Peripheral Artery Disease
Conditions
Keywords
Peripheral artery disease Atherothrombotic events Atherosclerosis
Brief summary
The purpose of this study is to compare the effects of ticagrelor and clopidogrel in patients with Peripheral Artery Disease.
Detailed description
A randomized, double-blind, parallel group, multicentre phase IIIb study to compare ticagrelor with clopidogrel treatment on the risk of cardiovascular death, myocardial infarction and ischemic stroke in patients with established Peripheral Artery Disease (EUCLID Examining Use of tiCagreLor In paD)
Interventions
DRUGTicagrelor
Ticagrelor 90 mg bd (and Clopidogrel placebo od) taken orally as tablets
DRUGClopidogrel
Clopidogrel 75 mg od (and Ticagrelor placebo bd) taken orally as tablets
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Male and Female patients 50 years old or older Symptomatic peripheral artery disease
Exclusion criteria
* Patients needing dual anti-platlet drug treatment before start of study Planned revascularisation or amputation * Patients with known bleeding disorders * Patients with a history of intracranial bleed * Patients considered to be at risk of bradycardic events unless already treated with a permanent pacemaker
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of Cardiovascular (CV) Death/MI/Ischemic Stroke | From randomization to PACD, an average of 2.5 years | Participants with CV death, myocardial infarction (MI) or ischemic stroke. If no event, censoring occurs at the minimum of (primary analysis censoring date (PACD), last endpoint assessment date, non-CV death date) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CV Death | From randomization to PACD, an average of 2.5 years | Participants with CV death. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date) |
| MI | From randomization to PACD, an average of 2.5 years | Participants with MI. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date) |
| All-cause Mortality | From randomization to PACD, an average of 2.5 years | Participants with all-cause death. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date) |
| Composite of CV Death, MI, Ischemic Stroke, and ALI | From randomization to PACD, an average of 2.5 years | Participants with CV death, MI, ischemic stroke or acute limb ischemia (ALI). If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date) |
| ALI | From randomization to PACD, an average of 2.5 years | Participants with ALI. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date) |
| Lower Extremity Revascularization | From randomization to PACD, an average of 2.5 years | Participants with lower extremity revascularization (LER). If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date) |
| Any Revascularisation (Coronary, Peripheral [Limb, Mesenteric, Renal, Carotid and Other]) | From randomization to PACD, an average of 2.5 years | Participants with any revascularization. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date) |
| Composite of CV Death, MI, and All-cause Stroke (Ischemic or Hemorrhagic) | From randomization to PACD, an average of 2.5 years | Participants with CV death, MI or all-cause stroke. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Major Amputation Caused by PAD | From randomization to PACD, an average of 2.5 years | Participants with major amputation caused by PAD. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date) |
| CV-related Hospitalization | From randomization to PACD, an average of 2.5 years | Participants with hospitalization associated with CV death, hospitalization due to MI, ischemic stroke, lower extremity revascularization, major amputation due to PAD, transient ischemic attack (TIA), coronary revascularization or unstable angina. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date) |
| TIMI Major Bleeding Events | From the date of first dose and up to and including 7 days following the date of last dose of study drug | Participants with TIMI major bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug) |
| Net Clinical Benefit (Composite of CV Death/MI/Ischemic Stroke/Fatal Bleeding/Intracranial Bleeding) | From randomization to PACD, an average of 2.5 years | Participants with CV death, MI, ischemic stroke, fatal bleeding or intracranial bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date) |
| PLATO Major Bleeding Events | From the date of first dose and up to and including 7 days following the date of last dose of study drug | Participants with PLATO major bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug) |
| Premature Permanent Discontinuation of Study Drug Due to Any Bleeding Event | From the date of first dose and up to and including 7 days following the date of last dose of study drug | Participants with a permanent discontinuation of study drug due to any bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug) |
