Antiplatelet agents for intermittent claudication.

BACKGROUND: Peripheral arterial disease (PAD) is common and is a marker of systemic atherosclerosis. Patients with symptoms of intermittent claudication (IC) are at increased risk of cardiovascular events (myocardial infarction (MI) and stroke) and of both cardiovascular and all cause mortality. OBJECTIVES: To determine the effectiveness of antiplatelet agents in reducing mortality (all cause and cardiovascular) and cardiovascular events in patients with intermittent claudication. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases group searched their Specialised Register (last searched April 2011) and CENTRAL (2011, Issue 2) for publications on antiplatelet agents and IC. In addition reference lists of relevant articles were also searched. SELECTION CRITERIA: Double-blind randomised controlled trials comparing oral antiplatelet agents versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication were included. Patients with asymptomatic PAD (stage I Fontaine), stage III and IV Fontaine PAD, and those undergoing or awaiting endovascular or surgical intervention were excluded. DATA COLLECTION AND ANALYSIS: Data on methodological quality, participants, interventions and outcomes including all cause mortality, cardiovascular mortality, cardiovascular events, adverse events, pain free walking distance, need for revascularisation, limb amputation and ankle brachial pressure indices were collected. For each outcome, the pooled risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) was calculated. MAIN RESULTS: A total of 12 studies with a combined total of 12,168 patients were included in this review. Antiplatelet agents reduced all cause (RR 0.76, 95% CI 0.60 to 0.98) and cardiovascular mortality (RR 0.54, 95% CI 0.32 to 0.93) in patients with IC compared with placebo. A reduction in total cardiovascular events was not statistically significant (RR 0.80, 95% CI 0.63 to 1.01). Data from two trials (which tested clopidogrel and picotamide respectively against aspirin) showed a significantly lower risk of all cause mortality (RR 0.73, 95% CI 0.58 to 0.93) and cardiovascular events (RR 0.81, 95% CI 0.67 to 0.98) with antiplatelets other than aspirin compared with aspirin. Antiplatelet therapy was associated with a higher risk of adverse events, including gastrointestinal symptoms (dyspepsia) (RR 2.11, 95% CI 1.23 to 3.61) and adverse events leading to cessation of therapy (RR 2.05, 95% CI 1.53 to 2.75) compared with placebo; data on major bleeding (RR 1.73, 95% CI 0.51, 5.83) and on adverse events in trials of aspirin versus alternative antiplatelet were limited. Risk of limb deterioration leading to revascularisation was significantly reduced by antiplatelet treatment compared with placebo (RR 0.65, 95% CI 0.43 to 0.97). AUTHORS' CONCLUSIONS: Antiplatelet agents have a beneficial effect in reducing all cause mortality and fatal cardiovascular events in patients with IC. Treatment with antiplatelet agents in this patient group however is associated with an increase in adverse effects, including GI symptoms, and healthcare professionals and patients need to be aware of the potential harm as well as the benefit of therapy; more data are required on the effect of antiplatelets on major bleeding. Evidence on the effectiveness of aspirin versus either placebo or an alternative antiplatelet agent is lacking. Evidence for thienopyridine antiplatelet agents was particularly compelling and there is an urgent need for multicentre trials to compare the effects of aspirin against thienopyridines.

The pleiotropic effects of statins and omega-3 fatty acids against sepsis: a new perspective.

The available therapeutic options for sepsis are restricted by their effectiveness and high cost. Emerging preliminary data suggest that statins and omega-3 fatty acids (OM3FA) may be associated with improved outcomes in terms of prevention and treatment of sepsis. We sought to review the current evidence on the effectiveness of their combined administration against sepsis, by carrying out a review of PubMed and Scopus databases for relevant studies, without imposing language or time restrictions. No clinical studies were identified regarding the effect of the combination treatment with statins and OM3FA on sepsis in terms of prevention or treatment. However, there is experimental evidence that both statins and OM3FA inhibit the inflammatory process at different levels, but also enhance inhibition at those levels that are common. There are also preliminary data supporting the beneficial effect of this combination on platelet function and other haemostatic mechanisms. Appropriately designed and powered clinical trials are warranted to investigate the effectiveness and safety of the combined administration of statins and OM3FA for the prevention and treatment of sepsis.

Could statins be useful in the treatment of patients with migraine?

Migraine is a common and disabling neurological disorder. Studies have shown that patients with migraine (especially those with typical aura with migraine) have an unfavorable cardiovascular risk profile and an increased risk of early-onset (<45 years) ischemic stroke. Statins are effective hypolipidemic drugs that reduce cardiovascular-related morbidity and death in patients with or without established atherosclerotic vascular disease. We report a patient whose frequent attacks of typical aura with migraine completely resolved after the initiation of treatment with a statin. In this context, we comment on the possible effects of statins on the pathophysiology of migraine. We suggest that statins may be useful drugs in the treatment of migraine because they could reduce the increased cardiovascular risk in these patients and also attenuate migraine attacks. Only a randomized prospective study in this population could provide a definite answer to these speculations.