Martine Gilard

Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin: The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study

OBJECTIVES This trial sought to assess the influence of omeprazole on clopidogrel efficacy. BACKGROUND Clopidogrel has proved its benefit in the treatment of atherothrombotic diseases. In a previous observational study, we found clopidogrel activity on platelets, tested by vasodilator-stimulated phosphoprotein (VASP) phosphorylation, to be diminished in patients receiving proton pump inhibitor (PPI) treatment. METHODS In this double-blind placebo-controlled trial, all consecutive patients undergoing coronary artery stent implantation received aspirin (75 mg/day) and clopidogrel (loading dose, followed by 75 mg/day) and were randomized to receive either associated omeprazole (20 mg/day) or placebo for 7 days. Clopidogrel effect was tested on days 1 and 7 in both groups by measuring platelet phosphorylated-VASP expressed as a platelet reactivity index (PRI). Our main end point compared PRI value at the 7-day treatment period in the 2 groups. RESULTS Data for 124 patients were analyzed. On day 1, mean PRI was 83.2% (standard deviation [SD] 5.6) and 83.9% (SD 4.6), respectively, in the placebo and omeprazole groups (p = NS), and on day 7, 39.8% (SD 15.4) and 51.4% (SD 16.4), respectively (p < 0.0001). RESULTS Omeprazole significantly decreased clopidogrel inhibitory effect on platelet P2Y12 as assessed by VASP phosphorylation test. Aspirin-clopidogrel antiplatelet dual therapy is widely prescribed worldwide, with PPIs frequently associated to prevent gastrointestinal bleeding. The clinical impact of these results remains uncertain but merits further investigation.

Registry of transcatheter aortic-valve implantation in high-risk patients

BACKGROUND Transcatheter aortic-valve implantation (TAVI) is an emerging intervention for the treatment of high-risk patients with severe aortic stenosis and coexisting illnesses. We report the results of a prospective multicenter study of the French national transcatheter aortic-valve implantation registry, FRANCE 2. METHODS All TAVIs performed in France, as listed in the FRANCE 2 registry, were prospectively included in the study. The primary end point was death from any cause. RESULTS A total of 3195 patients were enrolled between January 2010 and October 2011 at 34 centers. The mean (±SD) age was 82.7±7.2 years; 49% of the patients were women. All patients were highly symptomatic and were at high surgical risk for aortic-valve replacement. Edwards SAPIEN and Medtronic CoreValve devices were implanted in 66.9% and 33.1% of patients, respectively. Approaches were either transarterial (transfemoral, 74.6%; subclavian, 5.8%; and other, 1.8%) or transapical (17.8%). The procedural success rate was 96.9%. Rates of death at 30 days and 1 year were 9.7% and 24.0%, respectively. At 1 year, the incidence of stroke was 4.1%, and the incidence of periprosthetic aortic regurgitation was 64.5%. In a multivariate model, a higher logistic risk score on the European System for Cardiac Operative Risk Evaluation (EuroSCORE), New York Heart Association functional class III or IV symptoms, the use of a transapical TAVI approach, and a higher amount of periprosthetic regurgitation were significantly associated with reduced survival. CONCLUSIONS This prospective registry study reflected real-life TAVI experience in high-risk elderly patients with aortic stenosis, in whom TAVI appeared to be a reasonable option. (Funded by Edwards Lifesciences and Medtronic.).

Evaluation of Different Ventricular Pacing Sites in Patients With Severe Heart Failure Results of an Acute Hemodynamic Study