| TIMI Major or Minor Bleeding Events | From the date of first dose and up to and including 7 days following the date of last dose of study drug | Participants with TIMI major or minor bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug) |
| Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/Fatal Bleeding/Intracranial Bleeding) | From randomization to PACD, an average of 2.5 years | Participants with all-cause death, MI, ischemic stroke, fatal bleeding or intracranial bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date) |
| Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/ALI/Major Amputation/Fatal Bleeding/Intracranial Bleeding) | From randomization to PACD, an average of 2.5 years | Participants with all-cause death, MI, ischemic stroke, ALI, major amputation, fatal bleeding or intracranial bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date) |
| Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/ALI/Major Amputation/TIMI Major Bleeding) | From randomization to PACD, an average of 2.5 years | Participants with all-cause death, MI, ischemic stroke, ALI, major amputation or Thrombolysis in Myocardial Infarction (TIMI) major bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date) |
| Non-CV Death | From randomization to PACD, an average of 2.5 years | Participants with non-CV death. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, CV death) |
| Changes in Fontaine Stage | From randomization to PACD, an average of 2.5 years | Progression of the clinical/symptomatic status of the limb by changes in Fontaine stage. Stage I - Asymptomatic Stage IIa - Intermittent claudication after more than 200 meters of pain free walking Stage IIb - Intermittent claudication after less than 200 meters of walking Stage III - Rest pain Stage IV - Ischemic ulcers or gangrene |
| Changes in Rutherford Classification | From randomization to PACD, an average of 2.5 years | Progression of the clinical/symptomatic status of the limb by changes in Rutherford classification. Category 0 - Asymptomatic Category 1 - Mild claudication Category 2 - Moderate claudication - The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters. Category 3 - Severe claudication Category 4 - Rest pain Category 5 - Ischemic ulceration not exceeding ulcer of the digits of the foot Category 6 - Severe ischemic ulcers or frank gangrene |
| Change in ABI/TBI From Baseline | From randomization to PACD, an average of 2.5 years | Change in ankle brachial index (ABI) / toe brachial index (TBI). Ankle brachial index (ABI) is the ratio of blood pressures from the ankle and arm and is used for diagnosing peripheral arterial occlusive disease (PAOD): Normal: 1 to 1.29 Borderline: 0.91 to 0.99 Mild PAOD: 0.71 to 0.90 Medium severe PAOD: 0.41 to 0.7 Severe PAOD: \<0.4 Toe brachial index (TBI) is the ratio between the toe pressure and the higher brachial pressure, used for diagnosing PAOD when the ABI cannot be used: Normal: \>0.7 Mild: 0.5-0.7 Moderate: 0.35-0.5 Moderate-Severe: \<0.35 and toe pressure 40 mmHg Severe: \<0.35 and toe pressure \< 30 mmHg |
| Any Amputation Caused by PAD | From randomization to PACD, an average of 2.5 years | Participants with any amputation caused by peripheral arterial disease (PAD). If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date) |
Countries
Argentina, Brazil, Bulgaria, Canada, Chile, China, Czechia, France, Germany, Hungary, Italy, Japan, Mexico, Netherlands, Philippines, Poland, Romania, Russia, Slovakia, South Korea, Spain, Sweden, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States, Vietnam
Participant flow
Recruitment details
This study was conducted at 821 centres randomising patients across 28 countries. The first patient was enrolled on 04 December 2012. The last visit of the last patient took place on 26 September 2016. In total, 16237 patients were screened.
Pre-assignment details
Screened patients randomised to study drug: 85.5%; n=13885 Patients who were not randomised: 14.5%; n=2352 Patients with inclusion criteria for symptomatic lower extremity PAD failed: n=489 Patients with poor metabolizer status for CYP2C19: n=616 Patients with other reason: n=1374
Participants by arm
| Arm | Count |
|---|---|
| Ticagrelor 90mg bd | 6,930 |
| Clopidogrel 75mg od | 6,955 |
| Total | 13,885 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 123 | 113 |
Baseline characteristics
| Characteristic | Ticagrelor 90mg bd | Clopidogrel 75mg od | Total |
|---|---|---|---|
| Age, Continuous Age | 66.6 Years STANDARD_DEVIATION 8.4 | 66.5 Years STANDARD_DEVIATION 8.5 | 66.6 Years STANDARD_DEVIATION 8.4 |
| Age, Customized <65 years | 2900 Participants | 2985 Participants | 5885 Participants |
| Age, Customized >75 years | 1105 Participants | 1120 Participants | 2225 Participants |
| Age, Customized Between 65 and 75 years | 2925 Participants | 2850 Participants | 5775 Participants |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 63 Participants | 62 Participants | 125 Participants |
