The aspirin controversy in primary prevention.

PURPOSE OF REVIEW: Apparently conflicting meta-analysis results have led to renewed debate about the role of aspirin for the primary prevention of cardiovascular disease. We review the results of meta-analyses comparing aspirin with placebo or no aspirin for the primary prevention of cardiovascular disease and critically evaluate whether aspirin provides a net benefit. RECENT FINDINGS: The results of four independently conducted meta-analyses between 2009 and 2012 involving between 95 000 and 102 621 individuals at low risk of cardiovascular disease are consistent with the results of the 2002 Antithrombotic Trialists' Collaboration meta-analysis, which found that aspirin reduces cardiovascular events primarily by reducing nonfatal myocardial infarction (MI). There is no convincing evidence that aspirin reduces cardiovascular mortality, but estimates from all of the meta-analyses suggest a modest reduction in all-cause mortality. Aspirin reduces ischaemic stroke but increases haemorrhagic stroke and major bleeding. SUMMARY: 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.

Effect of colchicine compared with placebo on high sensitivity C-reactive protein in patients with acute coronary syndrome or acute stroke: a pilot randomized controlled trial.

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.

Effect of aspirin on mortality in the primary prevention of cardiovascular disease.

OBJECTIVE: The lack of a mortality benefit of aspirin in prior meta-analyses of primary prevention trials of cardiovascular disease has contributed to uncertainty about the balance of benefits and risks of aspirin in primary prevention. We performed an updated meta-analysis of randomized controlled trials of aspirin to obtain best estimates of the effect of aspirin on mortality in primary prevention. METHODS: Eligible articles were identified by searches of electronic databases and reference lists. Outcomes of interest were all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and bleeding. Data were pooled from individual trials using the DerSimonian-Laird random-effects model, and results are presented as relative risk (RR) and 95% confidence intervals (CIs). RESULTS: Nine randomized controlled trials enrolling 100,076 participants were included. Aspirin reduced all-cause mortality (RR 0.94; 95% CI, 0.88-1.00), myocardial infarction (RR 0.83; 95% CI, 0.69-1.00), ischemic stroke (RR 0.86; 95% CI, 0.75-0.98), and the composite of myocardial infarction, stroke, or cardiovascular death (RR 0.88; 95% CI, 0.83-0.94), but did not reduce cardiovascular mortality (RR 0.96; 95% CI, 0.84-1.09). Aspirin increased the risk of hemorrhagic stroke (RR 1.36; 95% CI, 1.01-1.82), major bleeding (RR 1.66; 95% CI, 1.41-1.95), and gastrointestinal bleeding (RR 1.37; 95% CI, 1.15-1.62). A lack of availability of patient-level data precluded exploration of benefits and risks of aspirin in key subgroups. CONCLUSION: Aspirin prevents deaths, myocardial infarction, and ischemic stroke, and increases hemorrhagic stroke and major bleeding when used in the primary prevention of cardiovascular disease.

Preventing thrombophilia-related complications of pregnancy.

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.

Platelet ADP-receptor antagonists for cardiovascular disease: past, present and future.

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.