Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS(2) score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach.

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Background and Purpose-Bleeding risks from combined antiplatelet-warfarin therapy have not been well-described in clinical practice. We examined antiplatelet therapy among warfarin users and the impact on major bleeding rates. Methods-Retrospective cohort analysis of persons discharged on warfarin after an atrial fibrillation admission using data from Medicare's National Stroke Project. Data included Medicare claims, enrollment information, and medical record abstracted data. Logistic regression and Cox proportional hazards models were used to predict concurrent antiplatelet use and hospitalization with a major acute bleed within 90 days after discharge from the index AF admission. Results-10 093 warfarin patients met inclusion criteria with a mean age of 77 years; 19.4% received antiplatelet therapy.Antiplatelet use was less common among women, older persons, and persons with cancer, terminal diagnoses, dementia, and bleeding history. Persons with coronary disease were more likely to receive an antiplatelet agent. Antiplatelets increased major bleeding rates from 1.3% to 1.9% (Pϭ0.052). In the multivariate analysis, factors associated with bleeding events included age (OR, 1.03; 95% CI, 1.002 to 1.05), anemia (OR, 2.52; 95% CI, 1.64 to 3.88), a history of bleeding (OR, 2.40; 95% CI, 1.71 to 3.38), and concurrent antiplatelet therapy (OR, 1.53; 95% CI, 1.05 to 2.22). Conclusions-Although concerns about increased bleeding risk with combined warfarin-antiplatelet therapy are not unfounded, the risk of bleeding is moderately increased. The decision to use concurrent antiplatelet therapy appears to be tempered by cardiac and bleeding risk factors.

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SummaryBackgroundIntensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy.MethodsWe did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388.Findings3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001).InterpretationAmong patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice.FundingNational Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.

Treating patients intolerant to statins with rosuvastatin EOD was tolerated by the majority of patients and reduced LDL-C in our study. This dosing strategy may be useful in patients intolerant to once-daily statin dosing, although such an approach has not been documented to reduce cardiovascular events.

Nonsteroidal anti-inflammatory drugs (NSAID) inhibit cyclooxygenase (COX) enzymes, which exist in at least two isoforms, COX-1 and COX-2. Aspirin and older agents in this class are nonselective inhibitors of both COX-1 and COX-2. Newer agents termed "coxibs" are selective inhibitors of COX-2. Among the NSAID, only aspirin has been proven to significantly reduce cardiovascular risk, primarily through inhibition of COX-1-mediated platelet aggregation. It has been suggested that other nonselective agents, especially naproxen, may provide some lesser degree of cardioprotection, but conclusive evidence is lacking. Conversely, there are concerns that the COX-2 inhibitors may increase cardiovascular risk. However, mechanisms for this potentially adverse cardiovascular effect are unknown, and it is becoming increasingly clear that our understanding of the role of COX-2 in cardiovascular function is incomplete. Some studies have demonstrated a potentially beneficial effect of COX-2 on cardiovascular function that could be negated by COX-2 inhibition, while other studies have reported improved endothelial function with COX-2 inhibitors. Additionally, the impact of combined therapy with aspirin and other COX inhibitors is not yet clear. This article will review the studies that have examined these issues.

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