Comparison of Incidence and Prognostic Impact of Ischemic, Major Bleeding and Heart Failure Events in Patients With Chronic Coronary Syndrome: Insights From the CORONOR Registry.

BACKGROUND: Evaluation of the residual risk in patient with chronic coronary syndrome is challenging in daily practice. Several types of events (myocardial infarction, ischemic stroke, bleeding, and heart failure [HF]) may occur, and their impact on subsequent mortality is unclear in the era of modern evidence-based pharmacotherapy. METHODS: CORONOR (Suivi d'une cohorte de patients Coronariens stables en région Nord-pas-de-Calais) is a prospective multicenter cohort that enrolled 4184 consecutive unselected outpatients with chronic coronary syndrome. We analyzed the incidence, correlates, and impact of ischemic events (a composite of myocardial infarction and ischemic stroke), major bleeding (Bleeding Academic Research Consortium 3 or higher), and hospitalization for HF on subsequent patient mortality. RESULTS: During follow-up (median, 4.9 years), 677 patients (16.5%) died. The 5-year cumulative incidences (death as competing event) of ischemic events, major bleeding, and HF hospitalization were 6.3% (5.6%-7.1%), 3.1% (2.5%-3.6%), and 8.1% (7.3%-9%), respectively. Ischemic events, major bleeding, and HF hospitalization were each associated with all-cause mortality. Major bleeding and hospitalization for HF were associated with the highest mortality rates in the postevent period (42.4%/y and 34.7%/y, respectively) compared with incident ischemic events (13.1%/y). The age- and sex-adjusted hazard ratios for all-cause mortality were 3.57 (95% CI, 2.77-4.61), 9.88 (95% CI, 7.55-12.93), and 8.60 (95% CI, 7.15-10.35) for ischemic events, major bleeding, and hospitalization for HF, respectively (all P<0.001). CONCLUSIONS: Hospitalization for HF has become both the most frequent and one of the most ominous events among patients with chronic coronary syndrome. Although less frequent, major bleeding is strongly associated with worse patient survival. Secondary prevention should not be limited to preventing ischemic events. Minimizing bleeding and preventing HF may be at least as important.

Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction.

BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions (complete revascularization) is superior to treatment of the culprit lesion alone. However, whether complete revascularization that is guided by fractional flow reserve (FFR) is superior to an angiography-guided procedure is unclear. METHODS: In this multicenter trial, we randomly assigned patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year. RESULTS: The mean (±SD) number of stents that were placed per patient for nonculprit lesions was 1.01±0.99 in the FFR-guided group and 1.50±0.86 in the angiography-guided group. During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively. CONCLUSIONS: In patients with STEMI undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization at 1 year. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation. (Funded by the French Ministry of Health and Abbott; FLOWER-MI ClinicalTrials.gov number, NCT02943954.).

Incidence, source, and prognostic impact of major bleeding across the spectrum of aortic stenosis.

BACKGROUND: Severe aortic stenosis (AS) has been associated with bleeding. However, there is a lack of prospective assessment of bleeding events and their clinical significance in a large population of outpatients with variable degree of AS severity. OBJECTIVES: To assess the incidence, source, determinants, and prognostic impact of major bleeding in patients with variable degree of AS severity. METHODS: Between May 2016 and December 2017, consecutive outpatients were included. Major bleeding was defined as type ≥3 bleed using the Bleeding Academic Research Consortium definition. Cumulative incidence was calculated with death as the competing event. Data was censored at time of aortic valve replacement. RESULTS: Among 2,830 patients, 46 major bleeding events occurred (0.7%/year) during a median follow-up of 2.1 years (interquartile range: 1.4-2.7). Most frequent sites of bleeding were gastrointestinal (50%) and intracranial (30.4%). Major bleeding was significantly associated with all-cause mortality (hazard ratio: 5.93 (95% confidence interval 3.64-9.65); P < .001). AS severity was associated with major bleedings (P = .041). By multivariable analysis, severe AS was an independent determinant of major bleeding (hazard ratio vs mild AS: 3.59 [95% confidence interval 1.56-8.29]; P = .003). The increased risk of bleeding associated with severe AS was significantly exacerbated in patients using oral anticoagulation. CONCLUSION: In AS patients, major bleeding is rare but a strong independent predictor of death. AS severity is a determinant of bleeding events. Severe AS and oral anticoagulation should be identified as an association at very high risk of major bleeding.

