Events In Aspirin-treated Patients Research Articles

Yosprala: A Fixed Dose Combination of Aspirin and Omeprazole.

Cardiovascular disease is the leading cause of morbidity and mortality in the United States. Patients who survive a primary cerebrovascular or cardiovascular event are at increased risk of a subsequent occurrence. Antiplatelet therapy plays an essential role for secondary prevention in individuals with stroke, transient ischemic attack, acute or chronic artery disease, or peripheral arterial disease. Maintaining high-risk patients on low-dose aspirin therapy is a fundamental component of management. However, poor adherence, secondary to the drug's gastrointestinal side effects, has been associated with negative cardiovascular outcomes. Numerous studies have indicated that proton-pump inhibitors significantly reduce the risk of upper gastrointestinal adverse events in aspirin-treated patients. The US Food and Drug Administration approved Yosprala (Aralez Pharmaceuticals), a fixed-dose combination of delayed-release aspirin and immediate-release omeprazole, on September 15, 2016. It is the first product to become available in the United States that combines these 2 pharmacologic drug classes, and represents a new therapeutic option for patients and healthcare providers who strive to improve adherence to daily aspirin therapy.

Antiplatelet Strategies and Outcomes in Patients with Noncardioembolic Ischemic Stroke from a Real-World Study with a Five-Year Follow-Up.

Aspirin and clopidogrel are both acceptable antiplatelet options for the secondary prevention of noncardioembolic ischemic stroke. Associations between Essen Stroke Risk Score (ESRS) and antiplatelet treatment in Chinese patients with noncardioembolic ischemic stroke were assessed. This retrospective study was taken in a tertiary care hospital located in eastern China. Patients with noncardioembolic ischemic stroke hospitalized during January 1, 2009, to December 31, 2011, were classified according to ESRS during index stroke hospitalization. Antiplatelet strategy at the time of discharge was categorized as aspirin (100mg/day) vs. clopidogrel (75mg/day). Patients received follow-up from July 1, 2014, to December 31, 2015, and the efficacy of clopidogrel and aspirin in different ESRS subgroups was assessed with respect to reducing the risk of a combined vascular event of recurrent stroke, myocardial infarction, or primary intracranial hemorrhage. Totally, 1175 non-cardiac stroke patients were included, among which 878 patients completed follow-up surveys. Of the patients who completed the follow-up, 458 (52.2%) had an ESRS>3, and 621 (70.7%) received aspirin. Patients who received clopidogrel tended to be older, and more patients had hypertension, diabetes, and an ESRS>3 than patients who received aspirin. Over a mean follow-up of 5.2years, the rate of combined vascular events was 19.3% in the aspirin group and 16.7% in the clopidogrel group. Compared with clopidogrel-treated patients, a significant (P=0.044) reduction in combined vascular events in aspirin-treated patients was observed in patients with an ESRS≤3 (OR, odds ratio 0.5; 95% CI 0.3 to 0.9). However, a significant (P=0.002) increase in combined vascular events was observed in patients with an ESRS>3 (OR 2.2; 95% CI 1.3 to 3.8). More clopidogrel-treated patients with ESRS<3 and ESRS=3 discontinued treatment than their counterparts who took aspirin (P<0.05). Adverse drug events, such as digestive discomfort and bleeding, were similar. In conclusion, clopidogrel is suggested for patients with an ESRS>3 and aspirin for patients with an ESRS≤3 for the secondary prevention of noncardioembolic ischemic stroke in Chinese patients.

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.

Use of the PFA-100 closure time to predict cardiovascular events in aspirin-treated cardiovascular patients: a systematic review and meta-analysis.

PFA-100 is a point-of-care assay that evaluates platelet reactivity in high-shear-stress conditions by measuring the closure time (CT) of a membrane aperture. When determined with a collagen/epinephrine cartridge (CEPI), the CT is usually prolonged by aspirin. Studies of the predictive value of a short PFA-100CT(CEPI) for ischemic events in aspirin-treated patients have given variable results. To conduct a systematic review and meta-analysis of studies on the clinical predictive value of a short PFA-100CT(CEPI) in aspirin-treated cardiovascular patients. Relevant studies were identified by scanning electronic databases. Studies were selected if they included aspirin-treated patients with symptomatic atherosclerosis, measured the PFA-100CT(CEPI), used a CT cut-off value to define aspirin 'responders' and 'non-responders', and reported ischemic events. We selected seven non-prospective studies (1466 patients) and eight prospective studies (1227 patients). In non-prospective studies, the PFA-100CT(CEPI) was performed after the ischemic clinical endpoint, and a publication bias was identified. In prospective studies, the global odds ratio (OR) for the recurrence of an ischemic event in 'aspirin non-responders' relative to 'aspirin responders' was 2.1 [95% confidence interval (CI) 1.4-3.4, P < 0.001]. Pooled analysis with a random effect model revealed no heterogeneity (Q Cochran P = 0.36 and I(2) = 9.4%). A short PFA-100CT(CEPI) is associated with increased recurrence of ischemic events in aspirin-treated cardiovascular patients. This finding needs to be confirmed in stable ischemic patients, and the PFA-100CT(CEPI) cut-off needs to be refined in these patients.

