Finding evidence of efficacy and safety of statin use in patients with acute coronary syndrome : systematic review approach

Cilj istraživanja: Pronalazak najboljih dostupnih dokaza o sigurnosti i djelotvornosti primjene statina u liječenju akutnog koronarnog sindroma. Materijali i metode: Na stranici CENTRAL (Cochrane knjižnica) pronađen je sustavni pregled „Statins for acute coronary syndrome (Review)“ koji je okosnica ovog istraživanja. Sljedeći korak bilo je pretraživanje u bazama CENTRAL, DARE i MEDLINE (PubMed) za pronalazak ostalih sustavnih pregleda i RCT-ova na tu istu temu, objavljenih nakon navedenog Cochrane sustavnog pregleda. Služeći se kriterijima uključenja, donesena je odluka o njihovom uključenju u ovaj rad. Završni korak bilo je ocjenjivanje Cochrane sustavnog pregleda služeći se R-AMSTAR ljestvicom. Rezultati: Osamnaest studija, koje su ukupno uključivale 14 303 ispitanika, bavilo se uspoređivanjem ranog liječenja statinima s placebom ili bez liječenja u bolesnika s akutnim koronarnim sindromom. Na temelju dokaza umjerene kvalitete, rana terapija statinima nije smanjila kombinirani primarni ishod smrti, nefatalni infarkta miokarda i moždani udar nakon jednog ili četiri mjeseca praćenja u usporedbi s placebom ili bez liječenja. U odnosu na krajnje točke, koje su uključivale ukupnu smrt, kardiovaskularnu smrt, ukupni infarkt miokarda, ukupni moždani udar, akutno zatajenje srca i postupke revaskularizacije nakon jednog ili četiri mjeseca, nije bilo dokazano statistički značajno smanjnje rizika kod korištenja statina. Unatoč tome, bili su vidljivi povoljni trendovi povezani s korištenjem statina u svakoj od ovih krajnjih točaka. Incidencija nestabilne angine značajno je smanjena četiri mjeseca nakon akutnog koronarnog sindroma, što sugeriraju dokazi umjerene kvalitete. U ispitanika liječenih statinima bilo je devet osoba s miopatijom (povišene razine kreatinin kinaze više od 10 puta iznad gornje granice normale) (0,13%) u usporedbi s jednom (0,015%) u kontrolnim skupinama. Slučajevi s ozbiljnom mišićnom toksičnosti, u većini slučajeva, bili su ograničeni na bolesnike koji su bili lijčeni simvastatinom u dozi od 80 mg. Pronađena su ukupno 2 randomizirana kontrolna ispitivanja koja su uključena u ovo istraživanje. Jedna studija nije pokazala značajno smanjenje velikih štetnih kardiovaskularnih događaja nakon 30 dana,dok je druga studija pokazala značajno smanjenje u ukupnoj smrtnosti u pacijenata koji su nakon perkutane koronarne intervencije zbog akutnog koronarnog sindroma primali visoku dozu statina u odnosu na kontrolnu skupinu. Niti jedna od uključenih studija nije pokazala povećanu vjerojatnost od razvoja rabdomiolize ili jetrenog zatajenja u ispitanika liječenih statinima u odnosu na one u kontrolnoj skupini. Cochrane sustavni pregled ocijenjen je sa 37 od moguća 44 boda po R-AMSTARU, što ukazuje na visoku kvalitetu Cochrane sustavnog pregleda. Zaključak: Služeći se rezultatima pronađenih sustavnih pregleda i randomiziranih kontroliranih studija može se zaključiti da statini utječu na smanjenje pojavnosti nestabilne angine pektoris nakon četiri mjeseca od akutnog koronarnog sindroma, ali ne u istoj mjeri na smanjenje ukupne smrti, infarkta miokarda ili moždanog udara.Research objective: Finding the best available evidence on the safety and effectiveness of statin use in the treatment of acute coronary syndrome. Materials and methods: A systematic review "Statins for acute coronary syndrome (Review)" was found on the CENTRAL page (Cochrane library), which is the backbone of this research. The next step was to search the databases CENTRAL, DARE and MEDLINE (PubMed) to find other systematic reviews and RCTs on the same topic, published after the mentioned Cochrane systematic review. Using the inclusion criteria, a decision was made to include them in this paper. The final step was the evaluation of the Cochrane systematic review,which was done with the use of the R-AMSTAR scale. Results: Eighteen researches, which included a total of 14 303 subjects, did a comparison of early statin treatment with placebo or no treatment in patients with acute coronary syndrome. The combined primary outcome including death, non-fatal myocardial infarction and stroke at one- or four- month follow up was not reduced by early statin therapy, which was based on moderate-quality evidence. In relation to the endpoints, which included total death, cardiovascular death, total myocardial infarction, total stroke, acute heart failure, and revascularization procedures at one or four months, no statistically significant risk reduction was demonstrated with statin use. Nevertheless, favorable trends associated with statin use were seen in each of these endpoints. The incidence of unstable angina was significantly reduced four months after acute coronary syndrome, suggested by moderate-quality evidence. Nine patients who were treated with statins were reported to have myopathy (0.13%) compared with only one patient (0.015%) in the control groups. Cases of severe myopathy were, in most cases, restricted to patients who were given simvastatin 80 mg. A total of 2 randomized control trials were found that were included in this study. One study showed no significant reduction in major adverse cardiovascular events after 30 days, while another study showed a significant reduction in total mortality in patients who received high-dose statins after percutaneous coronary intervention for acute coronary syndrome compared to the control group. None of the included studies showed an increased likelihood of developing rhabdomyolysis or liver failure in subjects treated with statins compared to those in the control group. The Cochrane systematic review was rated 37 out of a possible 44 points by R-AMSTAR, which indicates the high quality of the Cochrane systematic review. Conclusion: Using the results of systematic reviews and randomized controlled trials, it can be concluded that statins affect the reduction of the incidence of unstable angina pectoris after four months of acute coronary syndrome, but not to the same degree on the reduction of total death, myocardial infarction or stroke