Jennifer Yu1, Roxana Mehran1, Usman Baber1, Sze-Yuan Ooi1, Bernhard Witzenbichler1, Giora Weisz1, Michael J Rinaldi1, Franz-Josef Neumann1, D Christopher Metzger1, Timothy D Henry1, David A Cox1, Peter L Duffy1, Ernest L Mazzaferri1, Bruce R Brodie1, Thomas D Stuckey1, Akiko Maehara1, Ke Xu1, Ori Ben-Yehuda1, Ajay J Kirtane1, Gregg W Stone2. 1. From The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.Y., R.M., U.B.); Prince of Wales Clinical School, University of NSW, Australia (J.Y., S.-Y.O.); Clinical Trials Center, Cardiovascular Research Foundation, New York, NY (R.M., G.W., A.M., K.X., O.B.-Y., A.J.K., G.W.S.); Department of Cardiology and Pneumology, Helios Amper-Klinikum, Dachau, Germany (B.W.); Els & Charles Bendheim Department of Cardiology, Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); Center for Interventional Vascular Therapy, Division of Cardiology, Columbia University Medical Center, New York, NY (G.W., A.M., O.B.-Y., A.J.K., G.W.S.); Sanger Heart and Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Heart Center, University of Freiburg, Bad Krozingen, Germany (F.-J.N.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, MN (T.D.H.); Cedars-Sinai Heart Institute, Los Angeles, CA (T.D.H.); Lehigh Valley Health Network, Allentown, PA (D.A.C.); Reid Heart Center, FirstHealth of the Carolinas, Pinehurst, NC (P.L.D.); The Ohio State University Wexner Medical Center, Columbus (E.L.M.); and LeBauer Cardiovascular Research Foundation/Cone Health, Greensboro, NC (B.R.B., T.D.S.). 2. From The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.Y., R.M., U.B.); Prince of Wales Clinical School, University of NSW, Australia (J.Y., S.-Y.O.); Clinical Trials Center, Cardiovascular Research Foundation, New York, NY (R.M., G.W., A.M., K.X., O.B.-Y., A.J.K., G.W.S.); Department of Cardiology and Pneumology, Helios Amper-Klinikum, Dachau, Germany (B.W.); Els & Charles Bendheim Department of Cardiology, Shaare Zedek Medical Center, Jerusalem, Israel (G.W.); Center for Interventional Vascular Therapy, Division of Cardiology, Columbia University Medical Center, New York, NY (G.W., A.M., O.B.-Y., A.J.K., G.W.S.); Sanger Heart and Vascular Institute/Carolinas HealthCare System, Charlotte, NC (M.J.R.); Heart Center, University of Freiburg, Bad Krozingen, Germany (F.-J.N.); Wellmont CVA Heart Institute, Kingsport, TN (D.C.M.); Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, MN (T.D.H.); Cedars-Sinai Heart Institute, Los Angeles, CA (T.D.H.); Lehigh Valley Health Network, Allentown, PA (D.A.C.); Reid Heart Center, FirstHealth of the Carolinas, Pinehurst, NC (P.L.D.); The Ohio State University Wexner Medical Center, Columbus (E.L.M.); and LeBauer Cardiovascular Research Foundation/Cone Health, Greensboro, NC (B.R.B., T.D.S.). gs2184@columbia.edu.
