TY - JOUR
T1 - Effect of darapladib on major coronary events after an acute coronary syndrome
T2 - The SOLID-TIMI 52 randomized clinical trial
AU - SOLID-TIMI 52 Investigators
AU - O'Donoghue, Michelle L.
AU - Braunwald, Eugene
AU - White, Harvey D.
AU - Steen, Dylan P.
AU - Lukas, Mary Ann
AU - Tarka, Elizabeth
AU - Steg, P. Gabriel
AU - Hochman, Judith S.
AU - Bode, Christoph
AU - Maggioni, Aldo P.
AU - Im, Kyung Ah
AU - Shannon, Jennifer B.
AU - Davies, Richard Y.
AU - Murphy, Sabina A.
AU - Crugnale, Sharon E.
AU - Wiviott, Stephen D.
AU - Bonaca, Marc P.
AU - Watson, David F.
AU - Weaver, W. Douglas
AU - Serruys, Patrick W.
AU - Cannon, Christopher P.
AU - Steen, D. P.
AU - Lamp, J. M.
AU - McCourt, A.
AU - Barakat, D.
AU - Mezzetti, J.
AU - Morrison, C.
AU - Stevens, M.
AU - Ward, C.
AU - Ardissino, D.
AU - Aylward, P. E.
AU - Babilonia, N.
AU - Britto, F.
AU - Budaj, A.
AU - Chen, S. A.
AU - Corbalán, R.
AU - Dalby, A. J.
AU - Dellborg, M.
AU - deWinter, R. J.
AU - Dorobantu, M.
AU - Duris, T.
AU - Gao, R.
AU - Goudev, A. R.
AU - Grande, P.
AU - Gratsiansky, N.
AU - Guneri, S.
AU - Hamm, C.
AU - Husted, S.
AU - Hasin, Y.
AU - Rozenman, Y.
PY - 2014/9/10
Y1 - 2014/9/10
N2 - IMPORTANCE: Lipoprotein-associated phospholipase A2(Lp-PLA2) has been hypothesized to be involved in atherogenesis through pathways related to inflammation. Darapladib is an oral, selective inhibitor of the Lp-PLA2enzyme. OBJECTIVE: To evaluate the efficacy and safety of darapladib in patients after an acute coronary syndrome (ACS) event. DESIGN, SETTING, AND PARTICIPANTS: SOLID-TIMI 52was a multinational, double-blind, placebo-controlled trial that randomized 13 026 participants within 30 days of hospitalization with an ACS (non-ST-elevation or ST-elevationmyocardial infarction [MI]) at 868 sites in 36 countries. INTERVENTIONS: Patients were randomized to either once-daily darapladib (160mg) or placebo on a background of guideline-recommended therapy. Patients were followed up for a median of 2.5 years between December 7, 2009, and December 6, 2013. MAIN OUTCOMES AND MEASURES: The primary end point (major coronary events)was the composite of coronary heart disease (CHD) death, MI, or urgent coronary revascularization formyocardial ischemia. Kaplan-Meier event rates are reported at 3 years. RESULTS: During a median duration of 2.5 years, the primary end point occurred in 903 patients in the darapladib group and 910 in the placebo group (16.3%vs 15.6%at 3 years; hazard ratio [HR], 1.00 [95%CI, 0.91-1.09]; P = .93). The composite of cardiovascular death, MI, or stroke occurred in 824 in the darapladib group and 838 in the placebo group (15.0%vs 15.0%at 3 years; HR, 0.99 [95%CI, 0.90-1.09]; P = .78). There were no differences between the treatment groups for additional secondary end points, for individual components of the primary end point, or in all-cause mortality (371 events in the darapladib group and 395 in the placebo group [7.3%vs 7.1%at 3 years; HR, 0.94 [95%CI, 0.82-1.08]; P = .40). Patients were more likely to report an odor-related concern in the darapladib group vs the placebo group (11.5%vs 2.5%) and also more likely to report diarrhea (10.6%vs 5.6%). CONCLUSIONS AND RELEVANCE: In patients who experienced an ACS event, direct inhibition of Lp-PLA2with darapladib added to optimal medical therapy and initiated within 30 days of hospitalization did not reduce the risk of major coronary events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01000727
AB - IMPORTANCE: Lipoprotein-associated phospholipase A2(Lp-PLA2) has been hypothesized to be involved in atherogenesis through pathways related to inflammation. Darapladib is an oral, selective inhibitor of the Lp-PLA2enzyme. OBJECTIVE: To evaluate the efficacy and safety of darapladib in patients after an acute coronary syndrome (ACS) event. DESIGN, SETTING, AND PARTICIPANTS: SOLID-TIMI 52was a multinational, double-blind, placebo-controlled trial that randomized 13 026 participants within 30 days of hospitalization with an ACS (non-ST-elevation or ST-elevationmyocardial infarction [MI]) at 868 sites in 36 countries. INTERVENTIONS: Patients were randomized to either once-daily darapladib (160mg) or placebo on a background of guideline-recommended therapy. Patients were followed up for a median of 2.5 years between December 7, 2009, and December 6, 2013. MAIN OUTCOMES AND MEASURES: The primary end point (major coronary events)was the composite of coronary heart disease (CHD) death, MI, or urgent coronary revascularization formyocardial ischemia. Kaplan-Meier event rates are reported at 3 years. RESULTS: During a median duration of 2.5 years, the primary end point occurred in 903 patients in the darapladib group and 910 in the placebo group (16.3%vs 15.6%at 3 years; hazard ratio [HR], 1.00 [95%CI, 0.91-1.09]; P = .93). The composite of cardiovascular death, MI, or stroke occurred in 824 in the darapladib group and 838 in the placebo group (15.0%vs 15.0%at 3 years; HR, 0.99 [95%CI, 0.90-1.09]; P = .78). There were no differences between the treatment groups for additional secondary end points, for individual components of the primary end point, or in all-cause mortality (371 events in the darapladib group and 395 in the placebo group [7.3%vs 7.1%at 3 years; HR, 0.94 [95%CI, 0.82-1.08]; P = .40). Patients were more likely to report an odor-related concern in the darapladib group vs the placebo group (11.5%vs 2.5%) and also more likely to report diarrhea (10.6%vs 5.6%). CONCLUSIONS AND RELEVANCE: In patients who experienced an ACS event, direct inhibition of Lp-PLA2with darapladib added to optimal medical therapy and initiated within 30 days of hospitalization did not reduce the risk of major coronary events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01000727
UR - http://www.scopus.com/inward/record.url?scp=84907007906&partnerID=8YFLogxK
U2 - 10.1001/jama.2014.11061
DO - 10.1001/jama.2014.11061
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C2 - 25173516
AN - SCOPUS:84907007906
SN - 0098-7484
VL - 312
SP - 1006
EP - 1015
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 10
ER -