| Race/Ethnicity, Customized Asian | 824 Participants | 810 Participants | 1634 Participants |
| Race/Ethnicity, Customized Black Or African American | 280 Participants | 289 Participants | 569 Participants |
| Race/Ethnicity, Customized Hispanic Or Latino | 1046 Participants | 1067 Participants | 2113 Participants |
| Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Not Hispanic Or Latino | 5884 Participants | 5888 Participants | 11772 Participants |
| Race/Ethnicity, Customized Other | 110 Participants | 132 Participants | 242 Participants |
| Race/Ethnicity, Customized White | 5651 Participants | 5659 Participants | 11310 Participants |
| Sex: Female, Male Female | 1908 Participants | 1980 Participants | 3888 Participants |
| Sex: Female, Male Male | 5022 Participants | 4975 Participants | 9997 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 989 / 6,932 | 1,682 / 6,910 |
| serious Total, serious adverse events | 1,788 / 6,932 | 1,716 / 6,910 |
Outcome results
Primary
Composite of Cardiovascular (CV) Death/MI/Ischemic Stroke
Participants with CV death, myocardial infarction (MI) or ischemic stroke. If no event, censoring occurs at the minimum of (primary analysis censoring date (PACD), last endpoint assessment date, non-CV death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Composite of Cardiovascular (CV) Death/MI/Ischemic Stroke | 751 Participants |
| Clopidogrel 75 mg od | Composite of Cardiovascular (CV) Death/MI/Ischemic Stroke | 740 Participants |
p-value: 0.6595% CI: [0.92, 1.13]Regression, Cox
Secondary
ALI
Participants with ALI. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | ALI | 117 Participant |
| Clopidogrel 75 mg od | ALI | 115 Participant |
p-value: 0.84695% CI: [0.79, 1.33]Regression, Cox
Secondary
All-cause Mortality
Participants with all-cause death. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | All-cause Mortality | 628 Participant |
| Clopidogrel 75 mg od | All-cause Mortality | 635 Participant |
p-value: 0.91395% CI: [0.89, 1.11]Regression, Cox
Secondary
Any Revascularisation (Coronary, Peripheral [Limb, Mesenteric, Renal, Carotid and Other])
Participants with any revascularization. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Any Revascularisation (Coronary, Peripheral [Limb, Mesenteric, Renal, Carotid and Other]) | 1211 Participant |
| Clopidogrel 75 mg od | Any Revascularisation (Coronary, Peripheral [Limb, Mesenteric, Renal, Carotid and Other]) | 1250 Participant |
p-value: 0.46295% CI: [0.9, 1.05]Regression, Cox
Secondary
Composite of CV Death, MI, and All-cause Stroke (Ischemic or Hemorrhagic)
Participants with CV death, MI or all-cause stroke. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Composite of CV Death, MI, and All-cause Stroke (Ischemic or Hemorrhagic) | 766 Participant |
| Clopidogrel 75 mg od | Composite of CV Death, MI, and All-cause Stroke (Ischemic or Hemorrhagic) | 759 Participant |
p-value: 0.72495% CI: [0.92, 1.13]Regression, Cox
Secondary
Composite of CV Death, MI, Ischemic Stroke, and ALI
Participants with CV death, MI, ischemic stroke or acute limb ischemia (ALI). If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Composite of CV Death, MI, Ischemic Stroke, and ALI | 839 Participant |
| Clopidogrel 75 mg od | Composite of CV Death, MI, Ischemic Stroke, and ALI | 833 Participant |
p-value: 0.73895% CI: [0.92, 1.12]Regression, Cox
Secondary
CV Death
Participants with CV death. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | CV Death | 363 Participant |
| Clopidogrel 75 mg od | CV Death | 343 Participant |
p-value: 0.495% CI: [0.92, 1.23]Regression, Cox
Secondary
Lower Extremity Revascularization
Participants with lower extremity revascularization (LER). If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Lower Extremity Revascularization | 846 Participant |
| Clopidogrel 75 mg od | Lower Extremity Revascularization | 892 Participant |
p-value: 0.29895% CI: [0.87, 1.05]Regression, Cox
Secondary
MI
Participants with MI. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | MI | 349 Participant |
| Clopidogrel 75 mg od | MI | 334 Participant |
p-value: 0.48295% CI: [0.91, 1.23]Regression, Cox
Other Pre-specified
Any Amputation Caused by PAD
Participants with any amputation caused by peripheral arterial disease (PAD). If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Any Amputation Caused by PAD | 179 Participant |
| Clopidogrel 75 mg od | Any Amputation Caused by PAD | 208 Participant |
p-value: 0.16495% CI: [0.71, 1.06]Regression, Cox
Other Pre-specified
Change in ABI/TBI From Baseline
Change in ankle brachial index (ABI) / toe brachial index (TBI). Ankle brachial index (ABI) is the ratio of blood pressures from the ankle and arm and is used for diagnosing peripheral arterial occlusive disease (PAOD): Normal: 1 to 1.29 Borderline: 0.91 to 0.99 Mild PAOD: 0.71 to 0.90 Medium severe PAOD: 0.41 to 0.7 Severe PAOD: \<0.4 Toe brachial index (TBI) is the ratio between the toe pressure and the higher brachial pressure, used for diagnosing PAOD when the ABI cannot be used: Normal: \>0.7 Mild: 0.5-0.7 Moderate: 0.35-0.5 Moderate-Severe: \<0.35 and toe pressure 40 mmHg Severe: \<0.35 and toe pressure \< 30 mmHg
