Primjena direktnih oralnih antikoagulansa u kliničkoj praksi

Cilj istraživanja: Cilj ovoga rada je istražiti mjesto direktnih oralnih antikoagulansa u kliničkoj praksi kod pacijenata s dijagnozom tromboembolijske bolesti. Radi se o novoj skupini lijekova, koja se pojavila na tržištu prije svega nekoliko godina. U tu svrhu provedeno je retrospektivno opservacijsko istraživanje, a dobiveni podaci su analizirani, na temelju čega je donesen zaključak o usklađenosti propisane terapije s najnovijim smjernicama. Dobiveni rezultati su uspoređeni i s rezultatima sličnih europskih i svjetskih istraživanja. Također je dan uvid u farmakološke karakteristike starih i novih lijekova, u glavna stanja u kojima je indicirana upotreba istih, te u njihove kliničke studije. Osim toga, željelo se i procijeniti kakav je međusoban odnos predstavnika direktnih oralnih antikoagulansa, kada govorimo o učinkovitosti i sigurnosti, te da li bi neki od njih bili bolji izbor od drugih. Materijali i metode: Kao materijal za izradu ovog rada poslužili su članci iz relevantnih znanstvenih časopisa, razna kongresna izvješća, poglavlja udžbenika na temu antikoagulacijskih lijekova, te važeće smjernice hrvatskih, europskih i svjetskih udruženja. Za izradu eksperimentalnog dijela korišteni su podaci iz baze podataka Kliničke bolnice Dubrava, i to sljedeći: dob, spol, dijagnoza i propisana terapija skupine bolesnika otpuštenih s dijagnozom tromboembolijske bolesti. Provedena je retrospektivna opservacijska studija u razdoblju od 01.01.2018. do 01.06.2018. Dobiveni podaci su analizirani deskriptivnom statističkom metodom, te kao takvi uspoređeni. Praćena je propisana antikoagulantna terapija u ovisnosti o dobi, spolu i dijagnozi pacijenata, te je napravljena statistička analiza, na temelju koje je ustanovljena uskađenost propisane terapije s važećim smjernicama. Dobiveni podaci su stavljeni u kontekst hrvatskog tržišta i upotrebe novih lijekova u odnosu na varfarin. Napravljena je i usporedba sa sličnim istrživanjima u drugim zemljama, te su izvučeni zaključci. Rezultati: Rezultati su pokazali da je od ukupno 201 pacijenata uključenih u istraživanje, velika većina ispitanika prilikom izlaska iz bolnice otpuštena s varfarinom u terapiji i to njih 79% (158/201), dok je samo 21% (43/201) ispitanika dobilo preporuku za direktni oralni antikoagulans. Od DOAK-a najzastupljeniji je bio rivaroksaban - 67%, potom dabigatran – 30%, te apiksaban – 3%. Kada je praćena propisana terapija u ovisnosti o dijagnozi došlo se do sljedećih podataka. Od 48 pacijenata s atrijskom fibrilacijom 88% (42/48) ih je dobilo varfarin, a tek 12% (6/48) DOAK. Slični su rezultati i kod pacijenata s dijagnozom plućne embolije. Od 42 ispitanika, čak 79% (33/42) ih je dobilo varfarin, a samo 21% (9/42) DOAK. Kada pak govorimo o dijagnozi duboke venske tromboze, 78% (87/111) takvih pacijenata je dobilo varfarin, a svega 22% (24/111) DOAK. Podjelom ispitanika prema spolu, ustanovljeno je da je 83% (82/101) žena otpušteno iz bolnice s varfarinom kao i 75% (75/100) muškaraca. Očekivano, mlađa, radno aktivna populacija imala je najveći udio uvedenih direktnih oralnih antikoagulansa, čak 37% (22/59). Najmanji udio imala je srednja dobna skupinu ispitanika, dakle svi stariji od 65 i mlađi od 80 godina, svega 9% (6/68). Nešto malo veći postotak su imali najstariji ispitanici, gdje je 20% (15/74) njih izašlo iz bolnice s DOAK-om. U svakoj navedenoj skupini, najviše se propisivao rivaroksaban. Zaključak: Rezultati kliničkih studija direktnih oralnih antikoagulansa su ohrabrujući, a DOAK-i imaju i brojne prednosti u odnosu na varfarin, poput izbjegavanja laboratorijskog praćenja, fiksnog doziranja, brzog nastupa i prekida djelovanja, nemaju interakcija s hranom, imaju puno manje interakcija s drugim lijekovima. Glavni nedostatak nove skupine lijekova je zapravo njihova cijena, koja je nekoliko puta viša od one liječenja varfarinom. Rezultati dobiveni iz eksperimentalnog dijela ovoga rada pokazuju da u Kliničkoj bolnici Dubrava kada je u pitanju propisivanje oralne antikoagulantne terapije i dalje prevladava varfarin (79%), u svim dobnim skupinama i u svim indiciranim dijagnozama. Kada se DOAK i propiše, onda se u 67% takvih slučajeva propiše rivaroksaban, koji je ujedno najbrže rastući DOAK na hrvatskom tržištu. Na dabigatranu završi dvostruko manje pacijenata, dok je apiksaban u KB Dubrava gotovo nezastupljen, čemu pogoduje činjenica da je zadnji došao na tržište i očito još nije ostvario značajniju primjenu u kliničkoj praksi. Iz svega navedenog može se zaključiti da trend porasta propisivanja DOAK-a postoji i u KB Dubravi, ali je dosta sporiji u odnosu na porast u Republici Hrvatskoj. Za pretpostaviti je da će se ovakvi trendovi nastaviti i u budućnosti, te dovesti do daljnjeg rasta zastupljenosti direktnih oralnih antikoagulansa u terapiji