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

Abstract

Introduction: 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.