Five-year outcomes following timely primary percutaneous intervention, late primary percutaneous intervention, or a pharmaco-invasive strategy in ST-segment elevation myocardial infarction: the FAST-MI programme.

AIMS: ST-segment elevation myocardial infarction (STEMI) guidelines recommend primary percutaneous coronary intervention (pPCI) as the default reperfusion strategy when feasible ≤120 min of diagnostic ECG, and a pharmaco-invasive strategy otherwise. There is, however, a lack of direct evidence to support the guidelines, and in real-world situations, pPCI is often performed beyond recommended timelines. To assess 5-year outcomes according to timing of pPCI (timely vs. late) compared with a pharmaco-invasive strategy (fibrinolysis with referral to PCI centre). METHODS AND RESULTS: The French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) programme consists of nationwide observational surveys consecutively recruiting patients admitted for acute myocardial infarction every 5 years. Among the 4250 STEMI patients in the 2005 and 2010 cohorts, those with reperfusion therapy and onset-to-first call time <12 h (n = 2942) were included. Outcomes at 5 years were compared according to type of reperfusion strategy and timing of pPCI, using Cox multivariable analyses and propensity score matching. Among those, 1288 (54%) patients had timely pPCI (≤120 min from ECG), 830 (28%) late pPCI (>120 min), and 824 (28%) intravenous fibrinolysis. Five-year survival was higher with a pharmaco-invasive strategy (89.8%) compared with late pPCI [79.5%; adjusted hazard ratio (HR) 1.51; 1.13-2.02] and similar to timely pPCI (88.2%, adjusted HR 1.02; 0.75-1.38). Concordant results were observed in propensity score-matched cohorts and for event-free survival. CONCLUSION: A substantial proportion of patients have pPCI beyond recommended timelines. As foreseen by the guidelines, these patients have poorer 5-year outcomes, compared with a pharmaco-invasive strategy.

Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial.

Importance: The optimal transfusion strategy in patients with acute myocardial infarction and anemia is unclear. Objective: To determine whether a restrictive transfusion strategy would be clinically noninferior to a liberal strategy. Design, Setting, and Participants: Open-label, noninferiority, randomized trial conducted in 35 hospitals in France and Spain including 668 patients with myocardial infarction and hemoglobin level between 7 and 10 g/dL. Enrollment could be considered at any time during the index admission for myocardial infarction. The first participant was enrolled in March 2016 and the last was enrolled in September 2019. The final 30-day follow-up was accrued in November 2019. Interventions: Patients were randomly assigned to undergo a restrictive (transfusion triggered by hemoglobin ≤8; n = 342) or a liberal (transfusion triggered by hemoglobin ≤10 g/dL; n = 324) transfusion strategy. Main Outcomes and Measures: The primary clinical outcome was major adverse cardiovascular events (MACE; composite of all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization prompted by ischemia) at 30 days. Noninferiority required that the upper bound of the 1-sided 97.5% CI for the relative risk of the primary outcome be less than 1.25. The secondary outcomes included the individual components of the primary outcome. Results: Among 668 patients who were randomized, 666 patients (median [interquartile range] age, 77 [69-84] years; 281 [42.2%] women) completed the 30-day follow-up, including 342 in the restrictive transfusion group (122 [35.7%] received transfusion; 342 total units of packed red blood cells transfused) and 324 in the liberal transfusion group (323 [99.7%] received transfusion; 758 total units transfused). At 30 days, MACE occurred in 36 patients (11.0% [95% CI, 7.5%-14.6%]) in the restrictive group and in 45 patients (14.0% [95% CI, 10.0%-17.9%]) in the liberal group (difference, -3.0% [95% CI, -8.4% to 2.4%]). The relative risk of the primary outcome was 0.79 (1-sided 97.5% CI, 0.00-1.19), meeting the prespecified noninferiority criterion. In the restrictive vs liberal group, all-cause death occurred in 5.6% vs 7.7% of patients, recurrent myocardial infarction occurred in 2.1% vs 3.1%, emergency revascularization prompted by ischemia occurred in 1.5% vs 1.9%, and nonfatal ischemic stroke occurred in 0.6% of patients in both groups. Conclusions and Relevance: Among patients with acute myocardial infarction and anemia, a restrictive compared with a liberal transfusion strategy resulted in a noninferior rate of MACE after 30 days. However, the CI included what may be a clinically important harm. Trial Registration: ClinicalTrials.gov Identifier: NCT02648113.

TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial.

Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.

Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR. METHODS: We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation. RESULTS: After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year. CONCLUSIONS: The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.).

Twenty-year trends in profile, management and outcomes of patients with ST-segment elevation myocardial infarction according to use of reperfusion therapy: Data from the FAST-MI program 1995-2015.

The increased use of reperfusion therapy in ST-segment-elevation myocardial infarction (STEMI) patients in the past decades is generally considered the main determinant of improved outcomes. The aim was to assess 20-year trends in profile, management, and one-year outcomes in STEMI patients in relation with use or non-use of reperfusion therapy (primary percutaneous coronary intervention (pPCI) or fibrinolysis). METHODS: We used data from 5 one-month French nationwide registries, conducted 5 years apart from 2005 to 2015, including 8579 STEMI patients (67% with and 33% without reperfusion therapy) admitted to cardiac intensive care units in France. RESULTS: Use of reperfusion therapy increased from 49% in 1995 to 82% in 2015, with a shift from fibrinolysis (37.5% to 6%) to pPCI (12% to 76%). Early use of evidence-based medications gradually increased over the period in both patients with and without reperfusion therapy, although it remained lower at all times in those without reperfusion therapy. One-year mortality decreased in patients with reperfusion therapy (from 11.9% in 1995 to 5.9% in 2010 and 2015, hazard ratio [HR] adjusted on baseline profile 0.40; 95% CI: 0.29-0.54, P < .001) and in those without reperfusion therapy (from 25.0% to 18.2% in 2010 and 8.1% in 2015, HR: 0.33; 95% CI: 0.24-0.47, P < .001). CONCLUSIONS: In STEMI patients, one-year mortality continues to decline, both related to increased use of reperfusion therapy and progress in overall patient management. In patients with reperfusion therapy, mortality has remained stable since 2010, while it has continued to decline in patients without reperfusion therapy.

Antithrombotic efficacy of bivalirudin compared to unfractionated heparin during percutaneous coronary intervention for acute coronary syndrome.

Bivalirudin is associated with an increased risk of acute stent thrombosis (AST) compared to unfractionated heparin (UFH) in acute coronary syndrome patients (ACS) during short-duration percutaneous coronary intervention (PCI). The mechanisms involved are unknown. We aimed to investigate the antithrombotic efficacy of bivalirudin compared to UFH during PCI. In a monocenter study, we prospectively enrolled 30 patients undergoing PCI for a non-ST elevation ACS. They were randomly assigned to a single intravenous (IV) bolus of UFH (70 IU/kg) or an IV bolus of bivalirudin 0.75 mg/kg followed by a 1.75 mg/kg/h infusion during PCI. All patients received a loading dose (LD) of 180 mg of ticagrelor at the time of PCI. The VASP index and activated partial thromboplastin time (aPTT) were used to assess the course of platelet reactivity (PR) and antithrombotic activity. The two groups were similar regarding baseline, angiographic, and interventional characteristics. There was no difference between the two groups in the course of PR following ticagrelor LD. An optimal PR inhibition was obtained 4 h after the LD of ticagrelor. The level of antithrombotic activity was significantly lower in the bivalirudin group compared to the UFH group (p < 0.001) during PCI but similar at 2 and 4 h post-PCI. We observed that, in ACS undergoing PCI, the antithrombotic efficacy of an IV bolus of bivalirudin is significantly lower than that of a 70-IU/kg UFH bolus. This could contribute to the excess in thrombotic acute events observed during short-duration PCI.

