Evaluation of a pharmacogenetic-based warfarin dosing algorithm in patients without stable dose

• Grant number: 16/23454-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2017
• End date: March 31, 2021
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Paulo Caleb Júnior de Lima Santos
• Grantee: Leiliane Rodrigues Marcatto
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/09295-3 - Pharmacogenetic of cardiovascular system drugs focusing on implementation, AP.JP

Abstract

Background: Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (<50%) are associated with greater risk of thromboembolic and bleeding events. Recently, we developed a pharmacogenetic-based warfarin dosing algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (<50%) from a tertiary cardiovascular hospital. Methods/design: This study is a randomized controlled trial in patients (n=300) with atrial fibrillation with TTR<50%, based on the last three INR values. At the first consultation, patients will be randomized into two groups: TA group (traditional anticoagulation) and PA group (pharmacogenetic anticoagulation). For the first group, the physician will adjust the dose according to current INR value and, for the second group, a pharmacogenetic algorithm will be used. At the second, third, fourth and fifth consultations (with an interval of 7 days each) INR will be measured and, if necessary, the dose will be adjusted based on guidelines. Afterwards, patients who are INR stable will begin measuring their INR in 30 day intervals; if the patient´s INR is not stable, the patient will return in 7 days for a new measurement of the INR. Outcomes measures will include the time to achieve the therapeutic target and the percentage of TTR at 4 and 12 weeks. In addition, as a secondary end-point, pharmacoeconomic analysis will be carried out. Ethical approval was granted by the Ethics Committee for Medical Research on Human Beings of the Clinical Hospital of the University of São Paulo Medical School.

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TAVARES, LETICIA C.; DUARTE, NUBIA E.; MARCATTO, LEILIANE R.; SOARES, RENATA A. G.; KRIEGER, JOSE E.; PEREIRA, ALEXANDRE C.; JUNIOR LIMA SANTOS, PAULO CALEB. Impact of incorporating ABCB1 and CYP4F2 polymorphisms in a pharmacogenetics-guided warfarin dosing algorithm for the Brazilian population. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, v. 74, n. 12, p. 1555-1566, DEC 2018. (16/22507-8, 16/23454-5, 13/09295-3)

STEINER, HEIDI E.; GILES, JASON B.; PATTERSON, HAYLEY KNIGHT; FENG, JIANGLIN; EL ROUBY, NIHAL; CLAUDIO, KARLA; MARCATTO, LEILIANE RODRIGUES; TAVARES, LETICIA CAMARGO; GALVEZ, JUBBY MARCELA; CALDERON-OSPINA, CARLOS-ALBERTO; et al. Machine Learning for Prediction of Stable Warfarin Dose in US Latinos and Latin Americans. FRONTIERS IN PHARMACOLOGY, v. 12, OCT 29 2021. (16/23454-5, 13/09295-3, 19/08338-7)

MARCATTO, LEILIANE RODRIGUES; SACILOTTO, LUCIANA; TAVARES, LETICIA CAMARGO; PEREIRA SOUZA, DEBORA STEPHANIE; OLIVETTI, NATALIA; CASSARO STRUNZ, CELIA MARIA; COSTA DARRIEUX, FRANCISCO CARLOS; SCANAVACCA, MAURICIO IBRAHIM; KRIEGER, JOSE EDUARDO; PEREIRA, ALEXANDRE COSTA; et al. Evaluation of the Long-Term Impact on Quality After the End of Pharmacist-Driven Warfarin Therapy Management in Patients With Poor Quality of Anticoagulation Therapy. FRONTIERS IN PHARMACOLOGY, v. 11, JUL 14 2020. (16/23454-5, 16/22507-8, 13/09295-3, 19/08338-7)

MARCATTO, LEILIANE RODRIGUES; SACILOTTO, LUCIANA; TAVARES, LETICIA CAMARGO; FACIN, MIRELLA; OLIVETTI, NATALIA; CASSARO STRUNZ, CELIA MARIA; COSTA DARRIEUX, FRANCISCO CARLOS; SCANAVACCA, MAURICIO IBRAHIM; KRIEGER, JOSE EDUARDO; PEREIRA, ALEXANDRE COSTA; et al. Pharmaceutical Care Increases Time in Therapeutic Range of Patients With Poor Quality of Anticoagulation With Warfarin. FRONTIERS IN PHARMACOLOGY, v. 9, SEP 21 2018. (16/23454-5, 13/09295-3)

MARCATTO, LEILIANE; BOER, BRUNO; SACILOTTO, LUCIANA; OLIVETTI, NATALIA; DARRIEUX, FRANCISCO CARLOS COSTA; SCANAVACCA, MAURICIO IBRAHIM; PEREIRA, ALEXANDRE COSTA; SANTOS, PAULO CALEB JUNIOR LIMA. Impact of adherence to warfarin therapy during 12 weeks of pharmaceutical care in patients with poor time in the therapeutic range. JOURNAL OF THROMBOSIS AND THROMBOLYSIS, v. 51, n. 4, SI, p. 1043-1049, MAY 2021. (13/09295-3, 16/23454-5)

MARCATTO, LEILIANE; BOER, BRUNO; SACILOTTO, LUCIANA; OLIVETTI, NATALIA; DARRIEUX, FRANCISCO CARLOS COSTA; SCANAVACCA, MAURICIO IBRAHIM; PEREIRA, ALEXANDRE COSTA; SANTOS, PAULO CALEB JUNIOR LIMA. Impact of adherence to warfarin therapy during 12 weeks of pharmaceutical care in patients with poor time in the therapeutic range. JOURNAL OF THROMBOSIS AND THROMBOLYSIS, v. 51, n. 4, p. 7-pg., 2020-09-24. (13/09295-3, 16/23454-5)

TAVARES, LETICIA C.; MARCATTO, LEILIANE R.; SANTOS, PAULO C. J. L.. Genotype-guided warfarin therapy: current status. PHARMACOGENOMICS, v. 19, n. 7, p. 667-685, MAY 2018. (16/23454-5, 13/09295-3, 16/22507-8)

TAVARES, LETICIA C.; MARCATTO, LEILIANE R.; SOARES, RENATA A. G.; KRIEGER, JOSE E.; PEREIRA, ALEXANDRE C.; SANTOS, PAULO C. J. L.. Association Between ABCB1 Polymorphism and Stable Warfarin Dose Requirements in Brazilian Patients. FRONTIERS IN PHARMACOLOGY, v. 9, MAY 23 2018. (16/23454-5, 13/09295-3, 16/22507-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MARCATTO, Leiliane Rodrigues. Evaluation of the impact of pharmaceutical care on the quality of warfarin therapy in patients without stable dose. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.