Jacques Boschat

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.

Evaluation of left ventricular based pacing in patients with congestive heart failure and atrial fibrillation

Acute hemodynamic data of left ventricular based pacing were assessed in 2 groups of patients with severe cardiac failure: 11 patients with atrial fibrillation and 17 patients with sinus rhythm. Both biventricular and left ventricular pacing significantly improved acute hemodynamic findings to a similar degree in both groups, suggesting that left ventricular based pacing may be beneficial in patients with severe cardiac failure regardless of whether or not they are in sinus rhythm.

Angiographic Anatomy of the Coronary Sinus and Its Tributaries

Permanent left ventricular pacing has been shown to imporve the hemodynamic and clinical status of patients with severe heart failure. To pace the left ventricle, the electrode is implanted in tributaries of the coronary sinus (CS). However, the anatomy of cardiac veins with this purpose in mind has not been described in detail. Methods: One hundred consecutive patients admitted for coronary angiography had a simultaneous coronary venography performed after the injection of 8 to 10 mL of contrast material into the left coronary artery. Cardiac veins were analyzed in antero‐posterior, left anterior oblique 60±, and right anterior oblique 30± views by three different observers. The number, dimension, angulation, and position of the coronary sinus and of its tributaries were studied. Results: Two veins are consistently present: the middle cardiac vein (mean diameter 2.62 ± 1.26 mm) and the great cardiac vein (mean diameter 3.55 ± 1.24 mm). The left posterior vein(s) (LPV) (mean diameter 2.25 ± 1.2 mm) is (are) variable in number (ranging from 0 to 3), size, and angulation. The absence of LPV limits the ability to pace the left ventricle endovenously. The diameter of the vein (< 2 mm) and its angulation may also complicate the insertion of the lead. Conclusion: Angiographic analysis of dimensions, tortuosity, number, and angulation of venous tributaries of the CS seems to allow the insertion of commercially available pacing leads in approximately 85% of cases. An increase in this percentage hinges on the development of new, dedicated leads.

Effect of the Direct Nitric Oxide Donors Linsidomine and Molsidomine on Angiographic Restenosis After Coronary Balloon Angioplasty The ACCORD Study

BACKGROUND Nitric oxide (NO) donors, in addition to their vasodilator effect, decrease platelet aggregation and inhibit vascular smooth muscle cell proliferation. These actions could have beneficial effects on restenosis after coronary balloon angioplasty. METHODS AND RESULTS In a prospective multicenter, randomized trial, 700 stable coronary patients scheduled for angioplasty received direct NO donors (infusion of linsidomine followed by oral molsidomine) or oral diltiazem. Treatment was started before angioplasty and continued until 12 to 24 hours before follow-up angiography at 6 months. The primary study end point was minimal lumen diameter, assessed by quantitative coronary angiography, 6 months after balloon angioplasty. Clinical variables were well matched in both groups. However, despite intracoronary administration of isosorbide dinitrate, the reference diameter in the NO donor group was significantly greater than in the diltiazem group on the preangioplasty, postangioplasty, and follow-up angiograms. Pretreatment with an NO donor was associated with a modest improvement in the immediate angiographic result compared with pretreatment with diltiazem (minimum luminal diameter, 1.94 versus 1.81 mm; P = .001); this improvement was maintained at the 6-month angiographic follow-up (minimal lumen diameter, 1.54 versus 1.38 mm; P = .007). The extent of late luminal narrowing did not differ significantly between groups (loss index in the NO donor and diltiazam groups, 0.35 +/- 0.78 and 0.46 +/- 0.74, respectively; P = .103). Restenosis, defined as a binary variable (> or = 50% stenosis), occurred less often in the NO donor group (38.0% versus 46.5%; P = .026). Combined major clinical events (death, nonfatal myocardial infarction, and coronary revascularization) were similar in the two groups (32.2% versus 32.4%). CONCLUSIONS Treatment with linsidomine and molsidomine was associated with a modest improvement in the long-term angiographic result after angioplasty but had no effect on clinical outcome. The improved angiographic result related predominantly to a better immediate procedural result, because late luminal loss did not differ significantly between groups.

