The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial

Summary

This study will test whether darapladib can safely lower the chances of having a cardiovascular event (such as a heart attack or stroke) in people with coronary heart disease.

Timeline

Start

2008-12-01

Primary completion

2013-10-01

Completion

2013-10-17

Outcome

Results reported · no primary-endpoint met/missed verdict (typical of a dose-finding / safety study)

registry Placebo vs Darapladib; p = 0.199; Hazard Ratio (HR) 0.94 (95.1% CI 0.85 to 1.03) NCT00799903 ↗

paper darapladib did not significantly reduce the risk of the primary composite end point PMID 24678955 ↗

Publications

• Jiang W, Huang G, Du J, Yang H, Zhou S, Dai D, Tang K, Fang L, Wang X, Deng X. White blood cell counts can predict 4-year cardiovascular disease risk in patients with stable coronary heart disease: a prospective cohort study. Front Cardiovasc Med. 2024 Sep 26;11:1358378. doi: 10.3389/fcvm.2024.1358378. eCollection 2024.
• Sjolin K, Aulin J, Wallentin L, Eriksson N, Held C, Kultima K, Oldgren J, Burman J. Serum Neurofilament Light Chain in Patients With Atrial Fibrillation. J Am Heart Assoc. 2022 Jul 19;11(14):e025910. doi: 10.1161/JAHA.122.025910. Epub 2022 Jul 15.
• Held C, Hadziosmanovic N, Aylward PE, Hagstrom E, Hochman JS, Stewart RAH, White HD, Wallentin L. Body Mass Index and Association With Cardiovascular Outcomes in Patients With Stable Coronary Heart Disease - A STABILITY Substudy. J Am Heart Assoc. 2022 Feb;11(3):e023667. doi: 10.1161/JAHA.121.023667. Epub 2022 Jan 21.
• Siddiqui MK, Smith G, St Jean P, Dawed AY, Bell S, Soto-Pedre E, Kennedy G, Carr F, Wallentin L, White H, Macphee CH, Waterworth D, Palmer CNA. Diabetes status modifies the long-term effect of lipoprotein-associated phospholipase A2 on major coronary events. Diabetologia. 2022 Jan;65(1):101-112. doi: 10.1007/s00125-021-05574-5. Epub 2021 Sep 25.
• Wallentin L, Eriksson N, Olszowka M, Grammer TB, Hagstrom E, Held C, Kleber ME, Koenig W, Marz W, Stewart RAH, White HD, Aberg M, Siegbahn A. Plasma proteins associated with cardiovascular death in patients with chronic coronary heart disease: A retrospective study. PLoS Med. 2021 Jan 13;18(1):e1003513. doi: 10.1371/journal.pmed.1003513. eCollection 2021 Jan.
• White HD, Stewart RAH, Dalby AJ, Stebbins A, Cannon CP, Budaj A, Linhart A, Pais P, Diaz R, Steg PG, Krug-Gourley S, Granger CB, Hochman JS, Koenig W, Harrington RA, Held C, Wallentin L; STABILITY Investigators. In patients with stable coronary heart disease, low-density lipoprotein-cholesterol levels < 70 mg/dL and glycosylated hemoglobin A1c < 7% are associated with lower major cardiovascular events. Am Heart J. 2020 Jul;225:97-107. doi: 10.1016/j.ahj.2020.04.004. Epub 2020 Apr 18.
• Hilvo M, Wallentin L, Ghukasyan Lakic T, Held C, Kauhanen D, Jylha A, Lindback J, Siegbahn A, Granger CB, Koenig W, Stewart RAH, White H, Laaksonen R; STABILITY Investigators. Prediction of Residual Risk by Ceramide-Phospholipid Score in Patients With Stable Coronary Heart Disease on Optimal Medical Therapy. J Am Heart Assoc. 2020 May 18;9(10):e015258. doi: 10.1161/JAHA.119.015258. Epub 2020 May 7.
• Stewart RAH, Held C, Krug-Gourley S, Waterworth D, Stebbins A, Chiswell K, Hagstrom E, Armstrong PW, Wallentin L, White H. Cardiovascular and Lifestyle Risk Factors and Cognitive Function in Patients With Stable Coronary Heart Disease. J Am Heart Assoc. 2019 Apr 2;8(7):e010641. doi: 10.1161/JAHA.118.010641.
• Held C, White HD, Stewart RAH, Budaj A, Cannon CP, Hochman JS, Koenig W, Siegbahn A, Steg PG, Soffer J, Weaver WD, Ostlund O, Wallentin L; STABILITY Investigators. Inflammatory Biomarkers Interleukin-6 and C-Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial. J Am Heart Assoc. 2017 Oct 24;6(10):e005077. doi: 10.1161/JAHA.116.005077.
• Hagstrom E, Norlund F, Stebbins A, Armstrong PW, Chiswell K, Granger CB, Lopez-Sendon J, Pella D, Soffer J, Sy R, Wallentin L, White HD, Stewart RAH, Held C. Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease. J Intern Med. 2018 Jan;283(1):83-92. doi: 10.1111/joim.12692. Epub 2017 Oct 23.
• Guimaraes PO, Granger CB, Stebbins A, Chiswell K, Held C, Hochman JS, Krug-Gourley S, Lonn E, Lopes RD, Stewart RAH, Vinereanu D, Wallentin L, White HD, Hagstrom E, Danchin N. Sex Differences in Clinical Characteristics, Psychosocial Factors, and Outcomes Among Patients With Stable Coronary Heart Disease: Insights from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial. J Am Heart Assoc. 2017 Sep 14;6(9):e006695. doi: 10.1161/JAHA.117.006695.
