PLATO: Ticagrelor Lowers Stent Thrombosis vs. Clopidogrel Across the Board in ACS

Download this article's Factoid (PDF & PPT for Gold Subscribers)

Among patients with acute coronary syndromes (ACS) who undergo stent implantation, ticagrelor’s superior ability to reduce stent thrombosis compared with clopidogrel is consistent across a broad range of patient, stent, and treatment subgroups. The findings, from a new analysis of the PLATO trial, were published online July 30, 2013, ahead of print in Circulation.

PLATO enrolled 18,624 patients hospitalized for ACS from October 2006 through July 2008. All received aspirin and were also randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). Overall results from the trial, published in the New England Journal of Medicine in 2009, showed ticagrelor reduced not only the composite of cardiovascular death, MI, or stroke (primary endpoint) but also 12-month rates of stent thrombosis.

For the current report, Philippe Gabriel Steg, MD, of Hôpital Bichat (Paris, France), and colleagues sought to better understand the effects of ticagrelor vs. clopidogrel among the 61% (n = 11,289) of PLATO patients who had coronary stents, either previously implanted (n = 1,404) or inserted during the course of the trial (n = 9,885).

Consistent Benefit Seen

As reported in the N Engl J Med paper, ticagrelor decreased stent thrombosis at 12 months compared with clopidogrel regardless of how stringently the endpoint was defined by Academic Research Consortium criteria (table 1).

Table 1. Stent Thrombosis at 12 Months

 

Definite stent thrombosis was consistently lower with ticagrelor irrespective of ACS type, diabetes status, BMS vs. DES use, enrollment in North America vs. elsewhere, aspirin loading dose, intended treatment strategy (invasive or medical management), CYP2C19 genotype, or GPI use. Ticagrelor’s benefit remained consistent no matter patients’ clopidogrel dose (pre-randomization or total loading dose), though it appeared more substantial in patients receiving 600-mg vs. lower loading doses.

Of the 147 cases of definite stent thrombosis that occurred, most were subacute (24 hours-30 days; 58.5%), followed by late (> 30 days; 24.5%) and acute (≤ 24 hours; 17.0%). Ticagrelor reduced stent thrombosis in the subacute and late phases, although not in the acute phase. In addition, most events occurred while patients were taking their assigned treatment (61.9%).

Patients who experienced stent thrombosis saw higher rates of major bleeding and all-cause death after their events compared with before (32.7% vs. 7.6% and 21.6% vs. 0.18%, respectively).

Multivariable analysis identified several independent predictors of definite stent thrombosis (table 2).

Table 2. Independent Baseline Predictors of Definite Stent Thrombosis

 

Additional predictors for definite/probable stent thrombosis were diabetes, ethnicity, and enrollment in Asia/Australia, while any thrombosis also was predicted by chronic obstructive pulmonary disease and prior MI. For all definitions, ticagrelor use was inversely associated with stent thrombosis risk.

Ticagrelor ‘Vastly Superior’

“This analysis confirms that ticagrelor is vastly superior to clopidogrel, even when using a loading dose of 600 mg, in prevention of stent thrombosis,” Dr. Steg told TCTMD in an e-mail communication, citing the drug’s consistent level of benefit. One particularly noteworthy finding, he said, is the fact that the CYP2C19 genotype, “the major gene controlling clopidogrel metabolism,” did not influence the equation.

Ticagrelor “should be preferred for [its ability to prevent stent thrombosis] in addition to the documented clinical benefits previously reported in PLATO,” Dr. Steg concluded.

Also in an e-mail communication with TCTMD, Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), agreed that the analysis confirms ticagrelor’s wide-ranging advantage. “The benefits are clinically relevant, as stent thrombosis remains a serious concern among interventional cardiologists. It is something we worry about,” he said.

Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), commented in a telephone interview that “[t]here’s really nothing remarkably new here. It confirms the original report.” He also pointed out that “a major proviso” of this study is its lack of a core angiographic lab to adjudicate stent thrombosis events.

Though the absolute differences in stent thrombosis are small, stent thrombosis is “associated with a very high rate of death and myocardial infarction, as confirmed once again in this study, so it would best be avoided if possible,” he commented.

Some Known Downsides

The drawbacks of ticagrelor are its higher price compared with generic clopidogrel, twice daily administration, and increased rate of dyspnea at the onset of therapy, Dr. Steg acknowledged. He stressed, however, that “dyspnea rarely led to discontinuation and generally will disappear even when patients continue treatment.”

In addition to the possibility of dyspnea, which “tends to occur early if it is going to occur,” Dr. Bhatt mentioned that ticagrelor can lead to more bleeding than clopidogrel.

 

 

Related Stories:

• PLATO Substudy: Ticagrelor Advantage Persists After First Ischemic Event
• Ticagrelor More Effective Than Clopidogrel in ACS-With No Extra Bleeding
• PLATO Substudy Shows Greater Platelet Inhibition with Ticagrelor vs. Clopidogrel