Background Dual antiplatelet therapy in older versus younger patients with acute coronary syndromes is understudied. Low-dose prasugrel (5 mg/d) is recommended for younger, lower-body-weight patients and elderly patients with acute coronary syndromes to mitigate the bleeding risk of standard-dose prasugrel (10 mg/d). Methods and Results A total of 9326 medically managed patients with acute coronary syndromes from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial (<75 years of age, n=7243; 75 years of age, n=2083) were randomized to prasugrel (10 mg/d; 5 mg/d for those 75 or <75 years of age and <60 kg in weight) or clopidogrel (75 mg/d) plus aspirin for 30 months. A total of 515 participants 75 years of age (25% of total elderly population) had serial platelet reactivity unit measurements in a platelet-function substudy. Cumulative risks of the primary end point (cardiovascular death/myocardial infarction/stroke) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding increased progressively with age and were 2-fold higher in older participants. Among those 75 years of age, TIMI major bleeding (4.1% versus 3.4%; hazard ratio, 1.09; 95% confidence interval, 0.57-2.08) and the primary end point rates were similar with reduced-dose prasugrel and clopidogrel. Despite a correlation between lower 30-day on-treatment platelet reactivity unit values and lower weight only in the prasugrel group, there was a nonsignificant treatment-by-weight interaction for platelet reactivity unit values among participants 75 years of age in the platelet-function substudy (P=0.06). No differences in weight were seen in all participants 75 years of age with versus without TIMI major/minor bleeding in both treatment groups. Conclusions Older age is associated with substantially increased long-term cardiovascular risk and bleeding among patients with medically managed acute coronary syndromes, with no differences in ischemic or bleeding outcomes with reduced-dose prasugrel compared with clopidogrel in elderly patients. No significant interactions among weight, pharmacodynamic response, and bleeding risk were observed between reduced-dose prasugrel and clopidogrel in elderly patients. Clinical Trial Registration URL: . Unique identifier: NCT0069999.

Elderly patients with acute coronary syndromes managed without revascularization: insights into the safety oflong-term dual antiplatelet therapy with reduced-dose prasugrel versus standard-dose clopidogrel / Roe, Mt; Goodman, Sg; Ohman, Em; Stevens, Sr; Hochman, Js; Gottlieb, S; Martinez, F; Dalby, Aj; Boden, We; White, Hd; Prabhakaran, D; Winters, Kj; Aylward, Pe; Bassand, Jp; Mcguire, Dk; Ardissino, D; Fox, Ka; Armstrong, Pw. - In: CIRCULATION. - ISSN 0009-7322. - 128:8(2013), pp. 823-833. [10.1161/CIRCULATIONAHA.113.002303]

Elderly patients with acute coronary syndromes managed without revascularization: insights into the safety oflong-term dual antiplatelet therapy with reduced-dose prasugrel versus standard-dose clopidogrel

Ardissino D;
2013-01-01

Abstract

Background Dual antiplatelet therapy in older versus younger patients with acute coronary syndromes is understudied. Low-dose prasugrel (5 mg/d) is recommended for younger, lower-body-weight patients and elderly patients with acute coronary syndromes to mitigate the bleeding risk of standard-dose prasugrel (10 mg/d). Methods and Results A total of 9326 medically managed patients with acute coronary syndromes from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial (<75 years of age, n=7243; 75 years of age, n=2083) were randomized to prasugrel (10 mg/d; 5 mg/d for those 75 or <75 years of age and <60 kg in weight) or clopidogrel (75 mg/d) plus aspirin for 30 months. A total of 515 participants 75 years of age (25% of total elderly population) had serial platelet reactivity unit measurements in a platelet-function substudy. Cumulative risks of the primary end point (cardiovascular death/myocardial infarction/stroke) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding increased progressively with age and were 2-fold higher in older participants. Among those 75 years of age, TIMI major bleeding (4.1% versus 3.4%; hazard ratio, 1.09; 95% confidence interval, 0.57-2.08) and the primary end point rates were similar with reduced-dose prasugrel and clopidogrel. Despite a correlation between lower 30-day on-treatment platelet reactivity unit values and lower weight only in the prasugrel group, there was a nonsignificant treatment-by-weight interaction for platelet reactivity unit values among participants 75 years of age in the platelet-function substudy (P=0.06). No differences in weight were seen in all participants 75 years of age with versus without TIMI major/minor bleeding in both treatment groups. Conclusions Older age is associated with substantially increased long-term cardiovascular risk and bleeding among patients with medically managed acute coronary syndromes, with no differences in ischemic or bleeding outcomes with reduced-dose prasugrel compared with clopidogrel in elderly patients. No significant interactions among weight, pharmacodynamic response, and bleeding risk were observed between reduced-dose prasugrel and clopidogrel in elderly patients. Clinical Trial Registration URL: . Unique identifier: NCT0069999.
2013
Elderly patients with acute coronary syndromes managed without revascularization: insights into the safety oflong-term dual antiplatelet therapy with reduced-dose prasugrel versus standard-dose clopidogrel / Roe, Mt; Goodman, Sg; Ohman, Em; Stevens, Sr; Hochman, Js; Gottlieb, S; Martinez, F; Dalby, Aj; Boden, We; White, Hd; Prabhakaran, D; Winters, Kj; Aylward, Pe; Bassand, Jp; Mcguire, Dk; Ardissino, D; Fox, Ka; Armstrong, Pw. - In: CIRCULATION. - ISSN 0009-7322. - 128:8(2013), pp. 823-833. [10.1161/CIRCULATIONAHA.113.002303]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2883745
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