Does Cardiology Hold Pharmacogenetics to an Inconsistent Standard? A Comparison of Evidence Among Recommendations

Abstract

Current guideline recommendations for pharmacogenetic testing for clopidogrel by the American Heart Association/American College of Cardiology (AHA/ACC) contradict the Clinical Pharmacogenetics Implementation Consortium and the US FDA. The AHA/ACC recommends against routine pharmacogenetic testing for clopidogrel because no randomized controlled trials have demonstrated that testing improves patients' outcomes. However the AHA/ACC and the National Comprehensive Cancer Network (NCCN) recommend other pharmacogenetic tests in the absence of randomized controlled trials evidence. Using clopidogrel as a case example, we compared the evidence for other pharmacogenetic tests recommended by the AHA/ACC and NCCN. In patients that received percutaneous coronary intervention, the evidence supporting pharmacogenetic testing for clopidogrel is stronger than other pharmacogenetic tests recommended by the AHA/ACC and NCCN.

Moving Pharmacogenetics Into Practice: It’s All About the Evidence!

“…RCTs of genotype‐guided thiopurine dosing in inflammatory conditions have been conducted, but none of them showed that genotype‐guided thiopurine dosing significantly improved outcomes 77 . Regardless, the American College of Gastroenterology clinical guideline for the management of Crohn’s disease in adults states “Thiopurine methyltransferase (TPMT) testing should be considered before initial use of azathioprine or 6‐mercaptopurine to treat patients with Crohn’s disease (strong recommendation, low level of evidence).” 78 Another example is in the 2017 AHA/ACC/HRS guideline for the management of patients with syncope, which states “The response to beta‐blockers depends on the genotype…” 79 The data supporting that statement comes solely from two observational registries 80 . Nearly half of drug‐gene pairs have differences in their guideline recommendations, 81 which demonstrates variable interpretations of the available evidence in practice guidelines.…”

Pharmacogenetics in the Treatment of Cardiovascular Diseases and Its Current Progress Regarding Implementation in the Clinical Routine

“…Despite the evidence and the PGx guidelines, the current guidelines for the treatment of ACS by the American Heart Association/American College of Cardiology (AHA/ACC) and the guideline recommendations by European Society of Cardiology do not make references to the possibility of carrying out the pharmacogenetic test even in high-risk patients (ACS–PCI–stent) and, in consequence, they contradict the CPIC and DPGW guidelines and the FDA and EMA recommendations. A recent and very good review of the lack of updating of the American and European cardiology guidelines of ACS with respect to the clopidogrel test has been published by Luzum and Cheung [7]. The AHA/ACC recommends against routine pharmacogenetic testing for clopidogrel because no RCTs have demonstrated the testing improves patient’s outcomes [55].…”

“…The AHA/ACC recommends against routine pharmacogenetic testing for clopidogrel because no RCTs have demonstrated the testing improves patient’s outcomes [55]. According to the authors of this article [7], the level of evidence supporting by CYP2C19 genotype-guided clopidogrel therapy in patients that received PCI is at least as strong as the other genetic tests recommended by the AHA/ACC. Fortunately, several institutions have implemented pharmacogenetic testing for clopidogrel despite the negative recommendation by AHA/ACC [35,45,56,57] and they found improvement in the clinical results of patients [58,59].…”

“…Among them, we can highlight the lack of correlation between the different PGx guidelines and those published by other professional organizations (oncology, cardiology, etc.) [7], the lack of a clinically relevant PGx test panel, the need for training of health personnel and patients, and the lack of information on cost-effectiveness studies [8,9]. All of those reasons prevent physicians from demanding a proactive approach to PGx.…”

Multi-Ethnic Analysis of Cardiac Pharmacogenetic Markers of Cytochrome P450 and Membrane Transporters Genes in the Russian Population

“…На сегодняшний день рекомендации кардиологических профессиональных сообществ касательно применения ФГТ противоречивы и неутешительны. Ярким примером служат рекомендации Американской ассоциации сердца и Американской коллегии кардиологов (AHA\ACCA), противоречащие позиции надзорного органа по контролю качества пищевых продуктов, лекарственных препаратов в США (US FDA) и Консорциума по внедрению клинической фармакогенетики (CPIC) относительно целесообразности применения фармакогенетического тестирования по CYP2C19 для клопидогрела у пациентов с острым коронарным синдромом [75]. Подобные несоответствия во многом обусловлены недостаточным количеством крупных сравнительных проспективных клинических исследований, подтверждающих преимущества фармакогенетического подхода к терапии по сравнению со стандартным -то есть, целесообразность использования маркеров в клинической практике.…”