By Dr. Brit Cooper-Jones
A common challenge in the area of cardiovascular care is balancing bleeding risk versus clotting risk. Many people have heard of “antiplatelet drugs” (medications that reduce the risk of the blood forming clots) and may even be taking them themselves. Antiplatelet drugs play an important role in reducing the risk of heart attacks, strokes, and other clotting-related conditions. However, these same medications, by their very mechanism of reducing clot formation, also put patients at a higher risk of bleeding.
As such, decisions around whom to prescribe antiplatelet drugs to – including what drug(s), and for how long – are not ones that are taken lightly. While antiplatelet drugs can be a lifesaving medication in many cases, we want to ensure that the benefits outweigh the risks before deciding how to proceed.
One area of medicine where antiplatelet drugs are routinely given is following percutaneous coronary intervention, or “PCI.” PCI is frequently performed in patients following a heart attack, or for the treatment of angina (pain that results from a partial blockage of one or more coronary arteries).
The procedure involves inserting a catheter into the patient’s groin or arm, and then threading the catheter through the patient’s blood vessels until it reaches the narrowed or blocked artery. A balloon is then inflated to help re-open the affected artery, and a stent is often inserted.
Following PCI with stent insertion, antiplatelet drugs are important because they help to prevent subsequent heart attacks, strokes, clots at the site of the stent, and other complications. Typically, two drugs are given: aspirin, and something called a P2Y12 inhibitor. Examples of P2Y12 inhibitors include clopidogrel, prasugrel, and ticagrelor. When both aspirin and a P2Y12 inhibitor are prescribed, it is called dual antiplatelet therapy, or “DAPT.”
Of note, the question facing the health care community is not whether to prescribe DAPT following PCI with stent insertion — this has already been established as the standard of care. Rather, the key questions are: how long should DAPT be prescribed (the standard duration of six to 12 months or for an extended duration of greater than 12 months), in what subsets of patients should extended treatment be considered, what P2Y12 inhibitor (if any) is superior to the other(s), and should extended DAPT be publicly funded?
To help answer these questions, and to guide decisions about the optimal prescribing of DAPT post-PCI, decision-makers and the health care community turned to CADTH – an independent agency that finds, assesses, and summarizes the research on drugs, medical devices, tests, and procedures – to find out what the evidence says.
CADTH conducted a Health Technology Assessment (HTA) that evaluated the comparative clinical effectiveness and safety, as well as the comparative cost-effectiveness, of standard-duration versus extended-duration DAPT following PCI with stent insertion. The HTA also looked at the evidence for clinically relevant subgroups, to see if certain subsets of patients may benefit more than others from extended treatment. Three different P2Y12 inhibitors were considered: clopidogrel, prasugrel, and ticagrelor. The Canadian Drug Expert Committee (CDEC) then developed recommendations based on the findings from CADTH’s report.
Overall, the evidence found that extended-duration DAPT was beneficial, both from a clinical effectiveness and a cost-effectiveness standpoint, for many but not all patients. The main benefits included a decreased risk of subsequent heart attacks and/or clots at the site of the stent. However, these benefits were accompanied by an increased risk of bleeding. As a result, CDEC recommended the reimbursement of extended DAPT, but also noted that the risk-to-benefit ratio of extended DAPT varies based on the individual characteristics and risk factors of each patient.
At the time of their deliberations, there was insufficient evidence for CDEC to make specific subgroup-level prescribing recommendations. The committee instead noted that the decision to extend treatment needs to be highly individualized and based on a cardiovascular specialist’s assessment of each patient.
With regards to drug choice, there was insufficient evidence to determine whether clopidogrel, prasugrel, or ticagrelor was preferable for patients receiving extended DAPT. Therefore, it was recommended that all three drugs be reimbursed, and that the choice of drug be left to the discretion of the treating physician.
Finally, while the majority of the patients in the research studies had drug-eluting stents (and therefore CDEC’s recommendations pertained to patients with drug-eluting stents), CDEC noted that this should not preclude the reimbursement of extended DAPT for patient with bare metal stents.
To view CADTH’s full report, see: https://cadth.ca/dual-antiplatelet-therapy-following-percutaneous-coronary-intervention-clinical-and-economic-impact
And if you would like to learn more about CADTH, visit cadth.ca, follow us on Twitter @CADTH_ACMTS, or speak to a Liaison Officer in your region: cadth.ca/Liaison-Officers
By Dr. Brit Cooper-Jones is a Knowledge Mobilization Officer at CADTH.