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

Acta Physiol (Oxf). 2018 May;223(1):e13028. doi: 10.1111/apha.13028. Epub 2018 Jan 19.


The current guidelines following an acute coronary syndrome recommend dual-antiplatelet therapy (DAPT) (aspirin plus a P2Y12 antagonist) alongside lifestyle modifications, including more regular physical activity. It is currently unknown whether regular exercise affects the pharmacology of DAPT.

Aim: To 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).

Methods: A 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 in vitro, 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.

Results: Platelets 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.

Discussion: A 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.

Keywords: aspirin; nitric oxide; physical activity; platelet aggregation inhibitors; prostacyclin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin / pharmacology
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Cross-Sectional Studies
  • Epoprostenol / pharmacology
  • Exercise*
  • Femoral Artery / diagnostic imaging
  • Femoral Artery / physiology*
  • Habits
  • Healthy Lifestyle*
  • Humans
  • Lower Extremity / blood supply*
  • Male
  • Middle Aged
  • Nitric Oxide / pharmacology
  • Platelet Activation / drug effects*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Function Tests
  • Regional Blood Flow
  • Sedentary Behavior*
  • Ticagrelor / pharmacology
  • Ultrasonography, Doppler
  • Vasodilation


  • Platelet Aggregation Inhibitors
  • Nitric Oxide
  • Epoprostenol
  • Ticagrelor
  • Aspirin