Julie Rouette1,2, Hui Yin1, Emily G McDonald3,4, Alan Barkun5, Laurent Azoulay6,7,8. 1. Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montreal, QC, H3T 1E2, Canada. 2. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. 3. Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montreal, Canada. 4. Division of Experimental Medicine, McGill University, Montreal, Canada. 5. Division of Gastroenterology, McGill University Health Centre, Montreal, QC, Canada. 6. Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montreal, QC, H3T 1E2, Canada. laurent.azoulay@mcgill.ca. 7. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. laurent.azoulay@mcgill.ca. 8. Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada. laurent.azoulay@mcgill.ca.
Abstract
INTRODUCTION: There are conflicting reports on the effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) on acute pancreatitis incidence. OBJECTIVE: The aim was to determine whether use of ACE inhibitors and ARBs is associated with the incidence of acute pancreatitis, compared with use of dihydropyridine calcium channel blockers (dCCBs). METHODS: We assembled two population-based, new-user, active comparator cohorts using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository and Office for National Statistics from 1998 to 2018, with follow-up until 2019. The first cohort included 304,083 ACE inhibitor initiators and 194,431 dCCB initiators. The second cohort included 29,160 ARB initiators and 203,610 dCCB initiators. Cox proportional hazards models were fit to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of acute pancreatitis, comparing ACE inhibitors and ARBs, separately, with dCCBs. Models were weighted using standardized mortality ratio weights generated from calendar time-specific propensity scores. RESULTS: ACE inhibitors were associated with an increased risk of acute pancreatitis, compared with dCCBs (64.3 vs 45.2 per 100,000 person-years, respectively; HR 1.45, 95% CI 1.15-1.83). The number needed to harm after 2 and 5 years of use was 2438 and 1019, respectively. In contrast, ARBs were not associated with an increased risk of acute pancreatitis, compared with dCCBs (40.1 vs 47.6 per 100,000 person-years, respectively; HR 0.88, 95% CI 0.60-1.31). CONCLUSIONS: ACE inhibitors were associated with a modest increased risk of acute pancreatitis compared with dCCBs. This association should be balanced with the known clinical benefits of ACE inhibitors in hypertension management. In contrast, no association was observed with ARBs.
INTRODUCTION: There are conflicting reports on the effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) on acute pancreatitis incidence. OBJECTIVE: The aim was to determine whether use of ACE inhibitors and ARBs is associated with the incidence of acute pancreatitis, compared with use of dihydropyridine calcium channel blockers (dCCBs). METHODS: We assembled two population-based, new-user, active comparator cohorts using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository and Office for National Statistics from 1998 to 2018, with follow-up until 2019. The first cohort included 304,083 ACE inhibitor initiators and 194,431 dCCB initiators. The second cohort included 29,160 ARB initiators and 203,610 dCCB initiators. Cox proportional hazards models were fit to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of acute pancreatitis, comparing ACE inhibitors and ARBs, separately, with dCCBs. Models were weighted using standardized mortality ratio weights generated from calendar time-specific propensity scores. RESULTS: ACE inhibitors were associated with an increased risk of acute pancreatitis, compared with dCCBs (64.3 vs 45.2 per 100,000 person-years, respectively; HR 1.45, 95% CI 1.15-1.83). The number needed to harm after 2 and 5 years of use was 2438 and 1019, respectively. In contrast, ARBs were not associated with an increased risk of acute pancreatitis, compared with dCCBs (40.1 vs 47.6 per 100,000 person-years, respectively; HR 0.88, 95% CI 0.60-1.31). CONCLUSIONS: ACE inhibitors were associated with a modest increased risk of acute pancreatitis compared with dCCBs. This association should be balanced with the known clinical benefits of ACE inhibitors in hypertension management. In contrast, no association was observed with ARBs.
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