BACKGROUND Multisite ventricular pacing has recently been proposed as an additional treatment for patients with severe congestive heart failure. To further assess the potential value of this technique, we compared the acute hemodynamic changes associated with pacing the right ventricular apex (RVA) or outflow tract (RVOT) alone, the left ventricle (LV) alone, or biventricular (BIV) pacing of the RVA and LV together. METHODS AND RESULTS Acute hemodynamic findings were measured in 27 patients with severe heart failure despite optimal therapy and either first-degree AV block and/or an intraventricular conduction defect. In the 23 patients with a high pulmonary capillary wedge pressure (PCWP) (>15 mm Hg), data were collected after transvenous pacing at different ventricular sites in either the VDD mode (AV delay=100 ms) or the VVI mode in patients with atrial fibrillation (n=6). The mean baseline cardiac index was 1.82 L x min(-1) x m(-2). Mean+/-SD baseline systolic blood pressure (SBP) (118.5+/-15.2 mm Hg), PCWP (26.4+/-6.6 mm Hg), and V-wave amplitude (39.1+/-14.6 mm Hg) were similar before and after either RVA or RVOT pacing. In contrast, LV-based pacing (either LV alone or BIV pacing) resulted in higher SBP (P<.03) and lower PCWP (P<.01) and V-wave amplitude (P<.001) than either baseline or RV pacing measurements. With LV pacing alone, SBP, PCWP, and V waves were 126.5+/-15.1, 20.7+/-5.9, and 25.5+/-8.1 mm Hg, respectively. The results with LV pacing alone were similar to those obtained with BIV pacing. CONCLUSIONS In patients with severe congestive heart failure, both LV pacing alone and BIV pacing resulted in a similar and significant acute improvement in SBP, PCWP, and V-wave amplitude compared with baseline measurements and RV pacing alone. These results provide a strong basis for initiating long-term studies examining the chronic effects of LV-based pacing in patients with medically refractory congestive heart failure.

Transcatheter aortic valve implantation: early results of the FRANCE (FRench Aortic National CoreValve and Edwards) registry

AIMS Transcatheter aortic valve implantation is a therapeutic alternative for high-surgical-risk patients with severe symptomatic aortic stenosis. Two models of prosthesis are currently commercialized in France, which can be implanted either via a transarterial or a transapical approach. The aim of the study was to evaluate in a national French registry the early safety and efficacy of transcatheter aortic valve replacement (AVR) using either the Edwards SAPIEN™ or CoreValve™ in high-surgical-risk patients with severe aortic stenosis. METHODS AND RESULTS The multicentre national registry was conducted in 16 centres between February 2009 and June 2009, under the authority of the French Societies of Cardiology and Thoracic and Cardio-Vascular Surgery. The primary endpoint was mortality at 1 month. Two hundred and forty-four high-surgical-risk patients (logistic EuroSCORE ≥20%, STS ≥10%, or contra-indication to AVR) were enrolled. Mean age was 82 ± 7 years and 43.9% were female. Edwards SAPIEN and CoreValve were implanted in 68 and 32% of patients, respectively. The approaches used were transarterial (transfemoral: 66%; subclavian: 5%) or transapical in 29%. Device success rate was 98.3% and 30-day mortality was 12.7%. Severe complications included stroke (3.6%), tamponade (2%), acute coronary occlusion (1.2%), and vascular complications (7.3%). Pacemaker was required in 11.8%. At 1 month, 88% of patients were in NYHA class II or less. CONCLUSION This prospective registry reflects the real-life experience of transcatheter aortic valve implantation in high-risk elderly patients in France. The early results are satisfactory in terms of feasibility, short-term haemodynamic and functional improvement, and safety. Longer term follow-up will be further assessed.

Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS)

Atrial fibrillation (AF) confers a substantial risk of mortality and morbidity from stroke and thrombo-embolism, and this common cardiac arrhythmia represents a major healthcare burden in Europe.1 Stroke prevention is central to the management of AF patients, with the 2012 focused update of the European Society of Cardiology (ESC) guidelines2 recommending oral anticoagulation (OAC) using well-controlled adjusted dose vitamin K antagonists (VKAs, e.g. warfarin) or non-VKA oral anticoagulants (NOACs, previously referred to as new or novel OACs3) for patients with AF and ≥1 stroke risk factor(s). Also, these guidelines strongly advocate a clinical practice shift so that the initial decision step now is the identification of ‘truly low risk’ patients, essentially those aged <65 years without any stroke risk factor (both male and female), who do not need any antithrombotic therapy.2 The ESC guidelines also recommend the use of the CHA2DS2-VASc score4 for stroke risk assessment, and define ‘low-risk’ patients as those with a CHA2DS2-VASc score = 0 (males) or score = 1 (females). Subsequent to this initial step of identifying the low-risk patients, effective stroke prevention (which is essentially OAC) can then be offered to AF patients with ≥1 stroke risk factor(s), with treatment decisions made in consultation with patients and incorporating their preferences. In everyday clinical practice, over 80% of all patients with AF have an indication for OAC, and vascular disease co-exists in ∼30% of them.5–7 With an estimated prevalence of AF of 1–2% and ∼20% of these requiring percutaneous cardiovascular interventions over time,8 ∼1–2 million AF patients in Europe who are …