Acute Myocardial Infarction: Changes in Patient Characteristics, Management, and 6-Month Outcomes Over a Period of 20 Years in the FAST-MI Program (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) 1995 to 2015.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) management has evolved considerably over the past 2 decades. Little information on mortality trends in the most recent years is available. We assessed trends in characteristics, treatments, and outcomes for acute myocardial infarction in France between 1995 and 2015. METHODS: We used data from 5 one-month registries, conducted 5 years apart, from 1995 to 2015, including 14 423 patients with acute myocardial infarction (59% STEMI) admitted to cardiac intensive care units in metropolitan France. RESULTS: From 1995 to 2015, mean age decreased from 66±14 to 63±14 years in patients with STEMI; it remained stable (68±14 years) in patients with NSTEMI, whereas diabetes mellitus, obesity, and hypertension increased. At the acute stage, intended primary percutaneous coronary intervention increased from 12% (1995) to 76% (2015) in patients with STEMI. In patients with NSTEMI, percutaneous coronary intervention ≤72 hours from admission increased from 9% (1995) to 60% (2015). Six-month mortality consistently decreased in patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in 2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in patients with NSTEMI. Mortality still decreased after 2010 in patients with STEMI without reperfusion therapy, whereas no further mortality gain was found in patients with STEMI with reperfusion therapy or in patients with NSTEMI, whether or not they were treated with percutaneous coronary intervention. CONCLUSIONS: Over the past 20 years, 6-month mortality after acute myocardial infarction has decreased considerably for patients with STEMI and NSTEMI. Mortality figures continued to decline in patients with STEMI until 2015, whereas mortality in patients with NSTEMI appears stable since 2010.

First Hospitalization for Heart Failure in Outpatients With Stable Coronary Artery Disease: Determinants, Role of Incident Myocardial Infarction, and Prognosis.

BACKGROUND: We lack recent data on the incidence, correlates, and prognosis associated with heart failure (HF) development in patients with stable coronary artery disease (CAD). Here, we analyzed HF development in a contemporary population of outpatients with stable CAD. METHODS AND RESULTS: Of 4184 unselected outpatients with stable CAD (ie, myocardial infarction [MI] and/or coronary revascularization >1 year earlier) included in the multicenter CORONOR registry, we identified 3871 patients with no history of hospitalization for HF at inclusion and followed 3785 (98%) of them for 5 years. During follow-up, 211 patients were hospitalized for HF (5-year cumulative incidence 5.7%) and 163 patients had incident MIs. Independent predictors of hospitalization for HF were older age, lower left ventricular ejection fraction (LVEF), atrial fibrillation, higher body mass index, diabetes mellitus, history of hypertension, angina at inclusion, and multivessel CAD. Most hospitalizations for HF (62.6%) occurred in patients with LVEF ≥50% at inclusion, and most (92.4%) were not preceded by an incident MI. Hospitalization for HF was a powerful predictor of mortality (adjusted hazard ratio 5.97, 95% confidence interval 4.55-7.83; P < .0001). After hospitalization for HF, mortality rates were similar in patients with LVEFs ≥50% and <50% at hospitalization. CONCLUSIONS: Outpatients with stable CAD were frequently hospitalized for HF, and HF was associated with high mortality. Most HF hospitalizations were associated with preserved LVEF at inclusion and were not preceded by an incident MI.

Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure.

