Jacques Machecourt

Impact of Type of Preadmission Sulfonylureas on Mortality and Cardiovascular Outcomes in Diabetic Patients with Acute Myocardial Infarction

BACKGROUND The impact of antidiabetic medications on clinical outcomes in patients developing acute myocardial infarction (MI) is controversial. We sought to determine whether in-hospital outcomes in patients who were on sulfonylureas (SUs) when they developed their MIs differed from that of diabetic patients not receiving SUs and whether clinical outcomes were related to the pancreatic cells specificity of SUs. METHODS AND RESULTS We analyzed the outcomes of the 1310 diabetic patients included in the nationwide French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction in 2005. Medications used before the acute episode were recorded. In-hospital complications were analyzed according to prior antidiabetic treatment. Mortality was lower in patients previously treated with SUs (3.9%) vs. those on other oral medications (6.4%), insulin (9.4%), or no medication (8.4%) (P = 0.014). Among SU-treated patients, in-hospital mortality was lower in patients receiving pancreatic cells-specific SUs (gliclazide or glimepiride) (2.7%), compared with glibenclamide (7.5%) (P = 0.019). Arrhythmias and ischemic complications were also less frequent in patients receiving gliclazide/glimepiride. The lower risk in patients receiving gliclazide/glimepiride vs. glibenclamide persisted after multivariate adjustment (odds ratio 0.15; 95% confidence interval 0.04-0.56) and in propensity score-matched cohorts. CONCLUSION In this nationwide registry of patients hospitalized for acute MI, no hazard was associated with the use of SUs before the acute episode. In addition, patients previously receiving gliclazide/glimepiride had improved in-hospital outcomes, compared with those on glibenclamide.

Circulating levels of secretory- and lipoprotein-associated phospholipase A2 activities: relation to atherosclerotic plaques and future all-cause mortality

AIMS Secretory- and lipoprotein-associated phospholipases A2 (sPLA2 and Lp-PLA2) are enzymes both suggested to be of importance for atherosclerosis. We investigated relationships between the activities of these enzymes in the circulation and atherosclerosis as well as future clinical events. METHODS AND RESULTS The population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study included 1016 randomly selected subjects, all aged 70. The prevalence of carotid artery plaques was recorded by ultrasound (n= 954), and arterial stenosis was assessed by whole-body magnetic resonance angiography (WBMRA, n= 302). Secretory-associated phospholipase A2 [odds ratio 1.23 for 1 SD increase, 95% confidence interval (CI): 1.05-1.44, P= 0.007], but not Lp-PLA2 (P= 0.26), activity was significantly related to carotid atherosclerosis and to the amount of stenosis at WBMRA (P= 0.006) following adjustment for multiple risk factors (waist circumference, serum triglycerides, body mass index, C-reactive protein, high density lipoprotein-C, low density lipoprotein-C, triglycerides, GFR, fasting glucose, blood pressure, statin use, and exercise habits). Secretory-associated phospholipase A2 [hazard ratio (HR) 1.45 for 1 SD increase, 95% CI: 1.15-1.84, P= 0.001], but not Lp-PLA2 (HR 0.95, P= 0.55), activity was a significant risk factor for all-cause mortality (114 had died) during 7.0 years follow-up after adjustment for the risk factors described above. In a sample of 1029 post-myocardial infarction (MI) patients (French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction), sPLA2 (adjusted HR 1.32 for 1 unit increase, 95% CI: 1.02-1.71, P= 0.036), but not Lp-PLA2 (HR 1.03, P= 0.90), activity predicted death or recurrent MI during 1-year follow-up (n= 136 cases). CONCLUSION sPLA2 activity was related to atherosclerosis and predicted all-cause mortality in a sample of elderly subjects, as well as death or MI in post-MI patients.

The favorable price evolution between bare metal stents and drug eluting stents increases the cost effectiveness of drug eluting stents.

AIMS We aimed to assess the cost effectiveness of the sirolimus-eluting stent (SES) in diabetic and non-diabetic patients vs. bare metal stents (BMS). METHODS EVASTENT was a matched cohort registry of patients undergoing revascularization exclusively with SES; for each diabetic patient (db+) included, stratified according to single (SVD) or multiple (MVD) vessel disease, a non-diabetic patient (db-) was subsequently included. Efficacy, safety and cost data were obtained from the SES database, and then data from the BMS group were derived by using an original method of transition probabilities of events (Markov model and Monte Carlo simulations) if BMS had been implanted in the same patient, over a 3-year time period. Sensitivity analysis was performed by varying the price difference between BMS and SES from 2008 to 2012. RESULTS In this study, 1731 patients were included with 97% complete follow-up at 3-years. In 2008, compared to BMS the SES was cost effective only in MVD db+ (7494€ per avoided revascularization (PAR) vs. >10,000€ in other groups). In 2012, after a reduction in the price difference between SES and BMS, SES were cost effective in MVD db+ (-891), SVD db+ (3519), MVD db- (3050), and SVD db- (6329) patients. Otherwise, the cardiovascular mortality rate was higher (p<0.0001) in MVD db+ than in SVD db+, MVD db- and SVD db-. CONCLUSION The SES is now cost effective in diabetic and non-diabetic patients, after a favorable price evolution between drug eluting and bare metal stents.

Platelet hyperactivity during exercise leading to iterative coronary stent thrombosis: clinical implications

Exercise may induce platelet activation in spite of using antiplatelet treatment. We present a case where the initial acute coronary syndrome and the iterative stent thrombosis always occurred after intense and prolonged physical effort. For this patient the at rest response to platelet inhibition with antiplatelet treatments was assessed as adequate, but after exercise the patient developed platelet activation which could be the trigger of his stent thrombosis.