Robert Roberts, MD, MACC, FRSC, FRCPC, LLD (Hon.)

Clopidogrel has been shown to be an excellent antiplatelet therapy to treat people after MI, PCI or CABG. Clopidogrel has to be metabolized before it is effective as an antiplatelet agent, and it has been recognized that up to approximately 30% of people do not have the necessary gene to make the necessary enzyme to make the conversion. Studies showed that if a patient did not have that gene, their platelets were still sticky and the drug did not work.

As a result, newer drugs that don’t have to be metabolized like prasugrel and ticagrelor were developed. These drugs were just as good as clopidogrel but carried some increased bleeding risk. The present study compared those drugs with clopidogrel, and after genotyping, people who did not have the gene to convert clopidogrel to an active metabolite received prasugrel or ticagrelor. Using that approach, clopidogrel was equal to the more expensive drugs at preventing ischemic events and was associated with slightly less bleeding.

Clopidogrel has remained the No. 1 antiplatelet therapy drug in the world, but all too often, particularly in the United States, people would select the more expensive drugs because they did not have to worry about conversion to an active metabolite. The present study showed that clopidogrel, which is now off-patent and costs a few cents per pill, is comparable with these other drugs which cost a few dollars per pill. The study clearly proves that a clopidogrel-based regimen is just as good as the others when implemented effectively and is associated with less bleeding. The necessary genetic testing can be done at the bedside by a nurse or technician and does not need to go to the lab.

Therefore, this is a landmark study for clopidogrel. It may be more effective than the other drugs because of less bleeding, and is much reduced in price. Many patients with MI, PCI or cardiac surgery are recommended for dual antiplatelet therapy for at least 1 year. That was a very expensive proposition that has just become very affordable. Clopidogrel is working as personalized medicine. I expect that insurance companies, especially CMS, in the future will not pay for the more expensive agents unless genotyping has been performed and shows the necessary gene to metabolize clopidogrel is missing.

Clopidogrel had been the standard for antiplatelet therapy but lost that reputation because of prasugrel and ticagrelor. In recent years, the question has emerged of how many medications can you add before bleeding becomes a problem. Remember that most of the people who receive this therapy are in their 60s and 70s. Using this protocol could go a long way toward addressing the bleeding problem.

The clear message is that this clopidogrel-based protocol minimizes cost and bleeding and can benefit millions of patients.