pacijenata u odnosu na antagoniste vitamina K.Aim: The aim of this research is to investigate the place of direct oral anticoagulants in clinical practice in patients with thromboembolic disease diagnosis. Direct oral anticoagulants are relative new drugs, which appeared on the market just a few years ago. For that purpose a retrospective observational study was made and provided data were analyzed. Based on that analyze a conclusion on the compatibility of prescribed therapy with the latest guidelines was made. The obtained results were compared with the results of similar European and world research. It is also given an insight into the pharmacological characteristics of old and new drugs, the main conditions in which they are indicated, and their clinical studies. In addition, we also wanted to evaluate the relationship between direct oral anticoagulants, when speaking about efficiency and safety, in order to figure out which of them could be better. Materials and methods: Articles from relevant scientific journals, various congress reports, chapters of textbooks, valid guidelines of Croatian, European and world associations on the subject of anticoagulation medications served as material for making this work. Data from the Clinical Hospital Dubrava database, like age, name, sex, diagnosis and prescribed therapy of patients who had diagnosis of thromboembolic disease were used for developing the experimental part of this work. A retrospective observation study was carried out in the period from January 1st, 2017 to June 1st, 2018. The obtained data were analyzed by a descriptive statistical method, and as such compared. Anticoagulant therapy was monitored depending on age, gender and patient diagnosis, and a statistical analysis was performed, in purpose to compare the compatibility of prescribed therapy with the valid guidelines. The obtained data were placed in the context of the Croatian market and the use of new drugs compared to warfarin. Comparison with similar researches in other countries was made, and conclusions were brought. Results: The results showed that most of the respondents were released from the hospital with warfarin in therapy - 79% (158/201), while only 21% (43/201) of the respondents received direct oral anticoagulants. The most used DOAC is rivaroxaban - 67%, then dabigatran - 30%, and apixaban - 3%. When the prescribed therapy was followed, depending on the diagnosis, the following data were obtained: among 48 patients with atrial fibrillation 88% (42/48) received warfarin and only 12% (6/48) DOACs. Similar results were found in patients with pulmonary embolism. Among 42 respondents, 79% (33/42) received warfarin, and only 21% (9/42) DOACs. When we talk about deep vein thrombosis diagnosis, 78% (87/111) of the patients received warfarin, and only 22% (24/111) DOACs. According to the classification of respondents toward sex, it was found that 83% (82/101) of women were released from the hospital with warfarin as well as 25% (25/100) of men. Expected, younger, working-active population had the highest share of direct oral anticoagulants, up to 37% (22/59). The smallest share had a middle age group of respondents (all older than 65 and younger than 80 years) only 9% (6/68). The oldest respondents had a slightly higher percentage, where 20% (15/74) of them were released from the hospital with DOAC. In each of the mentioned groups, rivaroxaban was the most prescribed DOAC. Conclusion: The results of clinical studies of direct oral anticoagulants are encouraging. DOACs have also many advantages in related to warfarin, such as avoiding laboratory monitoring, fixed dosage, rapid onset and interruption of action, no food interaction and much less interactions with other drugs. The main disadvantage of the new drug group is actually their price, which is several times higher than warfarin. The results from the experimental part of this paper show that in the Clinical Hospital Dubrava when it comes to prescribing oral anticoagulant therapy, predominantly warfarin (79%) prevails in all age groups and in all indicated diagnoses. When DOAC is prescribed, then 67% of such cases rivaroxaban is prescribed. Rivaroxaban is also the fastest growing DOAC in the Croatian market. The prescription of dabigatran is 33%, twice less than rivaroxaban, while apixaban in Clinical Hospital Dubrava is almost uninhibited, for the reason that he has recently come to the market and has obviously not yet lived in practice. It can be concluded that the trend of increasing DOACs exists also in Clinical Hospital Dubrava, but is much slower in relation to the growth of the whole country. It is supposed that these trends will continue in the future and lead to a further increase in the presence of direct oral anticoagulants in patient therapy compared to vitamin K antagonists