Clinical predictors of dual aspirin and clopidogrel poor responsiveness in stable cardiovascular patients from the ADRIE study.

BACKGROUND: Poor response to both aspirin and clopidogrel (dual poor responsiveness [DPR]) is a major risk factor for recurrent ischemic events. OBJECTIVES: The aim of this study was to identify factors associated with DPR, defined with specific tests, and derive a predictive clinical score. METHODS: We studied 771 consecutive stable cardiovascular patients treated with aspirin (n = 223), clopidogrel (n = 111), or both drugs (n = 37). Aspirin responsiveness was evaluated by serum thromboxane (Tx)B2 assay, and clopidogrel responsiveness by calculating the platelet reactivity index (PRI) on the basis of the phosphorylation status of the vasodilator phosphoprotein. The analysis was focused on patients treated with both drugs, and on independent predictors of DPR. RESULTS: Among patients on dual therapy, there was no relevant correlation between TxB2 levels and PRI values (r = 0.11). Sixty-seven patients (15.4%) had DPR. Diabetes [odds ratio (OR) 1.89, 95% confidence interval (CI) 1.06-3.39], high body weight (> 86 kg vs. < 77 kg, OR 4.74, 95% CI 2.49-9.73), low aspirin dose (75-81 mg vs. ≥ 160 mg, OR 0.12, 95% CI 0.09-0.93) and high C-reactive protein (CRP) level (> 1.6 mg L⁻¹ vs. < 0.6 mg L⁻¹, OR 3.66, 95% CI 1.74-8.72) were independently associated with DPR, via increased TxB(2) levels, increased PRI, or both. These associations with TxB2 and PRI were reproduced across the whole population. With use of a factor-weighed score (c-index = 0.74), the predicted prevalence of DPR was 57% in the highest strata of the score as compared with < 4% for the lowest strata. CONCLUSIONS: Diabetes, body weight, the aspirin dose and CRP levels are readily available independent predictors of DPR, and some are potential targets for reducing its prevalence.

Clinical implications of clopidogrel non-response in cardiovascular patients: a systematic review and meta-analysis.

UNLABELLED: BSUMMARY BACKGROUND: Previous studies have shown an important risk of cardiovascular events in patients with clopidogrel biological non-response, and data have shown considerable, unexplored heterogeneity. OBJECTIVES: To evaluate the magnitude of cardiovascular risk associated with clopidogrel non-response and to explore heterogeneity. METHODS: This was a systematic review and meta-analysis of prospective studies of patients treated with clopidogrel for symptomatic atherothrombosis, evaluated by light transmission aggregometry with ADP and monitored prospectively for clinical ischemic events. RESULTS: Fifteen studies were included, totaling 3960 patients, of whom 25% were considered to be clopidogrel non-responders. The global relative risk (RR) for recurrent ischemic events in clopidogrel non-responders was 3.5 [95% confidence interval (CI) 2.4-5.2, P < 0.0001]. The results of the different studies were heterogeneous (Cochran P = 0.01 and I(2) = 52%). The most recent studies yielded lower RRs [global RR = 2.9 (95% CI 2.3-3.8) after 2007, and global RR = 6.6 (95% CI 3.7-11.9) before 2007, P = 0.01]. Heterogeneity was present in the group of studies in which more than 10% of patients took glycoprotein (GP)IIb-IIIa inhibitors [Cochran P = 0.003 and I(2) = 70%; RR = 3.8 (95% CI 2.9-5.1)] and was absent in the other studies [Cochran P = 0.88 and I(2) = 0; RR = 2.5 (95% CI 1.7-3.6)]. The RR was significantly higher in studies using higher ADP maximal aggregation cut-offs (> 65%) for clopidogrel non-response than in studies using lower cut-offs [RR = 5.8 (95% CI 3.2-10.3) and RR = 2.9 (95% CI 2.2-3.7), respectively, P = 0.03]. CONCLUSIONS: The risk of ischemic events associated with clopidogrel non-response is now more precisely defined. The risk is heterogeneous across studies, possibly because of an interaction with GPIIb-IIIa inhibitors and the use of different cut-offs to identify non-responders.

[The concept of aspirin "resistance": mechanisms and clinical relevance]. / Le concept de "résistance" à l'aspirine: mécanismes et pertinence clinique.

Aspirin, a 110-year-old molecule, is a cornerstone in the treatment of atherothrombotic patients. The concept of aspirin "resistance" emerged approximately 15 years ago and is of growing interest. Aspirin resistance, defined as a lack of inhibition of cyclo-oxygenase-1 (COX-1), is a rare phenomenon and its clinical relevance can hardly be studied. On the contrary, residual platelet hyperactivity is more common and affects 20 to 30% of aspirin-treated patients. This latter phenomenon corresponds to sustained platelet reactivity despite a proper inhibition of COX-1 by aspirin. Several meta-analyses suggest that residual platelet hyperactivity could be a risk factor for the recurrence of ischemic events in aspirin-treated patients. Causes of biological non-responsiveness to aspirin are discussed, including the role of compliance, drug-drug interactions, genetic polymorphisms and diabetes mellitus. Ongoing studies are designed to find out the mechanisms of residual platelet hyperactivity, determine its potential clinical relevance and delineate the more appropriate assays in order to identify patients who may benefit of a tailored antiplatelet therapy.

[Acute Q fever, antiphopholipid antibodies and renal artery thrombosis: case report and literature review]. / Fièvre Q aiguë, antiphospholipides et thrombose artérielle rénale : à propos d'un cas et revue de la littérature.

INTRODUCTION: Antiphospholipid antibodies (aPL) can be associated with numerous infectious and particularly Q fever. Data on the pathogenicity of aPL in the course of acute Q fever are scarce. CASE REPORT: We report the case an acute Coxiella burnetii infection associated with clinical and biological manifestations of the aPL syndrome, including a renal infarction. Along with antibiotic treatment, anticoagulation and intravenous immunoglobulins, the clinical outcome was favourable. Antiphospholipid antibodies and Q fever antibody titers had a closely related evolution. CONCLUSION: Arterial thrombosis associated with Q fever and aPL is exceptional. The nosology and potential mechanisms are discussed.