Ključne poruke
• Korištenje inhalatora koji sadrži dugodjelujuće antagoniste muskarinskih receptora s dugodjelujućim agonistima beta2-adrenergičkih receptora (LAMA+LABA) u liječenju kronične opstruktivne plućne bolesti (KOPB) najvjerojatnije poboljšava respiratornu funkciju i smanjuje rizik od upale pluća u odnosu na LABA s inhalacijskim kortikosteroidima (LABA+ICS).
• Kombinacija LAMA+LABA i kombinacija LABA+ICS najvjerojatnije su jednako učinkovite u smanjenju egzacerbacija KOPB-a i poboljšanju kvalitete života.
• Osobe koje su uzimale kombinaciju LAMA+LABA imale su nešto veći rizik od smrtnog ishoda.
Što je kronična opstruktivna plućna bolest i kako se liječi?
Kronična opstruktivna plućna bolest (KOPB) dugoročno je stanje koje karakterizira kašalj, stvaranje sputuma odnosno iskašljaja (tekućine iz pluća, tj. sluzi) te otežano disanje.
KOPB se liječi lijekovima koji se nazivaju 'bronhodilatatori', koji opuštanjem respiratornih mišića i širenjem dišnih puteva olakšavaju disanje. Dvije glavne vrste bronhodilatatora su dugodjelujući antagonisti muskarinskih receptora (engl. long-acting muscarinic antagonists, LAMA) i dugodjelujući agonisti beta2-adrenergičkih receptora (engl. long-acting beta-agonists, LABA). Smjernice za zdravstvenu zaštitu danas preporučuju da osobe sa stabilnom visokorizičnom KOPB koriste inhalatore koji sadrže ili kombinacijsku terapiju LAMA+LABA ili kombinacijsku terapiju LABA s inhalacijskim kortikosteroidima (LABA+ICS). Kortikosteroidi su protuupalni lijekovi.
Koji je cilj ovog sustavnog pregleda?
Kako bi se usporedila učinkovitost kombinacijskih terapija LAMA+LABA i LABA+ICS, razmotrili su se rezultati ispitivanja tijekom kojih su sudionici nasumično primali jednu od terapija.
Kako je proveden ovaj sustavni pregled?
Tražena su ispitivanja u kojima su se pratile prednosti i mane kombinacije LAMA+LABA te kombinacije LABA+ICS u liječenju osoba koje boluju od KOPB-a. Rezultati su sažeti te je procijenjena pouzdanost dokaza.
Što je pronađeno?
U ovom je sustavnom pregledu uključeno 19 istraživanja koja su uključivala 22,354 sudionika. Istraživanja su trajala od 6 do 52 tjedana. Istraživanja su uključivala više muškaraca nego žena (približno 70% sudionika bili su muškarci), a sudionici su imali oko 64 godine. Većina je istraživanja uključivala osobe s umjerenom do teškom KOPB. Sudjelovanje farmaceutskih tvrtki u većini istraživanja moglo bi utjecati na pouzdanost rezultata.
U usporedbi s kombinacijom LABA+ICS, kombinacija LAMA+LABA dovela je do poboljšanja funkcije pluća, smanjila upalu pluća s 5% na 3%, ali je povećala rizik od smrti s 1% na 1,4%. U odnosu na kombinaciju LABA+ICS, kombinacija LAMA+LABA najvjerojatnije je imala malen ili nikakav utjecaj na egzacerbacijame (pogoršanja) KOPB-a. Kvaliteta života u obje skupine pacijenata bila je podjednaka te su obje skupine bile jednako podložne ozbiljnim nuspojavama, do kojih je rijetko došlo.
Koja su ograničenja dokaza?
Budući da su obuhvaćena istraživanja bila dobro osmišljena te su uključivala dovoljan broj sudionika pretežno s umjerenom do teškom KOPB, dokazi su srednje do visoke razine pouzdanosti.
Datum pretraživanja dokaza
U ovaj su sustavni pregled uključeni dokazi objavljeni do 10. rujna 2022. godine. Očekuju se rezultati budućih istraživanja te istraživanja u tijeku, u kojima se procjenjuju najnoviji lijekovi. Ovaj sustavni pregled potrebno je obnoviti za nekoliko godina.