• Stewart RAH, Hagstrom E, Held C, Wang TKM, Armstrong PW, Aylward PE, Cannon CP, Koenig W, Lopez-Sendon JL, Mohler ER 3rd, Hadziosmanovic N, Krug-Gourley S, Ramos Corrales MA, Siddique S, Steg PG, White HD, Wallentin L; STABILITY Investigators. Self-Reported Health and Outcomes in Patients With Stable Coronary Heart Disease. J Am Heart Assoc. 2017 Aug 22;6(8):e006096. doi: 10.1161/JAHA.117.006096.
• Lindholm D, Lindback J, Armstrong PW, Budaj A, Cannon CP, Granger CB, Hagstrom E, Held C, Koenig W, Ostlund O, Stewart RAH, Soffer J, White HD, de Winter RJ, Steg PG, Siegbahn A, Kleber ME, Dressel A, Grammer TB, Marz W, Wallentin L. Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease. J Am Coll Cardiol. 2017 Aug 15;70(7):813-826. doi: 10.1016/j.jacc.2017.06.030.
• Vedin O, Hagstrom E, Ostlund O, Avezum A, Budaj A, Flather MD, Harrington RA, Koenig W, Soffer J, Siegbahn A, Steg PG, Stewart RAH, Wallentin L, White HD, Held C; STABILITY Investigators. Associations between tooth loss and prognostic biomarkers and the risk for cardiovascular events in patients with stable coronary heart disease. Int J Cardiol. 2017 Oct 15;245:271-276. doi: 10.1016/j.ijcard.2017.07.036. Epub 2017 Jul 17.
• Hagstrom E, Held C, Stewart RA, Aylward PE, Budaj A, Cannon CP, Koenig W, Krug-Gourley S, Mohler ER 3rd, Steg PG, Tarka E, Ostlund O, White HD, Siegbahn A, Wallentin L; STABILITY Investigators. Growth Differentiation Factor 15 Predicts All-Cause Morbidity and Mortality in Stable Coronary Heart Disease. Clin Chem. 2017 Jan;63(1):325-333. doi: 10.1373/clinchem.2016.260570. Epub 2016 Nov 3.
• Wallentin L, Held C, Armstrong PW, Cannon CP, Davies RY, Granger CB, Hagstrom E, Harrington RA, Hochman JS, Koenig W, Krug-Gourley S, Mohler ER 3rd, Siegbahn A, Tarka E, Steg PG, Stewart RA, Weiss R, Ostlund O, White HD; STABILITY Investigators. Lipoprotein-Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease. J Am Heart Assoc. 2016 Jun 21;5(6):e003407. doi: 10.1161/JAHA.116.003407.
• Hijazi Z, Lindback J, Alexander JH, Hanna M, Held C, Hylek EM, Lopes RD, Oldgren J, Siegbahn A, Stewart RA, White HD, Granger CB, Wallentin L; ARISTOTLE and STABILITY Investigators. The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation. Eur Heart J. 2016 May 21;37(20):1582-90. doi: 10.1093/eurheartj/ehw054. Epub 2016 Feb 25.
• Vedin O, Hagstrom E, Budaj A, Denchev S, Harrington RA, Koenig W, Soffer J, Sritara P, Stebbins A, Stewart RH, Swart HP, Viigimaa M, Vinereanu D, Wallentin L, White HD, Held C; STABILITY Investigators. Tooth loss is independently associated with poor outcomes in stable coronary heart disease. Eur J Prev Cardiol. 2016 May;23(8):839-46. doi: 10.1177/2047487315621978. Epub 2015 Dec 16.
• Vedin O, Hagstrom E, Gallup D, Neely ML, Stewart R, Koenig W, Budaj A, Sritara P, Wallentin L, White HD, Held C. Periodontal disease in patients with chronic coronary heart disease: Prevalence and association with cardiovascular risk factors. Eur J Prev Cardiol. 2015 Jun;22(6):771-8. doi: 10.1177/2047487314530660. Epub 2014 Apr 10.
• STABILITY Investigators; White HD, Held C, Stewart R, Tarka E, Brown R, Davies RY, Budaj A, Harrington RA, Steg PG, Ardissino D, Armstrong PW, Avezum A, Aylward PE, Bryce A, Chen H, Chen MF, Corbalan R, Dalby AJ, Danchin N, De Winter RJ, Denchev S, Diaz R, Elisaf M, Flather MD, Goudev AR, Granger CB, Grinfeld L, Hochman JS, Husted S, Kim HS, Koenig W, Linhart A, Lonn E, Lopez-Sendon J, Manolis AJ, Mohler ER 3rd, Nicolau JC, Pais P, Parkhomenko A, Pedersen TR, Pella D, Ramos-Corrales MA, Ruda M, Sereg M, Siddique S, Sinnaeve P, Smith P, Sritara P, Swart HP, Sy RG, Teramoto T, Tse HF, Watson D, Weaver WD, Weiss R, Viigimaa M, Vinereanu D, Zhu J, Cannon CP, Wallentin L. Darapladib for preventing ischemic events in stable coronary heart disease. N Engl J Med. 2014 May 1;370(18):1702-11. doi: 10.1056/NEJMoa1315878. Epub 2014 Mar 30.
• Vedin O, Hagstrom E, Stewart R, Brown R, Krug-Gourley S, Davies R, Wallentin L, White H, Held C. Secondary prevention and risk factor target achievement in a global, high-risk population with established coronary heart disease: baseline results from the STABILITY study. Eur J Prev Cardiol. 2013 Aug;20(4):678-85. doi: 10.1177/2047487312444995. Epub 2012 Apr 10.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Darapladib	Small molecule	160 mg	Oral

Indications