Changing the Approach to Anticoagulant Therapy in Older Patients with Multimorbidity Using a Precision Medicine Approach

Abstract

The ageing of the world population has resulted in an increase in the number of older patients with multimorbid conditions receiving multiple therapies. This emerging clinical scenario poses new challenges, which are mostly related to the increased incidence of adverse effects. This translates into poor clinical care, reduced cost-effectiveness of drug therapies, and social isolation of multimorbid patients due to reduced autonomy. A strategy to address these emerging challenges could involve the personalization of therapies based on the clinical, molecular, and genetic characterization of multimorbid patients. Anticoagulation therapy is a feasible model to implement personalized medicine since it generally involves older multimorbid patients receiving multiple drugs. In this study, in patients with atrial fibrillation, the use of the new generation of anticoagulation therapy, i.e., direct oral anti-coagulants (DOACs), is based on a preliminary assessment of the molecular targets of DOACS and any possible drug–drug interactions. Then, the genetic polymorphism of enzymes metabolizing DOACs is studied. After DOAC prescription, its circulating levels are measured. Clinical data are being collected to assess whether this personalized approach improves the safety and efficacy profiles of anticoagulation therapy using DOACs, thereby reducing the costs of healthcare for ageing multimorbid patients.

Prescription Advice Based on Data of Drug-Drug-Gene Interaction of Patients with Polypharmacy

“…Based on the fact that the ageing of the world population results in an increase in elderly people with multi-morbid conditions receiving multiple drugs, DDIs resulting in ADRs will increase and pose new challenges for physicians. 24 …”

“…Based on the fact that the ageing of the world population results in an increase in elderly people with multi-morbid conditions receiving multiple drugs, DDIs resulting in ADRs will increase and pose new challenges for physicians. 24 The risk associated with the different drugs is calculated by the software not only on the basis of the pharmacodynamic properties but also taking into account certain patient characteristics, such as sex, age, weight, lifestyle habits (coffee, alcohol, nicotine consumption), liver and kidney function, pharmacogenetic profile and concomitant therapies. 25 The ranking is thus based on the likelihood of a drug having adverse effects in the overall context of multimorbid and polytreated patients (which is the population most susceptible to drug-related adverse events).…”

Oral anticoagulation challenges and therapeutic dilemmas in the very elderly: to treat and how to treat octogenarians and nonagenarians?

“…117 Interestingly, evidence suggests that DOACs (and possibly well -controlled VKA treatment) could even play a protective role in the prevention of cognitive decline. 118 Hence, frailty, cognitive impairment, and risk of falls should not discourage either the patients or the clinicians from DOAC initiation and adherence.…”