P4454N-terminal pro-brain natriuretic peptide and resistance to chronic therapy with 75 mg acetylsalicylic acid assessed by point-of-care test - prospective single center study
Authors: Cygulska K M , Figiel Ł , Slawek D , Karzkowiak A , Wraga M , Dabrowa M , Kasprzak J D 
Published: October 2019

Abstract

Background
Acetylsalicylic acid (ASA) remains the principal medication for secondary prevention of atherosclerotic complications. Resistance to ASA (ASAres) is multifactorial and results in insufficient reduction of platelet reactivity through incomplete inhibition of thromboxane A2 (TXA2) synthesis. There is controversy regarding the optimal preventive ASA dose with common daily use of 75 mg in many European countries.

Purpose
The aim of our study is to reassess the prevalence and predictors of ASAres in contemporary cohort of coronary disease (CAD) patients (pts) on stable therapy with 75 mg ASA.

Methods
We studied 205 patients (36,6% females) with stable CAD and concomitant atherosclerotic disease history (ischemic stroke 10,2%, peripheral vascular disease 8,3%,) and type 2 diabetes in 39,5% on stable regimen 75 mg ASA for a minimum of 1 month (mean age 68,2±9,7 years, mean BMI 27,3±4,7 kg/m2). ASAres was defined as ARU (aspirin reaction unit) ≥550 using point-of-care VerifyNow Aspirin test. Exclusion criteria were: recent (up to 2 months) acute coronary syndrome, cancer, dermatological disease, epilepsy or other chronic neurological diseases, exacerbation of allergic disease, rheumatoid arthritis, periodontal disease, alcoholism, drug addiction, vegetarianism, veganism and other specific diets, and known thrombophilia. The population received standard concomitant preventive treatments including RAA blockade in 88,3%, beta-blockers in 85,9%, statins in 93,2%, and proton pump inhibitors (PPI) in 65,4%. History of infarction was present in 37% and mean left ventricular ejection fraction was 47% (18–75%).

Results
ASAres was detected in 11,7% of patients. Modest but significant correlations (Spearman's coefficient of rank correlation rho) were detected between ARU and C-reactive protein (CRP) (rs=0,15; p=0,030), N-terminal pro-brain natriuretic peptide (NT-proBNP) (rs=0,15; p=0,039), body weight (rs=0,22; p=0,0014), BMI (rs=0,207, p=0,0029). No significant differences in ASAres we found with regard to sex, other risk factors or concomitant medication, including PPI. However, in ASAres pts median concentrations of NT-proBNP were significantly higher (median 311 vs. 646pg/ml; p=0,046). In multivariate analysis NT-proBNP emerged as the only independent predictor of ASAres (AUC=0,626; p=0,027 with threshold value of 327,3 pg/ml resulting with negative predictive value of 16,98% and positive predictive value of 93,95% for ASAres).

Conclusion
ASAres has significant prevalence in this secondary prevention CAD cohort treated with 75 mg daily dose. NT-proBNP was identified as the only independent predictor in multivariate analysis. This finding may be important especially for pts with heart failure of ischemic etiology. The implications of switching into 100 mg or higher ASA doses remain to be investigated.

Acknowledgement/Funding
study was supported from unrestricted research grant from Aflofarm SA