Didier Blanchard

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.

Comparison of Thrombolysis Followed by Broad Use of Percutaneous Coronary Intervention With Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Acute Myocardial Infarction : Data From the French Registry on Acute ST-Elevation Myocardial Infarction (FAST-MI)

Background— Intravenous thrombolysis remains a widely used treatment for ST-elevation myocardial infarction; however, it carries a higher risk of reinfarction than primary PCI (PPCI). There are few data comparing PPCI with thrombolysis followed by routine angiography and PCI. The purpose of the present study was to assess contemporary outcomes in ST-elevation myocardial infarction patients, with specific emphasis on comparing a pharmacoinvasive strategy (thrombolysis followed by routine angiography) with PPCI. Methods and Results— This nationwide registry in France included 223 centers and 1714 patients over a 1-month period at the end of 2005, with 1-year follow-up. Sixty percent of the patients underwent reperfusion therapy, 33% with PPCI and 29% with intravenous thrombolysis (18% prehospital). At baseline, the Global Registry of Acute Coronary Events score was similar in thrombolysis and PPCI patients. Time to initiation of reperfusion therapy was significantly shorter in thrombolysis than in PPCI (median 130 versus 300 minutes). After thrombolysis, 96% of patients had coronary angiography, and 84% had subsequent PCI (58% within 24 hours). In-hospital mortality was 4.3% for thrombolysis and 5.0% for PPCI. In patients with thrombolysis, 30-day mortality was 9.2% when PCI was not used and 3.9% when PCI was subsequently performed (4.0% if PCI was performed in the same hospital and 3.3% if performed after transfer to another facility). One-year survival was 94% for thrombolysis and 92% for PPCI (P=0.31). After propensity score matching, 1-year survival was 94% and 93%, respectively. Conclusions— When used early after the onset of symptoms, a pharmacoinvasive strategy that combines thrombolysis with a liberal use of PCI yields early and 1-year survival rates that are comparable to those of PPCI.

Association of Changes in Clinical Characteristics and Management With Improvement in Survival Among Patients With ST-Elevation Myocardial Infarction

CONTEXT The contemporary decline in mortality reported in patients with ST-segment elevation myocardial infarction (STEMI) has been attributed mainly to improved use of reperfusion therapy. OBJECTIVE To determine potential factors-beyond reperfusion therapy-associated with improved survival in patients with STEMI over a 15-year period. DESIGN, SETTING, AND PATIENTS Four 1-month French nationwide registries, conducted 5 years apart (between 1995, 2000, 2005, 2010), including a total of 6707 STEMI patients admitted to intensive care or coronary care units. MAIN OUTCOME MEASURES Changes over time in crude 30-day mortality, and mortality standardized to the 2010 population characteristics. RESULTS Mean (SD) age decreased from 66.2 (14.0) to 63.3 (14.5) years, with a concomitant decline in history of cardiovascular events and comorbidities. The proportion of younger patients increased, particularly in women younger than 60 years (from 11.8% to 25.5%), in whom prevalence of current smoking (37.3% to 73.1%) and obesity (17.6% to 27.1%) increased. Time from symptom onset to hospital admission decreased, with a shorter time from onset to first call, and broader use of mobile intensive care units. Reperfusion therapy increased from 49.4% to 74.7%, driven by primary percutaneous coronary intervention (11.9% to 60.8%). Early use of recommended medications increased, particularly low-molecular-weight heparins and statins. Crude 30-day mortality decreased from 13.7% (95% CI, 12.0-15.4) to 4.4% (95% CI, 3.5-5.4), whereas standardized mortality decreased from 11.3% (95% CI, 9.5-13.2) to 4.4% (95% CI, 3.5-5.4). Multivariable analysis showed a consistent reduction in mortality from 1995 to 2010 after controlling for clinical characteristics in addition to the initial population risk score and use of reperfusion therapy, with odds mortality ratios of 0.39 (95%, 0.29-0.53, P <.001) in 2010 compared with 1995. CONCLUSION In France, the overall rate of cardiovascular mortality among patients with STEMI decreased from 1995 to 2010, accompanied by an increase in the proportion of women younger than 60 years with STEMI, changes in other population characteristics, and greater use of reperfusion therapy and recommended medications.