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor 90 mg bd | Change in ABI/TBI From Baseline | ABI - 6 months N = 6184(Tica), 6319(Clopi) | 0.016 Change in ABI/TBI | Standard Deviation 0.136 |
| Ticagrelor 90 mg bd | Change in ABI/TBI From Baseline | ABI - End of treatment N = 4951(Tica), 5073(Clopi) | 0.022 Change in ABI/TBI | Standard Deviation 0.167 |
| Ticagrelor 90 mg bd | Change in ABI/TBI From Baseline | TBI - 6 months N = 55(Tica), 48(Clopi) | 0.050 Change in ABI/TBI | Standard Deviation 0.132 |
| Ticagrelor 90 mg bd | Change in ABI/TBI From Baseline | TBI - End of treatment N = 36(Tica), 21(Clopi) | 0.059 Change in ABI/TBI | Standard Deviation 0.115 |
| Clopidogrel 75 mg od | Change in ABI/TBI From Baseline | TBI - End of treatment N = 36(Tica), 21(Clopi) | -0.065 Change in ABI/TBI | Standard Deviation 0.304 |
| Clopidogrel 75 mg od | Change in ABI/TBI From Baseline | ABI - 6 months N = 6184(Tica), 6319(Clopi) | 0.011 Change in ABI/TBI | Standard Deviation 0.134 |
| Clopidogrel 75 mg od | Change in ABI/TBI From Baseline | TBI - 6 months N = 55(Tica), 48(Clopi) | 0.036 Change in ABI/TBI | Standard Deviation 0.137 |
| Clopidogrel 75 mg od | Change in ABI/TBI From Baseline | ABI - End of treatment N = 4951(Tica), 5073(Clopi) | 0.016 Change in ABI/TBI | Standard Deviation 0.167 |
Other Pre-specified
Changes in Fontaine Stage
Progression of the clinical/symptomatic status of the limb by changes in Fontaine stage. Stage I - Asymptomatic Stage IIa - Intermittent claudication after more than 200 meters of pain free walking Stage IIb - Intermittent claudication after less than 200 meters of walking Stage III - Rest pain Stage IV - Ischemic ulcers or gangrene
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ticagrelor 90 mg bd | Changes in Fontaine Stage | Stage I - End of treatment | 775 Participant |
| Ticagrelor 90 mg bd | Changes in Fontaine Stage | Stage IIb - End of treatment | 45 Participant |
| Ticagrelor 90 mg bd | Changes in Fontaine Stage | Missing - End of treatment | 248 Participant |
| Ticagrelor 90 mg bd | Changes in Fontaine Stage | Stage IV - End of treatment | 7 Participant |
| Ticagrelor 90 mg bd | Changes in Fontaine Stage | Stage IIa - End of treatment | 227 Participant |
| Ticagrelor 90 mg bd | Changes in Fontaine Stage | Stage III - End of treatment | 7 Participant |
| Clopidogrel 75 mg od | Changes in Fontaine Stage | Stage IIa - End of treatment | 1948 Participant |
| Clopidogrel 75 mg od | Changes in Fontaine Stage | Stage IV - End of treatment | 7 Participant |
| Clopidogrel 75 mg od | Changes in Fontaine Stage | Stage IIb - End of treatment | 269 Participant |
| Clopidogrel 75 mg od | Changes in Fontaine Stage | Stage I - End of treatment | 683 Participant |
| Clopidogrel 75 mg od | Changes in Fontaine Stage | Stage III - End of treatment | 24 Participant |
| Clopidogrel 75 mg od | Changes in Fontaine Stage | Missing - End of treatment | 743 Participant |
| Ticagrelor - Stage IIb | Changes in Fontaine Stage | Stage I - End of treatment | 171 Participant |
| Ticagrelor - Stage IIb | Changes in Fontaine Stage | Missing - End of treatment | 403 Participant |
| Ticagrelor - Stage IIb | Changes in Fontaine Stage | Stage IIa - End of treatment | 560 Participant |
| Ticagrelor - Stage IIb | Changes in Fontaine Stage | Stage IV - End of treatment | 5 Participant |
| Ticagrelor - Stage IIb | Changes in Fontaine Stage | Stage III - End of treatment | 12 Participant |
| Ticagrelor - Stage IIb | Changes in Fontaine Stage | Stage IIb - End of treatment | 469 Participant |
| Ticagrelor - Stage III | Changes in Fontaine Stage | Stage III - End of treatment | 31 Participant |
| Ticagrelor - Stage III | Changes in Fontaine Stage | Stage IIb - End of treatment | 39 Participant |
| Ticagrelor - Stage III | Changes in Fontaine Stage | Missing - End of treatment | 59 Participant |
| Ticagrelor - Stage III | Changes in Fontaine Stage | Stage I - End of treatment | 15 Participant |
| Ticagrelor - Stage III | Changes in Fontaine Stage | Stage IIa - End of treatment | 41 Participant |
| Ticagrelor - Stage III | Changes in Fontaine Stage | Stage IV - End of treatment | 1 Participant |
| Ticagrelor - Stage IV | Changes in Fontaine Stage | Stage IIa - End of treatment | 28 Participant |
| Ticagrelor - Stage IV | Changes in Fontaine Stage | Stage I - End of treatment | 26 Participant |
| Ticagrelor - Stage IV | Changes in Fontaine Stage | Stage IIb - End of treatment | 19 Participant |
| Ticagrelor - Stage IV | Changes in Fontaine Stage | Stage III - End of treatment | 7 Participant |
| Ticagrelor - Stage IV | Changes in Fontaine Stage | Stage IV - End of treatment | 13 Participant |
| Ticagrelor - Stage IV | Changes in Fontaine Stage | Missing - End of treatment | 47 Participant |
