Clopidogrel plus aspirin are standard dual antiplatelet therapy after PCI for preventing cardiovascular events and stent thrombosis. Large studies have been conducted to investigate if double-dose antiplatelet therapy is more effective than standard therapy in preventing cardiovascular events and stent thrombosis; N Engl J Med. 2010 Sep 2;363(10):930-42, Lancet. 2010 Oct 9;376(9748):1233-43, one showed no difference and one showed a difference. In double-dose strategy, after a loading dose of 600 mg, clopidogrel is followed by 150 mg daily for 6 days and 75 mg daily thereafter.
In some centers; however, the 150 mg daily dose is extended to the first month after PCI. The question is if there is any evidence supporting clopidogrel in double-dose extending from the first week to the first month after PCI? what about risk of major bleeding events?
I don't know evidence about the use of double-dose clopidogrel for 30 days. I think possible the increase of bleeding events risk. Besides, there are other antiplatelet drugs with different potential effect that can be used, if more platelet inhibition is desirable.
I think first of all it is neccessary to keep under the control the coagulation system indexes during the treatment. Second- I think it is necessary to take in concideration the baseline condition of the patients: how was his indexes before and after PCI etc. Of cause it is possible to increase the dose to max but I have experience that , in some patients, especially with some known condition gastric (ulcer, etc) was increased bleeding. I think to increase the dose it is necessary to have very serious reasons.
Tnx for your responses. The patient is a 53-year old male without any previous specific cardiovascular risk factors such as dyslipidemia, diabetes, hypertension, smoking etc. but type A personality and a chronic psychological stress ! He experienced recent chest discomfort at exercise, referred to a cardiologist, undergone exercise test which was positive, then undergone angiography which revealed severe LAD stenosis at proximal and thus undergone PCI with DES placement.
He received Plavix 600 mg loading dose then 150 mg daily dose plus aspirin 325 mg daily until now; 12th day.
By coagulation indexes you mean what and to what point? I saw that one of the largest study (N Engl J Med. 2012 Nov 29;367(22):2100-9) reported "no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring".
Look Plavix is decreasing the ability of platelets to aggregates and unfortunately I have not read this article. I will try to do that, but there is no doubt that Plavix affects the aggregation function of platelets and it has duration at least 7 days (until re-synthesis of platelets) after receiving the max dose. So could you imagine if duration takes one mon and in combination with aspirin (which has other pharmacodynamics),
So I think it is better to keep standard anti-platelet dose and add just anti-stress treatment.
Clopidogrel is a prodrug. It's final product inhibits specifically and irreversibly the ADP receptor of the trombocyte. But to reach the active form, the prodrug has to be metabolized. This is done in the liver, by cytochrom P450 system - which includes CYP2C19. In some individuals a poor metabolizer status is associated with diminished antiplatelet response to clopidogrel. A higher dose regimen in poor metabolizers increases antiplatelet response, so to double the dose in these cases could be a logical approach. However, an appropriate dose regimen for this patient population has not been approved.
Dear András. Why to use clopidogrel double-dose intead of other antiplatelet drug? I think more rational.
Dear José, there could be a great many (rational :)) causes to try to administer clopidogrel to this patient in the efficient dose. My answer just pointed out the situation when this dose regimen could be greater than mentioned in the leaflet.
As possible motivation to stick with clopi :
1 ease of administration (clopi p.o - versus Glycoprotein IIb/IIIa inhibitors like abciximab which are for iv use),
2 fewer side effects (compared to other ADP-receptor inhibitor like ticlopidine or to phosphodiesterase inhibitors like cilostazol)
3 A great body of evidence in clinical use, compared to the new classes of thromboxane inhibitors (ifetroban, etc)
4. And not to mention availability, financial issues, etc
The concept of double dose clopidogrel is no more tenable in this era of ticagrelor,more so because of clopidogrel resistance also documented in many patients.