Paris (FRONTLINE MEDICAL NEWS) – A strategy of switching from prasugrel or ticagrelor to clopidogrel 1 month after percutaneous coronary intervention for acute coronary syndrome is superior to the guideline-recommended full 12 months of dual-antiplatelet therapy with either of the newer P2Y12 inhibitors, according to Thomas Cuisset, MD.
In the randomized TOPIC (Timing of Platelet Inhibition After Acute Coronary Syndrome) trial, this switch strategy resulted in a marked reduction in bleeding without an increased risk of ischemic events, compared with a full 12 months of standard dual-antiplatelet therapy (DAPT) using prasugrel (Effient) or ticagrelor (Brilinta).
“The clinical implication of this study is that it provides a new potential strategy of DAPT that integrates the concept of dynamic risk post ACS [acute coronary syndrome],” Dr. Cuisset said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
He added that the cost savings of this switch strategy would be enormous, since generic clopidogrel is vastly less expensive than prasugrel or ticagrelor.
Twelve months of DAPT with aspirin plus either prasugrel or ticagrelor is the guideline-recommended DAPT regimen following PCI for ACS on the strength of the TRITON and PLATO trials, respectively, which showed that those agents were more effective than clopidogrel for the prevention of thrombotic events. But Dr. Cuisset and his coinvestigators noted that the risk of ischemic events was highest in the first month or so following ACS, while the risk of DAPT-related serious bleeding increased after the first month and continued for the duration.
“We need to use the new drugs, and we need to go for 1 year with DAPT. But does that mean we need to go for 1 year with the new drugs?” he asked.
This question was the impetus for TOPIC, an open-label, single-center randomized trial that included 646 ACS patients who were free of major adverse cardiovascular events during their first month on DAPT with prasugrel or ticagrelor. At that point they were randomized to remain on their standard regimen or switch to aspirin at 75 mg/day plus clopidogrel at 75 mg/day for months 2-12. The switch strategy is similar to the way pulmonary embolism is managed: an early phase of high-intensity therapy followed by a backing off to a less intensive regimen, said Dr. Cuisset, a cardiologist at Aix-Marseille University, Provence, France.
The primary endpoint in TOPIC was the cumulative 1-year rate of a composite of all-cause mortality, stroke, urgent revascularization, or clinically significant bleeding as reflected in a Bleeding Academic Research Consortium (BARC) grade 2 or greater bleeding. The primary endpoint occurred in 13.4% of the switch group, a 52% relative risk reduction, compared with the 26.3% cumulative incidence with standard DAPT.
This difference wasn’t due to any between-group disparity in ischemic events, but rather to a 70% reduction in the risk of BARC grade 2 or greater bleeding in the switch group: 4.0% vs. 14.9%.
Some physicians have already been switching to clopidogrel for DAPT after ACS, either because of safety or cost concerns. Now their practice is evidence based, Dr. Cuisset noted.
Asked why TOPIC didn’t use the more stringent bleeding endpoint of BARC grade 3-5 bleeding, the cardiologist replied that it would have required a larger trial to show a significant difference. Besides, he added, BARC grade 2 bleeding is clinically important because it has a negative impact on quality of life and can cause patients to discontinue DAPT, thereby increasing their risk of thrombosis.
The TOPIC protocol didn’t utilize a loading dose of clopidogrel when making the switch. Investigators started clopidogrel the day after stopping prasugrel and at least 12 hours after the final dose of ticagrelor.
Ideally, the novel TOPIC findings should be confirmed in a much larger, randomized, double-blind clinical trial capable of detecting any small differences in stent thrombosis or MI rates before physicians adopt a change in practice, but discussant Chaim Lotan, MD, director of the Heart Institute at Hadassah Medical Center in Jerusalem, dismissed that prospect as unlikely.
“I tried myself to do a similar study and found I got a lot of opposition from the pharma companies as well as from physicians who said, ‘How can you go against the guidelines?’ ” he said.
“I want to congratulate your team because I think this is a groundbreaking study that is going to dictate a changing of the guidelines,” he told Dr. Cuisset.
Dr. Cuisset reported having no financial conflicts regarding this investigator-driven study funded without commercial support.
Simultaneous with his presentation in Paris, the TOPIC findings were published online (Eur Heart J. 2017 May 16. doi: 10.1093/eurheartj/ehx175 ).
Dr. Cuisset reported no financial conflicts regarding this investigator-driven study funded without commercial support.