| Clopidogrel - Stage I | Changes in Fontaine Stage | Stage IIb - End of treatment | 56 Participant |
| Clopidogrel - Stage I | Changes in Fontaine Stage | Stage IIa - End of treatment | 230 Participant |
| Clopidogrel - Stage I | Changes in Fontaine Stage | Missing - End of treatment | 250 Participant |
| Clopidogrel - Stage I | Changes in Fontaine Stage | Stage I - End of treatment | 743 Participant |
| Clopidogrel - Stage I | Changes in Fontaine Stage | Stage IV - End of treatment | 4 Participant |
| Clopidogrel - Stage I | Changes in Fontaine Stage | Stage III - End of treatment | 9 Participant |
| Clopidogrel - Stage IIa | Changes in Fontaine Stage | Stage IIb - End of treatment | 311 Participant |
| Clopidogrel - Stage IIa | Changes in Fontaine Stage | Stage III - End of treatment | 15 Participant |
| Clopidogrel - Stage IIa | Changes in Fontaine Stage | Stage IIa - End of treatment | 1956 Participant |
| Clopidogrel - Stage IIa | Changes in Fontaine Stage | Stage IV - End of treatment | 7 Participant |
| Clopidogrel - Stage IIa | Changes in Fontaine Stage | Stage I - End of treatment | 723 Participant |
| Clopidogrel - Stage IIa | Changes in Fontaine Stage | Missing - End of treatment | 724 Participant |
| Clopidogrel - Stage IIb | Changes in Fontaine Stage | Stage III - End of treatment | 23 Participant |
| Clopidogrel - Stage IIb | Changes in Fontaine Stage | Missing - End of treatment | 370 Participant |
| Clopidogrel - Stage IIb | Changes in Fontaine Stage | Stage IIb - End of treatment | 450 Participant |
| Clopidogrel - Stage IIb | Changes in Fontaine Stage | Stage IV - End of treatment | 10 Participant |
| Clopidogrel - Stage IIb | Changes in Fontaine Stage | Stage I - End of treatment | 198 Participant |
| Clopidogrel - Stage IIb | Changes in Fontaine Stage | Stage IIa - End of treatment | 557 Participant |
| Clopidogrel - Stage III | Changes in Fontaine Stage | Stage I - End of treatment | 33 Participant |
| Clopidogrel - Stage III | Changes in Fontaine Stage | Stage IIb - End of treatment | 38 Participant |
| Clopidogrel - Stage III | Changes in Fontaine Stage | Missing - End of treatment | 60 Participant |
| Clopidogrel - Stage III | Changes in Fontaine Stage | Stage IIa - End of treatment | 33 Participant |
| Clopidogrel - Stage III | Changes in Fontaine Stage | Stage III - End of treatment | 23 Participant |
| Clopidogrel - Stage III | Changes in Fontaine Stage | Stage IV - End of treatment | 5 Participant |
| Clopidogrel - Stage IV | Changes in Fontaine Stage | Stage III - End of treatment | 12 Participant |
| Clopidogrel - Stage IV | Changes in Fontaine Stage | Stage IV - End of treatment | 13 Participant |
| Clopidogrel - Stage IV | Changes in Fontaine Stage | Stage IIb - End of treatment | 15 Participant |
| Clopidogrel - Stage IV | Changes in Fontaine Stage | Missing - End of treatment | 45 Participant |
| Clopidogrel - Stage IV | Changes in Fontaine Stage | Stage I - End of treatment | 19 Participant |
| Clopidogrel - Stage IV | Changes in Fontaine Stage | Stage IIa - End of treatment | 21 Participant |
Other Pre-specified
Changes in Rutherford Classification
Progression of the clinical/symptomatic status of the limb by changes in Rutherford classification. Category 0 - Asymptomatic Category 1 - Mild claudication Category 2 - Moderate claudication - The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters. Category 3 - Severe claudication Category 4 - Rest pain Category 5 - Ischemic ulceration not exceeding ulcer of the digits of the foot Category 6 - Severe ischemic ulcers or frank gangrene
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ticagrelor 90 mg bd | Changes in Rutherford Classification | Category 1/2 - End of treatment | 227 Participant |
| Ticagrelor 90 mg bd | Changes in Rutherford Classification | Missing - End of treatment | 248 Participant |
| Ticagrelor 90 mg bd | Changes in Rutherford Classification | Category 0 - End of treatment | 775 Participant |
| Ticagrelor 90 mg bd | Changes in Rutherford Classification | Category 4 - End of treatment | 7 Participant |
| Ticagrelor 90 mg bd | Changes in Rutherford Classification | Category 6 - End of treatment | 2 Participant |
| Ticagrelor 90 mg bd | Changes in Rutherford Classification | Category 3 - End of treatment | 45 Participant |
| Ticagrelor 90 mg bd | Changes in Rutherford Classification | Category 5 - End of treatment | 5 Participant |
| Clopidogrel 75 mg od | Changes in Rutherford Classification | Missing - End of treatment | 743 Participant |
| Clopidogrel 75 mg od | Changes in Rutherford Classification | Category 1/2 - End of treatment | 1948 Participant |
| Clopidogrel 75 mg od | Changes in Rutherford Classification | Category 6 - End of treatment | 3 Participant |
| Clopidogrel 75 mg od | Changes in Rutherford Classification | Category 0 - End of treatment | 683 Participant |
