Trial Outcomes & Findings for Trial to Assess the Effects of Vorapaxar (SCH 530348; MK-5348) in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA 2°P - TIMI 50) (P04737) (NCT NCT00526474)

Last Updated: 2018-09-21

Results Overview

The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, MI, stroke, or UCR. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, MI, stroke, or UCR within 3 years from randomization.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

26449 participants

Primary outcome timeframe

up to 3 years

Results posted on

2018-09-21

Participant Flow

Prior to planned study completion, the Data Safety Monitoring Board (DSMB) recommended discontinuation of study drug in all participants with a pre- or post-randomization history of stroke. A total of 4510 participants had study medication stopped, however these participants were included in the overall population for efficacy and safety analyses.

The Intent to Treat (ITT) Population, defined as all enrolled participants who were randomly assigned to a treatment group.

Participant milestones

Participant milestones
Measure	Placebo 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Overall Study STARTED	13224	13225
Overall Study Received Study Drug	13166	13186
Overall Study COMPLETED	12932	12953
Overall Study NOT COMPLETED	292	272

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial to Assess the Effects of Vorapaxar (SCH 530348; MK-5348) in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA 2°P - TIMI 50) (P04737)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Total n=26449 Participants Total of all reporting groups
Age, Customized <65 years	8273 Participants n=5 Participants	8188 Participants n=7 Participants	16461 Participants n=5 Participants
Age, Customized 65-<75 years	3445 Participants n=5 Participants	3523 Participants n=7 Participants	6968 Participants n=5 Participants
Age, Customized >=75 years	1506 Participants n=5 Participants	1514 Participants n=7 Participants	3020 Participants n=5 Participants
Sex: Female, Male Female	3172 Participants n=5 Participants	3154 Participants n=7 Participants	6326 Participants n=5 Participants
Sex: Female, Male Male	10052 Participants n=5 Participants	10071 Participants n=7 Participants	20123 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 3 years

Population: Intent to Treat (ITT) Population, defined as all participants who were randomly assigned to a treatment arm.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, or Urgent Coronary Revascularization (UCR) Within 3 Years From Randomization	12.4 Percentage of Participants	11.2 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, MI, or stroke. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, MI, or stroke within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, or Stroke Within 3 Years From Randomization	10.5 Percentage of Participants	9.3 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: As Treated Population, which included all participants who received at least 1 dose of study medication.

Adverse events were categorized as "bleeding events" if the intensity, frequency, or type of the event was other or more than would be normally expected in the given situation (eg, mild nosebleed in a person who does not normally have nosebleeds, greater bruising than expected for a given injury, greater volume of blood loss than expected for a given procedure). The investigator graded the intensity of bleeding events according to the GUSTO cooperative group criteria as follows: Mild , Moderate or Severe and the grading was adjudicated by the CEC. The Kaplan-Meier estimate reports the percentage of participants who experienced GUSTO moderate or severe bleeding within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13166 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13186 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Met Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) Moderate or Severe Bleeding Criteria Within 3 Years From Randomization	2.9 Percentage of Participants	4.2 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: As Treated Population, which included all participants who received at least 1 dose of study medication.

