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The continuous progress in cardiovascular (CV) risk prevention strategies has led to an impressive reduction in mortality and recurrent ischemic events in patients with coronary artery disease (CAD). However, the control of several CV risk factors remains suboptimal in many CAD patients, with a high rate of recurrent events, underlying the need for more new prevention strategies. The GAPS-I (GLP1 analogues, Antithrombotic agents, PCSK9 inhibitors, SGLT2 inhibitors and Immunomodulators) strategy offers a promising potential in patients with a high-residual CV risk, who are frequently encountered in daily practice, by offering an individualised and structured approach to addressing their individual risk factors. The current review summarises the evidence to date on each of its components, with respect to clinical outcomes and economic feasibility. The current evidence points to an efficacy of GAPS-I in reducing MACE and mortality, without a compromise on safety, albeit with the need for longer follow-up data. Key Points: - Secondary prevention remains suboptimal in many CAD patients, highlighting the need for innovative prevention strategies. - The present review discusses the current evidence on efficacy of the GAPS-I strategy in reducing MACE and mortality in patients with CAD. - The GAPS-I strategy, if widely adopted, provides a promising potential to assist cardiologists in managing patients at a heightened risk for further CV events.

In the 2020 European Society of Cardiology guidelines on non-ST-segment elevation acute coronary syndromes (NSTE-ACS), the experts proposed to put an end to the equipoise of ticagrelor and prasugrel in addition to aspirin in patients with NSTE-ACS who proceed to percutaneous coronary intervention (PCI). They gave a strong level of recommendation (IIa) in favor of prasugrel over ticagrelor in these patients. We challenge this proposition, which was mainly driven by the results of ISAR-REACT 5, an open-label prospective head-to-head study of a prasugrel-based strategy compared with a ticagrelor-based strategy in patients with ACS undergoing PCI. In addition to the methodological concerns regarding the ISAR-REACT 5 study, we also question this decision in light of the ISAR-REACT 5 diabetes mellitus subgroup analysis and previous studies and meta-analysis that showed no difference between ticagrelor and prasugrel in patients with ACS. Although we agree with the "one size does not fit all" concept for antiplatelet regimens in patients with ACS who proceed to PCI, we believe that the decision to strongly favor prasugrel was premature and not supported enough by the ISAR-REACT 5 results. In our opinion, equipoise remains between the ticagrelor- and prasugrel-based strategies and more data are needed to settle the debate.

In patients admitted for acute myocardial infarction, the communication and transition from specialists to primary care physicians is often delayed, and the information imparted to subsequent healthcare providers (HCPs) may be sub-optimal. A French group of cardiologists, lipidologists and diabetologists decided to establish a consensus to optimize the discharge letter after hospitalization for acute myocardial infarction. The aim is to improve both the timeframe and the quality of the content transmitted to subsequent HCPs, including information regarding baseline assessment, procedures during hospitalization, residual risk, discharge treatments, therapeutic targets and follow-up recommendations in compliance with European Society of Cardiology guidelines. A consensus was obtained regarding a template discharge letter, to be released within two days after patient’s discharge, and containing the description of the patient’s history, risk factors, acute management, risk assessment, discharge treatments and follow-up pathway. Specifically for post acute MI patients, tailored details are necessary regarding the antithrombotic regimen, lipid-lowering and anti-diabetic treatments, including therapeutic targets. Lastly, the follow-up pathway needs to be precisely mentioned in the discharge letter. Additional information such as technical descriptions, imaging, and quality indicators may be provided separately. A template for a standardized discharge letter based on 8 major headings could be useful for implementation in routine practice and help to improve the quality and timing of information transmission between HCPs after acute MI.

International audience; Despite major advances in cardiovascular research over the past decade, women with type 2 diabetes have a high risk of cardiovascular events. Several factors contribute to the poor prognosis for women, including higher levels of frailty and comorbidities, but their cardiovascular risk is underestimated and there is suboptimal implementation and uptitration of new evidence-based therapies, leading to high morbidity and mortality. Recent studies highlight the need for better management of diabetes in women that can be pursued and achieved in light of recent results from randomised controlled trials demonstrating evidence of the benefits of new therapeutic strategies in improving cardiovascular outcomes and quality of life of women covering the entire cardiovascular continuum. This review critically discusses the multiple benefits for women of new pharmacological treatments, such as glucagon-like peptide-1 receptor agonists, sodium–glucose cotransporter type 2 inhibitors (SGLT2i), proprotein convertase subtilisin/kexin type 9 inhibitors, inclisiran, icosapent ethyl and bempedoic acid in preventing cardiovascular events, and treatments, such as angiotensin receptor neprilysin inhibitors, SGLT2i, vericiguat and omecamtiv mecarbil, for preventing heart failure.