RATIONALE: Long noncoding RNAs represent a novel class of molecules regulating gene expression. Long noncoding RNAs are present in body fluids, but their potential as biomarkers was never investigated in cardiovascular disease. OBJECTIVE: To study the role of long noncoding RNAs as potential biomarkers in heart disease. METHODS AND RESULTS: Global transcriptomic analyses were done in plasma RNA from patients with or without left ventricular remodeling after myocardial infarction. Regulated candidates were validated in 3 independent patient cohorts developing cardiac remodeling and heart failure (788 patients). The mitochondrial long noncoding RNA uc022bqs.1 (LIPCAR) was downregulated early after myocardial infarction but upregulated during later stages. LIPCAR levels identified patients developing cardiac remodeling and were independently to other risk markers associated with future cardiovascular deaths. CONCLUSIONS: LIPCAR is a novel biomarker of cardiac remodeling and predicts future death in patients with heart failure.

Clopidogrel Use as Single Antiplatelet Therapy in Outpatients with Stable Coronary Artery Disease: Prevalence, Correlates and Association with Prognosis (from the CORONOR Study).

BACKGROUND: Clopidogrel use as single antiplatelet therapy (SAPT) has never been evaluated in stable coronary artery disease (CAD) outpatients either as compared to placebo or aspirin. METHODS: We therefore studied 2,823 outpatients included in a prospective registry. The patients were divided into 2 groups according to their antiplatelet therapy regimen: patients treated with clopidogrel were compared with those treated with aspirin alone. RESULTS: The mean time since CAD diagnosis was 7.9 years. Altogether, 776 (27.5%) patients received clopidogrel as SAPT. Factors independently associated with clopidogrel use were prior aortic or peripheral intervention, drug-eluting stent implantation, stroke, carotid endarterectomy and time since CAD diagnosis. Clopidogrel tended to be used in higher-risk patients: composite of cardiovascular death, myocardial infarction or stroke at 5.8 versus 4.2% (p = 0.056). However, after propensity score matching, similar event rates were observed between the groups: 5.9% when treated with clopidogrel versus 4.4% with aspirin (p = 0.207). The rate of bleeding was also similar between the groups. CONCLUSIONS: Our study shows that a significant proportion of stable CAD patients are treated with clopidogrel as SAPT in modern practice. Several correlates of such an attitude were identified. Our results suggest that this strategy is not beneficial as compared to aspirin alone in terms of ischaemic or bleeding events.

Screening for asymptomatic coronary artery disease in patients with diabetes mellitus: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Screening diabetic patients for the presence of asymptomatic coronary artery disease (CAD) may potentially impact therapeutic management and outcome. We performed a systematic review and meta-analysis of randomized trials addressing this question. METHODS: We searched the PubMed database for studies reporting a randomized comparison of systematic screening for CAD in diabetic patients versus no systematic screening. The screening protocols were variable with the use of exercise electrocardiogram test, or stress echocardiography, or nuclear test, or coronary computed tomography angiography. RESULTS: The final analysis included 5 randomized studies and 3,314 patients altogether. The screening strategy had no detectable impact on outcome with odds ratios (OR) [95 % confidence interval (CI)] of 1.00 [0.67-1.50], 0.72 [0.33-1.57], 0.71 [0.40-1.27], and 0.60 [0.23-1.52] for all-cause death, cardiovascular death, non-fatal myocardial infarction, and the composite cardiovascular death or non-fatal myocardial infarction, respectively. Protocol-related coronary procedures were relatively infrequent in screened patients: coronary angiography was performed in 8 % of the cases, percutaneous coronary intervention in 2.5 %, and coronary artery bypass surgery in 1.5 %. There was no evidence for an effect of screening on the use of statins (OR = 1.19 [0.94-1.51]), aspirin (OR = 1.02 [0.83-1.25]), or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (OR = 0.97 [0.79-1.19]). CONCLUSION: The present analysis shows no evidence for a benefit of screening diabetic patients for the presence of asymptomatic CAD. The proportion of patients who undergo myocardial revascularization as a consequence of screening was low.

