Postoperative Dysfunction Following Cardiac Surgery Clinical Trial
Official title:
Multiple Daily Doses of Aspirin to Overcome Hyporesponsiveness Post Cardiac Bypass Surgery (ASACABG)- Part B
Cardiac bypass surgery is an important treatment for patients with severely blocked arteries
(tubes that delivery oxygen and nutrients to the heart). Hundreds of thousands of these
operations are done each year to help relieve patients' chest pain and to prevent future
heart attacks. The surgery is done by "bypassing" blood flow around badly clogged arteries
by sewing on healthy vessels from another part of the body (usually from the leg or the
chest). Aspirin (a blood thinner) is given to patients once a day after their surgery
because it stops "sticky" cells in the blood (platelets) from blocking these new vessels
(which may lead to a future heart attack).
Research has shown that aspirin does not work as well in people after they have bypass
surgery as the investigators might expect (for reasons that are not fully understood). One
reason aspirin may not work as well after surgery is because the body makes many more
platelets after surgery than it would under normal circumstances. All of these new platelets
overwhelm the aspirin and continue to be "sticky" and ready to block off arteries. The
investigators believe that giving multiple daily doses of aspirin following bypass surgery
is more effective at blocking platelet activity than giving aspirin once daily.
Background:
Cardiovascular disease caused by athero-thrombosis is the number one cause of long-term
morbidity and death worldwide. Many patients with advanced coronary disease benefit from
Coronary Artery Bypass Graft (CABG) by improving symptoms and increasing their longevity.
However, the benefits of CABG surgery are attenuated by early graft failure. The
administration of aspirin in the post-operative period has been shown in randomized
controlled trials (RCT) to reduce the risk of graft occlusion, although rates remain
unacceptably high. Patients undergoing CABG surgery transiently develop aspirin resistance,
which likely contributes to vein graft failure.
The investigators believe the aspirin resistance is a consequence of rapid platelet turnover
in the early postoperative period, resulting in a large number of platelets unexposed to
aspirin (due to its short half life). The investigators hypothesize that by increasing the
frequency of aspirin dosing, the investigators can reverse the aspirin resistance
encountered post CABG surgery. The investigators are proposing a RCT comparing two different
doses of aspirin (81mg and 325mg daily) to 162mg BID to determine whether multiple daily
dosing can overcome aspirin resistance.
(1)Given that platelet production is increased many-fold after CABG surgery (and the short
half-life of aspirin), the investigators hypothesize that increasing the frequency of
aspirin dosing will lead to the acetylation of a greater number of platelets over the course
of the day leading to an improved antiplatelet effect (as measured by serum thromboxane and
platelet aggregation assays); (2) The investigators will examine three platelet-related
single nucleotide polymorphisms (SNP) that have been implicated in aspirin
hyporesponsiveness.
The investigators are proposing a single centre, randomized, open-label, RCT in 60 patients
undergoing elective or urgent CABG surgery, to receive ASA 81mg daily, 325mg daily or 162mg
bid starting day 1 post-operatively. All patients will receive 325mg 6hrs following the
procedure (day of operation) as long as there is no contraindication for antiplatelet
therapy (ie significant bleeding) - as per the investigators centre's standard clinical
practice. Further details on aspirin administration and outcome measurements are reported
below.
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Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Treatment