Association between Beta1 -Adrenergic Receptor Polymorphism and Risk of ICD Shock in Heart Failure Patients.

BACKGROUND: Sympathetic activation in heart failure patients favors the development of ventricular arrhythmias, thus leading to an increased risk of sudden cardiac death. ß1 - and ß2 -adrenergic receptor polymorphisms have been linked to the risk of sudden death. Implantable cardioverter-defibrillators (ICD) are implanted in a large percentage of heart failure patients, and beyond preventing sudden cardiac death they provide a continuous monitoring of major ventricular arrhythmias and of their own interventions. We investigated whether functionally relevant ß1 - and ß2 -adrenergic receptor polymorphisms are associated with risk of ICD shocks, as evidenced in ICD memory. METHODS: 311 patients with systolic heart failure were enrolled, and number and timing of shocks in ICD memory were recorded. Four selected polymorphisms were determined: ß1 -adrenergic receptor polymorphisms Ser(49) Gly and Arg(389) Gly and ß2 -adrenergic receptor polymorphisms Arg(16) Gly and Gln(27) Glu. RESULTS: Only Ser(49) Gly was significantly correlated with time free from ICD shocks, both considering time to the first event in a Cox model (hazard ratio 2.117), and modeling repeated events with the Andersen-Gill method (hazard ratio 2.088). Gly allele carriers had a higher probability of ICD shock. The relationship remained significant even after adjusting for ejection fraction and beta-blocker dosage (hazard ratio 1.910). CONCLUSIONS: Data from our study suggest that the ß adrenoreceptor Gly 49 allele of the ß1 -adrenergic receptor Ser(49) Gly polymorphisms may increase the risk of ICD shock in patients with heart failure, independent of beta-blocker dosage.

Prevalence, predictors, and long-term prognosis of premature discontinuation of oral antiplatelet therapy after drug eluting stent implantation.

To date, limited information is available on the long-term discontinuation rates of antiplatelet therapy after drug-eluting stent implantation. The aim of the present study was to determine the prevalence and predictors of premature discontinuation of oral antiplatelet therapy after drug-eluting stent implantation and to evaluate its effects on long-term prognosis. We studied 1,358 consecutive patients successfully treated with drug-eluting stents and discharged with dual oral antiplatelet therapy. Aspirin was to be maintained lifelong, and clopidogrel was prescribed for 12 months. The patients were followed for 36 months. The prevalence and predictors of aspirin and clopidogrel discontinuation were assessed. Major adverse cardiac events, defined as death, myocardial infarction, destabilizing symptoms leading to hospitalization, and nonfatal stroke, were recorded. Definite, probable, and possible stent thrombosis (ST) and major and minor bleeding were also determined. Of the 1,358 patients, 8.8% had discontinued one or both antiplatelet agents within the first 12 months ("early" discontinuation) and 4.8% had discontinued aspirin after 1 year ("late" discontinuation). Early discontinuation was predicted by in-hospital major bleeding, the use of oral anticoagulants at discharge, and the lack of a statin prescription. Previous stroke was the only independent predictor of late discontinuation. Patients with early discontinuation experienced a greater incidence of major adverse cardiac events (28.6% vs 13.7%, p <0.001) and ST (7.6% vs 3.4%, p = 0.038). All-cause mortality (13.4% vs 4.7%, p <0.001) and cardiovascular death (5% vs 1.2%, p = 0.007) were significantly more frequent among patients with early discontinuation. In patients with late discontinuation, a nonstatistically significant increase was seen in major adverse cardiac events (20% vs 13.3%, p = 0.128) and ST (6.2% vs 3.2%, p = 0.275). In conclusion, premature discontinuation of antiplatelet therapy is relatively common, especially within the first year, and strongly associated with increased cardiovascular events, including ST and death.

Safety of clopidogrel and proton pump inhibitors in patients undergoing drug-eluting stent implantation.

OBJECTIVE: A pharmacodynamic interaction between clopidogrel and proton pump inhibitors (PPIs) has been suggested, leading to reduced clopidogrel-induced platelet inhibitory effects. However, data from clinical studies are conflicting. The aim of this study was to evaluate the safety of long-term clopidogrel and PPI therapy. METHODS: A total of 1328 consecutive patients (age 63±11 years; 81% male) undergoing drug-eluting stent implantation and 1-year follow-up were included. All patients were treated with a standard aspirin and clopidogrel treatment regimen for 12 months. The concomitant PPI therapy for the same duration was at the discretion of the clinical cardiologist. PPI therapy included lansoprazole (30 mg/day), pantoprazole (20 mg/day), or omeprazole (20 mg/day). At 1-year follow-up, major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), acute coronary syndrome leading to hospitalization and nonfatal stroke, were recorded. All cause death, any stent thrombosis (ST), and bleeding (Thrombolysis in MI major and minor) were also assessed. RESULTS: Lansoprazole, pantoprazole, and omeprazole were administered to 855, 178, and 125 patients, whereas 170 were not prescribed any PPI therapy. Among patients treated with PPIs, those on pantoprazole had more often prior MI, multivessel coronary artery disease, and chronic kidney disease, whereas earlier peptic ulcer was more frequent among patients treated with omeprazole. The incidence of 1-year MACE was not statistically different between patients in the PPI and no-PPI groups (7.5 vs. 5.0%; P=0.26). Similarly, 1-year rates of all cause death, ST, and Thrombolysis in MI major and minor bleedings did not significantly differ. After statistical adjustment for potential confounders, the concomitant use of clopidogrel and PPIs was not associated with the risk of 1-year MACE [odds ratio (OR) 1.54, P=0.38], death (OR: 0.97, P=0.961), and ST (OR: 1.01, P=0.998). No differences across the three PPI types were found. CONCLUSION: The association of clopidogrel and PPIs after drug-eluting stent implantation, prescribed on clinical judgement, seems safe.

Usefulness of ultrasonographic markers of carotid atherosclerosis (intima-media thickness, unstable carotid plaques and severe carotid stenosis) for predicting presence and extent of coronary artery disease.

OBJECTIVE: To investigate the usefulness of carotid ultrasound evaluation in predicting the presence and the extent of coronary artery disease in a consecutive series of patients. DESIGN: We examined retrospectively 1337 patients in whom both coronary angiography and carotid ultrasound were evaluated, from 1995 to 2005. Markers of carotid artery disease were considered, such as intima-media thickness more than 0.90 mm, unstable plaque and severe stenosis (> or =70%). Carotid risk score was defined as the sum of these parameters. We considered as affected by significant coronary artery disease those patients with at least one lesion more than 50% within the main branches of the coronary arteries. RESULTS: The markers of carotid atherosclerosis increased proportionally in patients with one-, two- or three-vessel coronary artery disease. At univariate analysis, intima-media thickness more than 0.90 mm was associated with an odds ratio of coronary artery disease of 2.28 (1.8-2.9) (P < 0.0001), unstable plaque 3.6 (2.3-5.7) (P < 0.001) and severe carotid stenosis 4.2 (2.0-8.7) (P = 0.0001). At multivariate analysis, the three markers mentioned above were independent risk factors for coronary artery disease even when considering other risk factors. CONCLUSION: We confirmed the usefulness of carotid ultrasound evaluation in predicting the presence and extent of coronary artery disease. Considering the high correlation between carotid and coronary artery disease, carotid screening is useful in patients with coronary artery disease. In patients with an occasional finding of a carotid risk score of at least 2, a careful search for coronary artery disease seems warranted.