Cyclosporine before PCI in Patients with Acute Myocardial Infarction

BACKGROUND Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFRCT: outcome and resource impacts study

Aims In symptomatic patients with suspected coronary artery disease (CAD), computed tomographic angiography (CTA) improves patient selection for invasive coronary angiography (ICA) compared with functional testing. The impact of measuring fractional flow reserve by CTA (FFRCT) is unknown. Methods and results At 11 sites, 584 patients with new onset chest pain were prospectively assigned to receive either usual testing (n = 287) or CTA/FFRCT (n = 297). Test interpretation and care decisions were made by the clinical care team. The primary endpoint was the percentage of those with planned ICA in whom no significant obstructive CAD (no stenosis ≥50% by core laboratory quantitative analysis or invasive FFR < 0.80) was found at ICA within 90 days. Secondary endpoints including death, myocardial infarction, and unplanned revascularization were independently and blindly adjudicated. Subjects averaged 61 ± 11 years of age, 40% were female, and the mean pre-test probability of obstructive CAD was 49 ± 17%. Among those with intended ICA (FFRCT-guided = 193; usual care = 187), no obstructive CAD was found at ICA in 24 (12%) in the CTA/FFRCT arm and 137 (73%) in the usual care arm (risk difference 61%, 95% confidence interval 53–69, P< 0.0001), with similar mean cumulative radiation exposure (9.9 vs. 9.4 mSv, P = 0.20). Invasive coronary angiography was cancelled in 61% after receiving CTA/FFRCT results. Among those with intended non-invasive testing, the rates of finding no obstructive CAD at ICA were 13% (CTA/FFRCT) and 6% (usual care; P = 0.95). Clinical event rates within 90 days were low in usual care and CTA/FFRCT arms. Conclusions Computed tomographic angiography/fractional flow reserve by CTA was a feasible and safe alternative to ICA and was associated with a significantly lower rate of invasive angiography showing no obstructive CAD.

Long-term left ventricular pacing: assessment and comparison with biventricular pacing in patients with severe congestive heart failure.

OBJECTIVE The purpose of this study is to report prospectively the results of six-month follow-up of permanent left ventricular (LV) based pacing in patients with severe congestive heart failure (CHF) and left bundle branch block (LBBB). BACKGROUND Left ventricular pacing alone has been demonstrated to result in identical improvement compared to biventricular pacing (BiV) during acute hemodynamic evaluation in patients with advanced CHF and LBBB. However, to our knowledge, the clinical outcome during permanent LV pacing alone versus BiV pacing mode has not been evaluated. METHODS Pacing configuration (LV or BiV) was selected according to the physicians preference. Patient evaluation was performed at baseline and at six months. RESULTS Thirty-three patients with advanced CHF and LBBB were included. Baseline characteristics of LV (18 patients) and BiV (15 patients) pacing groups were similar. During the six-month follow-up period, seven patients died three BiV and four LV). In the surviving patients at 6 months, 8 of 14 patients in the LV group and 9 of 12 in the BiV group were in New York Heart Association class I or II (p = 0.39). No significant difference was observed between the two groups in terms of objective parameters except for LV end-diastolic diameter decrease (-4.4 mm in BiV group vs. -0.7 mm in LV group; p = 0.04). CONCLUSION At six-month follow-up, a trend toward improvement was observed in objective parameters in patients with severe CHF and LBBB following LV-based pacing. The two pacing modes (LV and BiV) were associated with almost equivalent improvement of subjective and objective parameters.

