Effect of darapladib on major coronary events after an acute coronary syndrome: The SOLID-TIMI 52 randomized clinical trial

SOLID-TIMI 52 Investigators

Research output: Contribution to journalArticle

213 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)1006-1015
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume312
Issue number10
DOIs
StatePublished - Sep 10 2014

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Acute Coronary Syndrome
Randomized Controlled Trials
Placebos
Hospitalization
1-Alkyl-2-acetylglycerophosphocholine Esterase
darapladib
Infarction
Coronary Disease
Diarrhea
Atherosclerosis
Therapeutics
Ischemia
Stroke
Outcome Assessment (Health Care)
Guidelines
Inflammation
Safety
Mortality

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Effect of darapladib on major coronary events after an acute coronary syndrome : The SOLID-TIMI 52 randomized clinical trial. / SOLID-TIMI 52 Investigators.

In: JAMA - Journal of the American Medical Association, Vol. 312, No. 10, 10.09.2014, p. 1006-1015.

Research output: Contribution to journalArticle

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title = "Effect of darapladib on major coronary events after an acute coronary syndrome: The SOLID-TIMI 52 randomized clinical trial",
abstract = "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",
author = "{SOLID-TIMI 52 Investigators} and O'Donoghue, {Michelle L.} and Eugene Braunwald and White, {Harvey D.} and Steen, {Dylan P.} and Lukas, {Mary Ann} and Elizabeth Tarka and Steg, {P. Gabriel} and Hochman, {Judith S.} and Christoph Bode and Maggioni, {Aldo P.} and Im, {Kyung Ah} and Shannon, {Jennifer B.} and Davies, {Richard Y.} and Murphy, {Sabina A.} and Crugnale, {Sharon E.} and Wiviott, {Stephen D.} and Bonaca, {Marc P.} and Watson, {David F.} and Weaver, {W. Douglas} and Serruys, {Patrick W.} and Cannon, {Christopher P.} and Steen, {D. P.} and Lamp, {J. M.} and A. McCourt and D. Barakat and J. Mezzetti and C. Morrison and M. Stevens and C. Ward and D. Ardissino and Aylward, {P. E.} and N. Babilonia and F. Britto and A. Budaj and Chen, {S. A.} and R. Corbal{\'a}n and Dalby, {A. J.} and M. Dellborg and deWinter, {R. J.} and M. Dorobantu and T. Duris and R. Gao and Goudev, {A. R.} and P. Grande and N. Gratsiansky and S. Guneri and C. Hamm and S. Husted and D. Isaza and {Del Core}, M.",
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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 - Isaza, D.

AU - Del Core, M.

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

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U2 - 10.1001/jama.2014.11061

DO - 10.1001/jama.2014.11061

M3 - Article

C2 - 25173516

AN - SCOPUS:84907007906

VL - 312

SP - 1006

EP - 1015

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 10

ER -