Time Course of Ischemic and Bleeding Burden in Elderly Patients With Acute Coronary Syndromes Randomized to Low‐Dose Prasugrel or Clopidogrel

Abstract

<jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en"> Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates ( <jats:styled-content style="fixed-case">ADIRs</jats:styled-content> ) and average daily bleeding rates ( <jats:styled-content style="fixed-case">ADBRs</jats:styled-content> ) over 1 year in patients aged &gt;74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly <jats:styled-content style="fixed-case">ACS</jats:styled-content> 2 trial, comparing low‐dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> <jats:styled-content style="fixed-case">ADIRs</jats:styled-content> and <jats:styled-content style="fixed-case">ADBRs</jats:styled-content> were calculated as the total number of events, including recurrent events, divided by the number of patient‐days of follow‐up and assessed within different clinical phases: acute (0–3 days), subacute (4–30 days), and late (31–365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of <jats:styled-content style="fixed-case">ADIRs</jats:styled-content> and <jats:styled-content style="fixed-case">ADBRs</jats:styled-content> and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, <jats:styled-content style="fixed-case">ADIRs</jats:styled-content> were 2.6 times (95% <jats:styled-content style="fixed-case">CI,</jats:styled-content> 2.4–2.9) higher than <jats:styled-content style="fixed-case">ADBRs</jats:styled-content> . <jats:styled-content style="fixed-case">ADIRs</jats:styled-content> were significantly higher in the clopidogrel arm than in the low‐dose prasugrel arm in the subacute phase ( <jats:italic>P</jats:italic> <jats:sub>adj</jats:sub> &lt;0.001) without a difference in <jats:styled-content style="fixed-case">ADBRs</jats:styled-content> ( <jats:italic>P</jats:italic> <jats:sub>adj</jats:sub> =0.35). In the late phase, <jats:styled-content style="fixed-case">ADIRs</jats:styled-content> remained significantly higher with clopidogrel ( <jats:italic>P</jats:italic> <jats:sub>adj</jats:sub> &lt;0.001), whereas <jats:styled-content style="fixed-case">ADBRs</jats:styled-content> were significantly higher with low‐dose prasugrel ( <jats:italic>P</jats:italic> <jats:sub>adj</jats:sub> &lt;0.001). </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en">Ischemic burden was greater than bleeding burden in all clinical phases of 1‐year follow‐up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low‐dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase.</jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Clinical Trial Registration</jats:title> <jats:p xml:lang="en"> <jats:styled-content style="fixed-case">URL</jats:styled-content> : <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link> . Unique identifier: <jats:styled-content style="fixed-case">NCT</jats:styled-content> 01777503. </jats:p> </jats:sec>