Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels

The current guidelines following an acute coronary syndrome recommend dual-antiplatelet therapy (DAPT) (aspirin plus a P2Y(12) antagonist) alongside lifestyle modifications, including more regular physical activity. It is currently unknown whether regular exercise affects the pharmacology of DAPT. AimTo explore how exercise-induced improvements in vascular and platelet function affect the efficacy of DAPT, in a cross-sectional study of men with different physical activity levels (training status). MethodsA total of 42 healthy, normal-weight, middle-aged men were divided into 3 groups: untrained, moderately trained and well-trained. Their platelet reactivity (agonist-induced % aggregation) was investigated in platelet-rich plasma at rest and after inhibition with aspirin and ticagrelor and/or prostacyclin and nitric oxide added to the blood invitro, and after physiological tests of vascular function; passive movement of the leg, flow-mediated dilation and one-leg knee-extensor exercise. Vascular function of the femoral artery (changes in arterial blood flow) was assessed by ultrasound Doppler. ResultsPlatelets from the well-trained subjects had lower basal reactivity, a higher sensitivity to the anti-aggregatory effects of prostacyclin and were more potently inhibited by DAPT compared to the untrained subjects. The moderately trained and well-trained subjects had a superior vascular function compared to untrained subjects, and their platelets were more inhibited by the passive movement, flow-mediated dilation and one-leg knee-extensor exercise. DiscussionA habitually active lifestyle leads to an increased platelet sensitivity to pharmacological and physiological platelet inhibitors. We suggest that physical activity habits (training status) should be considered when personalizing and optimizing antithrombotic treatment strategies.