Dual antiplatelet therapy in patients with stable coronary artery disease in modern practice: prevalence, correlates, and impact on prognosis (from the Suivi d'une cohorte de patients COROnariens stables en region NORd-Pas-de-Calais study).

BACKGROUND: The prevalence and correlates of dual-antiplatelet therapy (DAPT) use in stable coronary artery disease (CAD) are unknown. In addition, whether prolonged DAPT may impact prognosis in stable CAD has not been studied in real-life conditions. METHODS: We studied 3,691 patients included in a prospective registry on stable CAD. The patients were divided in 2 groups according to their antiplatelet therapy regimen at inclusion: patients treated with DAPT were compared with those treated with single-antiplatelet therapy (SAPT). The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke. RESULTS: Altogether, 868 (24%) patients received DAPT. Factors positively associated with DAPT use were persistent angina at inclusion, body mass index, myocardial infarction since 1 to 3 years, myocardial revascularization since 1 to 3 years, multivessel CAD, prior drug-eluting stent implantation, and prior aortic or peripheral intervention. Factors negatively associated with DAPT use were age, prior coronary bypass, and left ventricular ejection fraction. The rate of the primary outcome at 2 years was similar whether patients were treated with SAPT (4.6%) or DAPT (5.5%) (P = .301). Similar rates were also observed after propensity score matching: 5.7% when treated with SAPT versus 5.5% when treated with DAPT (P = .886). The rate of bleeding was similar between groups. CONCLUSIONS: Our study shows that a significant proportion of stable CAD patients are treated with DAPT in modern practice. Several correlates of DAPT were identified. Although no increase in bleeding was observed, our results do not support the prescription of prolonged DAPT.

Poor agreement between light transmission aggregometry, Verify Now P2Y12 and vasodilatator-stimulated phosphoprotein for clopidogrel low-response assessment: a potential explanation of negative results of recent randomized trials.

Clopidogrel low response as assessed by several different biological tests correlates with poor prognosis after percutaneous coronary intervention (PCI). However, recent randomized clinical trials (RCT) testing the strategy of individual antiplatelet therapy tailoring based on one sole test have all shown negative results. Poor correlation between the different tests may explain the difficulties of patient selection and identification of "true poor responders" to clopidogrel. In this prospective study, clopidogrel response was assessed in 100 consecutive patients between 18 and 24 hours after a 600 mg clopidogrel loading dose using three different tests: light transmission aggregometry with 10 µmol ADP (LTA, results expressed as platelet aggregation percentage: PAP), Verify Now P2Y12 (VN, results expressed as P2Y12 reaction unit: PRU) and vasodilatator-stimulated phosphoprotein (VASP, results expressed as platelet reactivity index: PRI). Patients under chronic clopidogrel therapy were excluded. The mean PAP, PRU and PRI values were 38.6%, 176.1 PRU and 52.4%, respectively. When clopidogrel response was analyzed as continuous variable, there was a good correlation between the different tests: LTA/VN (R(2 )= 0.642, p < 0.001), LTA/VASP (R(2 )= 0.409, p < 0.001) and VN/VASP (R(2 )= 0.616, p < 0.001). However, when clopidogrel response was analyzed as pre-specified cut-off points to define patients as "poor or good responders" (according to the literature: 50% PAP for LTA, 235 PRU for VN and 50% PRI for VASP), only 47% of the patients were defined as "good" or "poor responders" by the three tests. Altogether, 33% of the patients were defined as "poor responders" by only one test, 20% by two tests and only 16% by the three tests. The correlation between the different tests is good when clopidogrel response is analyzed as continuous variable. Each individual is however rarely (less than 50%) defined as "poor or good responder" by all the three tests when pre-specified cut-off values are used. A sole test might not be sufficient to manage antiplatelet therapy in an individual patient and these results may explain the results of recent RCT showing the lack of benefit of systematic antiplatelet therapy monitoring strategy.