Maintenance of Long-Term Clinical Benefit With Sirolimus-Eluting Coronary Stents Three-Year Results of the RAVEL Trial

Background—The use of sirolimus-eluting coronary stents has been associated with a nearly complete elimination of restenosis at 6 months and with a very low 1-year incidence of major adverse cardiac events (MACE). This analysis examined whether these beneficial effects persist over the longer term. Methods and Results—This multicenter trial randomly assigned 238 patients to revascularization of single, de novo, native coronary artery lesions with sirolimus-eluting versus conventional bare-metal stents. Survival free from target lesion revascularization (TLR), target vessel failure (TVF), and MACE up to 3 years of follow-up was compared between the 2 treatment groups. Complete data sets were available in 94.2% of patients treated with sirolimus-eluting stents and in 94.1% of patients randomized to the control group. The cumulative 1-, 2-, and 3-year event-free survival rates were 99.2%, 96.5%, and 93.7% for TLR and 95.8%, 92.3%, and 87.9% for TVF, respectively, in the sirolimus-eluting stent group, versus 75.9%, 75.9%, and 75.0% for TLR and 71.2%, 69.4%, and 67.3% for TVF in the control group (P<0.001 for both comparisons at 3 years). Rates of MACE at 3 years were 15.8% in patients randomly assigned to sirolimus-eluting stents versus 33.1% in patients assigned to bare-metal stents (P=0.002). One patient treated with a sirolimus-eluting stent died of a cardiac cause between 12 and 36 months. Conclusions—Treatment of de novo coronary stenosis with sirolimus-eluting stents was associated with a sustained clinical benefit and very low rates of TLR and of other MACE up to 3 years after device implantation.

Impact of Prehospital Thrombolysis for Acute Myocardial Infarction on 1-Year Outcome Results From the French Nationwide USIC 2000 Registry

Background—Limited data are available on the impact of prehospital thrombolysis (PHT) in the “real-world” setting. Methods and Results—Of 443 intensive care units in France, 369 (83%) prospectively collected all cases of infarction (≤48 hours of symptom onset) in November 2000; 1922 patients (median age, 67 years; 73% men) with ST-segment–elevation infarction were included, of whom 180 (9%) received intravenous thrombolysis before hospital admission (PHT). Patients with PHT were younger than those with in-hospital thrombolysis, primary percutaneous interventions, or no reperfusion therapy. Median time from symptom onset to hospital admission was 3.6 hours for PHT, 3.5 hours for in-hospital lysis, 3.2 hours for primary percutaneous interventions, and 12 hours for no reperfusion therapy. In-hospital death was 3.3% for PHT, 8.0% for in-hospital lysis, 6.7% for primary percutaneous interventions, and 12.2% for no reperfusion therapy. One-year survival was 94%, 89%, 89%, and 79%, respectively. In a multivariate analysis of predictors of 1-year survival, PHT was associated with a 0.49 relative risk of death (95% CI, 0.24 to 1.00; P=0.05). When the analysis was limited to patients receiving reperfusion therapy, the relative risk of death for PHT was 0.52 (95% CI, 0.25 to 1.08; P=0.08). In patients with PHT admitted in ≤3.5 hours, in-hospital mortality was 0% and 1-year survival was 99%. Conclusions—The 1-year outcome of patients treated with PHT compares favorably with that of patients treated with other modes of reperfusion therapy; this favorable trend persists after multivariate adjustment. Patients with PHT admitted very early have a very high 1-year survival rate.

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.

