Two's Company, Three's a Crowd

I had mentioned needing a topic for my second management conference presentation a few weeks ago. I got some great suggestions; however, a patient's drug therapy choices caught my attention a couple weeks ago. I'll go ahead and summarize my power point that I presented. I thought I would have some clear-cut conclusions at the end of my literature search; however, I ended up with more questions than answers. I'm learning that this is the case a lot of the time in the health care field.

Title: "Safety and efficacy of triple antithrombotic therapy in post-PCI stent patients who require long term anticoagulant therapy."

Background: Standard of practice post-stent: ASA + clopidogrel to prevent stent thrombosis. Standard of practice for mechanical heart valve, DVT, atrial fibrillation: oral anticoagulation (warfarin) to prevent stroke. Basically, the ASA-clopidogrel combination is less effective in preventing stroke than warfarin, and warfarin alone is not enough to prevent stent thrombosis. Okay, so why not just use all three medications to prevent stent thrombosis and stroke? Increased bleeding risk, obviously! We have a problem here, don't we?

Patient case:  67 y/o male with chief complaint of chest pain. Troponin of 0.8 x 1, so sent to the cath lab and received drug-eluting stents for STEMI. The attending on our team was considering warfarin for a thrombus prophylaxis s/p MI (d/t possible blood pooling in the left ventricle). The patient already needs ASA + clopidogrel for his stents - is this patient a candidate for warfarin as well?

Literature review: I found that the quality of literature on this topic was poor; however, I was able to make some conclusions from the studies that I chose to look at. I chose certain studies because they looked at both the efficacy of triple antithrombotic therapy (ability to prevent stent thrombosis and stroke) as well as safety of triple therapy (incidence of bleeding).The three studies I looked at were by: Karjalainen et al., Rossini et al., and Sarafoff et al.

Conclusions: 1) In patients with an indication for warfarin that isn't a mechanical mitral valve, aim for lower INR goals (2.0-2.5). 2) ASA + warfarin combination may lead to higher rates of stent rethrombosis (this was statistically significant in a couple of the trials) than other antithrombotic therapies. 3) Post-stent patients with an indication for warfarin may benefit from warfarin + clopidogrel therapy. 4) bare metal stents may be considered over drug-eluting stents for patients with a compelling indication for oral anticoagulation (BMS require a shorter clopidogrel duration ~1month).

Things to consider for this topic: What is the indication for warfarin? - most studies were done on atrial fibrillation patients. What is the CHADS2 score? - does it make a difference if the score is 1 vs 6? What type of stent does the patient have? - drug eluting vs. bare metal. Does the patient have a history of bleeds? What dose of ASA is appropriate for the patient? Should gastroprotectants be used to minimize bleeding risks?

Patient follow up: The patient was discharged on ASA + clopidogrel, without warfarin. The patient did not seem reliable in following up with the anticoagulation clinic and we believed his risk of bleeding would exceed the benefit of the addition of warfarin.

There is a future study coming out that compares warfarin + clopidogrel with warfarin + ASA + clopidogrel. The end points will be bleeds and major adverse cardiac events (MACE). This will be a study worth reading, especially because it's a prospective, randomized trial.

At first, this topic wasn't the most fulfilling to look into because of the lack of answers; however, I thought it was worth my time, since I now know the appropriate questions to ask about the patient before making any recommendations!