Abstract
BACKGROUND: Sex differences in the outcomes after percutaneous coronary intervention with drug-eluting stents and in the response to clopidogrel therapy have been reported; however, the differential risk of high platelet reactivity (HPR) on clopidogrel in women versus men is unknown. METHODS AND RESULTS: We compared 8448 patients enrolled in the ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) according to sex and the presence/absence of HPR on clopidogrel (defined as P2Y12 reactivity units >208). Study end points were definite and probable stent thrombosis (ST), clinically relevant bleeding, all-cause mortality, myocardial infarction, and major adverse cardiac events (comprising mortality, myocardial infarction, and target lesion revascularization). HPR was more common among women (1118/2163, 51.7%) than men (2491/6285, 39.6%). HPR was associated with a roughly double risk of 1-year ST in both women and men (women with versus without HPR: 1.4% versus 0.7%; hazard ratio [HR], 2.02; 95% confidence interval [CI], 0.82-4.95; P=0.12; and men: 1.2% versus 0.5%; HR, 2.42; 95% CI, 1.36-4.30; P=0.002; Pinteraction=0.73). HPR was associated with almost half the rate of clinically relevant bleeding in women (women: HPR versus no HPR, 5.3% versus 9.8%; HR, 0.54; 95% CI, 0.40-0.74; P<0.001), whereas men had similar rates of bleeding regardless of HPR status (men: HPR versus no HPR, 5.7% versus 5.9%; HR, 0.96; 95% CI, 0.78-1.18; P=0.70; Pinteraction=0.003). In propensity-adjusted models, HPR was an independent predictor of ST and myocardial infarction in men; although both associations were nonsignificant among women, no interaction was observed in the associations between HPR and either ST or myocardial infarction. Conversely, HPR was an independent predictor of reduced bleeding only in women (women: adjusted HR, 0.58; 95% CI, 0.41-0.82; P=0.002; and men: adjusted HR, 0.83; 95% CI, 0.65-1.04; P=0.11; Pinteraction=0.01). CONCLUSIONS: In the current analysis, the associated risk of HPR for ST was similar in both sexes. However, HPR was associated with significantly reduced bleeding only among women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.
BACKGROUND: Sex differences in the outcomes after percutaneous coronary intervention with drug-eluting stents and in the response to clopidogrel therapy have been reported; however, the differential risk of high platelet reactivity (HPR) on clopidogrel in women versus men is unknown. METHODS AND RESULTS: We compared 8448 patients enrolled in the ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) according to sex and the presence/absence of HPR on clopidogrel (defined as P2Y12 reactivity units >208). Study end points were definite and probable stent thrombosis (ST), clinically relevant bleeding, all-cause mortality, myocardial infarction, and major adverse cardiac events (comprising mortality, myocardial infarction, and target lesion revascularization). HPR was more common among women (1118/2163, 51.7%) than men (2491/6285, 39.6%). HPR was associated with a roughly double risk of 1-year ST in both women and men (women with versus without HPR: 1.4% versus 0.7%; hazard ratio [HR], 2.02; 95% confidence interval [CI], 0.82-4.95; P=0.12; and men: 1.2% versus 0.5%; HR, 2.42; 95% CI, 1.36-4.30; P=0.002; Pinteraction=0.73). HPR was associated with almost half the rate of clinically relevant bleeding in women (women: HPR versus no HPR, 5.3% versus 9.8%; HR, 0.54; 95% CI, 0.40-0.74; P<0.001), whereas men had similar rates of bleeding regardless of HPR status (men: HPR versus no HPR, 5.7% versus 5.9%; HR, 0.96; 95% CI, 0.78-1.18; P=0.70; Pinteraction=0.003). In propensity-adjusted models, HPR was an independent predictor of ST and myocardial infarction in men; although both associations were nonsignificant among women, no interaction was observed in the associations between HPR and either ST or myocardial infarction. Conversely, HPR was an independent predictor of reduced bleeding only in women (women: adjusted HR, 0.58; 95% CI, 0.41-0.82; P=0.002; and men: adjusted HR, 0.83; 95% CI, 0.65-1.04; P=0.11; Pinteraction=0.01). CONCLUSIONS: In the current analysis, the associated risk of HPR for ST was similar in both sexes. However, HPR was associated with significantly reduced bleeding only among women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.
Authors: Mina Madan; J Dawn Abbott; Ryan Lennon; Derek Y F So; Andrea M MacDougall; Mary Ann McLaughlin; Vishakantha Murthy; Jacqueline Saw; Charanjit Rihal; Michael E Farkouh; Naveen L Pereira; Shaun G Goodman Journal: J Am Heart Assoc Date: 2022-06-14 Impact factor: 6.106