Clinical Briefs
By Louis Kuritzky, MD
Effect of Ibuprofen on Cardioprotective Effect of Aspirin
A substantial amount of literature supports the efficacy of aspirin (ASA) for primary and secondary prevention of cardiovascular disease. The benefits of aspirin for reduction of cardiovascular risk are generally attributed to effects on platelets, mediated by ASA-induced cyclooxygenase-1 inhibition. Earlier in vitro data have indicated that ibuprofen (IBU), but not rofecoxib or diclofenac, competes with the effects of ASA upon platelets, and might hence reduce or abolish the cardioprotective effects. Whether this is reflected clinically has not yet received sufficient scrutiny.
MacDonald and Wei studied more than 7000 persons in the United Kingdom who carried a hospital discharge diagnosis of MI, angina, stroke, PAD, or TIA, were on low-dose ASA (< 325 mg/d), and survived for at least 1 month post-hospital discharge. This population was further subdivided into persons who concomitantly received IBU (n = 187), diclofenac (n = 206), any other NSAID (n = 429), or no other NSAID (ie, ASA alone n = 6285). The outcomes of the study were all-cause mortality or cardiovascular mortality.
All-cause mortality in the ASA + IBU group was significantly higher than in the ASA alone group (P = 0.0011), but persons who used ASA in combination with other NSAIDs did not show an increased risk. Data on cardiovascular mortality were similar to that demonstrated for all-cause mortality.
MacDonald and Wei conclude that these data support the possibility that the combination of IBU with ASA may be deleterious toward cardiovascular and total mortality risk, when compared with persons taking ASA alone. The NSAID comparators, other than IBU, did not display a similar detraction to the cardiovascular benefits of ASA.
MacDonald TM, Wei L. Lancet. 2003; 361:573-574.
Relapse Prevention with Antidepressant Drug Treatment in Depressive Disorders
Pharmacotherapy for depression is generally recognized to be effective to produce remission in the majority of sufferers. The recommended duration of treatment of depression has undergone evolution, subsequent to the observation that brief treatments (4-6 months, or less), subject the patient to an increased risk of relapse and recurrence.
Geddes and colleagues studied the efficacy of antidepressant treatment to prevent recurrence when continued into long-term (ie, > 6 months) treatment. Pooling data from 31 randomized trials (n = 4410), they evaluated the likelihood of relapse when a patient continued whatever pharmacotherapy had effected a remission, compared with the relapse rate for persons on placebo. The antidepressants included in the meta-analysis include tricyclics, SSRIs, and heterocyclic agents.
The results were consistent across all antidepressants evaluated: continuing therapy reduced the risk of relapse by approximately one half. Only 6 trials reported very long-term data (> 2 years), but even in this patient population, continued antidepressant therapy reduced risk of relapse by more than 50%.
Geddes et al conclude that in persons who respond to antidepressant therapy, continuation of medication produces substantial reduction in likelihood of relapse, which does not appear to diminish even in long-term maintenance trials.
Geddes JR, et al. Lancet. 2003;361: 653-661.
Incidence and Preventability of Adverse Drug Events Among Older Persons in the Ambulatory Setting
When one considers that more than 90% of persons older than age 65 use at least 1 medication per week, and that more than 40% of these individuals use 5 or more medications per week, it should come as no surprise that adverse events, even in the ambulatory setting, may occur. Although more attention has been given recently to hospital and nursing home medication misadventures, less scrutiny of ambulatory adverse events, and their potential for prevention, is available.
The population studied (n = 27,617) comprised predominantly persons enrolled in a Medicare + Choice Plan. Adverse events were tabulated for a 12-month period. When adverse events related to medications were identified (n = 1523), a physician panel adjudicated whether the event was preventable.
Cardiovascular drugs were the class most often represented by adverse effects (26%), followed by antimicrobials (14.7%), diuretics (13.3%), non-opioid analgesics (11.8%), and anticoagulants (7.9%). More than one fourth of the adverse medication related events were judged preventable by the clinician review. Among the serious, life threatening, or fatal adverse events, a substantially greater portion was judged to be preventable: 42.4%.
Medication-related adverse events are commonplace and not infrequently serious. Since a substantial number of such events are judged to be preventable, enhanced strategies for risk reduction are needed.
Gurwitz JH, et al. JAMA. 2003;289:1107-1116.
Dr. Kuritzky
is Clinical Assistant Professor at the University of Florida in Gainesville.
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