Clinical experience with novel oral antithrombotic drugs and some questions so far unanswered

The recent introduction in the market of several novel oral anticoagulant (dabigatran, rivaroxaban, and apixaban) and antiplatelet drugs

(ticagrelor and prasugrel) has been encouraged by positive results of pilot studies and has resulted in a massive explosion of publications, in

part supported by companies and, in part, based on rapidly gained extensive experience with novel antithrombotic drugs. The overall clinical

benefit of anticoagulant therapy is apparent virtually in all patients with nonvalvular atrial fibrillation, except for those with a CHA2DS2-VASc

score of 0. If the CHA2DS2-VASc score is used, the proportion of patients with atrial fibrillation who should be treated with oral anticoagulants

reaches 94%. Novel oral anticoagulant drugs have been shown in studies to be non-inferior in the incidence of stroke and systemic embolism;

apixaban and dabigatran 150 mg twice a day have been shown to be superior. In this dose, dabigatran has been the only one to have been

more effective in preventing ischaemic stroke. Likewise, all the novel oral anticoagulant drugs were non-inferior in the incidence of severe

bleeding, with apixaban and dabigatran 110 mg twice a day being superior. There has also been progress in the treatment of patients with acute

coronary syndrome. In the case of dual antiplatelet therapy with acetylsalicylic acid and clopidogrel routinely used so far, there is a problem of

polymorphism in the cytochrome P450 system with variability in the therapeutic effect of clopidogrel. Due to failure of metabolic conversion

to an active substance, clopidogrel can exhibit laboratory or clinical inefficacy in up to 20–35 % of patients, depending on the population.

Novel antiplatelet drugs have a more rapid and consistent onset of action compared to clopidogrel and, given their metabolism, there are

fewer patients who are resistant to this group of drugs. Prasugrel is contraindicated in patients after stroke or transient ischaemic attack, those

over 75 years of age, and those weighing under 60 kg, and its data show convenience of its administration particularly in patients with STEMI

or diabetics. Ticagrelor reduces the mortality rate in patients with acute coronary syndrome, with no differences in severe bleeding between

the groups treated with ticagrelor and clopidogrel, with a higher rate of major bleeding unrelated to aortocoronary bypass during ticagrelor

administration, including a higher incidence of fatal intracranial bleeding and a lower incidence of fatal bleeding of other types. In patients

with chronic kidney disease and a creatinine clearance of 30–60 ml/min, ticagrelor significantly reduces the primary end-point in comparison

with clopidogrel. In patients with chronic kidney disease, ticagrelor also reduces all-cause mortality.

Keywords: novel antithrombotic drugs, triple antithrombotic therapy, anticoagulant therapy, acute coronary syndrome