There is a need for more effective therapies to reduce morbidity and mortality from cardiovascular disease. Inflammation plays a central role in the pathogenesis of atherosclerosis but no randomized studies have evaluated anti-inflammatory therapy in patients with acute coronary or cerebrovascular disease. We performed a pilot randomized controlled trial comparing the effect of colchicine 1 mg per day with placebo on high sensitivity C-reactive protein (CRP) levels and platelet function in 80 patients with acute coronary syndrome or acute ischemic stroke who were followed for 30 days. Clinical status was ascertained for 74 (92.5%) patients and CRP levels were obtained in 68 (85%) of patients at follow up. Colchicine did not significantly reduce absolute hs-CRP at 30 days [median 1.0 mg/l (range 0.2, 162.0) versus 1.5 mg/l (0.2, 19.8), P = 0.22] or difference in CRP from baseline to 30 days [absolute difference 7.0 mg/l (-61.0, 87.8) vs. 7.1 mg/l (-1.0, 144), P = 0.64]. The proportion of patients with CRP <2 mg/l at follow up did not differ according to treatment allocation (77% vs. 62%, X (2) 1.84, P = 0.18). There was also no difference in platelet function assessed using platelet aggregation with ADP (5 μmol), arachidonic acid (0.5 mmol), collagen (1 μg/ml) and collagen (5 μg/ml) (P = 0.86, P = 0.64, P = 0.76, P = 0.20, respectively), and urine dehydrothromboxane B2 (P = 0.54). Colchicine was associated with an excess of diarrhoea (X(2) 4.14, P = 0.04). In conclusion, our pilot study provided no evidence that colchicine 1 mg daily for 30 days compared with placebo suppresses inflammation in patients with acute coronary syndrome or acute ischemic stroke.
Aspirin is the foundation antiplatelet therapy for patients at risk of cardiovascular events. The thienopyridine, clopidogrel, is modestly more effective than aspirin and in patients with stroke seems to be as effective as the combination of aspirin and dipyridamole. The addition of clopidogrel to aspirin further reduces the risk of cardiovascular events in patients with acute coronary syndromes and those who undergo percutaneous coronary intervention, but uncertainty remains about whether this combination has incremental efficacy over clopidogrel monotherapy in patients with stroke or peripheral arterial disease. Clopidogrel has pharmacological limitations that have prompted the search for more effective ADP-receptor antagonists. Promising results have been achieved with the thienopyridine, prasugrel, which has been compared with clopidogrel in patients treated with aspirin. The nonthienopyridine P2Y(12) inhibitors AZD6140 and cangrelor are presently being evaluated in phase III, randomized, controlled trials.
The meta-analysis results consistently indicate that, in individuals at low risk for cardiovascular disease, aspirin reduces the risk of MI at the cost of an increase in major bleeding and produces a modest nominally significant reduction in total mortality. These results suggest that recommendations for primary prevention with aspirin should be individualized, taking into account the balance between benefits and risks and individual values and preferences.
Pregnancy is associated with an increased risk of venous thromboembolism (VTE) and approximately half of all pregnancy-related VTEs are associated with thrombophilia. Recent studies suggest that there is a link between thrombophilia and other adverse pregnancy outcomes, such as fetal loss, preeclampsia, placental abruption and intrauterine growth restriction. However, the associations reported are modest, and high quality data are limited. Although the most compelling data derive from pregnant women with antiphospholipid antibodies, the use of anticoagulants for the prevention of pregnancy complications other than VTE in women with heritable thrombophilias is becoming more frequent. In this article, we review the impact of the various thrombophilias on pregnancy and its outcome, the evidence for therapies aimed at prevention of thrombophilia-related pregnancy complications, and briefly discuss the role of screening for thrombophilia in pregnancy.
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