Optimal doses of Effient and Brilinta different for Koreans

After the introduction of the ‘East Asian Paradox,’ various domestic studies have supported the theory

Efficacy demonstrated with half-dose… a customized, large-scale clinical study is required to verify the results

The theory that East Asians, including Koreans, require dose adjustments when receiving dual antiplatelet therapy (DAPT) prescriptions is gaining strength.

 

In other words, the ‘East Asian Paradox’ theory that antithrombotics' clinical effect and safety are different for East Asians compared to Westerners is now being recognized worldwide.

 

In Korea, with Young-Hoon Jung, director of the Cardiovascular Center at Gyeongsang National University Hospital, marking the start, domestic researchers have emphasized that East Asians show a different response to antithrombotics due to their lower risk of atherothrombotic events and a higher risk for serious bleeding events than Westerners and that an appropriate treatment guideline needs to be developed for Koreans.

 

This opinion had also been reflected in the joint statement published by the Korean Society of Myocardial Infarction last year.

 

As a result, various de-escalation strategies were studied on patients with acute myocardial infarction, all of which significantly reduced bleeding risk.

 

The TICO study that demonstrated the effect of aspirin discontinuation therapy after 3 months, the TALOS-AMI study that showed the effect of switching from 'Brilinta (ticagrelor)' ‘to 'Plavix (clopidogrel)' after 1 month, and the HOST-REDUCE-POLYTECH-ACS that showed the effect of the de-escalation therapy of reducing the dose of 'Effient (prasugrel)' to half, are representative cases of studies supporting dose reduction.

 

In addition, various pharmacokinetic and clinical observation studies that support reduced-dose therapies using Efficient and Brilinta were recently published in Korea and are expected to be used to revise the treatment guidelines in the future.

 

First, Professor Young-hoon Jeong’s team published the results of a multicenter A-MATCH study that was conducted at 8 university hospitals on acute coronary syndrome (ACS) patients in the latest issue of the international journal, Thrombosis and Haemostasis.

 

In the study, ACS patients before discharge were assigned to a standard-dose prasugrel 10mg, half-dose prasugrel 5mg, or platelet function test (PFT)-guided group for a 1-month treatment.

 

Results showed that the ratio of patients that show an appropriate antiplatelet effect was 3.8 times and 3.5 times higher in the latter two groups compared to the Effient 10mg treated group.

 

Bleeding frequency was also lower by 42% and 45% in the other two groups compared to the Effient 10mg treated group.

 

Patients who experienced bleeding were around twice more likely to change drugs within the 1-year treatment period.

 

Professor Jeong explained, “The standard-dose prasugrel had shown excessive strong platelet inhibition in Koreans.

 

On the other hand, the half-dose prasugrel showed a clear reduction in bleeding risk and appropriate antiplatelet effect.”

Also, in the HOPE-TAILOR study published in the international clinical medicine journal, J Clin Med, in June by Dong-A University Hospital’s Professor Mooh Hyun Kim and his Circulatory Internal Medicine team, the half-dose Effient and Brilinta demonstrated a more adequate optimal platelet reactivity (OPR) than the standard dose.

 

However, the half-dose Brilinta treatment still showed excessive strong platelet inhibition and had significantly increased bleeding events in the 9-month treatment period compared to half-dose Effient, and standard-dose Plavix (31.6% vs.

 

12.2%, HR=2.93), also presenting the need for a large-scale clinical study on the optimal drug and dose for Koreans.

 

Pusan National University Hospital’s Professor Jin Sup Park and his Circulatory Internal Medicine team also published their results of the BLEEDING-ACS study that was conducted on ACS patients in the latest issue of an international medical journal.

 

The researchers randomly assigned ACS patients with low platelet reactivity (LPR) to standard-dose (90mg) or half-dose (45mg) of Brilinta to compare their frequency of bleeding events and dyspnea.

 

Results showed that the frequency of bleeding events and dyspnea were similar between the two groups at 6 months, and was most frequent within 3 months of treatment, then decreased over time.

 

However, the researchers also saw a 70% reduction of the Bleeding Academic Research Consortium (BARC) events (BARC type ≥2) in the low-dose Brilinta group.

 

This reduction was more prominent in patients with a BMI of less than 25 kg/m2 or patients over 65 years of age.

 

As in the case of Effient, the result suggests that reducing Brilinta’s dose in patients with a higher risk of bleeding, such as older or underweight patients, may have a more noticeable effect.

 

Professor Park said, “No increase in ischemic events were observed in Korean patients with ACS when reducing the dose of ticagrelor by half.

 

The dose reduction only significantly reduced risk of serious bleeding events.”` Meanwhile, studies on the appropriate dose of Brilinta for Koreans are currently underway, just like the HOST-REDUCE-POLYTECH-ACS studies that demonstrated the effect of half-dose Effient.

 

The EASTYLE study, which is being conducted by Professor Mooh Hyun Kim and Professor Young-Hoon Jung's team, is studying the clinical efficacy of a de-escalation strategy, using 60mg Brilinta (45mg for older and underweight patients), and a hybrid therapy of discontinuing aspirin after 3 months in 2,000 Korean patients