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

O'Donoghue, Michelle L., Braunwald, Eugene, White, Harvey D., Steen, Dylan P., Lukas, Mary Ann, Tarka, Elizabeth, Steg, P. Gabriel, Hochman, Judith S., Bode, Christoph, Maggioni, Aldo P., Im, KyungAh, Shannon, Jennifer B., Davies, Richard Y., Murphy, Sabina A., Crugnale, Sharon E., Wiviott, Stephen D., Bonaca, Marc P., Watson, David F., Weaver, W. Douglas, Serruys, Patrick W. and Cannon, Christopher P. (2014) Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial. Journal of the American Medical Association, 312 10: 1006-1015. doi:10.1001/jama.2014.11061


Author O'Donoghue, Michelle L.
Braunwald, Eugene
White, Harvey D.
Steen, Dylan P.
Lukas, Mary Ann
Tarka, Elizabeth
Steg, P. Gabriel
Hochman, Judith S.
Bode, Christoph
Maggioni, Aldo P.
Im, KyungAh
Shannon, Jennifer B.
Davies, Richard Y.
Murphy, Sabina A.
Crugnale, Sharon E.
Wiviott, Stephen D.
Bonaca, Marc P.
Watson, David F.
Weaver, W. Douglas
Serruys, Patrick W.
Cannon, Christopher P.
Title Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial
Journal name Journal of the American Medical Association   Check publisher's open access policy
ISSN 1538-3598
0098-7484
Publication date 2014-09-10
Year available 2014
Sub-type Article (original research)
DOI 10.1001/jama.2014.11061
Open Access Status Not yet assessed
Volume 312
Issue 10
Start page 1006
End page 1015
Total pages 10
Place of publication Chicago, IL, United States
Publisher American Medical Association
Language eng
Formatted 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
Keyword Medicine, General & Internal
General & Internal Medicine
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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