The prognostic impact of high on-treatment platelet reactivity with aspirin or ADP receptor antagonists: systematic review and meta-analysis.

OBJECTIVE: Negative results of recent randomized clinical trials testing the hypothesis of target therapy for patients with high on-treatment platelet reactivity (HOPR) have questioned its independent impact on clinical outcomes. 26 studies with 28.178 patients were included, with a median age of 66.8 (64-68) and 22.7% (22.4-27.8), of female gender. After a median follow-up of 1 year (0.1-1), cardiac adverse events occurred in 8.3% (3-11; all results are reported as median and interquartile range) of patients. Pooling all studies together, on-treatment platelet reactivity significantly increased the risk of adverse events (OR 1.33 [1.09, 1.64], I(2) = 0%). However, a sensitivity analysis showed that HOPR did not increase the risk of adverse events for patients with ACS, AMI, or stable angina as well as patients resistant to aspirin, ADP antagonists, or both. For all studies, publication bias was formally evident; after adjusting for this, HOPR did not significantly increase adverse cardiac events (OR 1.1 : 0.89-1.22, I(2) 0%). CONCLUSIONS: After adjusting for clinical confounders (like risk factors and clinical presentation) and for relevant publication bias, HOPR was not an independent prognostic indicator in unselected patients with both stable and unstable coronary disease for an adverse cardiac event. The clinical importance of HOPR for high-risk populations remains to be assessed.

Laboratory aspirin resistance reversibility in diabetic patients: a pilot study using different pharmaceutical formulations.

PURPOSE: Aspirin resistance occurs most frequently in diabetic patients and is associated with poor prognosis. The purpose of this study was to evaluate the prevalence of aspirin resistance in a cohort of diabetic patients and whether it can be reversed using more bioavailable aspirin formulations. METHODS: Platelets function of 163 diabetic patients taking acetyl salicylic acid (ASA) 100 mg daily has been evaluated with PFA100 and VerifyNow. Patients found resistant by at least one test received an infusion of 288 mg of lysine acetylsalicylate (Flectadol®) corresponding to ASA 160 mg. Platelets function was measured again after 1 and 24 h. Patients whose the resistance was reversed received 288 mg of soluble salt of lysine acetylsalicylate (Cardirene 160®) corresponding to ASA160 mg instead of aspirin and their aggregation status was re-evaluated after 1 month of therapy. RESULTS: Prevalence of aspirin resistance in our population was 18,4 % (30/163). In 27 out of 30 patients (90 %) aspirin resistance was reversed within 24 h from the infusion. 25 out of 27 patients (92 %) were found fully aspirin-sensitive after 1 month of oral therapy with soluble salt; two patients were found with borderline value. No adverse reactions were observed. CONCLUSIONS: A significant number of diabetic patients are resistant to aspirin therapy. A single intravenous dose of lysine acetylsalicylate can reverse the platelet hyper-aggregability and laboratory aspirin resistance in large majority of patients. The efficacy of antiaggregation can be maintained by chronic therapy with an oral drug with a more favourable pharmacokinetic profile.

Bleeding rate during oral surgery of oral anticoagulant therapy patients with associated systemic pathologic entities: a prospective study of more than 500 extractions.

PURPOSE: Oral anticoagulant therapy (OAT) patients have international normalized ratio (INR) safety windows for oral surgery, the lower limit of which is determined by the thromboembolic risk, with the upper limit typically 3.0. We sought to assess whether these limits will also be true with comorbidities that favor bleeding, such as diabetes, liver disease, and chronic renal failure. MATERIALS AND METHODS: The study was designed for 500 consecutive extractions. Patients with an INR greater than 3.0 were switched to heparin and used as controls. The primary outcome was the incidence of bleeding with the need for reoperation, in connection with 3 principal predictors: the INR, reasons for OAT, and comorbidity type. Continuous variables were analyzed using the Mann-Whitney U test and categorical variables using χ2 or Fisher's exact test. Statistical significance was set at P < .05. The reliability of the INR as a bleeding predictor was assessed using receiver operating characteristic (ROC) curves. RESULTS: Extractions in patients receiving OAT without comorbidities had a success rate of 99.7% against severe bleeding. Despite equivalent INR values, patients with comorbidities had a significantly lower rate (81.3%, P < .001). For these patients, the ROC curve procedure indicated lower INR upper limits, 2.8 for mechanical heart prosthesis subjects and 2.3 for all others. Among the comorbidities, diabetes was associated with the greatest frequency of bleeding (31%) compared with liver disease (15%) and kidney failure (11%). CONCLUSIONS: Patients with comorbidities should be advised to bring their INR within narrower safety windows (upper limit of 2.5 to 2.8 for mechanical prosthesis and 2.0 to 2.3 otherwise) or be switched to heparin. Alternatively, we propose applying to the socket, a platelet-rich growth factor preparation to foster hemostasis.

Relationship of ECG findings to phenotypic expression in patients with hypertrophic cardiomyopathy: a cardiac magnetic resonance study.

BACKGROUND: The 12-lead electrocardiogram (ECG) is considered an essential screening tool for hypertrophic cardiomyopathy (HCM). A vast array of ECG abnormalities has been described in HCM, although their relationship to left ventricle (LV) morphology and degree of hypertrophy appears elusive. Aim of this study was to assess the relationship of ECG patterns with the HCM phenotype assessed according to the novel opportunities offered by cardiac magnetic imaging (CMR). METHODS: CMR and 12-lead ECG were performed in 257 HCM patients. Severity of ECG abnormalities was defined by the sum of 9 criteria: abnormal cardiac rhythm, QRS duration ≥ 100 ms, Romhilt-Estes score ≥ 5, fascicular block (LAHB) and/or bundle-branch block (LBBB or RBBB), ST-T abnormalities, ST-T segment elevation ≥ 0.2 mV, prolonged QTc interval, pathological Q waves, absence of normal Q wave. Four ECG groups were identified: normal (0 criteria); mildly abnormal (1-3 criteria); moderately abnormal (4-6 criteria); markedly abnormal (7-9 criteria). RESULTS: There was a direct relationship between severity of ECG abnormalities and HCM phenotype. LV mass index was normal in most patients with normal ECG and progressively increased with each class of ECG score, from 70.9 ± 18.6g/m(2) in patients with normal ECG to 107.1 ± 55.1g/m(2) among those with markedly abnormal ECG (p=<0.0001). Likewise, the prevalence and extent of late gadolinium enhancement (LGE) increased significantly with the ECG score, from 37% in patients with normal ECG to 93% in patients with markedly abnormal ECG (overall p=0.0012). A normal ECG had a negative predictive accuracy of 96% for markedly increased LV mass (>91 g/m(2) for men and >69 g/m(2) for women), and of 100% for maximum LV thickness ≥ 30 mm. CONCLUSIONS: In a large HCM cohort, the number and severity of ECG abnormalities were directly related to phenotypic expression as revealed by CMR. Although false negative ECG findings remain a challenge in population screenings for HCM, a normal ECG proved effective in ruling out severe LV hypertrophy, suggesting potential implications for long-term follow-up of HCM patients and family members. A simple score for quantification of ECG abnormalities in HCM patients is proposed.