Gerhard Kreiner

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.

Beneficial hemodynamic effects of prostaglandin E1 infusion in catecholamine-dependent heart failure: results of a prospective, randomized, controlled study.

ObjectiveTo study the hemodynamic effects of prostaglandin E1: (PGE1)administered in addition to a standard catecholamine infusion in patients with severe chronic heart failure. DesignProspective, placebo-controlled, randomized, single-blind study. SettingIntensive care unit at a university hospital. PatientsThirty patients with severe chronic heart failure, New York Heart Association functional class TV (28 men, two women, with a mean age of 54 ± 2 yrs, mean left ventricular ejection fraction 10 ± 0.6%). All patients received oral therapy with digitalis, furosemide (mean dose 300 ± 46 mg/day), and enalapril (20 ± 2.7 mg/day). InterventionsHemodynamic measurements using pulmonary artery flotation catheters were performed at baseline, ≥24 hrs after standardized catecholamine infusion with dopamine (3 μg/kg/min) and dobutamine (5 μg/kg/min), as well as 48 hrs after randomization to infusion therapy with PGE1 (30 μg/kg/min) or a placebo. Measurements and Main ResultsThe addition of PGE1 to an ongoing catecholamine infusion in 20 patients caused a 16 ± 4% decrease in mean pulmonary arterial pressure (p < .001), a 22 ± 5% decrease in pulmonary artery occlusion pressure (p < .0001), a 24 ± 8% decrease in pulmonary vascular resistance index (p < .001), a 20 ± 9% decrease in right atrial pressure (p < .01), a 14 ± 3% decrease in mean arterial pressure (p < .001), and a 29 ± 4% decrease in systemic vascular resistance index (p < .0001). These PGE1- induced decreases occurred without a change in heart rate.Stroke volume index increased with PGE1 therapy by 34 ± 7% (p < .0001), and cardiac index increased by 34 ± 6% (p < .0001). No hemodynamic changes were observed during combined infusion with catecholamines and placebo in ten patients. ConclusionPGE1 improves the hemodynamic state in end-stage chronic heart failure patients already receiving a standard dose dopamine/ dobutamine infusion. (Crit Care Med 1994; 22:1084–1090)

Sinus Node Dysfunction After Orthotopic Heart Transplantation: The Vienna Experience 1987–1993

In the present study, the annual incidence of postoperative sinus node dysfunction and the type of sinus node abnormality after cardiac transplantation were followed over a 6½‐year period in 185 patients. Each year the sinus node function was systematically characterized by rhythm and corrected sinus node recovery time in a significant number of patients. Over the entire study period, there were 131 patients with normal sinus node function (corrected sinus node recovery time 318 ± 55 msec) while 54 patients had latent (n = 24, sinus rhythm, corrected sinus node recovery time 8,053 ± 2,198 msec) or manifest (n = 30, absence of sinus rhythm or pacemaker dependence) sinus node dysfunction. Twenty‐nine patients had pacemaker placement. The incidence of sinus node dysfunction declined in absolute terms and when indexed by the actual number of patients transplanted per year (index 1987: 38.5; 1998: 17.6; 1989: 23.2; 1990: 29.1; 1991: 10.4; 1992: 7.5; 1993: 2.2). Among those with sinus node dysfunction, the annual percentage of patients presenting with prolonged recovery time, escape rhythm, and those reverting back to sinus rhythm until discharge did not change significantly over the study period (P = 0.22). On multivariate analysis, only the date of transplantation was significantly associated with the occurrence of postoperative sinus node deficiency (P = 0.0007) while age of recipient (P = 0.85) or donor (P = 0.96), the type of cardioplegia used (P = 0.09) and ischemic time (P = 0.09) were insignificant. This decline in the annual incidence of sinus node dysfunction most probably may be interpreted in terms of improvements in management (learning curve). It is unclear which changes in particular are responsible for this development. In view of the lack of other significant associations, this might be an indication that operative trauma plays a role in the etiology of sinus node dysfunction after cardiac transplantation.

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.

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

Abstract 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

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.

GENDER DIFFERENCES IN LONG-TERM CLINICAL OUTCOME AFTER PERCUTANEOUS REVASCULARISATION OF MULTIVESSEL CORONARY ARTERY DISEASE: INSIGHTS FROM AUTAX REGISTRY

Methods: Patients (n=97 female, n=344 male, age 70±11 and 63±12, p<0.001) with possible complete revascularization by PCI were prospectively included. Primary endpoint was the composite of major adverse cardiac (nonfatal acute myocardial infarction [AMI], all cause mortality, target vessel revascularization [TVR]) and cerebrovascular events (MACCE) at 2-year follow-up (FUP). The secondary endpoints included the break-down primary endpoints, and the stent thrombosis rates. Potential risk factor effects on 2-year MACCE-free survival were evaluated using multiple Cox regression models.