trial.
Methods and results
The COMPASS selection and exclusion criteria were applied to REACH patients with either coronary artery disease (CAD) or peripheral artery disease (PAD). We used the COMPASS primary composite outcome of cardiovascular (CV) death, myocardial infarction (MI), or stroke. In REACH, 31 873 patients had CAD or PAD and detailed information allowing evaluation of eligibility. Among these, 9518 (29.9%) patients had exclusion criteria and an additional 5480 patients (17.2%) did not fulfil the inclusion criteria and thus were not eligible. The ‘COMPASS-Eligible’ population therefore comprised 52.9% of the evaluable REACH patients (n = 16 875). The main reasons for exclusion were high-bleeding risk (51.8%), anticoagulant use (44.8%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI with stent, (25.9%), history of ischaemic stroke <1 year (12.4%), and severe renal failure (2.2%). Eligibility was highest among patients with PAD alone (68.4%). COMPASS-Eligible patients from REACH experienced higher annualized primary outcome event rates than patients actually enrolled in the reference aspirin arm of COMPASS (4.2% vs. 2.9% per year, P < 0.001).
Conclusion
COMPASS-Eligible patients represent a substantial fraction of stable CAD/PAD patients encountered in routine clinical practice in the large international REACH registry suggesting good external applicability. COMPASS-Eligible patients experienced a higher rate of the primary outcome compared with COMPASS participants in the aspirin alone treatment arm.
Abstract
Aims
We analysed the early and long-term clinical and haemodynamic outcomes of balloon-expandable transcatheter mitral valve implantation (TMVI) in an experienced centre.
Methods and results
...All patients undergoing TMVI from July 2010 to July 2017 in our centre were prospectively included. Indication for TMVI relied on the judgement of the local heart team. Patients were followed at 1 month, 1 year, and yearly thereafter. A total of 91 patients underwent TMVI. The median age was 73 (57–81) years and 70% of patients were women. Patients were at high risk for surgery with a median EuroSCORE II of 9.6 (4.0–14.6) %. Indication for TMVI was bioprosthesis failure (valve-in-valve) in 37.3%, annuloplasty failure (valve-in-ring) in 33.0%, and severe mitral annulus calcification (MAC) in 29.7%. The transseptal approach was used in 92.3% of patients and balloon-expandable valves were used in all patients. Technical success was achieved in 84.6% of patients, one patient died during the procedure and haemodynamically significant left ventricular outflow tract obstruction occurred in three patients (3.3%). At 30 days, 7.7% of patients had died, without significant differences between groups, and a major stroke occurred in 2.2% of patients. The cumulative rates of all-cause mortality at 1-year and 2-year follow-up were 21.0% 95% confidence interval (CI) 9.9–38.8 and 35.7% (95% CI 19.2–56.5), respectively, with a higher late mortality in patients with MAC. The 2-year rates of re-intervention and valve thrombosis were 8.8% and 14.4%, respectively. At 6 months to 1 year, 68.9% of patients were in New York Heart Association Class I or II, and 90.7% of patients had mild or less mitral regurgitation. The mean transmitral gradient decreased from 9.3 ± 3.9 mmHg at baseline to 6.0 ± 2.3 mmHg at discharge (P < 0.001) without changes at 6-month to 1-year follow-up.
Conclusion
Transcatheter mitral valve implantation using balloon-expandable valves in selected patients with bioprosthesis or annuloplasty failure or severe MAC was associated with a low rate of peri-procedural complications and acceptable long-term outcomes.
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 effects of ticagrelor in the subpopulation of patients with ST-elevation myocardial infarction (STEMI) were consistent with those observed in the overall Platelet Inhibition and Patient Outcomes ...(PLATO) study. However, this subgroup included patients initially or ultimately treated conservatively. The aim of this study is to compare treatment using ticagrelor with treatment using clopidogrel in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).
This post-hoc subgroup analysis compared ticagrelor with clopidogrel in 4949 PLATO patients with STEMI that were treated with primary PCI within 12 h of admission. The primary endpoint was cardiovascular death, myocardial infarction or stroke. The safety endpoint consisted of any major bleeding. Secondary endpoints included stent thrombosis. The analysis was not adequately powered to establish significance of any treatment effects.
During a median of 286 days, the primary endpoint occurred in 7.9% of ticagrelor-treated patients versus 8.6% of clopidogrel-treated patients (HR 0.91, 95% CI 0.75 to 1.12, p=0.38). Major bleeding occurred in 6.7% in ticagrelor-treated patients versus 6.8% of clopidogrel-treated patients (HR 0.97, 95% CI 0.77 to 1.22, p=0.79). No interactions were observed for the treatment effect of ticagrelor versus clopidogrel on the primary efficacy (p=0.40) and primary safety endpoints (p=0.15) as compared with the full PLATO population. Treatment with ticagrelor versus clopidogrel reduced the occurrence of definite stent thrombosis (HR 0.58, 95% CI 0.37 to 0.89, p=0.013).
In the subset of patients with STEMI treated with primary PCI, ticagrelor compared with clopidogrel was safe, and efficacy outcomes were consistent with the overall PLATO trial.
