Clopidogrel for the prevention of late cardiac events in patients with asymptomatic perioperative acute coronary syndrome.

Rationale:

Clopidogrel on top of standard treatment with aspirin has
been proven to be
effective and safe for the treatment and prevention of Acute Coronary
Syndromes (ACS).
In vascular surgical patients who have asymptomatic perioperative
myocardial ischemia
(PMI) measured by troponin T release no suitable treatment for the
prevention of
cardiovascular events during follow-up is available.


Objective:
To investigate the efficacy and safety of clopidogrel for the
prevention of
cardiovascular events during follow-up in patients with PMI during major
vascular
surgery. Furthermore we obtain to identify new preoperative risk factors
and novel
biomarkers for the development of cardiovascular events during follow-up
after major
vascular surgery.


Study design:
The current study has a open randomized intervention
design, with a 24
months follow-up. Data and blood sample collection will be done
pre-operatively
(outpatient clinic), perioperative and 30 days, 3, 6, and 12 months
after surgery.


Study population:
The proposed study consists of 750 patients above the
age of 18
years who develop asymptomatic troponin T release after elective major
vascular surgery
defined as: (1) abdominal aortic aneurysm (AAA) repair, (2) aortic
stenosis repair, (3)
above knee femoropopliteal bypass surgery, and (4) below knee
femoropopliteal bypass
surgery. The total study time is 4 years, including 3 years patient
inclusion and 1 year
follow-up of the last included patient.


Intervention:
All patients receive standard medical treatment with
aspirin, betablocker,
statin and proton pump therapy. If postoperative troponin T elevation is
present, patients
are randomized either to the clopidogrel group and receive a loading
dose of 300mg,
followed by a daily dose of 75mg during at least one year. The other
group receives the
standard medical treatment.


Main study parameters/endpoints:
The primary outcome is defined as the
composite
of cardiovascular death, MI, stroke, or severe ischemia of the coronary
or peripheral
arterial circulation leading to an intervention during the first 12
months of the follow-up
period. Safety outcomes include life-threatening, moderate bleeding and
minor bleeding
is considered as secondary outcome. Tertiary objectives include
identification of
preoperative risk factors and novel biomarkers of the primary endpoint.

Clopidogrel is effetive and safe for the prevention of cardiovascular events during follow-up in patients with Perioperative Myocardial Infarction during major vascular surgery.

- Troponin T measurement at days 1, 3 and 7 postoperatively.

- Outpatient clinic visits at 30 days, 3, 6, 12 months.
Telephonic or written contact.

Randomisation for use of clopidogrel on top of standard treatment with aspirin or use of aspirin only. Randomisation is executed after the patient develops an asymptomatic troponin T release during the perioperative period.