For patients with drug elution stent that complete the first 6 to 18 months of antiplatelet therapy of platelets, continuing with the long duration clopidogrel monotherapy was associated with a significantly reduced risk of both ischemic events and major bleeding compared with aspirin monotherapy in the HOST-EXAM randomized trial.
“These data confirm our working hypothesis that long-term maintenance antiplatelet monotherapy with clopidogrel produces better results than aspirin in patients who have no adverse events one year after coronary stent,” said Hyo-Soo Kim, MD , PhD, internal medicine professor at Seoul National University Hospital, Seoul, South Korea, and lead author of the study.
Kim presented the results of the HOST-EXAM study from South Korea on May 16 at the American College of Cardiology (ACC) virtual science session 2021. The study was was published simultaneously inside The Lancet.
The trial randomly assigned 5,530 patients who had received antiplatelet therapy without clinical events for 6 to 18 months after a drug-eluting stent to receive either clopidogrel 75 mg monotherapy once daily or aspirin. 100 mg once daily for 24 months.
The main final criterion, a compound of death for all causes, non-fatal myocardial infarction (MI), stroke, readmission due to acute coronary syndrome (ACS) and Bleeding Academic Research Consortium (BARC) bleeding type ≥3, occurred in 5.7% of patients in the clopidogrel group and 7.7% in the aspirin group, a relative reduction of 27%. with clopidogrel (risk ratio) [HR], 0.73; Pg = .0035).
The results also showed that clopidogrel reduced both ischemic and bleeding starting points compared to aspirin.
Secondary compound thrombotic endpoint of cardiac death, nonfatal MI, stroke, readmission due to ACS, or permanent or probable stent thrombosis occurred in 3.7% of patients in the clopidogrel group and 5.5% of patients in the aspirin group (HR, 0.68; Pg = .0028). The number needed to try to prevent a thrombotic event was 59.
Any bleeding (BARC type ≥2) occurred in 2.3% of patients in the clopidogrel group and in 3.3% of patients in the aspirin group (HR, 0.70; Pg = .036), giving a number needed to try to prevent a bleeding episode of 111.
Kim reported that most of the difference in bleeding events between the two groups referred to severe bleeding (BARC type 3C), including intracranial bleeding or intraocular bleeding that could lead to blindness. Gastrointestinal bleeding was also reduced with clopidogrel.
Particular endpoints that were reduced with clopidogrel included nonfatal MI (0.7% vs 1.0%), stroke (0.7% vs 1.6%), hemorrhagic stroke (0.2% vs 0.6%), DHW readmission (2.5% vs 4.1%) and major bleeding (BARC ≥3; 1.2% vs 2.0%).
All-cause death was numerically higher in the clopidogrel group (1.9% vs. 1.3%), although this was a non-significant difference.
Kim explained that current treatment guidelines recommend a dual platelet antiplatelet regimen 6 to 12 months after stent implantation, followed by monotherapy. But it is not clear the optimal antiplatelet agent for long-term maintenance therapy.
“Our results may be useful in helping physicians select antiplatelet monotherapy for patients who are in a chronic stable phase after a coronary stent,” he concluded.
“A very important and shocking test”
The study’s designated speaker at the ACC presentation, Cindy Grines, MD, said it was a “very important and impactful trial” that showed “a fascinating and provocative outcome,” despite an index of events lower than expected.
The results are similar to those of CAPRIE process, conducted more than 20 years ago, of clopidogrel versus aspirin for secondary prevention, but in this study, aspirin was administered at a dose of 325 mg, noted Grines, who is the scientific director of the Northside Cardiovascular Institute in Atlanta, Georgia.
“Showing a reduction in bleeding compared to aspirin at a dose of 100 mg is even more impressive and very amazing,” he said.
Grines asked Kim if she believed the results would be applicable outside of Asia, especially in the United States, where there is a much greater degree of racial diversity and where obesity rates are higher.
“There is definitely a difference in the balance of bleeding thrombosis between Asians and Caucasians, but clopidogrel resistance is a lesser problem in Caucasians, so I think the results should be applicable to them,” he replied.
