Pesan utama
- Inhaler yang mengandung antagonis muskarinik kerja panjang dan dengan beta-agonis kerja panjang (LAMA+LABA) untuk penyakit paru obstruktif kronis (PPOK) dapat meningkatkan fungsi pernapasan dan mengurangi risiko pneumonia dibandingkan dengan LABA dan kortikosteroid inhalasi (LABA+ICS).
- LAMA+LABA dan LABA+ICS mungkin bekerja sebaik satu sama lain dalam mengurangi eksaserbasi PPOK dan meningkatkan kualitas hidup.
- Risiko kematian sedikit lebih tinggi pada orang yang menggunakan LAMA+LABA.
Apa yang dimaksud dengan penyakit paru obstruktif kronis dan bagaimana pengobatannya?
Penyakit paru obstruktif kronis (PPOK) adalah kondisi paru-paru jangka panjang yang ditandai dengan batuk, produksi sputum (cairan dari paru-paru, yaitu dahak), dan kesulitan bernapas.
PPOK diobati dengan obat yang disebut 'bronkodilator' yang membuat bernapas menjadi lebih mudah dengan mengendurkan otot-otot di paru-paru dan melebarkan saluran udara. Dua jenis obat bronkodilator utama adalah antagonis muskarinik kerja panjang (LAMA) dan antagonis beta kerja panjang (LABA). Pedoman pelayanan kesehatan sekarang merekomendasikan agar penderita PPOK yang stabil dan berisiko tinggi untuk menggunakan inhaler yang mengandung kombinasi obat LAMA+LABA atau kombinasi obat LABA dan kortikosteroid inhalasi (LABA+ICS). Kortikosteroid adalah obat antiinflamasi.
Apa yang ingin diketahui?
Kami memeriksa temuan uji klinis yang mengacak partisipan untuk menerima LAMA+LABA atau LABA+ICS untuk melihat perbandingannya.
Apa yang sudah dilakukan?
Kami mencari uji klinis yang mengeksplorasi manfaat dan bahaya LAMA+LABA dan LABA+ICS untuk pengobatan penderita PPOK. Kami merangkum hasilnya dan menilai seberapa yakin kami terhadap bukti-bukti ilmiah tersebut.
Apa yang ditemukan?
Kami menyertakan 19 penelitian yang melibatkan 22.354 partisipan. Penelitian berlangsung dalam rentang 6 hari hingga 52 bulan. Penelitian ini melibatkan lebih banyak pria daripada wanita (sekitar 70% partisipan adalah pria) dan partisipan penelitian berusia sekitar 64 tahun. Sebagian besar penelitian melibatkan partisipan dengan PPOK sedang hingga berat. Perusahaan farmasi terlibat dalam sebagian besar penelitian yang mungkin memengaruhi seberapa besar kami dapat mempercayai hasilnya.
Dibandingkan dengan LABA+ICS, LAMA+LABA menghasilkan peningkatan fungsi paru-paru, mengurangi pneumonia dari 5% menjadi 3%, tetapi meningkatkan risiko kematian dari 1% menjadi 1,4%. LAMA+LABA mungkin hanya sedikit atau bahkan tidak ada bedanya dengan LABA+ICS pada eksaserbasi PPOK (kambuh). Partisipan pada masing-masing kelompok perlakuan melaporkan skor kualitas hidup yang sama dan memiliki kemungkinan yang sama untuk mengalami efek samping yang serius, yang jarang terjadi.
Apa keterbatasan dari bukti ilmiah tersebut?
Keyakinan kami terhadap bukti-bukti ilmiah yang ada adalah sedang hingga tinggi karena penelitian yang disertakan dirancang dengan baik dan memiliki jumlah partisipan yang cukup banyak, terutama yang menderita PPOK sedang hingga berat.
Seberapa mutakhir bukti ilmiah ini?
Tinjauan ini mutakhir hingga 10 September 2022. Diharapkan ke depannya terdapat uji klinis yang mengevaluasi obat-obatan yang baru dikembangkan. Tinjauan ini harus diperbarui lagi dalam beberapa tahun mendatang.
Read the full abstract
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.
Tujuan
To compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of people with stable COPD.
Metode penelusuran
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.
Kriteria seleksi
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.
Pengumpulan data dan analisis
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.
Hasil utama
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).
Kesimpulan penulis
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.
Diterjemahkan oleh Marchela Kurnia Dewanti (Universitas Gadjah Mada). Disunting oleh dr. Yudha Nur Patria, DCH, MMed (Clin Epi), MMS, PhD (Universitas Gadjah Mada). Email Kontak: cochrane-indonesia.fkkmk@ugm.ac.id.