Adverse events were categorized as "bleeding events" if the intensity, frequency, or type of the event was other or more than would be normally expected in the given situation (eg, mild nosebleed in a person who does not normally have nosebleeds, greater bruising than expected for a given injury, greater volume of blood loss than expected for a given procedure). The investigator graded the intensity of bleeding events according to the Thrombolysis in Myocardial Infarction (TIMI) Study Group criteria as major, minor or other. "Clinically Significant Bleeding" was defined as the composite of TIMI Major bleeding, TIMI Minor bleeding, or bleeding that required unplanned medical or surgical treatment or unplanned laboratory evaluation even if it did not meet the criteria for TIMI major or minor bleeding. The Kaplan-Meier estimate reports the percentage of participants who experienced clinically significant bleeding within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13166 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13186 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Clinically Significant Bleeding Within 3 Years From Randomization	11.3 Percentage of Participants	15.4 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to the occurrence of any of the following clinical outcomes was recorded: death from any cause, MI, stroke, or UCR. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced death from any cause, MI, stroke, or UCR within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Death From Any Cause, MI, Stroke, or UCR Within 3 Years From Randomization	14.2 Perentage of Participants	13.2 Perentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to the occurrence of CV death or MI. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death or MI within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death or an MI Within 3 Years From Randomization	8.2 Percentage of Participants	7.3 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, MI, stroke, UCR or UH-VCIN. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, MI, stroke, UCR, or UH-VCIN within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, Stroke, UCR, or Urgent Hospitalization for Vascular Cause of Ischemic Nature (UH-VCIN) Within 3 Years From Randomization	14.7 Percentage of Participants	13.1 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to death from any cause or the first occurrence of any of the following clinical outcomes was recorded: MI, stroke, or any revascularization procedure . A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who died from any cause, or experienced an MI, stroke, or any revascularization within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Died From Any Cause, or Experienced an MI, Stroke, or Any Revascularization Within 3 Years From Randomization	22.6 Percentage of Participants	20.7 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, MI, stroke, any revascularization, or UH-VCIN. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, MI, stroke, any revascularization procedure, or UH-VCIN within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, Stroke, Any Revascularization, or UH-VCIN Within 3 Years From Randomization	22.1 Percentage of Participants	19.9 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to CV death (if reported) was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death Within 3 Years From Randomization	3.0 Percentage of Participants	2.7 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to the first occurrence of an MI was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced an MI within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced an MI Within 3 Years From Randomization	6.1 Percentage of Participants	5.2 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to the first occurrence of UCR was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced UCR within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced UCR Within 3 Years From Randomization	2.6 Percentage of Participants	2.5 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to first experience of a stroke was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced a stroke within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced a Stroke Within 3 Years From Randomization	2.8 Percentage of Participants	2.8 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to death from any cause was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who died from any cause within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Died From Any Cause Within 3 Years From Randomization	5.3 Percentage of Participants	5.0 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to the first occurrence of an UH-VCIN was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who had a UH-VCIN within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Had a UH-VCIN Within 3 Years From Randomization	5.5 Percentage of Participants	4.7 Percentage of Participants

SECONDARY outcome

Timeframe: up to 3 years

Population: ITT Population, defined as all participants who were randomly assigned to a treatment arm.

The time (in days) from study start to the first occurrence of a revascularization was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who had any revascularization performed within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=13224 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13225 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Had Any Revascularization Performed Within 3 Years From Randomization	15.5 Percentage of Participants	13.6 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with coronary arterial disease (CAD) or peripheral arterial disease (PAD) and no history of a stroke or transient ischemic attack (TIA)

The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, MI, stroke, or UCR. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, MI, stroke, or UCR within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, Stroke, or UCR Within 3 Years From Randomization	11.8 Percentage of Participants	10.1 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, or Stroke Within 3 Years From Randomization	9.5 Percentage of Participants	7.9 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Safety Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA who received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	Placebo n=10049 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10059 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Met GUSTO Moderate or Severe Bleeding Criteria Within 3 Years From Randomization	2.7 Percentage of Participants	3.8 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Safety Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA who received at least 1 dose of study drug

Adverse events were categorized as "bleeding events" if the intensity, frequency, or type of the event was other or more than would be normally expected in the given situation (eg, mild nosebleed in a person who does not normally have nosebleeds, greater bruising than expected for a given injury, greater volume of blood loss than expected for a given procedure). The investigator graded the intensity of bleeding events according to the TIMI Study Group criteria as major, minor or other. "Clinically Significant Bleeding" was defined as the composite of TIMI Major bleeding, TIMI Minor bleeding, or bleeding that required unplanned medical or surgical treatment or unplanned laboratory evaluation even if it did not meet the criteria for TIMI major or minor bleeding. The Kaplan-Meier estimate reports the percentage of participants who experienced clinically significant bleeding within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=10049 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10059 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Clinically Significant Bleeding Within 3 Years From Randomization	11.1 Percentage of Participants	15.2 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Death From Any Cause, MI, Stroke, or UCR Within 3 Years From Randomization	13.5 Percentage of Participants	11.9 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

