All-Cause and Cardiovascular Mortality With Single Inhaler Triple Therapy Versus Double Therapies for COPD: A Systematic Review and Metanalysis

Hammadi, Ayoub; Hoyas-Sánchez, Clara; Romero-Linares, Alejandro; Álvarez-Muro, Lucia; Menéndez-Lobo, Antonio; Romeral-Navarro, Damaris; Jiménez-Antón, Andrea; Almansa-López, Angel; Casares-Martin-Moreno, Laura; Sánchez-Álvarez, Esther; Romero-Palacios, Pedro Jose; Alcázar-Navarrete, Bernardino

doi:10.1016/j.arbres.2025.02.004

Archivos de Bronconeumología

ISSN: 0300-2896

Archivos de Bronconeumologia is an international journal that publishes original studies whose content is based upon results of research initiatives dealing with several aspects of respiratory medicine including epidemiology, respiratory physiology, pathophysiology of respiratory diseases, clinical management, thoracic surgery, pediatric lung diseases, respiratory critical care, respiratory allergy and translational research. Other types of articles such as editorials, reviews, and different types of letters are also published in the journal. Additionally, the journal expresses the voice of the following scientific societies: the Spanish Respiratory Society of Pneumology and Thoracic Surgery (SEPAR; https://www.separ.es/), the Latin American Thoracic Society (ALAT; https://alatorax.org/), and the Iberian American Association of Thoracic Surgery (AIACT; http://www.aiatorax.com/).

It is a monthly journal in which all manuscripts are sent to peer-review and handled by the editor or an associate editor from the team and the final decision is made on the basis of the comments from the expert reviewers and the editors. The journal is published solely in English. All the published data is composed of novel manuscripts not previously published in any other journal and not being in consideration for publication in any other journal..

The journal is indexed at Science Citation Index Expanded, Medline/Pubmed, Embase and SCOPUS. Access to any published article is possible through the journal's web page as well as from Pubmed, ScienceDirect, and other international databases. Furthermore, the journal is also present in X, Facebook and Linkedin. Manuscripts can be submitted electronically using the following web site: https://www.editorialmanager.com/ARBR/.

Indexed in:

Medline, Science Citation Index Expanded (SCIE)

COPD is a major public health concern, often complicated by cardiovascular comorbidities. Single inhaler triple therapy (SITT) has been proposed as a superior treatment option compared to single inhaler double therapies (SIDT) as LABA/LAMA and LABA/ICS. This systematic review and meta-analysis aim to evaluate the comparative efficacy of these therapies in reducing cardiovascular mortality, major adverse cardiovascular events (MACEs), and all-cause mortality (ACM).

Methods

We conducted a systematic review and metanalysis including RCT studies comparing SITT with LABA/LAMA or LABA/ICS with mortality as efficacy or safety endpoints. Articles were selected after reviewing PubMed, SCOPUS, Embase, Scielo and clinicaltrials.gov and clinicaltrialsregister.eu from May’24 to Jul’24. Random-effects models were used to estimate the pooled odds ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular mortality, MACEs, and ACM. Heterogeneity and publication bias were assessed using standard statistical methods.

Results

The systematic review yielded 568 studies of which 11 were finally included, with 25,774 COPD patients. SITT was superior to LABA/LAMA on ACM (pooled HR 0.727; 95% CI 0.574–0.921, p=0.008) and cardiovascular mortality (pooled HR 0.455; 95% CI 0.292–0.710, p<0.001), with no effect on MACEs. SITT showed no difference versus LABA/ICS on ACM, cardiovascular mortality or MACEs.

Conclusions

SITT significantly reduces cardiovascular and all-cause mortality compared to LABA/LAMA. Compared to LABA/ICS, SITT does not show a significant difference.

PROSPERO IDENTIFIER: CRD42024510253.

Keywords:

Single inhaler triple therapy

Chronic Obstructive Pulmonary Disease

Cardiovascular mortality

Major adverse cardiovascular events

All-cause mortality

Meta-analysis

Graphical abstract