The Stabilization Of pLaques usIng Darapladib-Thrombolysis In Myocardial Infarction 52 Trial (SOLID-TIMI 52)

• The composite measure of major coronary events that include the first occurrence of coronary heart disease death, non-fatal myocardial infarction or urgent coronary revascularization for myocardial ischemia. [ Time Frame: Through the end of the study. ] [ Designated as safety issue: No ]
• The composite measure of total coronary events that include the first occurrence of coronary heart disease death, non-fatal MI, hospitalization for UA, or any coronary revasc procedure (excluding PCI planned prior to but performed after randomization). [ Time Frame: Through the end of the study. ] [ Designated as safety issue: No ]
• The individual components of MACE [cardiovascular death, myocardial infarction (fatal and non-fatal), stroke (fatal and non-fatal)]. [ Time Frame: Through the end of the study. ] [ Designated as safety issue: No ]
• The first occurrence of any component of the composite of all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke. [ Time Frame: Through the end of the study. ] [ Designated as safety issue: No ]
• All cause mortality. [ Time Frame: Through the end of the study. ] [ Designated as safety issue: No ]

• The composite measure of major coronary events that include the time to first occurrence of coronary heart disease death, non-fatal myocardial infarction or urgent coronary revascularization for myocardial ischemia. [ Time Frame: Through the end of the study. ] [ Designated as safety issue: No ]
• The composite measure of total coronary events that include the time to first occurrence of coronary heart disease death, non-fatal myocardial infarction, hospitalization for unstable angina, or any coronary revascularization procedure. [ Time Frame: Through the end of the study. ] [ Designated as safety issue: No ]
• The time to individual components of MACE [cardiovascular death, myocardial infarction (fatal and non-fatal), stroke (fatal and non-fatal)]. [ Time Frame: Through the end of the study. ] [ Designated as safety issue: No ]
• All cause mortality. [ Time Frame: Through the end of the study. ] [ Designated as safety issue: No ]
• The time to the first occurrence of any component of the composite of all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke. [ Time Frame: Through the end of the study. ] [ Designated as safety issue: No ]

This study will test whether darapladib can safely lower the chances of having a cardiovascular event (such as a heart attack or stroke) when treatment is started within 30 days after an acute coronary syndrome (also called ACS).

Subjects who qualify for the study will be randomized 1:1 to either darapladib or placebo administered in addition to standard therapy. Following the baseline visit, subjects will be expected to return for clinic visits at 1 month, 3 months, 6 months and every 6 months until the end of the study.

• Drug: Darapladib 160 mg
  Lp-PLA2 inhibitor administered in addition to standard therapy.
  Other Name: SB-480848
• Drug: Placebo
  Placebo administered in addition to standard therapy.

• Experimental: Darapladib 160 mg
  Single daily oral tablet
  Intervention: Drug: Darapladib 160 mg
• Placebo Comparator: Placebo
  Single daily oral tablet
  Intervention: Drug: Placebo

Inclusion Criteria:

• Signed written informed consent.
• Men or women at least 18 years old (in Taiwan, at least 20 years old). Women must be post-menopausal or using a highly effective method for avoidance of pregnancy.
• Hospitalization for acute coronary syndrome (ACS) within 30 days prior to study entry.
• Clinically stable for 24 hours prior to study entry.
• A planned percutaneous coronary intervention (PCI) should be performed prior to study entry, whenever possible.
• At least one of the following:
• At least 60 years old.
• Myocardial infarction prior to the qualifying ACS event.
• Diabetes mellitus requiring treatment with medication.
• Diagnosed mild or moderate reduction in kidney function.
• Cerebrovascular disease (carotid artery disease or ischemic stroke more than 3 months prior to study entry) OR peripheral artery disease.

Exclusion Criteria:

• ACS symptoms or lab results not believed to be caused by a narrowing or blocked coronary artery.
• No major coronary artery with a blockage of more than 50% (unless all stenoses are successfully treated by PCI).
• Planned coronary artery bypass graft (CABG) surgery, or CABG surgery performed after the qualifying ACS event and prior to study entry.
• Certain types of liver disease.
• Severe reduction in kidney function OR removal of a kidney OR kidney transplant.
• Severe heart failure.
• Blood pressure higher than normal despite lifestyle changes and treatment with medications.
• Any life-threatening disease with a life expectancy of less than 2 years (other than heart disease) that may prevent the subject from completing the study.
• Severe asthma that is poorly controlled with medication.
• Pregnancy (Note: A pregnancy test will be performed on all non-sterile women prior to study entry).
• Previous severe allergic reaction to food, medications, drink, insect stings, etc.
• Drug or alcohol abuse within the past 6 months. Mental/psychological impairment that may prevent the subject from complying with study procedures or understanding the goal and potential risks of participating in the study.
• Certain medications that may interfere with the study medication (these will be identified by the study doctor).
• If both birth parents are at least 50% Japanese, Chinese, or Korean ancestry, must have a blood sample collected for Lp-PLA2 activity. Those with Lp-PLA2 activity less than or equal to 20.0 nmol/min/mL are excluded.
• Previously took darapladib (SB-480848).
• Participation in a study of an investigational medication within the past 30 days.
• Current participation in a study of an investigational device.
• Any other reason the investigator deems the subject should not participate in the study.