Morten Würtz THE ANTIPLATELET EFFECT OF ASPIRIN DECLINES THROUGH 24 HOURS IN PATIENTS WITH PREVIOUS STENT THROMBOSIS
M. Würtz1, S.D. Kristensen1, A.M. Hvas2, E.L. Grove1
1Department of Cardiology, Aarhus University Hospital, 2Department of Clinical Biochemistry, Aarhus University Hospital
Background: Once-daily aspirin is considered to inhibit platelets for 24 hours, but recent studies suggest gradual attenuation of aspirin efficacy through this dosing interval. Stent thrombosis (ST) is a devastating complication of coronary interventions, and we have previously shown a reduced effect of aspirin in patients with ST.
Aim: We investigated if platelet inhibition by aspirin declines through 24 hours in patients with previous ST. Furthermore, we explored if platelet inhibition declines particularly rapid in patients with increased platelet turnover.
Methods: We included 50 patients with previous ST, 100 patients with stable coronary artery disease and 50 healthy volunteers all treated with aspirin 75 mg once daily. Platelet function was measured 1 and 24 hours after aspirin intake using platelet aggregometry (Multiplate® Analyzer).
Furthermore, COX-1 activity, platelet turnover, platelet production, and platelet activation were measured.
Results: Platelet aggregation increased from 1 to 24 hours after aspirin intake (p<0.0001) as did COX-1 activity (p<0.0001) and platelet activation (p<0.0001). Patients with previous ST displayed the highest levels of platelet aggregation (p≤0.05), platelet turnover (p<0.01) and platelet production (p<0.0001).
Conclusion: Platelet inhibition by aspirin declines significantly during the recommended 24-hour dosing interval. In particular, patients with previous ST have a prothombotic phenotype involving increased production and turnover of platelets. Once-daily aspirin does not provide consistent platelet inhibition through 24 hours, and a twice-daily treatment regimen thus may better protect against thrombotic events.
Søren Dinesen Østergaard
MEASURING PSYCHOTIC DEPRESSION
S.D. Østergaard1, 2, 3, B.S. Meyers4, A.J. Flint5, B.H. Mulsant5, 6, 7, E.M. Whyte7, C.M. Ulbricht8, P. Bech9, A.J. Rothschild10
1Unit for Psychiatric Research, Aalborg Psychiatric Hospital, Aalborg, Denmark, 2Department of Clinical Medicine, Aarhus University, 3Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, USA, 4Department of Psychiatry, Weill Medical College of Cornell University and New York Presbyterian Hospital, Westchester Division, White Plains, New York, USA, 5Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada, 6Centre for Addiction and Mental Health, Toronto, Ontario, Canada, 7Western Psychiatric Institute and Clinic, Department of Psychiatry, University of
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Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA, 8University of Massachusetts Medical School, Worcester, Massachusetts, USA, 9Psychiatric Research Unit, Psychiatric Center North Zealand, Copenhagen University Hospital, Hillerød, Denmark, 10University of Massachusetts Medical School and University of Massachusetts Memorial Health Care, Worcester, Massachusetts USA
Objective: Psychotic depression (PD) is a highly debilitating psychiatric condition, which needs intensive monitoring and treatment. However, there is no established rating scale for evaluating the severity and treatment outcome in PD. Thus, the aim of this analysis was to assess the psychometric properties of established depression rating scales and a number of new composite rating scales, covering both depressive and psychotic symptoms, in relation to PD.
Method: The psychometric properties of the rating scales were evaluated based on analyses of data from the Study of Pharmacotherapy of Psychotic Depression.
Results: A rating scale consisting of the 6-item Hamilton melancholia subscale (HAM-D6) plus five items from the Brief Psychiatric Rating Scale (BPRS), named the Psychotic Depression Assessment Scale (PDAS), displayed clinical validity (Spearman coefficient of correlation between PDAS and Clinical Global Impression - Severity (CGI-S) scores = 0.79 - 0.84), responsiveness (Spearman correlation coefficient between change in PDAS and Clinical Global Impression Improvement (CGII) scores = -0.74 - -0.78) and unidimensionality (Loevinger coefficient of homogeneity
= 0.41) in the evaluation of PD. The HAM-D6 fulfilled the same criteria, whereas the full 17-item Hamilton depression scale failed to meet criteria for unidimensionality.
Conclusion: Our results suggest that the PDAS has higher psychometric and clinical valididity than pure depression scales in the assessment of severity in psychotic depression.
Morten Schmidt CARDIOVASCULAR RISKS ASSOCIATED WITH NON-ASPIRIN NSAID USE M. Schmidt1, 2, T.L. Lash3, J.B. Jacobsen1, H.E. Bøtker2, H.T. Sørensen1
1Department of Clinical Epidemiology, Aarhus University Hospital,
2Department of Cardiology, Aarhus University Hospital, 3Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, USA
The cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs) is controversial because COX-2 inhibitors have been found to increase the risk of myocardial infarction. We hypothesized that the cardiovascular risks of NSAIDs (1) are reduced in patients on dual antiplatelet therapy; (2) are not restricted to the arterial system, but also affect the venous system; (3) include an increased risk of atrial fibrillation through adverse renal effects including fluid retention and blood pressure destabilization; and (4) increase mortality following ischemic stroke.
We conducted population-based cohort and case-control studies to examine these hypotheses. We identified use of NSAIDs from prescription
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registries and used the Danish National Patient Registry, the Western Denmark Heart Registry, the Civil Registration System, and the Danish Cause-of-death Registry to collect data on cardiovascular morbidity, comorbidity, and mortality.
We found that NSAID use was not associated with adverse arterial events in patients on dual antiplatelet therapy following coronary stent
implantation (Schmidt et al. Pharmacotherapy, 2011). However, use of NSAIDs was associated with a two-fold increased risk of venous
thromboembolism (Schmidt et al. JTH, 2011), a 40-70% increased risk of atrial fibrillation (Schmidt et al. BMJ, 2011), and a 30% increased short-term mortality following ischemic stroke (paper in preparation), especially when therapy was initiated with COX-2 inhibitors. Finally, in a methodology paper (submitted), we also described overall trends in use of NSAIDs in Denmark between 1999 and 2012 and how prescription registries provide a valuable source for identifying NSAID use.
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