Heart failure (HF) has high event rates, mortality, and is challenging to manage in clinical practice. Clinical management is complicated by complex therapeutic strategies in a population with a high prevalence of comorbidity and general frailty. In the last four years, an abundance of research has become available to support multidisciplinary management of heart failure from within the hospital through to discharge and primary care as well as supporting diagnosis and comorbidity management. Within the hospital setting, recent evidence supports sacubitril-valsartan combination in frail, deteriorating or de novo patients with LVEF ≤ 40%. Furthermore, new strategies such as SGLT2 inhibitors and vericiguat provide further benefit for patients with decompensating HF. Studies with tafamidis report major clinical benefits specifically for patients with ATTR cardiac amyloidosis, a remaining underdiagnosed and undertreated disease. New evidence for medical interventions supports his bundle pacing to reduce QRS width and improve haemodynamics as well as ICD defibrillation for non-ischemic cardiomyopathy. The Mitraclip reduces hospitalisations and mortality in patients with symptomatic, secondary mitral regurgitation and ablation reduces mortality and hospitalisations in patients with paroxysmal and persistent atrial fibrillation. In end-stage HF, the 2018 French Heart Allocation policy should improve access to heart transplants for stable, ambulatory patients and, mechanical circulatory support should be considered to avoid deteriorating on the waiting list. In the community, new evidence supports that improving discharge education, treatment and patient support improves outcomes. The authors believe that this review fills the gap between the guidelines and clinical practice and provides practical recommendations to improve HF management.

International audience

Introduction: Advanced heart failure (AdvHF) in HCM was overlooked. Hypothesis: Based on a systematic revision, we described prevalence & outcomes of the main HCM phenotypes responsible for AdvHF, heart transplantation (HTx), LVAD implantation & HF-death. Methods: We classified the HCM profiles responsible for AdvHF in 1) End-stage HCM (ES-HCM) defined by an LVEF≤50%; 2) LVOTO despite optimal medical therapy (OMT) (Refractory HOCM); 3) Nonobstructive HCM with preserved EF (HNOCMpEF). The study screened 130 manuscripts in MEDLINE and EMBASE on AdvHF in HCM patients (pts) published from 2000 till January 2020, in adults. 8 manuscripts were eligible for the analysis. AdvHF was defined by the presence of severe NYHA symptoms (III & IV) because in all the manuscripts this definition was used. Mean follow-up = 7.6 years. Results: Figure 1: Prevalence of phenotypes responsible for AdvHF&HTx/LVAD implantation/HF-Death. Of 205 HCM pts, 119 (58%) underwent HTx, LVAD implantation, or died for HF. Figure 2: Outcome per each clinical phenotype. Conclusions: AdvHF in HCM has an ominous prognosis (58% of pts met HTx/LVAD implantation/HF-death) but with significant differences among the 3 phenotypes. HOCM has a very good outcome, indeed only few cases developed a Refractory HOCM & AdvHF & only 1 died for HF. 29.7% of AdvHF were caused by HNOCMpEF due to massive hypertrophy & restrictive physiology & only 16.4% of them died due to HF. ES-HCM represents the main cause of AdvHF in HCM & the major determinant for poor outcomes among all HCM pts (Only 1/3 of them were event-free). This reflects poor attention and portrays an unmet need for ES-HCM pts. Recently it was demonstrated that an extensive amount of myocardial fibrosis (MF) is the major determinant for ES-evolution. Taken together these findings show the importance of a strict follow-up for HCM pts to timely identify ES-HCM & early start HF OMT. Developing specific therapies to lower the burden of MF & stop adverse remodeling it's crucial.

In 2019, the European Society of Cardiology and European Atherosclerosis Society released a new guideline document with substantial changes regarding the assessment of cardiovascular risk and treatments. The update of high-risk criteria and categories led to a better detection and primary prevention of patients at risk of a first cardiovascular event. Nonetheless, additional efforts are needed for a better inclusion of risk modifiers, especially specific to women, to improve risk stratification and direct primary prevention. Eventually, we discuss how these new guidelines implement PCSK9 inhibitors for very high-risk individuals and the evidence supporting new low-density lipoprotein cholesterol goals below, such as 55 and 40 mg/dL.

Type 2 diabetes mellitus (T2DM) portends high risk of atherosclerotic cardiovascular (CV) events and of CV mortality; moreover, this group of patients has a very high probability of developing heart failure (HF). In this review, we discuss new advances in pharmacological treatment both in CV prevention and in HF management with a special focus on T2DM patients. A large number of randomized clinical trials and meta-analyses provided strong evidence about therapeutic strategies acting on glucose metabolism, such as GLP-1 RA and SGLT2i and about lipid-lowering treatment, such as PCSK9i and icosapent ethyl. Moreover, SGLT2i demonstrated strong evidence of benefit particularly in HF management both in diabetic and non-diabetic patients. The pathophysiological bases of multiple mechanisms of benefit of this class of drug explain the unexpected and remarkable results demonstrated both by prevention trials and by trials dedicated only to HF (like DAPA-HF). These, new drugs in the CV therapeutic armamentarium are establishing a new comprehensive approach from prevention to therapy of HF, giving more emphasis on HF classification in four stages (A→D). New therapies, which are on the horizon, promise to further reduce CV mortality and morbidity in HF patients irrespective of diabetic status.

International audience; Patients with coronary artery disease (CAD) presenting with acute coronary syndrome or undergoing coronary stenting are indicated to treatment with dual antiplatelet therapy (DAPT) combining aspirin with a P2Y12 receptor inhibitor. The management of patients with CAD who present with a complex clinical profile due to multiple comorbidities, and/or undergoing complex interventional procedures, remains challenging as a high risk for both ischemic and bleeding events is often present; hence, the risk-benefit balance on the optimal DAPT duration is difficult to evaluate. The complexity of antiplatelet therapy in CAD patients is due to the fact that this complexity embraces several aspects: the coronary anatomy, the number of vascular districts at risk for atherothrombosis, and patient comorbidities, including global frailty. Recent randomized and epidemiological studies have highlighted subgroups that could benefit from prolonged antithrombotic treatment, as well as frail patients, who may be better suited to a shorter course of therapy. We provide an overview of the current knowledge regarding treatment with DAPT, along with suggestions on its management.