| Clopidogrel 75 mg od | Changes in Rutherford Classification | Category 5 - End of treatment | 4 Participant |
| Clopidogrel 75 mg od | Changes in Rutherford Classification | Category 4 - End of treatment | 24 Participant |
| Clopidogrel 75 mg od | Changes in Rutherford Classification | Category 3 - End of treatment | 269 Participant |
| Ticagrelor - Stage IIb | Changes in Rutherford Classification | Category 1/2 - End of treatment | 560 Participant |
| Ticagrelor - Stage IIb | Changes in Rutherford Classification | Category 5 - End of treatment | 3 Participant |
| Ticagrelor - Stage IIb | Changes in Rutherford Classification | Category 0 - End of treatment | 171 Participant |
| Ticagrelor - Stage IIb | Changes in Rutherford Classification | Missing - End of treatment | 403 Participant |
| Ticagrelor - Stage IIb | Changes in Rutherford Classification | Category 6 - End of treatment | 2 Participant |
| Ticagrelor - Stage IIb | Changes in Rutherford Classification | Category 3 - End of treatment | 469 Participant |
| Ticagrelor - Stage IIb | Changes in Rutherford Classification | Category 4 - End of treatment | 12 Participant |
| Ticagrelor - Stage III | Changes in Rutherford Classification | Missing - End of treatment | 59 Participant |
| Ticagrelor - Stage III | Changes in Rutherford Classification | Category 1/2 - End of treatment | 41 Participant |
| Ticagrelor - Stage III | Changes in Rutherford Classification | Category 0 - End of treatment | 15 Participant |
| Ticagrelor - Stage III | Changes in Rutherford Classification | Category 6 - End of treatment | 0 Participant |
| Ticagrelor - Stage III | Changes in Rutherford Classification | Category 5 - End of treatment | 1 Participant |
| Ticagrelor - Stage III | Changes in Rutherford Classification | Category 4 - End of treatment | 31 Participant |
| Ticagrelor - Stage III | Changes in Rutherford Classification | Category 3 - End of treatment | 39 Participant |
| Ticagrelor - Stage IV | Changes in Rutherford Classification | Category 6 - End of treatment | 0 Participant |
| Ticagrelor - Stage IV | Changes in Rutherford Classification | Missing - End of treatment | 33 Participant |
| Ticagrelor - Stage IV | Changes in Rutherford Classification | Category 4 - End of treatment | 4 Participant |
| Ticagrelor - Stage IV | Changes in Rutherford Classification | Category 3 - End of treatment | 13 Participant |
| Ticagrelor - Stage IV | Changes in Rutherford Classification | Category 1/2 - End of treatment | 23 Participant |
| Ticagrelor - Stage IV | Changes in Rutherford Classification | Category 5 - End of treatment | 11 Participant |
| Ticagrelor - Stage IV | Changes in Rutherford Classification | Category 0 - End of treatment | 23 Participant |
| Clopidogrel - Stage I | Changes in Rutherford Classification | Category 0 - End of treatment | 3 Participant |
| Clopidogrel - Stage I | Changes in Rutherford Classification | Category 6 - End of treatment | 2 Participant |
| Clopidogrel - Stage I | Changes in Rutherford Classification | Missing - End of treatment | 14 Participant |
| Clopidogrel - Stage I | Changes in Rutherford Classification | Category 4 - End of treatment | 3 Participant |
| Clopidogrel - Stage I | Changes in Rutherford Classification | Category 1/2 - End of treatment | 5 Participant |
| Clopidogrel - Stage I | Changes in Rutherford Classification | Category 5 - End of treatment | 0 Participant |
| Clopidogrel - Stage I | Changes in Rutherford Classification | Category 3 - End of treatment | 6 Participant |
| Clopidogrel - Stage IIa | Changes in Rutherford Classification | Category 4 - End of treatment | 9 Participant |
| Clopidogrel - Stage IIa | Changes in Rutherford Classification | Category 0 - End of treatment | 743 Participant |
| Clopidogrel - Stage IIa | Changes in Rutherford Classification | Category 1/2 - End of treatment | 230 Participant |
| Clopidogrel - Stage IIa | Changes in Rutherford Classification | Category 3 - End of treatment | 56 Participant |
| Clopidogrel - Stage IIa | Changes in Rutherford Classification | Category 5 - End of treatment | 2 Participant |
| Clopidogrel - Stage IIa | Changes in Rutherford Classification | Category 6 - End of treatment | 2 Participant |
| Clopidogrel - Stage IIa | Changes in Rutherford Classification | Missing - End of treatment | 250 Participant |
| Clopidogrel - Stage IIb | Changes in Rutherford Classification | Category 6 - End of treatment | 1 Participant |
| Clopidogrel - Stage IIb | Changes in Rutherford Classification | Category 4 - End of treatment | 15 Participant |
| Clopidogrel - Stage IIb | Changes in Rutherford Classification | Missing - End of treatment | 724 Participant |
| Clopidogrel - Stage IIb | Changes in Rutherford Classification | Category 0 - End of treatment | 723 Participant |
| Clopidogrel - Stage IIb | Changes in Rutherford Classification | Category 5 - End of treatment | 6 Participant |
| Clopidogrel - Stage IIb | Changes in Rutherford Classification | Category 3 - End of treatment | 311 Participant |
