Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Abbott, AstraZeneca, Boehringer Ingelheim, Daiichi, Sankyo, Forest Pharmaceuticals, Lilly, Novo Nordisk, Takeda.

Aspirin Resistance and Established Hypertension

Source: Ozben B, et al. Aspirin resistance in hypertensive adults. J Clin Hypertens 2010;12:714-720.

The prophylactic use of aspirin (asa) provides risk reduction when used for secondary prophylaxis. Nonetheless, the protective effects of ASA are imperfect, which is to some degree explained by the concept of ASA resistance, variously measured by failure of aspirin to reduce thromboxane production, platelet activation, or platelet aggregation. Because various methodologies have been used to measure antithrombotic activity of ASA (such as platelet aggregability or thromboxane), the prevalence of ASA resistance in the literature is widely variant. ASA resistance has not been the subject of much study, specifically in hypertensive patients.

Ozben et al used a device called the Ultegra Rapid Platelet Function Assay-ASA to measure the degree of platelet aggregation reduction attained in persons with established hypertension receiving 100-300 mg/d of ASA. The Ultegra device measures light transmission in whole blood to which a platelet activator has been added: If ASA is doing its job, platelets will not activate. If ASA is not doing its job, fibrinogen will agglutinate with platelets, obscuring light transmission. Patients who were taking any other agents that might influence platelet aggregation (e.g., clopidogrel) were excluded from the trial.

In the 200 study subjects, ASA resistance was found in 21%. ASA resistance was more common in uncontrolled hypertension, women, chronic kidney disease, and persons with lower platelet counts. Measurement of ASA resistance is not yet a readily applied clinical tool. Whether persons with ASA resistance merit higher doses of ASA, alternative pharmacotherapy (e.g., clopidogrel), or other intervention is unclear.

Dabigatran vs Warfarin for AFib

Source: Wallentin L, et al. Efficacy and safety of dabigatran compared with war-farin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation. Lancet 2010; 376:975-983.

Warfarin (war) does an impressive job of stroke reduction in patients with atrial fibrillation (AFib): Clinical trials indicate a relative risk reduction of 65%. Unfortunately, chronic WAR therapy is not without obstacles, including need for ongoing monitoring, expense, vigilance to diet and pharmacotherapy, etc. Dabigatran is an orally administered direct thrombin inhibitor that does not require routine monitoring, and is not significantly affected by vitamin K content in food. In October 2010, the FDA approved dabigatran for reduction of risk of stroke in persons with AFib.

The RE-LY trial randomized AFib patients (n = 18,113) to anticoagulation with warfarin (target INR, 2.0-3.0) or dabigatran. Dabigatran was administered as either 110 mg bid or 150 mg bid. Patients were followed for 2 years.

Initial reporting of RE-LY results found that lower-dose dabigatran (110 mg bid) was non-inferior to warfarin, and that higher-dose dabigatran (150 mg bid) was superior to warfarin. This article further examined whether trial results were impacted by the degree of success with which study sites were able to keep patients within the therapeutic range with warfarin.

Ultimately, the efficacy of dabigatran 150 mg bid relative to WAR for stroke prevention was found not to be dependent upon the efficacy with which clinical trial centers maintained INR within the therapeutic range. On the other hand, for the endpoints of all vascular events, non-hemorrhagic events, and mortality, differences between dabigatran and WAR were greater at study sites with less efficacy at maintaining in-range INR. Dabigatran appears to be at least as effective as WAR, although some advantages of dabigatran are magnified by inconsistencies in maintaining good INR control.

Dementia and Aggressive Behavior

Source: Kunik ME, et al. Causes of aggressive behavior in patients with dementia. J Clin Psych 2010;71:1145-1152.

Metrics designed to measure aggression in dementia patients list activities such as spitting, verbal aggression, hitting, kicking, pushing, biting, and making inappropriate sexual advances either verbally or physically. Because such behaviors can be highly disruptive, it would be helpful to shed light on factors associated with aggressive behavior.

To be included in the trial, subjects had to be free of a history of aggressive behaviors for the previous 12 months. Factors that were measured included depression (Hamilton Depression Scale), pain, caregiver burden (based upon a validated scoring system that measures psychological, physical, emotional, financial, and social impact of being a caregiver), and an item titled "mutuality," which measures the positive qualities of the caregiver-to-care-receiver relationship, including frequency of contact, positive interactions, degree of attachment, and emotional support. The authors looked at data from 215 patients with dementia, of whom 41% developed aggression over a 2-year interval.

Predictors of increased risk for aggression were low baseline mutuality, high caregiver burden, pain, and depression. Although some of the predictors for aggression may be difficult or impossible to modify, others are clearly modifiable and might reduce likelihood for aggression.