Prasugrel and ticagrelor are preferred over clopidogrel for patients with acute coronary syndrome who underwent percutaneous coronary intervention. We sought to determine the relative merits of 1 agent over the other. Multiple databases were queried to identify relevant randomized control trials (RCTs) and observational cohort studies. Random-effects model was used to calculate an unadjusted odds ratio (OR) for major adverse cardiovascular and cerbrovascular events (MACCE) and its components. A total of 27 (7 RCTs, 20 observational cohort studies) studies comprising 118,266 (prasugrel 62,716, ticagrelor 51,196) patients were included. At 30 days, prasugrel was associated with a significantly lower odds of MACCE (OR 0.75, 95% confidence interval [CI] 0.67 to 0.85, p ≤0.0001) and mortality (OR 0.65, 95% CI 0.59 to 0.71, p ≤0.0001). At 1 year, the overall odds of mortality favored prasugrel (OR 0.79, 95% CI 0.68 to 0.92, p = 0.002), but no significant interdrug difference was seen in terms of MACCE (OR 0.89, 95% CI 0.76 to 1.05, p = 0.16). There was no significant difference in the odds of overall myocardial infarction, revascularization, stent thrombosis, stroke, and major bleeding events between the 2 groups on both 30-day and 1-year follow-up. A subgroup analysis of RCTs data showed no significant difference between prasugrel and ticagrelor in terms of any end point at all time points. In conclusion, prasugrel might have lower odds of MACCE and mortality at 30 days. However, there was no difference in the safety and efficacy end points of 2 drugs at 1 year. The observed transient prasugrel-related mortality benefits were subject to the bias of nonrandomized assignment.

International audience; Purpose of ReviewThere has been significant progress made during the last few decades in the management of atherosclerotic cardiovascular disease (ASCVD). Despite this, residual risk remains an unmet need for secondary prevention and high-risk primary prevention patients. First onset and recurrent cardiovascular events remain a major issue despite recommendations for a healthy lifestyle and current optimal medical therapy, which includes the use of maximally tolerated statin therapy plus or minus add-on ezetimibe therapy.Recent FindingsThese findings have led to the development of new treatments that modulate lipid targets in order to improve prognosis of these patients at highest ASCVD risk. These include inhibitors of proprotein convertase subtilisin/kexin type 9 (evolocumab and alirocumab), an inhibitor of adenosine triphosphate citrate lyase (bempedoic acid), and a high-dose omega-3 formulation (icosapent ethyl), which have been evaluated in large phase III randomized clinical trials and/or currently undergoing continued study. The clinical efficacy of these drugs and their application in cardiovascular prevention are discussed in this review article. Of note, there are other novel lipid-lowering therapeutics with potential cardiovascular benefit, not discussed in this review, that include inhibitors of lipoprotein (a), apolipoprotein CIII, and angiopoietin-like 3. These drugs may also play a future role in reducing residual lipid-mediated ASCVD risk, if efficacy and safety confirmed in cardiovascular outcome trials.SummaryIn this review, we provide an overview of the current knowledge regarding treatment with several new lipid strategies for high-risk patients, along with suggestions on their use in ASCVD prevention management.

PCSK9 protein is a key regulator of LDL receptor activity. Gain-of-function mutations in PCSK9 are one of the genetic causes of familial hypercholesterolemia. Conversely, loss-of-function mutations are associated with lower levels of LDL cholesterol and reduced coronary heart disease. Monoclonal antibodies targeting PCSK9 are highly efficacious in lowering LDL-C levels, with a good tolerability and safety profile. Two PCSK9 inhibitors, alirocumab and evolocumab, have demonstrated a cardiovascular benefit in addition to statin therapy in patients with established cardiovascular disease. A recent European consensus has defined the candidates for PCSK9 inhibitors, e.g., patients with established cardiovascular disease and patients with familial hypercholesterolemia in primary prevention, with substantially elevated LDL-C levels despite maximally tolerated statin with or without ezetimibe therapy.

There is an apparent benefit with extension of dual antiplatelet therapy (DAPT) beyond 1 year after implantation of drug-eluting stents (DES). Assessment by a Double Randomization of a Conventional Antiplatelet Strategy vs a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation, and of Treatment Interruption vs Continuation One Year After Stenting (ARCTIC)-Generation assessed whether there is a difference of outcome between first- vs second-generation DES and if there is an interaction with DAPT duration in the ARCTIC-Interruption study. ARCTIC-Interruption randomly allocated 1259 patients 1 year after stent implantation to a strategy of interruption of DAPT (n = 624), in which aspirin antiplatelet treatment only was maintained, or DAPT continuation (n = 635) for 6 to 18 additional months. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization. A total of 520 and 722 patients received a first- and a second-generation DES, respectively. After a median follow-up of 17 months (interquartile range, 15-18 months) after randomization, the primary endpoint occurred in 32 (6.2%) and 19 (2.6%) patients with first- and second-generation DES, respectively (hazard ratio: 2.31, 95% confidence interval: 1.31-4.07, P = 0.004). This was observed irrespective of the strategy of interruption or continuation of DAPT and timing of study recruitment. Major bleeding events occurred in 4 (0.8%) and 3 patients (0.4%) with first- and second-generation DES, respectively (hazard ratio: 1.79, 95% confidence interval: 0.40-8.02, P = 0.44). Results did not change after multiple adjustments for potential confounding variables. ARCTIC-Generation showed worse clinical outcome with first- vs second-generation DES, a difference that appeared to persist even with prolonged DAPT.