Optical platelet aggregometry does not appear useful as a means of assessing the risk of recurrent vascular events in aspirin-treated patients

To investigate whether the results of optical platelet aggregometry indicate the risk of recurrent ischemic events. Cerebro- and cardiovascular patients taking aspirin for at least 30 days were studied retrospectively. Ischemic vascular events occurring prior to testing and the presence of vascular risk factors were recorded. 241 subjects were included. Among the 78 patients (32.4%) who displayed recurrent vascular episodes, the age (62.5 +/- 10.6 vs. 58.4 +/- 11.6, P = 0.009) and the proportion of hypertensives (80.8% vs. 68.1%, P = 0.040) were significantly higher when compared with the participants who exhibited single events. The degree of platelet aggregation did not differ significantly between the patients with and those without recurrent episodes. Logistic regression analysis identified only age (OR 1.033, 95% CI 1.008-1.058, P = 0.010), and not aggregation values, as a risk condition for recurrent vascular episodes. Results of optical platelet aggregometry were not indicative of the risk of recurrent vascular events. The role of conventional risk factors appeared to be more important.

Aspirin resistance: is this term meaningful?

To review data for and against the existence of 'aspirin resistance', a term coined to indicate aspirin-treated patients having ex-vivo tests of platelet activation insensitive to aspirin treatment and recurrence of cardiovascular disease. 'Aspirin resistance' defined by ex-vivo tests of platelet activation yielded values ranging from 21 to 78%, indicating that such tests do not provide a useful measurement. In long-term aspirin-treated patients, studies demonstrated small but functionally relevant platelet thromboxane A2 formation that was responsible for an enhanced platelet activation in response to platelet agonist. These studies, however, did not fully exclude that aspirin compliance may be implicated in such phenomena. Two trials performed in patients with coronary artery disease demonstrated that laboratory evidence of aspirin resistance was no longer detectable when aspirin compliance was accurately monitored. Given the multifactorial nature of atherothrombosis, recurrence of cardiovascular events in aspirin-treated patients does not necessarily suggest 'drug failure'. A cause-effect relationship between platelet insensitivity to aspirin and cardiovascular recurrence has not been defined overall because aspirin compliance has been scarcely considered. Until this information is taken into account, the existence of 'clinical resistance' to aspirin should be reconsidered.

Low-Molecular-Weight Heparin (Fragmin) During Instability in Coronary Artery Disease (FRISC)

This study evaluated whether the low-molecular-weight (LMW) heparin dalteparin sodium (Fragmin) had protective effects against cardiac events in aspirin-treated patients with unstable coronary artery syndromes. Patients (n = 1,506) with unstable angina or non-Q-wave myocardial infarction were randomized to double-blind, placebo-controlled treatment with LMW heparin. The treatment was given as subcutaneous injections: 120 U/kg body weight/12 hours during the first 5–7 days and 7,500 U once daily during the following 35–45 days. The primary endpoint, death or myocardial infarction after 6 days, showed a 3% (4.7%–1.7%) absolute and a 65% relative reduction in the LMW heparin group. There was a 6.8% (15.5%–8.7%) absolute and a 47% relative reduction of urgent revascularization or need for heparin or nitroglycerin infusions in combination with the primary endpoint. After 40 days there was an absolute reduction of death or myocardial infarction of 2.8% (10.7%–7.9%) and its combination with incapacitating angina was reduced by 5.9% (30.7%–24.8%). The survival analysis indicated a reactivation of the instability soon after lowering the dose at 5–7 days. With long-term follow-up, 3–4 months after termination of LMW heparin, the differences between groups were no longer statistically significant. However, the cumulative reduction in death, myocardial infarction, and revascularization because of incapacitating angina of 5.1% (25.3%–20.4%) was maintained. No cerebral and few major bleeds occurred. Compliance was adequate. Thus, subcutaneous LMW heparin protects against cardiac events in the acute phase of unstable coronary artery disease. The subcutaneous regimen also allows prolongation of treatment in the outpatient setting, which might maintain the initial benefits over a longer period.