Combination LAMA+LABA therapy probably holds similar benefits to LABA+ICS for exacerbations and quality of life, as measured by the St George's Respiratory Questionnaire, for people with moderate to severe COPD, but offers a larger improvement in FEV 1 and a slightly lower risk of pneumonia. There is little to no difference between LAMA+LABA and LAMA+ICS in the odds of having a serious adverse event. Whilst all-cause death may be lower with LABA+ICS, there was a very small number of events in the analysis, translating to a low absolute risk. Findings are based on moderate- to high-certainty evidence from heterogeneous trials with an observation period of less than one year. This review should be updated again in a few years.
Long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and inhaled corticosteroids (ICSs) are inhaled medications used to manage chronic obstructive pulmonary disease (COPD). When two classes of medications are required, a LAMA plus an ICS (LABA+ICS) were previously recommended within a single inhaler as the first-line treatment for managing stable COPD in people in high-risk categories. However, updated international guidance recommends a LAMA plus a LABA (LAMA+LABA). This systematic review is an update of a Cochrane Review first published in 2017.
To compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of people with stable COPD.
We performed an electronic search of the Cochrane Airways Group Specialised Register, ClinicalTrials.gov, and the World Health Organization Clinical Trials Search Portal, followed by handsearches. Two review authors screened the selected articles. The most recent search was run on 10 September 2022.
We included parallel or cross-over randomised controlled trials of at least one month's duration, comparing LAMA+LABA and LABA+ICS for stable COPD. We included studies conducted in an outpatient setting and irrespective of blinding.
Two review authors independently extracted data and evaluated risk of bias. We resolved any discrepancies through discussion. We analysed dichotomous data as odds ratios (ORs), and continuous data as mean differences (MDs), with 95% confidence intervals (CIs) using Review Manager 5. Primary outcomes were: participants with one or more exacerbations of COPD; serious adverse events; quality of life, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score change from baseline; and trough forced expiratory volume in one second (FEV 1 ). We used the GRADE framework to rate our certainty of the evidence in each meta-analysis as high, moderate, low or very low.
This review updates the first version of the review, published in 2017, and increases the number of included studies from 11 to 19 (22,354 participants). The median number of participants per study was 700. In each study, between 54% and 91% (median 70%) of participants were males. Study participants had an average age of 64 years and percentage predicted FEV 1 of 51.5% (medians of study means). Included studies had a generally low risk of selection, performance, detection, attrition, and reporting biases. All but two studies were sponsored by pharmaceutical companies, which had varying levels of involvement in study design, conduct, and data analysis.
Primary outcomes
The odds of having an exacerbation were similar for LAMA+LABA compared with LABA+ICS (OR 0.91, 95% CI 0.78 to 1.06; I 2 = 61%; 13 studies, 20,960 participants; moderate-certainty evidence). The odds of having a serious adverse event were also similar (OR 1.02, 95% CI 0.91 to 1.15; I 2 = 20%; 18 studies, 23,183 participants; high-certainty evidence). Participants receiving LAMA+LABA had a similar improvement in quality of life, as measured by the SGRQ, to those receiving LABA+ICS (MD -0.57, 95% CI -1.36 to 0.21; I 2 = 78%; 9 studies, 14,437 participants; moderate-certainty evidence) but showed a greater improvement in trough FEV 1 (MD 0.07, 95% CI 0.05 to 0.08; I 2 = 73%; 12 studies, 14,681 participants; moderate-certainty evidence).
Secondary outcomes
LAMA+LABA decreased the odds of pneumonia compared with LABA+ICS from 5% to 3% (OR 0.61, 95% CI 0.52 to 0.72; I 2 = 0%; 14 studies, 21,829 participants; high-certainty evidence) but increased the odds of all-cause death from 1% to 1.4% (OR 1.35, 95% CI 1.05 to 1.75; I 2 = 0%; 15 studies, 21,510 participants; moderate-certainty evidence). The odds of achieving a minimal clinically important difference of four or more points on the SGRQ were similar between LAMA+LABA and LABA+ICS (OR 1.06, 95% CI 0.90 to 1.25; I 2 = 77%; 4 studies, 13,614 participants; moderate-certainty evidence).
Hrvatski Cochrane. Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochraneovih sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochraneovih sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr