Inter-patient variability of platelet reactivity in patients treated with prasugrel and ticagrelor.

The aim of this study was to evaluate the distribution of platelet reactivity values in patients treated with prasugrel and ticagrelor. This prospective observational study enrolled 200 patients treated with prasugrel or ticagrelor. Platelet aggregation was determined by multiple electrode aggregometry after stimulation with adenosine diphosphate (ADP) in the maintenance phase of treatment with prasugrel or ticagrelor. Only 3% of patients in the prasugrel group and 2% of study participants in the ticagrelor group had high on treatment platelet reactivity (HTPR). The majority of patients displayed low on treatment platelet reactivity (LTPR; prasugrel: 69%; ticagrelor: 64%). The pharmacodynamic effect was similar in patients treated with prasugrel and ticagrelor: the median level of ADP-induced platelet aggregation was 15U (interquartile range IQR 9-21U) under prasugrel treatment and 17U (IQR 8-24U) under ticagrelor treatment (p=0.370). In conclusion, our study suggests that there is some degree of variability in ADP-induced platelet aggregation under treatment with prasugrel and ticagrelor.

Cost-effectiveness of percutaneous coronary intervention with drug-eluting stents in patients with multivessel coronary artery disease compared to coronary artery bypass surgery five-years after intervention.

OBJECTIVES: Cost-effectiveness of percutaneous coronary intervention (PCI) using drug-eluting stents (DES), and coronary artery bypass surgery (CABG) was analyzed in patients with multivessel coronary artery disease over a 5-year follow-up. BACKGROUND: DES implantation reducing revascularization rate and associated costs might be attractive for health economics as compared to CABG. METHODS: Consecutive patients with multivessel DES-PCI (n = 114, 3.3 ± 1.2 DES/patient) or CABG (n = 85, 2.7 ± 0.9 grafts/patient) were included prospectively. Primary endpoint was cost-benefit of multivessel DES-PCI over CABG, and the incremental cost-effectiveness ratio (ICER) was calculated. Secondary endpoint was the incidence of major adverse cardiac and cerebrovascular events (MACCE), including acute myocardial infarction (AMI), all-cause death, revascularization, and stroke. RESULTS: Despite multiple uses for DES, in-hospital costs were significantly less for PCI than CABG, with 4551 €/patient difference between the groups. At 5-years, the overall costs remained higher for CABG patients (mean difference 5400 € between groups). Cost-effectiveness planes including all patients or subgroups of elderly patients, diabetic patients, or Syntax score >32 indicated that CABG is a more effective, more costly treatment mode for multivessel disease. At the 5-year follow-up, a higher incidence of MACCE (37.7% vs. 25.8%; log rank P = 0.048) and a trend towards more AMI/death/stroke (25.4% vs. 21.2%, log rank P = 0.359) was observed in PCI as compared to CABG. ICER indicated 45615 € or 126683 € to prevent one MACCE or AMI/death/stroke if CABG is performed. CONCLUSIONS: Cost-effectiveness analysis of DES-PCI vs. CABG demonstrated that CABG is the most effective, but most costly, treatment for preventing MACCE in patients with multivessel disease.

Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel.

BACKGROUND: Clopidogrel is activated by CYP2C19, which also metabolizes proton pump inhibitors (PPI). As proton pump inhibitors are metabolized to varying degrees by CYP2C19, we hypothesized that the reported negative omeprazole-clopidogrel drug interaction may not be a class effect. METHODS: Responsiveness to clopidogrel was assessed by the vasodilator-stimulated phosphoprotein phosphorylation (VASP) assay and aggregometry (Multiplate Analyzer) in 300 patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). RESULTS: The mean platelet reactivity index (PRI, assessed by the VASP assay) was nearly the same in patients with (n = 226; PRI = 51%) or without PPI treatment (n = 74; PRI = 49%; P = .724). Likewise, the adenosine diphosphate-induced platelet aggregation did not differ significantly between patients with or without PPI treatment (45 vs. 41 U; P = .619). Similarly, there was no difference in the PRI or the adenosine diphosphate-induced platelet aggregation between patients with pantoprazole (n = 152; PRI = 50%; aggregation = 47 U), esomeprazole (n = 74; PRI = 54%; aggregation = 42 U), or without PPI (n = 74; PRI = 49%; aggregation = 41 U; P = .382). CONCLUSION: In contrast to the reported negative omeprazole-clopidogrel drug interaction, the intake of pantoprazole or esomeprazole is not associated with impaired response to clopidogrel.

Distribution of clinical events across platelet aggregation values in all-comers treated with prasugrel and ticagrelor.

The aim of this study was to investigate the distribution of clinical events across the platelet aggregation values in patients treated with prasugrel and ticagrelor. This prospective observational study enrolled 226 patients treated with prasugrel (n=121) or ticagrelor (n=105). Adenosine diphosphate (ADP)-induced platelet aggregation was determined by Multiplate Analyzer in the maintenance phase of treatment with prasugrel or ticagrelor. Clinical outcome was evaluated over 12 months. Platelet aggregation values were divided into quartiles. The first quartile comprised values <8 U, the second quartile values between 8 U and <15 U, the third one values between 15 U and 23 U, and the forth one values >23 U. Myocardial infarction events were observed in patients within the third quartile of aggregation values (15-23 U), and were not associated with high on-treatment platelet reactivity (HTPR>46 U). All bleeding events occurred in patients with aggregation values ≤ 23 U, which corresponded to the 75 percentile (p=0.031). There was no difference in the distribution of bleeding events between the 1st-3rd quartiles (p=0.873). In conclusion, patients with ADP-induced aggregation values over 23 U (fourth quartile) were at the lowest risk to develop bleeding during the follow-up.

[Percutaneous renal denervation in patients with resistant hypertension--first experiences in Austria]. / Perkutane renale Denervierung bei therapieresistenter Hypertonie--Erste Erfahrungen in Österreich.

BACKGROUND: Hypertension is a major public health issue. Many patients do not reach the target blood pressure despite antihypertensive combination therapy. Renal ablation is a new therapeutic approach for patients who are refractory. Using a percutaneous catheter-based approach the sympathetic nervous system is interrupted by radiofrequency ablation via both renal arteries. METHODS AND RESULTS: We describe the first renal denervation in Austria in a patient included in the "SIMPLICITY HTN-2" trial with resistant hypertension. We report of a 59-year-old patient in whom adequate blood-pressure control could not be achieved despite antihypertensive combination therapy with 6 different drugs. The averaged baseline blood-pressure was 238/132. Three months after renal denervation blood pressure dropped to 154/87 and medication was reduced on patient's request to 4 drugs. At 6-month follow-up 24h ambulatory blood-pressure monitoring was performed with an average value of 132/81. No adverse alterations of renal function could be detected. DISCUSSION: This case report is in line with studies, which show that renal denervation of the sympathetic nervous system is a promising and safe therapeutic option in patients with resistant hypertension. Nevertheless prospective randomized controlled trials will have to confirm the therapeutic effects and further implications of this new therapeutic modality.

2-year results of the AUTAX (Austrian Multivessel TAXUS-Stent) registry beyond the SYNTAX (synergy between percutaneous coronary intervention with TAXUS and cardiac surgery) study.

OBJECTIVES: The multicenter AUTAX (Austrian Multivessel TAXUS-Stent) registry investigated the 2-year clinical/angiographic outcomes of patients with multivessel coronary artery disease after implantation of TAXUS Express stents (Boston Scientific, Natick, Massachusetts), in a "real-world" setting. BACKGROUND: The AUTAX registry included patients with 2- or 3-vessel disease, with/without previous percutaneous coronary intervention (PCI) and concomitant surgery. METHODS: Patients (n = 441, 64 +/- 12 years, 78% men) (n = 1,080 lesions) with possible complete revascularization by PCI were prospectively included. Median clinical follow-up was 753 (quartiles 728 to 775) days after PCI in 95.7%, with control angiography of 78% at 6 months. The primary end point was the composite of major adverse cardiac (nonfatal acute myocardial infarction [AMI], all-cause mortality, target lesion revascularization [TLR]) and cerebrovascular events (MACCE). Potential risk factor effects on 2-year MACCE were evaluated using Cox regression. RESULTS: Complete revascularization was successful in 90.5%, with left main PCI of 6.8%. Rates of acute, subacute, and late stent thrombosis were 0.7%, 0.5%, and 0.5%. Two-year follow-up identified AMI (1.4%), death (3.6%), stroke (0.2%), and TLR (13.1%), for a composite MACCE of 18.3%. The binary restenosis rate was 10.8%. The median of cumulative SYNTAX score was 23.0 (range 12.0 to 56.5). The SYNTAX score did not predict TLR or MACCE, due to lack of scoring of restenotic or bypass stenoses (29.8%). Age (hazard ratio [HR]: 1.03, p = 0.019) and acute coronary syndrome (HR: 2.1, p = 0.001) were significant predictors of 2-year MACCE. Incomplete revascularization predicted death or AMI (HR: 3.84, p = 0.002). CONCLUSIONS: With the aim of complete revascularization, TAXUS stent implantations can be safe for patients with multivessel disease. The AUTAX registry including patients with post-PCI lesions provides additional information to the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) study. (Austrian Multivessel TAXUS-Stent Registry; NCT00738686).