ACC2018 Live Report in Orlando, USA
ACC 2018 was held on March 10-12, local time in Orlando, Florida, USA, and the highly anticipated PHIRAMCLO study arrived as scheduled. Research is like a spring breeze, breaking the current "more effective, more powerful" anti-platelet pattern, and creating a precedent of "more suitable and more correct".
Adverse clinical events in the gene therapy group were significantly reduced
The PHARMCLO study is a prospective, randomized, multicenter study exploring the use of pharmacogenomic methods to guide antiplatelet therapy in patients with acute coronary syndrome (ACS). For the first time, the study combined clinical features with genetic information to guide the selection of P2Y12 receptor antagonists in PATIENTS.
The study included 888 ACS hospitalized patients, half of whom received standard treatment, i.e. doctors administering clopidogrel, ticagrelor or pragrel based on the patient's clinical characteristics. The other half of patients undergo genetic testing, and doctors develop antiplatelet strategies based on genetic test results and clinical characteristics. The primary endpoints of the study were cardiovascular death, nonfatal myocardial infarction or stroke, and compound endpoints of BARC type 3 to 5 major bleeding events.
The results showed that clopidogrel use was significantly higher in the standard treatment group than in the genetic testing group (50.7% vs. 43.3%). At 12 months of follow-up, patients who received genetic testing had a 42% lower risk of primary endpoint events compared with patients who did not undergo genetic testing (HR 0.58, 95% CI 0.43 to 0.78, P<0.001, below).
PhARMCLO research pioneered "more appropriate and more correct"
Clopidogrel, as a precursor drug, requires the conversion of the liver enzyme CYP2C19 into an active drug. Genetic variations of this enzyme are common and may result in loss or enhancement of platelet function (insufficient clopidogrel metabolism) or enhancement of function (increased metabolism), which in turn leads to decreased platelet suppression or increased bleeding. A meta-analysis of nine studies found that even a loss of one function of the CYP2C19 allele was associated with an increased risk of cardiovascular events. As early as 2010, the FDA issued a black box warning, mainly for such clopidogrel poor metabolism, reduced effectiveness of patients.
Clarifying patient responsiveness to clopidogrel and adjusting strategies for antiplatelet drugs will help improve clinical outcomes in these patients. But several clinical trials using the individualized treatment regimen have shown no clinical benefit in the last decade or so, possibly because the targets tested in these studies are platelet reactivity rather than the patient's genotype. Genotyping may be a better detection tool than the CYP2C19 gene variant, which only explains about 11% antiplatelet reactivity.
Recently, easy-to-use CYP2C19 genetic testing has become possible. Prior to the PHARMCLO study, a multicenter, non-randomized trial using genotype-guided antiplatelet therapy found that patients with the CYP2C19 functional deletion allele had a higher risk of cardiovascular events following clopidogrel, and the results of the PHARMCLO study were similar.
For patients with ACS, in addition to considering the patient's etiology, the treatment regimen should be selected based on genetic data and clinical characteristics, and a more individualized, more accurate and effective antiplatelet therapy should be accepted to further reduce the risk of ischemia and bleeding. The PHARMCLO study is the first step in pharmacogenomics to advance clinical development, not to try to find more potent antithrombotic drugs, but to ensure that the most reasonable individualized treatment options are available for each patient.
Expert Profiles
Liu Huiliang, Director of the Cardiology Research Institute of the Armed Police Force, Major General, Honorary President of Beijing Electric Power Hospital, Chief Physician, Professor, Doctoral Supervisor. Graduated from Peking Union Medical College of China, engaged in cardiovascular major for 34 years, good at the diagnosis and treatment of various diseases of cardiovascular medicine and the rescue of acute and critical diseases, is one of the earliest experts in China to carry out interventional treatment of coronary heart disease of the radial artery, and successfully completed nearly 10,000 cases of various interventional surgeries, reaching the advanced level in China. He has won the Chinese Physician Award, enjoyed the special government allowance of the State Council, the military outstanding professional and technical personnel award, and the military outstanding professional and technical personnel first-class post allowance.
He has published more than 120 papers at home and abroad, of which more than 30 are included in SCI. He has edited and co-edited 14 monographs, and won 23 national, provincial and ministerial science and technology and medical achievement awards. He has served as a training instructor of the Interventional Training Base for Coronary Heart Disease and Congenital Heart Disease of the Ministry of Health, the chairman of the Cardiovascular Interventional Professional Committee of the Chinese Research Hospital Association, the deputy editor-in-chief of the Rescue Medicine Channel of medical reference newspaper, and the editorial board and standing editorial board of 11 journals such as Heart Journal.
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Edited by Tian Xinfang ┆ Edited by Chai Mingxia - Cen Cong