| Clopidogrel - Stage IIb | Changes in Rutherford Classification | Category 1/2 - End of treatment | 1956 Participant |
| Clopidogrel - Stage III | Changes in Rutherford Classification | Category 0 - End of treatment | 198 Participant |
| Clopidogrel - Stage III | Changes in Rutherford Classification | Category 1/2 - End of treatment | 557 Participant |
| Clopidogrel - Stage III | Changes in Rutherford Classification | Category 6 - End of treatment | 4 Participant |
| Clopidogrel - Stage III | Changes in Rutherford Classification | Category 4 - End of treatment | 23 Participant |
| Clopidogrel - Stage III | Changes in Rutherford Classification | Category 5 - End of treatment | 6 Participant |
| Clopidogrel - Stage III | Changes in Rutherford Classification | Missing - End of treatment | 370 Participant |
| Clopidogrel - Stage III | Changes in Rutherford Classification | Category 3 - End of treatment | 450 Participant |
| Clopidogrel - Stage IV | Changes in Rutherford Classification | Category 4 - End of treatment | 23 Participant |
| Clopidogrel - Stage IV | Changes in Rutherford Classification | Category 3 - End of treatment | 38 Participant |
| Clopidogrel - Stage IV | Changes in Rutherford Classification | Missing - End of treatment | 60 Participant |
| Clopidogrel - Stage IV | Changes in Rutherford Classification | Category 5 - End of treatment | 4 Participant |
| Clopidogrel - Stage IV | Changes in Rutherford Classification | Category 1/2 - End of treatment | 33 Participant |
| Clopidogrel - Stage IV | Changes in Rutherford Classification | Category 6 - End of treatment | 1 Participant |
| Clopidogrel - Stage IV | Changes in Rutherford Classification | Category 0 - End of treatment | 33 Participant |
| Clopidogrel - Cat 5 | Changes in Rutherford Classification | Category 1/2 - End of treatment | 18 Participant |
| Clopidogrel - Cat 5 | Changes in Rutherford Classification | Category 0 - End of treatment | 13 Participant |
| Clopidogrel - Cat 5 | Changes in Rutherford Classification | Category 5 - End of treatment | 12 Participant |
| Clopidogrel - Cat 5 | Changes in Rutherford Classification | Category 3 - End of treatment | 12 Participant |
| Clopidogrel - Cat 5 | Changes in Rutherford Classification | Category 4 - End of treatment | 11 Participant |
| Clopidogrel - Cat 5 | Changes in Rutherford Classification | Missing - End of treatment | 34 Participant |
| Clopidogrel - Cat 5 | Changes in Rutherford Classification | Category 6 - End of treatment | 0 Participant |
| Clopidogrel - Cat 6 | Changes in Rutherford Classification | Category 4 - End of treatment | 1 Participant |
| Clopidogrel - Cat 6 | Changes in Rutherford Classification | Category 6 - End of treatment | 0 Participant |
| Clopidogrel - Cat 6 | Changes in Rutherford Classification | Category 0 - End of treatment | 6 Participant |
| Clopidogrel - Cat 6 | Changes in Rutherford Classification | Category 3 - End of treatment | 3 Participant |
| Clopidogrel - Cat 6 | Changes in Rutherford Classification | Category 1/2 - End of treatment | 3 Participant |
| Clopidogrel - Cat 6 | Changes in Rutherford Classification | Category 5 - End of treatment | 1 Participant |
| Clopidogrel - Cat 6 | Changes in Rutherford Classification | Missing - End of treatment | 11 Participant |
Other Pre-specified
CV-related Hospitalization
Participants with hospitalization associated with CV death, hospitalization due to MI, ischemic stroke, lower extremity revascularization, major amputation due to PAD, transient ischemic attack (TIA), coronary revascularization or unstable angina. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | CV-related Hospitalization | 1312 Participant |
| Clopidogrel 75 mg od | CV-related Hospitalization | 1314 Participant |
p-value: 0.88795% CI: [0.93, 1.09]Regression, Cox
Other Pre-specified
Major Amputation Caused by PAD
Participants with major amputation caused by PAD. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Major Amputation Caused by PAD | 100 Participant |
| Clopidogrel 75 mg od | Major Amputation Caused by PAD | 116 Participant |
p-value: 0.30695% CI: [0.67, 1.14]Regression, Cox
Other Pre-specified
Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/ALI/Major Amputation/Fatal Bleeding/Intracranial Bleeding)
Participants with all-cause death, MI, ischemic stroke, ALI, major amputation, fatal bleeding or intracranial bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/ALI/Major Amputation/Fatal Bleeding/Intracranial Bleeding) | 1119 Participant |
| Clopidogrel 75 mg od | Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/ALI/Major Amputation/Fatal Bleeding/Intracranial Bleeding) | 1140 Participant |
p-value: 0.82995% CI: [0.91, 1.08]Regression, Cox
Other Pre-specified
Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/ALI/Major Amputation/TIMI Major Bleeding)
