US Updates ACS Guidance; Ticagrelor Gets Equal Billing to Other Antiplatelets

July 17, 2012

July 17, 2012 (Houston, Texas) — American cardiology societies have caught up with the European Society of Cardiology (ESC) by issuing their second update to the unstable angina/non-STEMI guidelines in 18 months, with the 2012 focused update replacing the 2011 one [1]. The new recommendations include ticagrelor (Brilinta, AstraZeneca) as one of the options for antiplatelet therapy alongside prasugrel (Effient, Lilly) and clopidogrel, bringing them in line with European guidance issued last September.

The European guidance, however, gave precedence to the new antiplatelets over clopidogrel, whereas the American update "places ticagrelor on an equal footing with the other two antiplatelets available--this is the main reason for the update," lead author Dr Hani Jneid (Baylor College of Medicine, Houston, TX), told heartwire . "Doctors now have a choice for second-line therapy after aspirin, depending on the patient's clinical scenario, physician preference, and cost," because the latter will come into play now that clopidogrel is available generically, he noted.

The US decision to recommend first prasugrel--in its 2011 update to the unstable angina/non-STEMI guidelines--and now ticagrelor as equivalent antiplatelet therapy choices to clopidogrel after aspirin puts it somewhat at odds with the Europeans, who reserve clopidogrel use for those who cannot take the newer agents.

But Jneid says the Americans have their reasons for this differing stance. While it's "biologically plausible" to recommend ticagrelor and prasugrel in preference to clopidogrel--"because they are faster acting and more potent"--the cost-effectiveness of the new agents is not known, he says. Nor is it clear how the efficacy observed in pivotal clinical trials of these agents is going to translate into real-world benefit, he says, adding that issues such as bleeding with prasugrel and compliance with a twice-daily drug such as ticagrelor remain concerns.

Bulk of 2012 Update on How to Use Ticagrelor

The 2012 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) focused update for the management of UA/NSTEMI stresses that all patients at medium/high risk should receive dual antiplatelet therapy on admission, with aspirin being first-line, indefinite therapy.

The bulk of the update centers on how to use ticagrelor which--like prasugrel or clopidogrel--can be added to aspirin for up to 12 months (or longer, at the discretion of the treating physician). Jneid notes it's important to remember that prasugrel can only be used in the cath lab in patients undergoing PCI, whereas ticagrelor, like clopidogrel, can be used in medically managed or PCI patients.

And he emphasizes that, in line with the FDA's black-box warning on ticagrelor, this new antiplatelet agent must only be administered with a "baby" dose of aspirin (81 mg in the US).

The 81-mg aspirin dose is also considered a reasonable option in preference to a higher maintenance dose of 325 mg in any ACS patient following PCI, he adds, as this strategy is believed to result in equal efficacy and lower bleeding risk.

With regard to how long antiplatelet therapy should be stopped before planned cardiac surgery, the recommendation is five days for ticagrelor--the same as that advised for clopidogrel. For prasugrel, the guidance is to stop therapy seven days prior to surgery.

Jneid also highlights other important recommendations from the 2011 focused update carried over to 2012:

It is "reasonable" to proceed with cardiac catheterization and revascularization within 12–24 hours of admission in initially stable, very high-risk patients with ACS.

An invasive strategy is "reasonable" in patients with mild and moderate chronic kidney disease.

In those with diabetes hospitalized with ACS, insulin use should target glucose levels <180 mg/dL, a less-intensive reduction than previously recommended.

Platelet function or genotype testing for clopidogrel resistance are both considered "reasonable" if physicians think the results will alter management, but it is acknowledged that "there is not much evidence to support these assays," says Jneid.

Committee Encourages Participation in Registries

Jneid observes that unstable angina and NSTEMI are "very common" conditions that carry a high risk of death and recurrent heart attacks, which is why "the AHA and ACCF constantly update their guidelines so that physicians can provide patients with the most appropriate, aggressive therapy with the goal of improving health and survival."

To this end, he notes that the writing panel encourages clinicians and hospitals to participate in quality of care registries designed to track and measure outcomes, complications, and adherence to evidence-based medicines.

Conflicts of interest for the writing committee are listed in the paper.