Utjecaj visoke doze statina primijenjene u prva 24 sata nakon akutnoga koronarnoga sindroma na kliničke ishode i reaktivnost trombocita

doctoral thesis

• Title (english): Impact of high-dose statins administered within 24h of an acute coronary syndrome on clinical outcomes and platelet reactivity.
• Author: Saša Pavasović
• Mentor: Davor Miličić (mentor)
• Committee member: Željko Reiner (predsjednik povjerenstva)
• Committee member: Tomislav Letilović (član povjerenstva)
• Committee member: Dražen Pulanić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2021-02-22, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Cilj ovog istraživanja bio je utvrditi utječe li primjena statina unutar 24 h od početka ACS-a na preživljenje bolesnika te utječe li interakcija dvojne agregacijske terapije (DAPT) tikagrelorom i acetilsalicilnom kiselinom u kombinaciji s atorvastatinom 80 mg na reaktivnost trombocita. Hipoteza je da će primjena visoke doze statina primijenjene unutar 24 h od početka simptoma u ACS-u poboljšati kliničke ishode i sinergistički djelovati s DAPT-om u smanjenju reaktivnosti trombocita. U istraživanje je uključen 2 841 bolesnik iz registra ISACS (NCT01218776), dok je u predefiniranu podskupinu za analizu reaktivnosti trombocita uključeno 120 bolesnika u sklopu projekta SPARELIFE (HRZZ IP-2014-09-8403). Preživljenje bolesnika analizirano je tijekom hospitalizacije te 30, 90 i 180 dana nakon hospitalizacije zbog ACS-a. Reaktivnost trombocita određivana je 18 h do 24 h nakon primjene DAPT-a u akutnoj fazi te 1 mjesec nakon hospitalizacije zbog ACS-a korištenjem uređaja Multiplate®. Rezultati su pokazali da rana primjena statina tj. unutar 24 h od početka ACS-a smanjuje rizik unutarbolničke (OR 0,25, 95% CI 0,12 – 0,51, p < 0,001), 30-dnevne(OR 0,37, 95% CI 0,18 – 0,73, p = 0,004) i 90-dnevne(OR 0,37, 95% CI 0,19 – 0,73, p = 0,004) smrtnosti, dok atorvastatin u dozi od 80 mg u kombinaciji s DAPT-om ne utječe na reaktivnost trombocita (p = 0,926). Ovi rezultati potvrđuju hipotezu o povoljnom učinku primjene rosuvastatina ili atorvastatina u maksimalnoj dozi unutar 24 h od hospitalizacije na preživljenje u bolesnika s ACS-om. Navedeni je učinak prisutan i u vrijeme modernih stentova koji luče lijekove (DES) i potentnih antitrombocitnih lijekova. Također je dokazano da atorvastatin u dozi od 80 mg ne utječe značajno na reaktivnost trombocita modificiranu tikagrelorom i acetilsalicilnom kiselinom.

Abstract (english)

Aim of this study is to ascertain if administering statins within 24 h from the onset of ACS influences survival and if the interaction of DAPT with ticagrelor and aspirin combined with atorvastatin 80 mg influences platelet reactivity (PR). Hypothesis of this study is that administration of high dose statins within 24 h of the onset of ACS improves clinical outcomes and exerts a synergistic effect with DAPT in further reducing PR. This study included 2 841 patients from the ISACS registry (NCT01218776) while the predefined subgroup for PR analysis included 120 patients which were a part of the SPARELIFE project (HRZZ IP-2014-09-8403). Patient survival was analyzed during hospital stay and 30, 90 and 190 days after discharge. PR was analyzed 18h to 24 h after DAPT administration during the acute phase of ACS ad 30 days after discharge using the Multiplate® PFA. Results showed that early statin administration reduces the risk of in hospital (OR 0,25, 95% CI 0,12 – 0,51, p < 0,001), 30-day (OR 0,37, 95% CI 0,18 – 0,73, p = 0,004) and 90-day (OR 0,37, 95% CI 0,19 – 0,73, p = 0,004) mortality while atorvastatin 80 mg does not affect PR assessed using the Multiplate® ADP test (p = 0,926). These results confirm the hypothesis about the beneficial effects of the administration of rosuvastatin or atorvastatin in maximum doses within 24 h of ACS hospitalization. This effect is present in the modern era of revascularization which utilizes DES and potent antithrombocyte drugs. We have also proven that atorvastatin 80 mg does not significantly impact PR modified by ticagrelor and acetylsalicylic acid.

• Keywords: akutni koronarni sindrom; ishodi; statini; reaktivnost trombocita; preživljenje
• Keywords (english): acute coronary syndromes; outcomes; statins; platelet reactivity; survival
• Language: croatian
• URN:NBN: urn:nbn:hr:105:689515
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 122 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-04-12 09:17:35