Aspirin and clopidogrel in acute coronary syndrome

Should aspirin use together with clopidogrel in acute coronary syndrome?
It is well known that antiplatelet agent is a must in treatment of all patients with acute coronary syndrome. The question is should we use combination treatment or not?

Some physician advocate individual use of the medication ,on the other hand, some physician advocate the use of combination treatment (ie. aspirin + clopidogrel, or aspirin + ticlopidine)

According to recently published CURE trial, the incidence of death in patients with combination therapy is further decrease from 9.3% to 11.4% compare to the use of aspirin alone.

Meanwhile, we also saw a lot of case with combination therapy presented with bleeding from various area include hematuria, bleeding Per Rectum, hemoptysis etc compared to patient on aspirin alone. And this also further endanger patients.

Should we give the best treatment to the patients? (bare in mind, clopidogrel is a expensive drugs but is free in government hospital in malaysia). And what is the best treatment you think? Combination or individual use?

So, let discuss about this topic. Should we or shouldn't we?

The CURE trial (Clopidogrel in Unstable Angina to Prevent Recurrent Events)
demonstrated that the combination of aspirin & clopidogrel is beneficial in the treatment of acute coronary syndrome (unstable angina and suspected myocardial infarction). The benefit of using clopidogrel in addition to aspirin was a 2.1% absolute risk reduction (from 11.4% to 9.3% - a relative risk reduction was ~20%) with an added increase in the risk of 'major' bleeding (defined as substantially disabling bleeding, intraocular bleeding leading to the loss of vision, or bleeding necessitating the transfusion of at least 2 units of blood) by 1% (2.7% to 3.7%), but importantly, no increase in life-threatening bleeding or intracranial hemorrhage.

With these results and further analysis of CURE, it was recommended, among others, that the current evidence strongly supports the use of dual antiplatelet therapy (aspirin and clopidogrel) in the long-term treatment (for at least 12 months) of patients with ACS (after PCI), after which aspirin should be continued indefinitely.

Apart from the CURE trial, other studies like CLopidogrel as an Adjunctive ReperfusIon TherapY (CLARITY), ClOpidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) and Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trials have also looked into this issue and consolidated the evidence.

In addition to the above, Aspirin Resistance is known to occur in about 10% of patients where adding an additional antiplatelet like clopidogrel helps.

The current practice hence, is to give combination therapy with aspirin and clopidogrel for at least 12 months after an episode of acute coronary syndrome. After this, low dose aspirin therapy (75-150mg/day) is continued for life.

Yes, as you say, clopidogrel is expensive and even though it is free in Govt hospitals, they are generally not available for long/indefinite use. But I feel that the benefit of taking clopidogrel exceeds the risk of bleeding and expenses.

I invite further comments and views too.

Oh...it is extremely wonderful and fruitful reply.I totally agree with the content mentioned above. Ie...using combination therapy is better.

By the way, there is one more important point. Some physicians also mention that aspirin and clopidogrel have different mechanism of action. So, with the combination therapy, the effect will be much more better.

Low dose aspirin(75mg-150mg/day) inhibit the cyclo-oxygenase pathways<inhibit thromboxane A2 production> and hence prevent platelet aggregation. (High dose will block prostacycline pathway too which is not advocated)
Clopidogrel or ticlopidine inhibit ADP-depedent activation of Glycoprotein 2b & 3a receptor and thus prevent platelet aggregation. (please note that it is not blocking the receptor directly)

Recently, new group of drug, ie receptor antagonist are introduce into market.Eg: Abciximab..They claims that it is more powerful. Howevers it is very very expensive. Can anyone discuss about it?? How far the clinical evidence go?

This discussion raises the issue of choosing between or negotiating individual experience and controlled trial data.

None of us would in any way be able to practically experience the benefit of clopidogrel in our individual patients (ie reduction of cardiac event and mortality etc) however bleeding is something which I get to readily experience with the addition of clopidogrel (with ward patients bleeding from their foley's catheter, nose bleed, bleeding pr etc.) So a mind which relies more on experiential inputs may not be fully able to rely on the drug unless the faith in the controlled trial data over-rides the experiential inputs. With the drug company manufacturers of clopidpogrel standing to gain immense profits from this positive trial of clopidogrel relying on just that data without any experiential inputs makes one uneasy.

rakesh

By reading the above posts, I understand that evidence supports the use of aspirin and clopidogrel together, but whether we use it or not depends on our experience.
What about a fresh student like me? When I start working after finishing my studies, my clinical experience would be nil. Do I use this combination or not? How to solve this?

Dear medstudent,

When you begin your career, it is unlikely that you would start working independently. Very often you will work in a hospital setting where you will have many seniors and colleagues.

During this time, you learn with them and tap on their experiences. Your experience is "nil" only on the first day (or is it really nil?), then onwards, you will go on accruing more and more experience. Just remember to be observant and curious. I always like to tell students "never to make the same mistake again" - that is learning by experience.