Direct Oral Anticoagulants (DOAC) are effective and safe alternatives to Vitamin-K Antagonists (VKA) in long-term anticoagulation for several medical conditions, including atrial fibrillation and venous thromboembolism. Both RCTs and observational studies showed that DOACs are at least as effective as VKA, with consistently better safety profiles. Moreover, DOACs do not require routine monitoring of their anticoagulant activity, this encountering great appreciation among both patients and clinicians, with increasing rate of adoption of DOACs in clinical practice.
However, patient's compliance to anticoagulants persists as one key factor to guarantee benefits in treated individuals. Adherence and persistence represent two main different dimensions: the former is related to the patient's observance of the medication regimen and appropriate intake of the drugs prescribed by the physicians; the latter is defined as the time from initiation to discontinuation of therapy. They should both be targeted to increase the success of any prescription, especially for anticoagulants, which have narrow therapeutic ranges.
No need for frequent monitoring and a fixed-dose scheme have been claimed as key determinants of high adherence and persistence with DOACs. However, pharmacokinetic studies showed that suboptimal adherence to DOACs may be less tolerated compared to VKAs. Furthermore, several alarming reports showed that real-world adherence and persistence to DOACs are consistently poorer than expected, with a reported 50% of non-persistence at 1 year.
Aim of this study is to explore and quantify the adherence and persistence in real-world patients treated with DOACs for any indications, through a systematic review and meta-analysis of observational studies. Meta-regression according to study-level data will also be performed, in order to explore factors associated with poor adherence and persistence to DOACs, as well as potential relationship with worse clinical outcomes.
Medication adherence call for action: Poor medication adherence represents one of the hottest topics in current medicine, due to the rise of non-communicable chronic diseases that requires long-term or even lifetimes treatment. For these reasons, the World Health Organisation (WHO) recommends accurate assessment of medication adherence and the implementation of strategies aimed at counteracts medication discontinuation, which are necessary for an optimal care of chronic diseases.
Understanding the medication adherence in DOACs users to improve outcomes: During last decade, DOACs have provided a reliable alternative to VKAs for the treatment of several chronic conditions which requires long-term or even lifetime anticoagulation. However, while data from randomized controlled trial have shown a comparable effectiveness and a better safety profile of DOACs compared to VKAs, data from real-world studies have shown slighter differences, with rate of adverse outcomes still considerable in patients with DOACs. Besides, observational studies have repeatedly shown an alarming rate of poor-adherence and persistence among patients treated with DOACs, this being in contrast with the misperception of better patient's compliance with novel anticoagulants. However, the actual burden of unsatisfactory adherence and persistence in patients treated with DOACs is still not fully assessed, with rates of low-adherence and non-persistence being inconsistents among different reael-world cohort studies.
Identification of the factors associated to poor medication adherence to plan tailored intervention: Pooled analysis and overall interpretation of this data, performed through a systematic review and meta-analysis of real-world studies will deepen our knowledges on the magnitude of this phenomenon, also allowing the identification of potentially modifiable detrimental factors that may impair compliance in these patients. Identification of the modifiable determinants of low adherence and persistence is pivotal to design and implement effective strategies to improve patient compliance, which results in better outcomes and allocation of resources, also from a public health point of view.