Summary Background General practitioners (GPs) play a pivotal role in the long-term management of patients with atrial fibrillation (AF), including anticoagulant prophylaxis for stroke prevention. Aims To investigate the antithrombotic prescription behaviours of GPs in France and compare them with the European Society of Cardiology (ESC) guidelines for stroke prevention, and to identify the major determinants of use of antithrombotic therapy. Methods We conducted a cross-sectional survey, using data from the French Longitudinal Patient Database, on the use of antithrombotic treatments for stroke prevention in 15,623 patients (≥ 18 years of age) with AF who attended at least one GP consultation between July 2010 and June 2011. Data were collected on patient baseline characteristics, stroke risk factors, and prescription of antithrombotic drugs. Results The mean age was 74.6 ± 11.1 years, 59.5% were men, and 83.1% had a CHADS2 score ≥ 1. Over half (52.6%) of the patients with a CHADS2 score ≥ 1 received a vitamin K antagonist (alone or in combination with an antiplatelet), 19.3% received aspirin alone, and 23.4% received no antithrombotic therapy; 3.6% of the patients received dual antiplatelet therapy and 1.1% clopidogrel alone. Over half of the patients (56.3%) were treated in accordance with the ESC 2010 guidelines. Of the remaining patients, 19.4% received no treatment, 13.0% were inadequately treated, and 11.2% were over-treated. Factors associated with antithrombotic treatment were anti-arrhythmic therapy, higher stroke risk, presence of atherothrombotic disease, and use of non-steroidal anti-inflammatory drugs. Female gender was associated with a lower likelihood of antithrombotic treatment. Conclusions In this large French study, approximately 45% of thromboembolic high-risk patients were either not treated or inadequately treated. Better compliance with evidence-based guidelines is needed to reduce the burden of stroke in the AF population.

International audience; Platelet activation and aggregability play a key role in the genesis of arterial thrombus secondary to plaque rupture. For coronary patients, inhibition of platelet function is crucial to decrease the rate of major adverse cardiac events but may expose them to excess bleeding risk. Switching P2Y12 inhibitors is common, yet the clinical consequences are unknown. The aim of this review is to provide an overview of the evidence from randomized, clinical trials and epidemiological studies, with a focus on the optimal duration of dual antiplatelet therapy (DAPT) and appropriate agent and dose selection. The report discusses the latest evidence regarding switching therapies during DAPT, the potential benefits of a personalized strategy, management of the preoperative period, and other clinical perspectives in this complex and rapidly changing field. Ongoing trials will be useful to answer to some important unresolved questions.

The new oral anticoagulants are announced as an important therapeutic revolution, particularly after their approval by authorities for stroke prevention in atrial fibrillation. However, the pharmacology of these new drugs is not homogeneous. In this review, we summarize the main pharmacological characteristics of the new direct anti-Xa and anti-IIa agents.

Most of the French patients diagnosed with atrial fibrillation (AF) are managed by general practitioners (GPs). The objective was to evaluate stroke prevention in AF patients ahead of the arrival of the non vitamin K oral anticoagulant in France.A cross-sectional study using a French GPs database of all patients with a diagnosis of AF consulting their GP between July-2010 and June-2011. Multivariate analyses were used to identify determinants of prevention prescription.Among 15,623 AF patients, 42.5 % were ≥75 years and 40.5 % women, 59.2 % had hypertension, 17.2 % diabetes, 11.4 % heart failure, 4.9 % stroke history. CHADS2 score was ≥1 for 83.1 % and ≥2 for 50.9 % of patients (CHA2DS2-VASc score ≥1 for 93.7 % and ≥2 for 82.3 %). Antithrombotic therapies were vitamin K antagonists (VKA) for 50.7 % of patients, followed by aspirin for 19.9 %, clopidogrel ± aspirin for 4.3 % and none for 25.1 %. For patients with CHADS2 scores ≥1, 73.3 % received an antithrombotic and for those with CHADS2 scores ≥2, 54.9 % were treated by a VKA. An age-stratified multivariate analysis showed that women had an odds ratio to be treated with VKA compared to 0.83 (95 % CI: 0.72-0.95) and 0.66 (95 % CI: 0.59-0.74) when aged 75 years and ≥75 years, respectively.Most AF patients followed by French GPs required stroke prevention according to European guidelines, but many of them did not receive the recommended antithrombotic treatment. Women over 75 were a third less likely to be treated with recommended anticoagulants than men of similar age.

