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DAPT Safer With Switch from P2Y12 Blockers Early After Stenting

<ѻý class="mpt-content-deck">— Substituting in clopidogrel after a month cuts bleeding risk, trial says
Last Updated May 17, 2017
MedpageToday

PARIS -- Switching from dual antiplatelet therapy (DAPT) with newer P2Y12 inhibitors to the combination of clopidogrel (Plavix) and aspirin after a month cuts bleeding risk, according to a single-center trial in stented acute coronary syndrome.

Compared with patients who got a full year of DAPT with aspirin and prasugrel (Effient) or ticagrelor (Brilinta), those who stayed on the regimen for 1 month before the switch to aspirin and clopidogrel had half as many deaths, urgent revascularizations, strokes, and BARC-2-or greater bleeds at 1 year (13.4% versus 26.5%, HR 0.48, 95% CI 0.34-0.68).

Action Points

  • Note that this randomized trial found that a switch from aspirin plus a P2Y12 inhibitor to aspirin plus clopidogrel 1 month after ACS was associated with less bleeding risk than remaining on the original regimen.
  • Given that the costs of this approach are significantly lower at current drug prices, this may prove an attractive treatment strategy.

But the benefit was driven by reduced BARC bleeding alone (4.0% versus 14.9%, HR 0.30, 95% CI 0.18-0.50), Thomas Cuisset, MD, PhD, of Centre Hospitalier Universitaire Timone in France, reported in a late-breaking trial presentation at the EuroPCR meeting and online in the .

The other single endpoints were comparable between the clopidogrel-switch and continued-P2Y12 groups in the TOPIC (Timing Of Platelet Inhibition after acute Coronary Syndrome) trial:

  • Ischemic events: 9.3% versus 11.5% (HR 0.80, 95% CI 0.50-1.29)
  • Cardiovascular death: 0.3% versus 1.2% (HR 0.30, 95% CI 0.05-1.73)
  • Unplanned revascularization: 8.7% versus 9.3% (HR 0.93, 95% CI 0.56-1.55)
  • Stent thrombosis 1.2% versus 0.9% (HR 1.34, 95% CI 0.30-6.0)
  • TIMI major bleeding (0.3% versus 1.2%, HR 0.30, 95% CI 0.05-1.73)

What about MI? "Glaringly absent" was how panelist Upendra Kaul, MD, of India's Fortis Hospitals, described it.

Cuisset responded that the authors felt justified that revascularization would sufficiently account for MIs.

"The more rational endpoints would be MI and stent thrombosis versus bleeding, since death and stroke events would be few in a sample size of around 500," said Eric Bates, MD, of Michigan Medicine in Ann Arbor, an interview with ѻý. That said, "the WOEST trial had similar limitations comparing triple therapy with DAPT, but was practice changing, as this trial may be."

Meanwhile, several clinicians voiced interest in the economic implications of the trial.

"So far, in many countries like China, ticagrelor is expensive and not reimbursed," said panelist Runlin Gao, of Fuwai Hospital there. Clinicians have already started to change P2Y12 inhibitors after several months -- and before TOPIC, there was no evidence for the practice, according to Gao.

"It is nice to see a pragmatic trial testing a strategy that some already use empirically. This is good news for U.S. patients with high co-pays for prasugrel or ticagrelor and for those with increased bleeding risk," Bates commented.

"I have also been using this strategy only in patients who could not continue on newer P2Y12 [inhibitors] such as after a bleeding or drug intolerance," said Marco Valgimigli, MD, PhD, of Switzerland's Bern University Hospital, in an interview.

"I am convinced the bleeding signal in this study is credible and most likely reproducible, but I am totally skeptical that this small study has enough power to reassure about the possible ischemic risks of switching," he said. "I will not be surprised if the community will react similarly to me."

TOPIC randomized 646 patients after 1 month of DAPT with aspirin and a newer P2Y12 inhibitor to stay on that regimen or switch to clopidogrel and aspirin for up to 1 year. Patients were eligible for inclusion if they had no adverse events 1 month after stenting for acute coronary syndrome (ACS). They largely got radial access interventions with drug-eluting stents (DES).

When moving from prasugrel to clopidogrel, Cuisset and colleagues saw no need to give a loading dose. With ticagrelor, however, it remains in question whether a loading dose should be used.

Ejection fraction tended to be slightly lower among the non-clopidogrel group (55.8% versus 57.1% for switched-drug cohort, P=0.04).

Chief among the study's limitations were its single-center nature and open-label design. The study was also underpowered for infrequent endpoints like stent thrombosis.

As to generalizability, "while the combination of ischemic events and bleeding might appear justified, it's not commonly seen in ACS studies, which makes comparison difficult," said Kaul, who added that the sample size calculation wasn't based on any contemporary trial.

Even so, "I think this is the first study (with all of the weaknesses) that is going to change the guidelines. Without the support of industry, without anything, the investigators are going to change the guidelines," suggested another discussant, Chaim Lotan, MD, of Hadassah Medical Center in Israel.

  • author['full_name']

    Nicole Lou is a reporter for ѻý, where she covers cardiology news and other developments in medicine.

Disclosures

Cuisset disclosed consulting for Daiichi Sankyo and Eli Lilly; and getting lecture fees from Abbott Vascular, AstraZeneca, Biotronik, Boston Scientific, Cordis, Daiichi Sankyo, Sanofi, Edwards, Eli Lilly, and Medtronic.

Bates had no disclosures.

Valgimigli reported no financial conflicts of interest but is co-principal investigator of the Global Leaders Study and MASTER DAPT trial.

Primary Source

European Heart Journal

Cuisset T, et al "Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (Timing Of Platelet Inhibition after acute Coronary Syndrome) randomized study" Eur Heart J; ehx175. DOI: https://doi.org/10.1093/eurheartj/ehx175