The time (in days) from study start to the occurrence of CV death or first occurrence of an MI. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death or MI within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death or an MI Within 3 Years From Randomization	8.3 Percentage of Partcipants	7.2 Percentage of Partcipants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, MI, stroke, UCR, or UH-VCIN . A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, MI, stroke, UCR, or UH-VCIN within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, Stroke, UCR, or UH-VCIN Within 3 Years From Randomization	13.9 Percentage of Participants	11.9 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Died From Any Cause, or Experienced an MI, Stroke, or Any Revascularization Within 3 Years From Randomization	22.5 Percentage of Participants	20.1 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, Stroke, Any Revascularization, or UH-VCIN Within 3 Years From Randomization	21.8 Percentage of Participants	19.3 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

The time (in days) from study start to the CV death (if reported) was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death Within 3 Years From Randomization	2.8 Percentage of Participants	2.4 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced an MI Within 3 Years From Randomization	6.4 Percentage of Participants	5.4 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced UCR Within 3 Years From Randomization	3.0 Percentage of Participants	2.8 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Experienced a Stroke Within 3 Years From Randomization	1.6 Percentage of Participants	1.2 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Died From Any Cause Within 3 Years From Randomization	4.8 Percentage of Participants	4.5 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

The time (in days) from study start to the first occurrence of a UH-VCIN was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who had a UH-VCIN within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Had a UH-VCIN Within 3 Years From Randomization	5.6 Percentage of Participants	4.9 Percentage of Participants

POST_HOC outcome

Timeframe: up to 3 years

Population: Intended Label Population: all enrolled participants with CAD or PAD and no history of a stroke or TIA

The time (in days) from study start to the first occurrence of any revascularization was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who had any revascularization performed within 3 years from randomization.

Outcome measures

Outcome measures
Measure	Placebo n=10090 Participants 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=10080 Participants one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
Kaplan-Meier Estimate of the Percentage of Participants Who Had Any Revascularization Performed Within 3 Years From Randomization	16.6 Percentage of Participants	14.7 Percentage of Participants

Adverse Events

Placebo

Serious events: 3419 serious events

Other events: 2280 other events

Deaths: 0 deaths

Vorapaxar

Serious events: 3514 serious events

Other events: 2541 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=13166 participants at risk 1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.	Vorapaxar n=13186 participants at risk one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.
General disorders CHEST PAIN	5.2% 687/13166 • Number of events 785 • up to 3 years Adverse events are reported using the As Treated Population, which included all participants who received at least 1 dose of study medication and are reported according to treatment received	5.1% 672/13186 • Number of events 789 • up to 3 years Adverse events are reported using the As Treated Population, which included all participants who received at least 1 dose of study medication and are reported according to treatment received
Nervous system disorders DIZZINESS	5.3% 704/13166 • Number of events 781 • up to 3 years Adverse events are reported using the As Treated Population, which included all participants who received at least 1 dose of study medication and are reported according to treatment received	5.0% 662/13186 • Number of events 746 • up to 3 years Adverse events are reported using the As Treated Population, which included all participants who received at least 1 dose of study medication and are reported according to treatment received
Respiratory, thoracic and mediastinal disorders EPISTAXIS	3.0% 401/13166 • Number of events 513 • up to 3 years Adverse events are reported using the As Treated Population, which included all participants who received at least 1 dose of study medication and are reported according to treatment received	6.1% 807/13186 • Number of events 1044 • up to 3 years Adverse events are reported using the As Treated Population, which included all participants who received at least 1 dose of study medication and are reported according to treatment received
Vascular disorders HYPERTENSION	5.6% 736/13166 • Number of events 789 • up to 3 years Adverse events are reported using the As Treated Population, which included all participants who received at least 1 dose of study medication and are reported according to treatment received	5.4% 712/13186 • Number of events 761 • up to 3 years Adverse events are reported using the As Treated Population, which included all participants who received at least 1 dose of study medication and are reported according to treatment received

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigators agreed not to publish or publicly present any interim results of the study without the prior written consent of the sponsor. The investigator further agreed to provide to the sponsor review copies of abstracts or manuscripts for publication 45 days prior to submission.
Publication restrictions are in place

Restriction type: OTHER