SummaryEffective antagonism of the P2Y12 platelet receptor is central to the treatment of acute coronary syndrome (ACS) patients, especially in the setting of percutaneous coronary intervention and stenting. According to consensus guidelines, early revascularization and intensive antiplatelet therapy are key to reducing the complications that arise from myocardial ischaemia and the recurrence of cardiovascular events. Until recently, clopidogrel was the key P2Y12 antagonist advocated, but due to several limitations as an antiplatelet agent, newer drugs with more predictable, rapid and potent effects have been developed. Prasugrel and ticagrelor are now the recommended first-line agents in patients presenting with non-ST-segment elevation ACS and ST-segment elevation ACS, due to large-scale randomized trials that demonstrated net clinical benefit of these agents over clopidogrel, as stated in the European guidelines. Although no study has directly compared the two agents, analysis of the data to date suggests that certain patient types, such as diabetics, those with ST-segment elevation myocardial infarction or renal failure and the elderly may have a better outcome with one agent over the other. Further studies are needed to confirm these differences and answer pending questions regarding the use of these drugs to optimize efficacy while minimizing adverse events, such as bleeding. The aim of this review is to provide an overview of the current P2Y12 receptor antagonists in the treatment of ACS, with a focus on issues of appropriate agent selection, timing of treatment, bleeding risk and the future role of personalized treatment using platelet function and genetic testing.

Background Elderly patients are at high-risk of bleedings, particularly in the setting of acute coronary syndrome treated with an invasive strategy. Treatment adjustment by platelet function testing (PFT) failed to improve clinical outcomes in the randomized ANTARCTIC trial. Purpose This prespecified substudy aims at determining the predictive value of PFT on occurrence of bleedings. Methods We analyzed the 877 patients over the age of 75 years included in the ANTARCTIC trial and randomized to a strategy of dose or drug antiplatelet therapy adjustment or a conventional “one size fits all” strategy without PFT. In the monitoring group, patients received prasugrel 5 mg daily after coronary stenting and PFT was done 14 days after randomization and repeated 14 days after treatment adjustment. Occurrence of bleedings was collected up to one year and correlated with PFT. Results Clinically relevant bleedings (Bleeding Academic Research Consortium types 2, 3 or 5) were frequently observed (20.6%, n = 181 patients) with one third occurring in the first month. Cutaneous and gastro-intestinal bleedings were the two predominant complications. There was no significant difference in the final treatment between patients with or without clinically relevant bleedings (respectively, clopidogrel 75 mg: 19.9% and 19.6%, prasugrel 5 mg: 77.3% and 77.9%, prasugrel 10 mg: 2.6% and 2.8%; P = 0.91) The main predictive factors of major bleedings in multivariate model were age > 85 years [adj.HR(95% CI): 2.48(1.25;4.91); P = 0.0093] and hemoglobin level (per gram of decrease) [adj.HR(95% CI): 1.45(1.18;1.79); P = 0.0004]. The last PFT was an independent predictive factor of clinically relevant bleedings (adj.HR(95% CI): 0.95(0.90;0.99); P = 0.017). Conclusion Clinically relevant bleedings were frequent in elderly patients in the setting of acute coronary syndrome. PFT did not improve clinical outcomes but identified the bleeding risk of these patients when the chronic treatment was installed.

International audience; In patients admitted for acute coronary syndrome (ACS), the guidelines of the European Society of Cardiology give a Class I, Level A recommendation for the prescription of high-intensity statins to be initiated as early as possible, regardless of the low-density lipoprotein cholesterol (LDL-C) level. Although statins are widely prescribed after ACS, the intensity of therapy and the proportion of patients achieving target LDL-C values are often not in line with recommendations due to a lack of compliance with guidelines by the physicians, a lack of compliance with treatment or poor tolerance by patients, and poor dose adaptation. In this context, a group of French physicians came together to define strategies to facilitate and improve the management of lipid-lowering therapy after ACS. This paper outlines the scientific rationale for the use of statins at the acute phase of ACS, the utility of ezetimibe, the measurement of LDL-C during the course of ACS, the opportunities for detecting familial hypercholesterolaemia and the results of the consensus for the management of lipid-lowering therapy, illustrated in two decision-making algorithms.

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.

Elderly (≥75 years old) patients with ST-segment elevation myocardial infarction (STEMI) have higher ischemic and bleeding risk compared with those adjusted = .01) was significantly lower with IV enoxaparin compared with IV UFH. Intravenous enoxaparin appears to be a safe alternative to IV UFH in primary PCI of the elderly patients with STEMI.

Objective of the study is to provide descriptive statistics on patterns of prasugrel usage in outpatient settings in France. The aim was to observe if the guidance for the use of Prasugrel from the European label was respected. Methods This retrospective study was conducted to describe treatment patterns of prasugrel in outpatient settings in France using the IMS Disease Analyzer database, which collects electronic medical records of patients followed by a national representative of 1200 French general practitioners (GPs). Anonymous data are collected prospectively and continuously during each follow-up visit. The study population consisted of patients who had at least 1 prescription of prasugrel in outsetting starting from launch to 3 years post launch. The patients were followed from the date of the first prasugrel prescription recorded in the data base (index date) until they died, changed of GP or reached the end of the study, whichever came first. Results In France, the IMS Disease Analyzer included 1.052 patients receiving at least one prescription of prasugrel from January 2010 until October 2012. 85% (n=894) were male (n=894), the mean age was 58.5 years. 5.7% of patients were aged more than 75 years, and 5.0% weighed 60kg or less. Only 0.2% (n=2) had a history of TIA/stroke among this cohort. Prasugrel was prescribed at a daily maintenance dose of 10mg for 99.8% of patients (1.050 patients). Concomitant medications were usual (aspirin, lipid lowering agents, beta blockers, angiotensin-converting-enzyme (ACE)-inhibitors. 55.1% of patients received an anti-ulcer medication (mainly Proton Pump Inhibitor [PPI). The persistence with prasugrel using the MPR (Medication Possession Ratio) was respectively 60.7% and 63.2% for patients with at 6 months (n=504) and 12 months follow-up (n=213). 13.7% of patients were switched from another thienopyridine (primarily clopidogrel). Conclusion In prasugrel-treated patients, respect of Prasugrel indications was highly fulfilled. Almost all patients received aspirin combined to prasugrel. Of note, half of patients were treated with an anti-ulcer medication. The main results reflect a good usage of prasugrel by French GPs, in collaboration with cardiologists, with a satisfying understanding and implementation of the European label, in contrast with recent American registry’s findings.