Participants with all-cause death, MI, ischemic stroke, ALI, major amputation or Thrombolysis in Myocardial Infarction (TIMI) major bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/ALI/Major Amputation/TIMI Major Bleeding) | 1183 Participant |
| Clopidogrel 75 mg od | Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/ALI/Major Amputation/TIMI Major Bleeding) | 1199 Participant |
p-value: 0.94995% CI: [0.92, 1.08]Regression, Cox
Other Pre-specified
Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/Fatal Bleeding/Intracranial Bleeding)
Participants with all-cause death, MI, ischemic stroke, fatal bleeding or intracranial bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/Fatal Bleeding/Intracranial Bleeding) | 983 Participant |
| Clopidogrel 75 mg od | Net Clinical Benefit (Composite of All-cause Mortality/MI/Ischemic Stroke/Fatal Bleeding/Intracranial Bleeding) | 992 Participant |
p-value: 195% CI: [0.92, 1.09]Regression, Cox
Other Pre-specified
Net Clinical Benefit (Composite of CV Death/MI/Ischemic Stroke/Fatal Bleeding/Intracranial Bleeding)
Participants with CV death, MI, ischemic stroke, fatal bleeding or intracranial bleeding. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, non-CV death date)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Net Clinical Benefit (Composite of CV Death/MI/Ischemic Stroke/Fatal Bleeding/Intracranial Bleeding) | 789 Participant |
| Clopidogrel 75 mg od | Net Clinical Benefit (Composite of CV Death/MI/Ischemic Stroke/Fatal Bleeding/Intracranial Bleeding) | 786 Participant |
p-value: 0.79395% CI: [0.92, 1.12]Regression, Cox
Other Pre-specified
Non-CV Death
Participants with non-CV death. If no event, censoring occurs at the minimum of (PACD, last endpoint assessment date, CV death)
Time frame: From randomization to PACD, an average of 2.5 years
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Non-CV Death | 250 Participant |
| Clopidogrel 75 mg od | Non-CV Death | 272 Participant |
p-value: 0.37795% CI: [0.78, 1.1]Regression, Cox
Other Pre-specified
PLATO Major Bleeding Events
Participants with PLATO major bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug)
Time frame: From the date of first dose and up to and including 7 days following the date of last dose of study drug
Population: The population was the safety analysis set, which included all patients who received at least 1 dose of randomized ticagrelor or clopidogrel and for whom post-dose data are available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | PLATO Major Bleeding Events | 206 Participant |
| Clopidogrel 75 mg od | PLATO Major Bleeding Events | 188 Participant |
p-value: 0.13995% CI: [0.95, 1.41]Regression, Cox
Other Pre-specified
Premature Permanent Discontinuation of Study Drug Due to Any Bleeding Event
Participants with a permanent discontinuation of study drug due to any bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug)
Time frame: From the date of first dose and up to and including 7 days following the date of last dose of study drug
Population: The population was the saftey analysis set, which included all patients who received at least 1 dose of randomized ticagrelor or clopidogrel and for whom post-dose data are available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | Premature Permanent Discontinuation of Study Drug Due to Any Bleeding Event | 168 Participant |
| Clopidogrel 75 mg od | Premature Permanent Discontinuation of Study Drug Due to Any Bleeding Event | 112 Participant |
p-value: <0.00195% CI: [1.24, 2]Regression, Cox
Other Pre-specified
TIMI Major Bleeding Events
Participants with TIMI major bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug)
Time frame: From the date of first dose and up to and including 7 days following the date of last dose of study drug
Population: The population was the safety analysis set, which included all patients who received at least 1 dose of randomized ticagrelor or clopidogrel and for whom post-dose data are available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | TIMI Major Bleeding Events | 113 Participant |
| Clopidogrel 75 mg od | TIMI Major Bleeding Events | 109 Participant |
p-value: 0.48995% CI: [0.84, 1.43]Regression, Cox
Other Pre-specified
TIMI Major or Minor Bleeding Events
Participants with TIMI major or minor bleeding event. If no event, censoring occurs at the minimum of (last endpoint assessment date, death date, 7 days after last dose of study drug)
Time frame: From the date of first dose and up to and including 7 days following the date of last dose of study drug
Population: The population was the safety analysis set, which included all patients who received at least 1 dose of randomized ticagrelor or clopidogrel and for whom post-dose data are available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg bd | TIMI Major or Minor Bleeding Events | 193 Participant |
| Clopidogrel 75 mg od | TIMI Major or Minor Bleeding Events | 175 Participant |
p-value: 0.13895% CI: [0.95, 1.43]Regression, Cox