Randomized double-blind placebo-controlled crossover study to determine the effects of esomeprazole on inhibition of platelet function by clopidogrel.

BACKGROUND: Pharmacokinetic studies suggest that clopidogrel and esomeprazole are metabolized by similar hepatic enzymes; however, previous studies have not identified a biochemical interaction. OBJECTIVES: To determine whether addition of esomeprazole to patients receiving aspirin and clopidogrel reduces the antiplatelet effects of clopidogrel. PATIENT/METHODS: Patients with a history of an acute coronary syndrome who had previously received clopidogrel were recruited. Subjects were commenced on clopidogrel and randomized to one of two treatment arms (esomeprazole or placebo) for 6 weeks. Following a 2-week washout period for study medications, patients were crossed over onto the alternative treatment arm for a further 6 weeks. Platelet function tests were undertaken at baseline, following the first treatment period, after washout and following the second treatment period. RESULTS: Thirty-one patients were enrolled. Significant attenuation of clopidogrel's antiplatelet effects was seen with co-administration of esomeprazole compared with placebo. Vasodilator stimulated phosphoprotein (VASP), platelet aggregometry (area under the curve (AUC)) and VerifyNow results were 54.7% ± 2.8 platelet reactivity index (PRI), 66.3 ± 2.6 AUC units and 213.1 ± 14.1 platelet reactivity units (PRU) with esomeprazole vs. 47% ± 2.7 PRI, 59.7 ± 3.7 AUC units and 181.4 ± 14.6 PRU with placebo (P < 0.01 esomeprazole vs. placebo for all measures). There was no significant difference in platelet aggregometry (maximal aggregation) between the esomeprazole group (68.9% ± 2.7 units) and placebo-treated group (64.5% ± 4.1 units; P > 0.05). CONCLUSION: Esomeprazole when co-administered with aspirin and clopidogrel results in a significant attenuation of clopidogrel's antiplatelet effects.

Cardiac magnetic resonance imaging in the evaluation of cardiac sarcoidosis: an Australian single-centre experience.

BACKGROUND: Cardiac involvement in systemic sarcoidosis is common; however, current diagnostic tools are imprecise. Recognition of cardiac sarcoidosis (CS) is important as it has a relatively poor prognosis. Gadolinium-enhanced cardiac magnetic resonance imaging (Gad-CMR) is emerging as an excellent technique in determining the presence of and extent to which cardiac muscle is affected by sarcoidosis. METHODS: A retrospective analysis was performed on all patients with biopsy-proven systemic sarcoidosis referred for Gad-CMR scanning to evaluate potential cardiac involvement. All patients also underwent an electrocardiogram, Holter monitor and echocardiography. Gallium-67 radionuclide investigation, positron emission tomography and cardiac biopsy were ordered at the discretion of the treating physician. RESULTS: Eleven of the 20 patients had Gad-CMR images supportive of the diagnosis of CS. Eight of these 11 patients met the Japanese Ministry of Health and Welfare (JMHW) criteria for the diagnosis of CS; three abnormal Gad-CME scans consistent with diagnosis of CS were seen in patients who did not meet JMHW criteria. No patients with normal Gad-CMR scan met JMHW criteria for CS. CONCLUSION: These findings suggest that Gad-CMR is potentially superior to the JMHW criteria in the diagnosis of cardiac sarcoidosis.

Cardiac sarcoidosis.

Cardiac sarcoidosis can have a variety of manifestations including conduction disease, congestive heart failure, valvular heart disease, pericardial effusions, tamponade, ventricular arrhythmias and sudden cardiac death. In patients with sarcoidosis, the reported incidence of cardiac involvement ranges from 20% in US autopsy studies to nearly 60% in Japan, where it accounts for the majority of deaths as a result of sarcoidosis. Despite this, the diagnosis of cardiac sarcoidosis remains difficult and no single diagnostic test has emerged that combines a high degree of sensitivity and specificity. Recent evidence suggests that gadolinium-enhanced magnetic resonance imaging can potentially offer high sensitivity and specificity for both disease presence and activity. It may also be possible to track response to treatment of cardiac sarcoidosis with cardiac magnetic resonance imaging. Corticosteroids are the mainstay of treatment for cardiac sarcoidosis as with systemic sarcoid but at present no prospective trial has shown a survival benefit. Pharmacological treatment of heart failure should follow standard heart failure guidelines, whereas anti-arrhythmic treatment is problematic. The role of implantable cardiac defibrillators in sarcoid has not been well defined, although the risk of ventricular arrhythmias and sudden cardiac death are high. Cardiac transplantation remains an option for younger patients, although overall cardiac involvement in sarcoidosis carries a relatively poor prognosis.