International audience; BackgroundThe CONNECT study compared clinician adherence to guideline-recommended secondary prevention therapies prescribed at discharge for patients hospitalized for acute coronary syndrome (ACS) in those managed initially with percutaneous coronary intervention (PCI; revascularized) and those who did not undergo revascularization.MethodsPatients aged greater than or equal to 18 years, hospitalized for a documented ST-segment elevation or non-ST-segment elevation ACS, were enrolled consecutively over 1 month at 238 sites in France.ResultsCompared with revascularized patients (n = 870), non-revascularized patients (n = 706) were significantly older, and a greater proportion were women, had high-blood pressure, type-2 diabetes or a history of atherothrombotic or cardiac disease, but a smaller proportion had a history of coronary angioplasty. On discharge, non-revascularized patients were prescribed beta-blockers, aspirin, statins, angiotensin-converting enzyme inhibitors or adenosine diphosphate receptor antagonists less frequently than revascularized patients. An adherence score greater than or equal to 80% (at least four of the five recommended agents prescribed at discharge) was found in 96.7% of revascularized patients and 74.4% of non-revascularized patients (P < 0.001).ConclusionsDespite a similar or even higher level of cardiovascular risk, non-revascularized ACS patients were prescribed guideline-recommended secondary prevention therapy less frequently than revascularized patients.Résumé; ObjectifsL’étude CONNECT a comparé la prise en charge thérapeutique, à la sortie de l’hôpital au décours d’un syndrome coronaire aigu (SCA), des patients ayant bénéficié d’une revascularisation coronaire percutanée par rapport aux patients non revascularisés, au moyen d’un score d’adhésion aux recommandations européennes.MéthodesLes patients âgés d’au moins 18 ans, et présentant un SCA avec ou sans sus-décalage du segment ST, ont été inclus, de façon consécutive, sur une période d’un mois par 238 centres investigateurs français.RésultatsComparés aux patients revascularisés (n = 870), les patients non revascularisés étaient significativement plus âgés, plus fréquemment des femmes, et présentaient plus souvent des antécédents d’hypertension artérielle, de diabète de type 2, d’insuffisance cardiaque, d’insuffisance rénale, avec une moindre fréquence d’antécédents d’angioplastie coronaire. À la sortie de l’hôpital, les patients non revascularisés bénéficiaient moins souvent d’un traitement par bêtabloquants, aspirine, statines, inhibiteurs de l’enzyme de conversion (IEC), antagonistes des récepteurs à l’ADP par rapport aux patients revascularisés. Un score d’adhésion aux traitements BASIC supérieur ou égal à 80 % (au moins quatre traitements recommandés présents sur l’ordonnance de sortie) était observé chez 96,7 % de patients revascularisés et chez 70,4 % de patients non revascularisés (p < 0,001).ConclusionAlors même que leur niveau de risque était au moins équivalent sinon supérieur, les patients présentant un SCA et non revascularisés recevaient moins souvent à la sortie de l’hospitalisation les traitements validés par rapport aux patients revascularisés.

Wear of the polyethylene liner is a frequent complication of total knee arthroplasty (TKA), which may lead to metallosis. The polyethylene wear usually occurs through delamination of the superficial layers of the liner into flakes that are shed within the joint. 1-5 Assessment of the degradation of the polyethylene liner is generally made by approximate assessment of its thickness on plain radiographs. More recently, sonography has been shown to also be a valuable method for evaluation of polyethylene wear in knee prosthesis. 6,7 Here we report a new sonographic sign of polyethylene wear in TKA with histologic correlation.

The ARCTIC study randomized 2440 patients scheduled for stent implantation 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. No significant improvement in clinical outcomes with platelet function monitoring was observed. The purpose of this study is to assess the relationships between CYP2C19 genotypes, clopidogrel pharmacodynamic response, and clinical outcome. In the ARCTIC-GENE study, 1394 patients were genotyped for loss- and gain-of-function CYP2C19 alleles. Randomization of treatment strategy was well balanced. Slow metabolizers identified as carriers of at least one loss-of-function allele CYP2C19*2 (n = 459) were more likely poor responders at randomization (41.6 vs. 31.6 %, p = 0.0112) and 14 days later (23.8 vs. 10.4 %, p

