Hypothesis formulation from subgroup analyses: Nonadherence or nonsteroidal anti-inflammatory drug use explains the lack of clinical benefit of aspirin on first myocardial infarction attributed to "aspirin resistance"
ABSTRACT "Aspirin resistance" has been defined as the occurrence of cardiovascular events despite regular intake of aspirin. One major analytic study suggesting that "aspirin resistance" is a clinical reality was unable to control for confounding by nonadherence or nonsteroidal anti-inflammatory drugs (NSAIDs).
We formulated a hypothesis from subgroup analyses in the Physicians' Health Study, a randomized double-blind placebo-controlled trial testing 325 mg of aspirin every other day among 22,071 apparently healthy US male physicians. We classified participants by nonadherence or NSAIDs and used time-varying Cox proportional hazard models to adjust for confounding.
After 5 years, the blinded aspirin component was terminated early based on the unanimous recommendation of the Data and Safety Monitoring Board. Of 378 confirmed first myocardial infarctions (139 aspirin and 239 placebo), the relative risk (RR) was 0.56 (95% CI 0.45-0.70, P < .00001). There was no statistically significant reduction among aspirin <150/180 pills/y (RR = 0.91, 95% CI 0.61-1.35, P = .62) or NSAID users >60 days per year (RR = 1.54, 95% CI 0.68-3.47, P = .31). There was a statistically significant reduction among aspirin >150/180 pills/y and NSAID users <60 days/y (RR = 0.55, 95% CI 0.44-0.70, P < or = .0001) and an increase among aspirin <150/180 pills/y and NSAID users >60 days/y (RR of 3.43, 95% CI 1.41-8.33, P = .007).
In subgroup analyses useful to formulate hypotheses from a large randomized trial in apparently healthy men, aspirin nonadherence or NSAID use explained the lack of clinical benefit of aspirin on first myocardial infarction that has been attributed to "aspirin resistance." Direct randomized comparisons are necessary in trials designed a priori to test this hypothesis.
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ABSTRACT: MEDICATION SAFETY Overlooked Renal Dosage Adjustments A retrospective analysis of 647 patients at hospital discharge com-pared required renal dosage adjust-ments to dosage actually prescribed. This study was conducted at VieCuri Medical Centre in Venlo, Netherlands. Patient demographics and renal function data were col-lected, and dosage adjustment needs were assessed via the pharmacy-supported discharge counseling ser-vice. The incidence of inappropriate dosing based on renal function was measured at hospital discharge. Thirty-seven percent of patients evaluated during the study period (237/647) had a creatinine clear-ance less than 51 mL/min/1.73 m 2 ; dosage adjustment was warranted in 23.9% (411/1,718) of prescrip-tions. When dosage adjustment should have been performed, more than 40% of prescriptions (169/411; 41.1%) were inappropri-ate for renal function (9.8% of pre-scriptions overall; 169/1,718). Fur-thermore, 60.4% (102/169) of inappropriate prescriptions pos-sessed the potential for moderate or severe clinical consequences, as evaluated by a panel of two clinical pharmacologists and one nephrolo-gist. Study authors also noted a lack of standardized dosing guidelines for agents requiring renal dosage adjustment. The authors also sug-gested that augmenting medication systems by adding dynamic renal dosing alerts would improve moni-toring. Summary: A comparison of suggested renal dosing and actual dosing at hospital discharge revealed that appropriate prescribing may be overlooked. van Dijk EA, Drabbe NRG, Kruijtbosch M, De Smet PAGM. Drug dosage adjust-ments according to renal function at hos-pital discharge. Ann Pharmacother. 2006;40:1254-1260.Hospital pharmacy 12/1122; 41(7). DOI:10.1310/hpj4311-937
- Der Internist 10/2010; 51(10):1330, 1332. · 0.31 Impact Factor
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ABSTRACT: Migraine with aura (MA) has been associated with increased risk of cardiovascular disease (CVD). The role of aspirin on this association remains unclear. Post-hoc subgroup analyses of the Women's Health Study, a randomized trial testing 100 mg aspirin on alternate days in primary prevention of CVD among 39,876 women aged ≥ 45. During 10 years, 998 major CVD events were confirmed in 39,757 women with complete migraine information. Aspirin reduced risk of ischaemic stroke (relative risk, RR, 0.76, 95% CI 0.63-0.93) but not other CVD. Migraine or MA did not modify the effect of aspirin on CVD except for myocardial infarction (MI) (p for interaction = 0.01). Women with MA on aspirin had increased risk of MI (RR 3.72, 95% CI 1.39-9.95). Further exploratory analyses indicate that this increased risk is only apparent among women with MA on aspirin who ever smoked or had history of hypertension (p for interaction<0.01). In post-hoc subgroup analyses, aspirin had similar protective effects on ischaemic stroke for women with or without migraine. By contrast, our data suggest that women with MA on aspirin had increased risk of MI. The small number of outcome events in subgroups, the exploratory nature of our analyses, and lack of plausible mechanisms raise the possibility of a chance finding, which must caution the interpretation.Cephalalgia 06/2011; 31(10):1106-15. DOI:10.1177/0333102411412628 · 4.89 Impact Factor