Reviewing Treatment Options, Health Outcomes for Patients With Acute Coronary Syndrome

^{By Julie Gould}

I'm Renato Lopes, cardiologist and professor of medicine at Duke University Medical Center, Durham, North Carolina. I'm a trialist. I've done many trials in anti-thrombotic therapies around atrial fibrillation and acute coronary syndrome, as well as registries both nationally and all over the world.

What existing data led you and your co-investigators to conduct this research?

One of the most challenging scenarios in clinical cardiology is treating patients with atrial fibrillation who also present with an acute coronary syndrome and receive a percutaneous coronary intervention, a PCI. The reason this is a challenge is because those patients have not been very well-studied until three, four years ago in prior studies.

Other studies, only include patients with ACS and PCI or only atrial fibrillation, but never both. Therefore, we did not have really high-quality evidence to guide the treatment of these patients in terms of antithrombotic therapies, because we need to combine antithrombotic agents such as antiplatelet drugs (aspirin and clopidogrel, for example) and oral anticoagulation.

How to combine these drugs, however, has never been really well-studied until three, four years ago. There has been an important gap in the literature. In the last three, four years several trials have been done, and last year we completed all of the key pivotal trials in this field.

The idea of this present study was to meta-analyze the totality of data that we have in this field to be able to generate high-quality, the most comprehensive and complete data up to date, in a field where we did not have good evidence to now be able to provide some results that can help physicians in clinical practice on how to treat these patients.

That was the rationale for performing a network meta-analysis with all the data that have been published so far.

Can you please briefly describe the study and the findings? Were any of the outcomes particularly surprising?

Based on that, we look at every randomized trial that have been done in this field, particularly with the non-vitamin K antagonist oral anticoagulants (NOACs) and perform a network meta-analysis comparing four different possible antithrombotic regimens.

Basically, two triple regimens - aspirin plus clopidogrel, and warfarin, versus aspirin plus clopidogrel, and a NOAC. Then, two other regimens that we call double therapy, which were clopidogrel plus warfarin, versus clopidogrel plus a NOAC, so both regimens without aspirin. The network meta-analysis compared all these 4 regimens at the same time within each other.

Basically, what we found is that in terms of bleeding, including intracranial hemorrhage, the best regimen is the one that includes a NOAC plus a P2Y12 inhibitor, such as clopidogrel, without aspirin. That is for sure the safest regimen for this population.

When we look at MACE events, in other words, cardiovascular endpoints, we do not find any difference in ischemic events among those four regimens. What these results basically show is that, in this challenging scenario, less antithrombotic drugs is more.

Therefore, going without aspirin as the standard-of-care, in other words going with clopidogrel and a NOAC in the appropriate dose for stroke prevention is enough and gives us the best net clinical benefit, with the greatest reduction in ischemic events, and a minimal cost of bleeding including intracranial hemorrhage.

Importantly, we also found that the classic triple antithrombotic therapy that has been defined and used for many years as warfarin plus aspirin, and clopidogrel had the worst bleeding profile, and therefore should be generally avoided in clinical practice.

Is there a future research that's going to be done? Do you expect to expand upon this current research?

Of course, through high quality research we can always refine what we know in clinical practice. There are so many antiplatelet agents and so many anticoagulants and in so many different doses that if we do the permutations of options that we can treat patients today, we have 2.8 million different combinations of treatment. We have studied four of them. Of course there are many, many other combinations that if one wants to study, or if one wants to decide if it can be used or not or for how long, they need to be studied. The best way to do determine what is an appropriate antithrombotic regimen to be used is by more future randomized clinical trials, because that is the best and only way to assess any treatment effect of any drug or any combination of drugs.

Just like we did with these four regimens above. We have studied them in randomized trials. Now, if anyone wants to further refine that or further refine durations of these drugs, or test other drugs or different doses, then we need to study them in more randomized clinical trials.

Finally, is there anything else you would like to add?

The message that we learned is that for sure in these patients with AFib and PCI, less is more. Less antithrombotic therapy, in other words dropping aspirin by the time of hospital discharge and going only with two drugs, a NOAC plus a P2Y12 inhibitor is enough and gives us the greatest net clinical benefit.

After 12 months, we should stop the P2Y12 inhibitor, and for most patients go with only the oral anticoagulant. Again, when trying to find the antithrombotic sweet spot, I think we showed that in the first 12 months the sweet spot is a double therapy with only two drugs without aspirin for most patients.

After 12 months, we showed that the sweet spot is basically with only one drug, which is the oral anticoagulant. We don't need to use antiplatelet agent routinely for those patients after 12 months of the ACS event or PCI when patients are already on an anticoagulant.

Reference:

Lopes RD, de Barros E Silva PGM, Damiani LP, et al. Major Adverse Cardiovascular Events After 12 Months Among Patients With Acute Coronary Syndrome Receiving Loading Doses of Atorvastatin Prior to Planned PCI. JAMA. 2020;323(8):787–789. doi:10.1001/jama.2020.0118