Introduction There has been a resurgence of popularity in performing bicruciate-retaining (BCR) total knee arthroplasty (TKA) as opposed to the more common posterior-stabilized (PS). BCR may be better for young and active patients since it restores knee kinematics better than other prosthetic designs. However, there is a belief in the community that BCR results in stiffer knees. There is not yet any study that shows clear clinical differences between BCR and PS TKAs. This study aims to clarify this point of contention. Materials and methods A prospective randomized control trial was conducted where patients were randomized to have either BCR or PS TKA implanted using a spacer-based gap balancing technique. A total of 32 BCR and 34 PS knees were evaluated (54 patients). Results were obtained at the preoperative visit and the subsequent postoperative visits up to 2 years and above. In this study, knee range of motion measurements, Knee injury and Osteoarthritis Outcome Score (KOOS), as well as Knee Society (KS) knee and function scores were compared between groups and visits. Resultats There was a significant difference in maximum knee flexion between BCR and PS patients at 6 weeks (BCRmean 94.8°, PSmean 113.6°, P Discussion The results confirm the suspicion that BCR TKA results in stiffer knees than PS TKA during the early postoperative period. However the difference in maximum flexion decreased and tended to resolve by the 2-year postoperative visit. The difference also did not seem to have an impact on the various clinical and functional outcome measurements that were collected after 6 weeks. Conclusion BCR TKA does not result in stiffer knees than PS TKA after 2 years. There appears to be a stiffening phenomenon that occurs after BCR TKA compared to PS TKA but it seems to resolve over time. Further investigation on the causes of this phenomenon is warranted. Further follow-up of this patient cohort will provide additional relevant information.

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.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.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).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.Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION Study Group), Fondation de France, Sanofi-Aventis, Cordis, Medtronic, Boston Scientific, Fondation SGAM.

Background— Individualizing antiplatelet therapy after platelet function testing did not improve outcome after coronary stenting in the Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting (ARCTIC) study. Whether results are different during the phase of secondary prevention starting after hospital discharge, when periprocedural events have been excluded, is unknown. Methods and Results— In ARCTIC, 2440 patients were randomized before coronary stenting to a strategy of platelet function monitoring (VerifyNow P2Y 12 /aspirin point-of-care assay) with drug adjustment in suboptimal responders to antiplatelet therapy or to a conventional strategy without monitoring and without drug or dose changes. We performed a landmark analysis starting at the time of hospital discharge evaluating the primary end point of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization through 1 year. After discharge, the primary end point occurred in 8.6% of patients in the monitoring arm and 7.9% in the conventional arm (hazard ratio, 1.105; 95% confidence interval, 0.835–1.461; P =0.48). Stent thrombosis or urgent revascularization occurred in 4.4% and 4.5% in the monitoring and conventional arms, respectively ( P =0.99). There was no difference for any of the other ischemic end points. Major bleeding event rates were 1.8% in the monitoring arm and 2.8% in the conventional arm ( P =0.11), whereas major or minor bleeding event rates were 2.3% and 3.4%, respectively ( P =0.10). Conclusions— Detection of platelet hyper-reactivity by platelet function testing in patients undergoing coronary stenting with further therapeutic adjustment does not reduce ischemic recurrences after intervention. On-treatment platelet hyperreactivity cannot be considered as a risk factor requiring intervention for secondary prevention after percutaneous coronary revascularization. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00827411.

Patients with diabetes mellitus (DM) are at significantly greater risk for major cardiovascular events (MACE) than non-DM patients. Primary and secondary prevention of cardiovascular disease (CVD) involves a multifactorial approach that aims to treat the cluster of risk factors associated with this condition including blood disorders and clinical features, such as hyperglycaemia, dyslipidemia, hypercoagulation, obesity and hypertension. Platelet activation and aggregability play a key role in the genesis of arterial thrombus secondary to plaque rupture. For patients in secondary prevention, inhibition of platelet function is crucial to significantly decrease the rate of MACE. Inhibiting plaque rupture would therefore prevent platelet aggregation. For patients with DM presenting with an acute coronary syndrome (ACS), a dual antiplatelet therapy with antagonism of COX1 and P2Y12 is central to their treatment, especially in the setting of percutaneous coronary intervention (PCI) and stenting. Large randomized trials have demonstrated that platelet inhibition with the P2Y12 antagonist clopidogrel, is associated with a better short and long-term prognosis after an acute coronary syndrome. Despite the clinical benefits of clopidogrel in patients with ACS, it has limitations in urgent and early PCI due to its slow onset of action, large interindividual variability and drug-drug interactions resulting in inconsistent drug response with reduced efficacy, especially in patients with diabetes. Therefore, newer drugs with a rapid onset of action, and a more potent and predictable effect have been developed. Prasugrel and ticagrelor have demonstrated net clinical benefit over clopidogrel in two major randomized trials, including a large number of diabetic patients, in patients presenting with non-ST elevation ACS (NSTE-ACS) and ST-elevation ACS (STE-ACS) revascularized by PCI. The aim of this review is to provide an overview of aspirin, P2Y12 receptor antagonists, and Glycoprotein (GP) IIb-IIIa inhibitors in the management of diabetic patients, with a focus on perspectives in optimal and appropriate agent selection and timing of treatment in both primary and secondary prevention.