The 2011-12 pilot European Sentinel Registry of Transcatheter Aortic Valve Implantation: in-hospital results in 4,571 patients.

AIMS The aim of this prospective multinational registry is to assess and identify predictors of in-hospital outcome and complications of contemporary TAVI practice. METHODS AND RESULTS The Transcatheter Valve Treatment Sentinel Pilot Registry is a prospective independent consecutive collection of individual patient data entered into a web-based case record form (CRF) or transferred from compatible national registries. A total of 4,571 patients underwent TAVI between January 2011 and May 2012 in 137 centres of 10 European countries. Average age was 81.4±7.1 years with equal representation of the two sexes. Logistic EuroSCORE (20.2±13.3), access site (femoral approach: 74.2%), type of anaesthesia and duration of hospital stay (9.3±8.1 days) showed wide variations among the participating countries. In-hospital mortality (7.4%), stroke (1.8%), myocardial infarction (0.9%), major vascular complications (3.1%) were similar in the SAPIEN XT and CoreValve (p=0.15). Mortality was lower in transfemoral (5.9%) than in transapical (12.8%) and other access routes (9.7%; p<0.01). Advanced age, high logistic EuroSCORE, pre-procedural ≥grade 2 mitral regurgitation and deployment failure predicted higher mortality at multivariate analysis. CONCLUSIONS Increased operator experience and the refinement of valve types and delivery catheters may explain the lower rate of mortality, stroke and vascular complications than in historical studies and registries.

Clinical Events as a Function of Proton Pump Inhibitor Use, Clopidogrel Use, and Cytochrome P450 2C19 Genotype in a Large Nationwide Cohort of Acute Myocardial Infarction Results From the French Registry of Acute ST-Elevation and Non–ST-Elevation Myocardial Infarction (FAST-MI) Registry

Background— Clopidogrel requires metabolic activation by cytochrome P450 2C19 (CYP2C19). Proton pump inhibitors (PPIs) that inhibit CYP2C19 are commonly coadministered with clopidogrel to reduce the risk of gastrointestinal bleeding. This analysis compares treatment outcomes for patients in the French Registry of Acute ST-Elevation and Non–ST-Elevation Myocardial Infarction (FAST-MI) who did or did not receive clopidogrel and/or PPIs. Methods and Results— The FAST-MI registry included 3670 patients (2744 clopidogrel- and PPI-naive patients) presenting with definite MI. Patients were categorized according to use of clopidogrel and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, stroke, bleeding, and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P =0.57) or 1-year MI, stroke, or death (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P =0.72). No differences were seen when the type of PPI or CYP2C19 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for patients with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively. Conclusion— PPI use was not associated with an increased risk of cardiovascular events or mortality in patients administered clopidogrel for recent MI, whatever the CYP2C19 genotype, although harm could not be formally excluded in patients with 2 loss-of-function alleles. Clinical Trial Registration— URL: . Unique identifier: [NCT00673036][1]. # Clinical Perspective {#article-title-33} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00673036&atom=%2Fcirculationaha%2F123%2F5%2F474.atomBackground— Clopidogrel requires metabolic activation by cytochrome P450 2C19 (CYP2C19). Proton pump inhibitors (PPIs) that inhibit CYP2C19 are commonly coadministered with clopidogrel to reduce the risk of gastrointestinal bleeding. This analysis compares treatment outcomes for patients in the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) who did or did not receive clopidogrel and/or PPIs. Methods and Results— The FAST-MI registry included 3670 patients (2744 clopidogrel- and PPI-naïve patients) presenting with definite MI. Patients were categorized according to use of clopidogrel and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, stroke, bleeding, and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, stroke, or death (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or CYP2C19 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for patients with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively. Conclusion— PPI use was not associated with an increased risk of cardiovascular events or mortality in patients administered clopidogrel for recent MI, whatever the CYP2C19 genotype, although harm could not be formally excluded in patients with 2 loss-of-function alleles. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00673036.