Improved outcome of cardiogenic shock at the acute stage of myocardial infarction: a report from the USIK 1995, USIC 2000, and FAST-MI French Nationwide Registries

AIM The historical evolution of incidence and outcome of cardiogenic shock (CS) in acute myocardial infarction (AMI) patients is debated. This study compared outcomes in AMI patients from 1995 to 2005, according to the presence of CS. METHOD AND RESULTS Three nationwide French registries were conducted 5 years apart, using a similar methodology in consecutive patients admitted over a 1-month period. All 7531 AMI patients presenting ≤48 h of symptom onset were included. The evolution of mortality was compared in the 486 patients with CS vs. those without CS. The incidence of CS tended to decrease over time (6.9% in 1995; 5.7% in 2005, P = 0.07). Thirty-day mortality was considerably higher in CS patients (60.9 vs. 5.2%). Over the 10-year period, mortality decreased for both patients with (70-51%, P = 0.003) and without CS (9-4%, P < 0.001). In CS patients, the use of percutaneous coronary intervention (PCI) increased from 20 to 50% (P < 0.001). Time period was an independent predictor of early mortality in CS patients (OR for death, 2005 vs. 1995 = 0.45; 95% CI: 0.27-0.75, P = 0.005), along with age, diabetes, and smoking status. When added to the multivariate model, PCI was associated with decreased mortality (OR = 0.38; 95% CI: 0.24-0.58, P < 0.001). In propensity-score-matched cohorts, CS patients with PCI had a significantly higher survival. CONCLUSIONS Cardiogenic shock remains a clinical concern, although early mortality has decreased. Improved survival is concomitant with a broader use of PCI and recommended medications at the acute stage. Beyond the acute stage, however, 1-year survival has remained unchanged.

Major impact of admission glycaemia on 30 day and one year mortality in non-diabetic patients admitted for myocardial infarction: results from the nationwide French USIC 2000 study

Objective: To analyse the short and long term prognostic significance of admission glycaemia in a large registry of non-diabetic patients with acute myocardial infarction. Methods: Assessment of short and long term prognostic significance of admission blood glucose in a consecutive population of 1604 non-diabetic patients admitted to intensive care units in France in November 2000 for a recent (⩽ 48 hours) myocardial infarction. Results: In-hospital mortality, compared with that of patients with admission glycaemia below the median value of 6.88 mmol/l (3.7%), rose gradually with each of the three upper sextiles of glycaemia: 6.5%, 12.5% and 15.2%. Conversely, one year survival decreased from 92.5% to 88%, 83% and 75% (p < 0.001). Admission glycaemia remained an independent predictor of in-hospital and one year mortality after multivariate analyses accounting for potential confounders. Increased admission glycaemia also was a predictor of poor outcome in all clinical subsets studied: patients without heart failure on admission, younger and older patients, patients with or without reperfusion therapy, and patients with or without ST segment elevation. Conclusion: In non-diabetic patients, raised admission blood glucose is a strong and independent predictor of both in-hospital and long term mortality.

Bypassing the emergency room reduces delays and mortality in ST elevation myocardial infarction. The USIC 2000 registry

Objective: To study the impact on outcomes of direct admission versus emergency room (ER) admission in patients with ST-segment elevation myocardial infarction (STEMI) Design: Nationwide observational registry of STEMI patients Setting: 369 intensive care units in France. Interventions: Patients were categorised on the basis of the initial management pathway (direct transfer to the coronary care unit or catheterisation laboratory versus transfer via the ER). Main outcome measures: Delays between symptom onset, admission and reperfusion therapy. Mortality at five days and one year. Results: Of 1204 patients enrolled, 66.9% were admitted direct and 33.1% via the ER. Bypassing the ER was associated with more frequent use of reperfusion (61.7% v 53.1%; p  =  0.001) and shorter delays between symptom onset and admission (244 (interquartile range 158) v 292 (172) min; p < 0.001), thrombolysis (204 (150) v 258 (240) min; p < 0.01), hospital thrombolysis (228 (156) v 256 (227) min, p  =  0.22), and primary percutaneous coronary intervention (294 (246) v 402 (312) min; p < 0.005). Five day mortality rates were lower in patients who bypassed the ER (4.9% v 8.6%; p  =  0.01), regardless of the use and type of reperfusion therapy. After adjusting for the simplified Thrombolysis in Myocardial Infarction (TIMI) risk score, admission via the ER was an independent predictor of five day mortality (odds ratio 1.67, 95% confidence interval 1.01 to 2.75). Conclusions: In this observational analysis, bypassing the ER was associated with more frequent and earlier use of reperfusion therapy, and with an apparent survival benefit compared with admission via the ER.

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.