Rational In France around 800,000 patients are diagnosed for atrial fibrillation (AF) with an increased risk of stroke. Oral anticoagulants (AC) dramatically reduce the risk of stroke but increase risk of major bleeding. As a consequence, guidelines recommend a risk-based approach to anticoagulation for AF. The CHADS2 score is the most widely used. In France, thrombo-prophylaxis of patients with AF is followed up in primary care. This study was to describe AF patients’ management by general practitioners (GP). Methods This cross-sectional study analyzed the Longitudinal Patient Database (LPD) which contains prescriptions, patients’ profiles and other information collected by a representative sample of 1,200 GPs. Data from all patients present in the database from July-2010 to June-2011, with a diagnosis of AF and aged 18 and above were extracted. CHADS 2 score based on 5 features (HTA, age ≥75, diabetes, previous stroke, transient ischaemic attack or systemic embolism, congestive heart failure or left ventricular dysfunction) was calculated for all patients. According to ESC guidelines, no antithrombotic therapy is preferred for AF patients with CHADS 2 score=0, aspirin or oral AC is recommended with CHADS 2 score=1 and chronic oral AC is recommended with a CHADS2 score ≥2. Results A total of 15,623 AF patients were identified. Mean age was 74.6 (±11.1) years old, 59.5% were men and mean CHADS 2 score was 1.5 (±1.1). Table 1: Antithrombotic therapy according to CHADS 2 score. CHADS 2 =0 N=2638 CHADS 2 =1 N=5026 CHADS 2 ≥2 N=7959 Total N=15623 Antithrombotic therapy N 2638 5026 7959 1562 VKA * n (%) 1090 (41.3%) 2460 (48.9%) 4372 (54.9%) 7922 (50.7%) Aspirin * n (%) 610 (23.1%) 1079 (21.5%) 1571 (19.8%) 3260 (20.9%) None n (%) 938 (35.5%) 1487 (29.6%) 2016 (25.3%) 4441 (28.4%) * Alone or associated Conclusion In this large French patient database, in primary care according to ESC guidelines, more than 40% of AF patients with a very low risk of stroke (CHADS2=0) are over treated, while 45% of high risk patients (CHADS2=2) are under-treated. Further analyses should be performed to investigate the gap between clinical practice and guidelines.

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.).

Objectives To evaluate the control of cardiovascular risk factors at 1 year follow-up and the therapeutic strategies in French patients, recruited in the REACH international registry, with several cardiovascular risk factors (CVRF) or suffering from established atherothrombotic disease (EAD). Methods The REACH registry has included patients, aged at least 45 years, and with several cardiovascular risk factors (CVRF) (>3), or suffering from established atherothrombotic disease (EAD: patients with coronary artery disease (CAD), with cerebrovascular disease (CVD), and patients with lower limb peripheral arterial occlusive disease (PAD)). In France, 713 investigators selected 4740 patients, with either CVRF (n=1226) or with EAD (n=3514) between December 2003 and June 2004. After exclusion of patients with missing data, 2916 patients (26.4% CVRF) were available for statistical analyses. Results Among the 2916 french patients of the REACH registry, 1169 (40.1%) suffered from CAD, 317 (10.9%) had documented CVD, 257 (8.8%) suffered from PAD, and 13.8% had symptomatic polyvascular disease. The rate of control of major CV risk differs between groups: target goals are obtained for 3.6% for patients with CVRF only, 20.9% for patients with monovascular disease, 15.2% for patients with polyvascular disease (two or three locations). Conclusion The rate of patients treated and controlled is globally poor, with significant differences between patients according to the number of symptomatic arterial beds. Same findings are observed for treatment strategies. These results underline the need for more widespread use of medications, and for optimise therapeutic education to induce lifestyle changes. Educational program will be evaluate. Objectifs Evaluer le controle des facteurs de risque cardiovasculaire et les strategies therapeutiques chez les patients francais presentant soit des facteurs de risque CV (FRCV), soit une maladie atherothrombotique etablie. Methodes Le registre REACH a inclus des patients âges d9au moins 45 ans, presentant des facteurs de risque cardiovasculaire(FRCV) (> 3), ou souffrant d9une maladie atherothrombotique etablie (MAE: apres un evenement documente de maladie coronaire, cerebrovasculaire, ou souffrant d9une arteriopathie obliterante des membres inferieurs (AOMI)). En France, 713 medecins investigateurs ont selectionne 4740 patients, presentant soit des FRCV (n=1226) soit une MAE (n=3514) entre decembre 2003 et juin 2004. Apres exclusion des sujets avec des donnees biologiques manquantes 2916 patients (26.4% FRCV) etaient disponibles pour les analyses. Resultats Parmi les 2916 patients francais du registre REACH, 1169 (40.1%) avaient une maladie coronaire, 317 (10.9%) avaient une maladie ischemique cerebrovasculaire, 257 (8.8%) avaient une AOMI documentee et 13.8% une affection polyarterielle. Le pourcentage des patients controles pour tous les facteurs de risque varie selon les caracteristiques: 3,6% pour les patients du groupe FRCV, 20,9% s9il existe une seule localisation atherothrombotique, et de 15,2% s9il y a 2 ou 3 localisations atherothrombotiques. Conclusion Le pourcentage de patients traites et controles est globalement faible et varie selon le statut des patients. Le meme constat est effectue pour les traitements valides. L’education therapeutique et la mise en place des strategies therapeutiques validees necessitent d’etre optimisees. Ces resultats associes aux donnees publiees sur les patients francais du registre pourraient servir de support aux campagnes de sensibilisation sur le risque cardiovasculaire. Le suivi sur 4 ans permettra de juger de l’evolution des pratiques et des evenements CV majeurs.