Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease

Larsen, Susan Weng; Grove, Erik Lerkevang; Neergaard‐Petersen, Søs; Würtz, Morten; Hvas, Anne‐Mette; Kristensen, Steen Dalby

doi:10.1161/jaha.117.006050

Cited by 14 publications

(17 citation statements)

References 48 publications

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“…A number of clinical studies have correlated aspirin resistance with long term adverse clinical events not only in patients with coronary artery disease but also in persons with ischemic stroke or peripheral arterial disease[ 14 – 16 ].However, this finding was not observed in other studies [ 19 ]. Data on the frequency of aspirin resistance varied greatly[ 11 – 13 ], largely because of the differences in the definition of resistance and the laboratory method used.…”

Section: Discussioncontrasting

confidence: 85%

Effects of Ramadan fasting on aspirin resistance in type 2 diabetic patients

et al. 2018

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AimsRamadan fasting (RF) may affect aspirin resistance. We conducted this study in patients with cardiovascular risk (CVR) factors to assess the effect of RF on aspirin resistance and explore whether type 2 diabetes mellitus (DM) would influence this effect.MethodsA total of 177 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking aspirin. Physical exam and standard biological tests including glycaemia and serum lipids data were performed before Ramadan (Pre-R), at the last week of Ramadan (R) and four weeks after the end of Ramadan (Post-R). In the same visits caloric intake was calculated and platelet reactivity to aspirin was assessed using Verify Now point-of-care assay.ResultsIn the overall population, there was no significant change in absolute aspirin reaction unit (ARU) values and in metabolic parameters. In DM patients (n = 127), ARU change from Pre-R values was+19.7 (p = 0.01) and +14.4 (p = 0.02) respectively at R and Post-R. During Ramadan, glycaemia, triglycerides, and cholesterol levels increased significantly and returned to Pre-R values thereafter. These changes were not observed in non-DM patients.ConclusionsDuring RF aspirin resistance increased only in DM patients. This effect persisted one month after Ramadan. Simultaneous alteration of glycemic control and increase of serum lipids levels could potentially be a favorable factor.Study registrationThe protocol was registered at clinicaltrials.gov under: NCT02720133.

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Section: Discussioncontrasting

confidence: 85%

Effects of Ramadan fasting on aspirin resistance in type 2 diabetic patients

et al. 2018

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“…20 The study population has previously been described in detail. 15,21,22 Briefly, in the main study, 900 patients with angiographically documented stable CAD were included, all receiving single antithrombotic therapy with aspirin 75 mg daily. 22 In this observational study, samples for analysis of fibrin clot properties were available in 786 patients, all receiving aspirin monotherapy.…”

Section: Study Populationmentioning

confidence: 99%

“…15,21,22 Briefly, in the main study, 900 patients with angiographically documented stable CAD were included, all receiving single antithrombotic therapy with aspirin 75 mg daily. 22 In this observational study, samples for analysis of fibrin clot properties were available in 786 patients, all receiving aspirin monotherapy. The present study cohort represents a high-risk population, since all patients had documented CAD and either prior myocardial infarction, type 2 diabetes, or both.…”

Section: Study Populationmentioning

confidence: 99%

Imbalance between Fibrin Clot Formation and Fibrinolysis Predicts Cardiovascular Events in Patients with Stable Coronary Artery Disease

et al. 2019

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Background Despite long-term antiplatelet therapy with aspirin, recurrent cardiovascular events remain common in patients with coronary artery disease (CAD). Objective We aimed to determine whether fibrin network characteristics are predictive of vascular events in patients with stable CAD treated with aspirin monotherapy. Methods We included 786 patients with angiographically documented CAD and either prior myocardial infarction, type 2 diabetes mellitus, or both. Median follow-up time was 3 years. At inclusion, fibrin clot properties were evaluated using a turbidimetric assay and the following clot parameters were studied: (1) maximum absorbance, a measure of clot density and fiber thickness; (2) lysis time, assessing fibrinolysis potential; and (3) area under the curve (AUC), a measure of clot formation and lysis. The primary endpoint was the composite of nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. Hazard ratios (HRs) were estimated using multivariable Cox proportional hazards regression. Results A total of 70 primary endpoints occurred. The primary endpoint occurred more frequently in CAD patients with increased clot AUC (crude HR for first vs. fourth quartile: 2.4 [95% confidence interval 1.2–4.6], p = 0.01). This finding remained significant after adjusting for potential confounders (adjusted HR: 2.4 [1.2–4.8], p = 0.01). Neither clot maximum absorbance nor lysis time showed significant association with future vascular events (adjusted HR for maximum absorbance 1.8 [0.9–3.7]; p = 0.09) and lysis time (1.6 [0.8–3.0]; p = 0.18). Conclusion We demonstrate that increased clot AUC predicts future cardiovascular events in stable CAD patients receiving aspirin monotherapy.

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“…Inhibition of activated Factor XII (FXIIa) provides thromboprotection by reducing clot firmness [ 63 ]. As revealed by intravital microscopy, Thrombi created in injured mesenteric vessels of FXII-deficient mice were unstable and prone to embolization [ 64 ]. A recombinant fully human FXIIa activity neutralizing antibody (3F7) has shown promise in animal studies.…”

Section: Novel Antithrombotic Drugs That May Impact On Thrombus Stabimentioning

confidence: 99%

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

Gorog

2018

J Thromb Thrombolysis

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The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.

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Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease

Cited by 14 publications

References 48 publications

Effects of Ramadan fasting on aspirin resistance in type 2 diabetic patients

Effects of Ramadan fasting on aspirin resistance in type 2 diabetic patients

Imbalance between Fibrin Clot Formation and Fibrinolysis Predicts Cardiovascular Events in Patients with Stable Coronary Artery Disease

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

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