Evolution of Spontaneous Atherosclerotic Plaque Rupture With Medical Therapy Long-Term Follow-Up With Intravascular Ultrasound

Background—Ruptured coronary atheromatous plaque is generally considered to involve a high risk of subsequent clinical events. Few data are available on the natural evolution of non–culprit-lesion ruptured plaque. We therefore used serial intravascular ultrasound (IVUS) to study how such lesions, detected in the context of a first acute coronary syndrome with elevated troponin I levels, develop. Methods and Results—Fourteen patients with 28 distinct plaque ruptures (2±1 per patient) without significant associated stenosis (minimal lumen cross-sectional area >4 mm2) were included and systematically treated with 40 mg statin and antiplatelet agent (clopidogrel and aspirin for ≥9 months). Mean clinical and IVUS follow-up was 22±13 months (median, 22 months). No clinical event related to the lesion under study occurred. On final IVUS examination, half (14 of 28) of the ruptured plaques had healed, and the degree of stenosis tended to diminish (stenosis, 22±17% versus 29±17% at baseline; P=0.056). No healing-prediction criterion could be identified. Conclusions—Nearly 2 years of follow-up found that spontaneous coronary atheromatous plaque rupture without significant stenosis detected on first acute coronary syndrome healed without significant plaque modification in 50% of cases with medical therapy.

Same-Day Combined Percutaneous Coronary Intervention and Coronary Artery Surgery

BACKGROUND Either percutaneous coronary intervention (PCI) or coronary artery bypass grafting can be chosen for the treatment of multiple-vessel coronary artery disease. We report the results of a hybrid procedure performed on the same day, combining PCI of the right coronary artery and internal mammary artery bypass grafting of the left coronary artery, for the treatment of diffuse extensive lesions. METHODS AND RESULTS Since January 2000, 70 patients (53 male, mean age 68.5 +/- 10 years) underwent this hybrid revascularization combining primary right coronary artery PCI and, within the next 16 h, left coronary artery grafting with left and/or right internal mammary artery. Thirty-one patients (98%) were treated on the same day. At a mean follow-up of 33 months (range: 2-70 months), 68 patients (97%) were asymptomatic at the time of writing. Three adverse events were reported: 2 were PCI-related, due to failure to take ticlopidine, and 1 was surgery-related, resulting in the patients death during hospitalization. CONCLUSION These preliminary results for a same-day combined procedure in patients with diffuse multivessel coronary artery disease are encouraging. This strategy optimizes revascularization when patients are unstable or present very severe coronary lesions, which requiring rapid treatment and are not ideally suitable for PCI management alone.

Antiplatelet therapy in patients with anticoagulants undergoing percutaneous coronary stenting (from STENTIng and oral antiCOagulants [STENTICO]).

We evaluated the safety and efficacy of dual antiplatelet therapy, in association with oral anticoagulant (OAC) therapy, in patients undergoing percutaneous coronary intervention (PCI). The use of this triple therapy increases the rate of adverse outcomes, as shown by retrospective studies. In this first prospective multicenter registry STENTIng and oral antiCOagulation (STENTICO), all patients with OAC therapy undergoing PCI were included and followed up at 2 and 12 months. A total of 359 patients were included from 40 French centers. In 234 (65.2%; group 1) of these 359 patients, OAC therapy was discontinued (22 +/- 31 days). In 125 patients (34.8%; group 2), triple therapy was continued. The baseline characteristics were similar in the 2 groups. In group 2, a radial approach was more often used (65.6% vs 43.8%, p = 0.003), fewer drug-eluting stents were implanted (33.3% vs 24.8%, p = 0.06), and fewer anti-glycoprotein IIb/IIIa antagonists were prescribed (5.6% vs 8.5%, p = 0.02). The stroke rate did not differ significantly, at 3.0% (95% confidence interval 0.8% to 5.2%) for group 1 versus 0.8% (95% confidence interval -0.8% to 2.4%) in group 2. Severe and moderate bleeding, according to the Global Use of Strategies to Open Coronary Arteries (GUSTO) criteria, occurred in 2.1% and 6.4% of groups 1 and 2, respectively (p = 0.04). A significant difference in bleeding risk was found between the femoral and radial approaches (10.3% vs 3.8%, respectively; p = 0.01). In conclusion, adding dual antiplatelet therapy to pre-existing OAC therapy increases the post-PCI bleeding risk. Temporary discontinuation decreased this bleeding risk but tended to increase the risk of stroke. A radial approach for PCI could be a good alternative to the conventional femoral route to avoid bleeding.

Left ventricular-based pacing in patients with chronic heart failure: Comparison of acute hemodynamic benefits according to underlying heart disease

Acute left ventricular‐based pacing has been shown to improve hemodynamics in patients with severe heart failure and left bundle branch block (LBBB). However, it is not known whether the cause of the underlying heart disease influences the potential effect of left ventricular‐based pacing.