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

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.

PROSPERO IDENTIFIER: CRD42024510253.