Discussing the HOST EXAM study at an ACC press conference, Claire Duvernoy, Ph.D., professor of medicine at the University of Michigan, Ann Arbor, Michigan, described the trial as “very provocative and can change practice “.
“Aspirin has been around for hundreds of years and has become the cornerstone of therapy in the fight to defeat coronary heart disease. It really is the cornerstone of the therapies we use, and yet , we all know that it carries a significant cost that can be poorly tolerated in terms of gastrointestinal side effects and has significant risks of bleeding, ”Duvernoy noted. “This test is another important finding in our search for alternatives.”
He said the study showed that patients whose conditions have been stable after stent placement can safely and effectively switch from antiplatelet therapy to clopidogrel monotherapy.
Duvernoy noted that clopidogrel monotherapy is not widely used in the United States. “In my practice, I don’t use clopidogrel very often as monotherapy. I usually use it only in patients who don’t tolerate aspirin. Most of us in the US use aspirin as long-term monotherapy afterwards. of stent placement, “he added. “This will be a fascinating alternative.”
On the issue of applying HOST-EXAM results to non-Asian populations, Duvernoy said he thought this would be possible.
“The Korean population studied in this trial has a high prevalence of the clopidogrel loss of function allele, which would have suggested that clopidogrel would be less effective, and yet the study found it to be more effective and safer, ”he noted. “For me, this suggests that we can apply these results to other populations as well. While I would like this strategy to be confirmed in multiethnic populations, for me this is very encouraging.”
Duvernoy also raised the question of whether patients receiving long-term monotherapy with clopidogrel could be operated on safely without having to stop taking the medication.
“We have felt comfortable slowly operating on patients with aspirin, but I have not yet seen a surgeon who is comfortable operating on patients who are taking antiplatelet therapy or monotherapy with clopidogrel,” he said. “While this study certainly suggests that the risk of bleeding is not higher and may be lower with clopidogrel, whether this also applies to perioperative bleeding is a critical question that will need to be answered to allow us to use this therapy in a general way “.
Asked why the all-cause mortality rate was higher in the clopidogrel group, Kim noted that the number of non-cardiac and cancer deaths was numerically higher in the clopidogrel group. He wondered if this could have been due to the fact that aspirin was related to lower mortality by colon cancer or it was just the play the opportunity.
“The highest numerical rate of these events in our study did not reach statistical significance, so we have no conclusive opinion on this,” he stated.
Researchers will continue to follow patients in this study for up to ten years. “With this long-term follow-up, we should be able to get a more detailed idea of this,” Kim added.
Also commenting on the findings, Deepak Bhatt, MD, executive director of cardiovascular intervention programs at Brigham and Women’s Hospital Heart and Vascular Center, Boston, Massachusetts, said he believed the numerical increase in death from all probable causes it was gambling.
“The much larger CAPRIE trial randomized high-risk prevention patients to aspirin or clopidogrel and found a reduction in ischemic events that favor clopidogrel, a reduction in hospitalization for gastrointestinal bleeding with clopidogrel, and no difference in mortality or cancer, ”Bhatt said.
“So it was a broader, long-term study in which the ischemic and hemorrhagic results reflected the results of this trial, but there was no concern about mortality or cancer, so I would say this is probably the statistical game of chance. But certainly a long-term follow-up will be very interesting. “
The HOST-EXAM trial was funded by grants from a consortium of four pharmaceutical companies (ChongKunDang, SamJin, HanMi, and DaeWoong) and by grants from the Patient-Centered Clinical Research Coordination Center and Project I. + D of Korean Health Technology. the Ministry of Health and Welfare of South Korea. Kim has received research grants or fees from speakers from Medtronic, Abbott Vascular, Edwards Life Science, Boston Scientific, Terumo, Biotronik and Dio, AmGen, Pfizer, AstraZeneca, MSD, Daiichi Sankyo and Boehringer Ingelheim.
Scientific session of the American College of Cardiology (ACC) 2021: presented on May 16, 2021.
Lancet. Published online May 16, 2021. Full text