Conclusions and implications for practice
Our findings and analysis of interpretive frameworks demonstrates the
pharmacovigilance principle that no one study or pooled analysis of
studies can adequately determine whether the harm risk of drug therapy
is real. A convergence of proof using data from various sources and
study designs is needed. Considering the data from the COMPASS RCT
together with the pharmaco-epidemiology observational studies leads us
to conclude that on balance, it is likely that long-term PPI use
increases all-cause mortality. Given the high prevalence of long-term
PPI utilization, this message needs to be conveyed to health
professionals and patients.
Competing interests: None declared.
Contributors: The authors are a group of Clinician-scientists
(Ben-Eltriki, Green, Musini, Bassett and Wright), medical researcher and
epidemiologist (Maclure) as well as Cochrane Hypertension authors and
reviewers (Musini, Bassett and Wright). The authors are experts in
analyzing clinical trials of drugs, and clarifying the state of
scientific evidence regarding effectiveness and safety of drug therapy.
All authors participated in the study design. Mohamed Ben-Eltriki and
Carolyn Green screened studies for eligibility, performed data
extraction, assessed the risk of bias, performed data analysis. All
authors interpreted the data analysis and assessed the certainty of
evidence. Mohamed Ben-Eltriki and Carolyn Green wrote the first draft of
the manuscript, and all other authors revised the manuscript.
Funding: Funds provided to Therapeutic Initiative by the
Ministry of Health of British Columbia through a grant provided to the
University of British Columbia, Vancouver, Canada. The funding source
had no role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; preparation,
review, or approval of the manuscript; and decision to submit the
manuscript for publication.
Acknowledgements: The authors thank the BJCP reviewers for peer
reviewing the study. The authors thank Cochrane Hypertension for the
help provided by Douglas Salzwedel, Information Specialist for Cochrane
Hypertension, for designing and conducting the searches, and for his
assistance.