Why the study?
The effectiveness and safety of anticoagulant pharmacotherapy in patients with coronary heart disease and atrial fibrillation, including genetic influences on adverse drug reactions, require assessment.
Does the type of anticoagulant and presence of SYP2C9 mutation affect the frequency of adverse drug reactions in patients with coronary heart disease and atrial fibrillation?
Cohort (n=193)
No
Does the type of anticoagulant and presence of SYP2C9 mutation affect the frequency of adverse drug reactions in patients with coronary heart disease and atrial fibrillation?
Absolute Event Rate: 33.3% vs 7.1%
p-value: p=0.0008
Adverse drug reactions, including organ dysfunction, are more prevalent in patients taking warfarin who possess SYP2C9 mutations, highlighting the potential clinical utility of pharmacogenetic testing.
Annotation. The issue of effectiveness and safety of pharmacotherapy is extremely important for the patient. The doctor’s awareness of the selection of the most compatible drugs makes it possible to reduce the number of adverse drug reactions and increases his adherence to treatment. The purpose of the study is to assess the frequency of adverse drug reactions during therapy with anticoagulants: warfarin, rivaroxaban, dabigatran in the complex therapy of coronary heart disease and atrial fibrillation, if necessary to comply with ESC recommendations. For a comprehensive examination of the patient, the following research methods were used: anamnestic, laboratory screening of key body systems, instrumental, functional diagnostics, survey of the patient according to 60 key parameters of drug tolerance, pharmacogenetic method. Statistical data processing was carried out using variance analysis - One way ANOVA & LSD test. The intergroup reliability of the difference in quantitative values was calculated by % - according to the χ2 criterion. Indicators were evaluated in four comparison groups: Rivoroxaban, Dabigatran, Warfarin group with the presence of a genetic mutation of polymorphic alleles of SYP2C9 (SYP2C9*2, SYP2C9*3), which were associated with a slower metabolism of Warfarin and a higher frequency of hemorrhagic complications; and Warfarin group without mutations. Unfortunately, about 2% of patients have bleeding on the background of the use of 2 or more different anticoagulants in a separate period of time. And about 2.5% have ischemic complications on the background of their admission. From 0.25% to 1% die from complications of such therapy. Among other serious complications, there were complaints about the functioning of the digestive system (dysfunction of the pancreas, liver, biliary tract), nervous system, and kidneys. These complaints were present in all groups, but prevailed in the Warfarin group with an existing mutation, probably due to the slowing of the elimination of drugs metabolized by cytochromes CYP2C9, CYP3A4 or greater influence of interaction with P-glycoprotein (due to interaction with digoxin and statins). This requires additional study in order to optimize ways of correcting unwanted reactions in cariological patients. It is obvious that promising genetic research should also be more widely implemented in medical practice.
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Panibratiuk et al. (2022) conducted a cohort in Coronary heart disease and atrial fibrillation (n=193). Warfarin with CYP2C9 mutation vs. Warfarin without CYP2C9 mutation was evaluated on Clinically significant bleeding (p=0.0008).
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