NCT00391872; Results.
The aim of this study was to describe the effects of chronic systemic corticosteroid treatment (SCT) on early and late outcomes after transcatheter aortic valve implantation (TAVI). From October 2006 ...to November 2018, 1,299 patients underwent TAVI in our institution. Among them, 48 (3.7%) received chronic SCT at the time of procedure (SCT group). They were more frequently women (p = 0.08) and needed more often dialysis (p = 0.002). All other baseline characteristics were similar between both groups. At 30 days, there was no difference on mortality. However, after adjustment, the SCT group had more major vascular complications: 16.7% versus 7.4%, hazard ratio (HR) 2.52 (95% confidence interval CI 1.14 to 5.9, p = 0.023), major or life-threatening bleedings: 22.9% versus 12.4%, HR 2.02 (95% CI 1.00 to 4.08, p = 0.05), and tamponades: 8.3% versus 2.4%, HR 4.05 (95% CI 1.35 to 12.15, p <0.001) than the non-SCT group. One-year all-cause mortality was significantly higher in the SCT than in the non-SCT group (37.5% vs 12.5%, p <0.0001). Multivariate analysis confirmed that SCT use was an independent predictor of 1-year mortality (HR 2.29, 95% CI 1.16 to 4.50, p = 0.017). In conclusion, chronic use of SCT significantly increases the rates of early vascular complications, major or life-threatening bleedings and tamponade and is an independent predictor of 1-year all-cause mortality after TAVI.
Objectives This study sought to determine whether red blood cell (RBC) transfusion increases in vivo platelet aggregation and inflammation in coronary and noncoronary patients. Background RBC ...transfusion increases in vitro platelet activation and aggregation in healthy volunteers, providing a possible explanation for the increase in recurrent ischemic events and mortality reported after RBC transfusion in patients with acute coronary syndromes (ACS). Methods Platelet reactivity was measured before and after RBC transfusion in 61 patients (33 with ACS patients and 28 without ACS). Relative changes between baseline and post-transfusion measurements of maximal and residual platelet aggregation were considered with different agonists as well as changes in vasodilator-stimulated phosphoprotein platelet reactivity index and P-selectin expression. Inflammatory and thrombotic biomarkers were also measured before and after transfusion. Results After RBC transfusion, platelet reactivity was increased when measured using adenosine diphosphate–induced light transmission aggregometry (11.6% relative increase in maximal platelet aggregation, p = 0.004; 10.8% increase in residual platelet aggregation, p = 0.005) and vasodilator-stimulated phosphoprotein platelet reactivity index (20.7% relative increase, p = 0.002), and there was a nonsignificant trend toward an increase in P-selectin expression. Similar results were found with the nonspecific agonist thrombin receptor–activated peptide (relative increases of 11.7% for maximal platelet aggregation, p = 0.04, and 12.7% for residual platelet aggregation, p = 0.02) but not with collagen or arachidonic acid agonists. There were no significant differences in inflammatory and thrombotic biomarkers before and after transfusion. Conclusions After RBC transfusion, there is an increase in platelet reactivity, especially with tests measuring the adenosine diphosphate–P2Y12 receptor pathway, without significant variations in inflammatory or thrombotic biomarkers. This in vivo effect may account for the excess of ischemic events observed in the context of patients with ACS treated using percutaneous coronary intervention and P2Y12 inhibitors.
The prognosis of patients with cardiogenic shock (CS) or refractory pulmonary edema because of severe aortic stenosis remains poor. The purpose of this study was to assess the outcomes of rescue ...percutaneous balloon aortic valvuloplasty (PBAV) in the transcatheter aortic valve implantation (TAVI) era. Patients were consecutively included between 2008 and 2016. CS was defined as ≥1 sign of systemic hypoperfusion and need of catecholamines. Refractory pulmonary edema was defined as not controlled by optimal medical treatment. A total of 40 patients, 22 men (55%), aged 79 ± 9 years, were included: 17 with CS (42.5%), 23 with refractory pulmonary edema (57.5%). After PBAV, mean transaortic gradient decreased from 47 ± 16 mm Hg to 32 ± 10 mm Hg (p < 0.001), aortic valve area increased from 0.60 ± 0.18 cm2 to 0.88 ± 0.22 cm2 (p < 0.0001), left ventricular ejection fraction increased from 35 ± 15 to 37 ± 14% (p = 0.02), and systolic pulmonary artery pressure decreased from 61 ± 15 to 48 ± 12 mm Hg (p = 0.002). There was no procedural death. Early death occurred in 12 patients (30%). After PBAV, 16 of the 28 survivors (57%) were bridged to surgical aortic valve replacement (SAVR; n = 7) or TAVI (n = 9), and 12 (43%) were denied definitive therapy. The 2-year estimated survival rate was 71 ± 17% after SAVR, 36 ± 19% after TAVI, and 8 ± 8% after PBAV alone. In conclusion, rescue PBAV is safe in patients with CS and high-risk aortic stenosis or refractory pulmonary edema and may improve their dismal prognosis when followed by TAVI or SAVR.
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