Luigino Calzetta1, Beatrice Ludovica Ritondo2, Maria Gabriella Matera3, Alfredo Chetta1, Paola Rogliani2. 1. Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Parma, Italy. 2. Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy. 3. Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, Italy.
Abstract
OBJECTIVES: The recent publication of additional data retrieval for patients missing week 52 vital status in the original analyses of the ETHOS study provides the urgent need of updating previous network meta-analyses (NMA) to produce stronger evidence on mortality in patients receiving dual and triple FDCs according with the level of ICS dose. METHODS: A NMA was performed to compare the effect of ICS/LABA/LAMA, ICS/LABA, and LABA/LAMA FDCs administered via the same inhaler device in COPD patients. The number need to treat (NNT) was also calculated. RESULTS: When considering on-treatment all-cause of death (analyzed patients: 18,864), MD ICS/LABA/LAMA and MD ICS/LABA FDCs significantly reduced the risk of mortality vs. LABA/LAMA FDC (RR 0.59 95%CrI 0.35-0.97 and 0.61 95%CrI 0.38-0.99 respectively, P < 0.05); NNT ranged between 123 and 129. MD ICS/LABA/LAMA FDC also significantly reduced the risk of adjudicated cardiovascular mortality vs. LABA/LAMA FDC (RR 0.44 95%CI 0.19-0.97, P < 0.05). Low-dose (LD) ICS/LABA FDC did not significantly modulate mortality. CONCLUSION: MD ICS/LABA/LAMA and MD ICS/LABA FDCs were effective in reducing on-treatment all-cause of death, with MD ICS/LABA/LAMA FDC being effective also against adjudicated cardiovascular mortality. The protection against mortality was related with the level of ICS dose in the FDCs.
OBJECTIVES: The recent publication of additional data retrieval for patients missing week 52 vital status in the original analyses of the ETHOS study provides the urgent need of updating previous network meta-analyses (NMA) to produce stronger evidence on mortality in patients receiving dual and triple FDCs according with the level of ICS dose. METHODS: A NMA was performed to compare the effect of ICS/LABA/LAMA, ICS/LABA, and LABA/LAMA FDCs administered via the same inhaler device in COPD patients. The number need to treat (NNT) was also calculated. RESULTS: When considering on-treatment all-cause of death (analyzed patients: 18,864), MD ICS/LABA/LAMA and MD ICS/LABA FDCs significantly reduced the risk of mortality vs. LABA/LAMA FDC (RR 0.59 95%CrI 0.35-0.97 and 0.61 95%CrI 0.38-0.99 respectively, P < 0.05); NNT ranged between 123 and 129. MD ICS/LABA/LAMA FDC also significantly reduced the risk of adjudicated cardiovascular mortality vs. LABA/LAMA FDC (RR 0.44 95%CI 0.19-0.97, P < 0.05). Low-dose (LD) ICS/LABA FDC did not significantly modulate mortality. CONCLUSION: MD ICS/LABA/LAMA and MD ICS/LABA FDCs were effective in reducing on-treatment all-cause of death, with MD ICS/LABA/LAMA FDC being effective also against adjudicated cardiovascular mortality. The protection against mortality was related with the level of ICS dose in the FDCs.