Search

Introduction:Dual antiplatelet therapy (DAPT) plays a critical role in secondary prevention after acute coronary syndrome (ACS), but some patients show suboptimal inhibition of platelet aggregability leading to an increased risk of recurrent ischemic events. On the other hand, reduced left ventricular ejection fraction (LVEF) is a major determinant of worse prognosis post-myocardial infarction (MI). However, little is known about the relationship between these two prognostic variables.Hypothesis:High-on treatment platelet reactivity (HPR) may be involved in impaired ventricular function after ACS.Methods:Reduced LVEF was defined as <40%, being the population categorized in LVEF <40% and LVEF ?40%. All patients received DAPT with aspirin and P2Y12antagonists (clopidogrel or ticagrelor). Platelet aggregability was evaluated between 5 and 7 days post-MI using the VerifyNow?P2Y12Assay or the Multiplate?ADP Analyzer. HPR for ADP was defined by VerifyNow as >208 reactions units (PRUs) or by Multiplate as >46 area under the curve (AU*min). Univariate and adjusted models were developed applying the chi-square, parametric and non-parametric test, and logistic regression (HPR as dependent variable) as indicated.Results:Four hundred and forty patients with ACS (61 ? 11 years-old, 69% men) were included in the study. Overall, 64 (14.55%) patients had LVEF <40% (Group I) and 376 (85.45%) LVEF ?40% (Group II). By univariate analysis, HPR incidence was significantly higher in Group I (39.06%) compared with Group II (19.15%), P <0.001). By multivariable analysis, HPR was independently associated with LVEF <40% adjusted odds ratio = 2.362, 95% CI = 1.198-4.657, P = 0.013).Conclusions:Among patients treated with DAPT for ACS, LVEF <40% is associated with poor antiplatelet inhibition. These findings suggest that HPR could influence left ventricular function after ACS, possibly through a worsening of coronary reperfusion. Additional research is desirable in order to test this hypothesis.

Introduction:In the PLATO trial, ticagrelor reduced ischemic events when compared to clopidogrel in patients (pts) with acute coronary syndromes. Increase in adenosine plasmatic concentration (APC) has emerged as a potential mechanism to explain such benefit. Moreover, chronic kidney disease (CKD) pts seemed to have even greater benefit with ticagrelor when compared with non-CKD pts, and this is not fully explained. Adenosine has been linked to important effects such as vasodilation, inflammatory modulation, coordination between kidney blood flow and glomerular filtration rate (GFR), among others. APC has been evaluated in different populations, although no data on pts with CKD (GFR < 60 ml/min/1.73m2) is available.Hypothesis:Whether APC is different in coronary artery disease (CAD) pts with and without CKD.Methods:We analyzed baseline data from 65 pts prospectively included in a single-center randomized clinical trial testing clopidogrel vs. ticagrelor in CAD pts with and without CKD. APC was measured before (data presented here) and after intervention, by high-performance liquid chromatography. Student?s t-test and Mann-Whitney were used for univariate analyses and linear regression models correlating APC with creatinine or GFR was also performed.Results:From the total 65 pts included, 33 were in the CKD group (age 71?5years, 70% men, GFR 41?13 ml/min) and 23 pts in the non-CKD group (age 70?5 years, 66% men, GFR 83?15 ml/min). Both groups were comparable for most baseline characteristics (hypertension, diabetes, dyslipidemia, tobacco use, previous myocardial infarction, previous PCI), except that CKD pts had lower ejection fraction (46?13% vs 54?10%; p=0.005). For the main results, mean APC was not significantly different between CKD and non-CKD pts (141?164 vs 139?104 nmol/L; p=0.21), and no independent association was found between APC and creatinine (p=0.11) or APC and GFR (p=0.54).Conclusion:In the first report ever made evaluating APC in CAD pts according to renal function, we did not find any significant difference of APC in pts with or without CKD. Whether the benefit of ticagrelor previously seen in this population was mediated predominantly by platelet inhibition or also by increase in APC should be clarified in further studies.

Introduction:Exercise training increases high-density lipoprotein cholesterol (HDL-C) levels. However, HDL-C levels only partially reflect the protective functions of HDL, including cholesterol esterification and reverse cholesterol transport. To exert those functions, the transfer of cholesterol to HDL, not only from cells, but also from other lipoproteins is necessary and it was shown by in vitro assay that patients with chronic coronary artery disease have deficient cholesterol transfer to HDL.Hypothesis:Exercise training may improve cholesterol transfer to HDL in post-myocardial infarction (MI) patients.Methods:Sixty-two previously sedentary patients 30?5 days after uncomplicated MI (59.2?9.9 years-old; 74.2%men; 58.1% with ST-elevation MI) were randomized to an intervention group that engaged in a supervised moderate intensity exercise training program (exercise training group) or to a control group that received information about healthy lifestyle but were not trained (control group). All patients were on high intensity statin. HDL-C and transfer of both unesterified (NEC) and esterified cholesterol (EC) to HDL were determined at baseline and at the end of the 3-month follow-up. NEC and EC transfer to HDL was measured by an in vitro assay using racioactively labeled lipid emulsion as cholesterol donor.Results:There were no significant differences on HDL-C levels (p=0.76) or NEC (p=0.48) and EC (p=0.69) transfer to HDL at baseline among groups. Comparisons between baseline and 3-month follow-up measures are depicted in table.Conclusions:In post-MI patients, 3 months of exercise-based cardiac rehabilitation resulted not only in HDL-C increase but also in improvement of NEC and EC transfer to HDL. This indicates a better HDL function and atheroprotective capacity in this high cardiovascular risk population. These findings reinforce the importance of exercise-based cardiac rehabilitation after MI.