Risk for Upper Gastrointestinal Bleeding from Different Drug Combinations.
Gastroenterology. 2014 Jun 14;
Authors: Masclee GM, Valkhoff VE, Coloma PM, de Ridder M, Romio S, Schuemie MJ, Herings R, Gini R, Mazzaglia G, Picelli G, Scotti L, Pedersen L, Kuipers EJ, van der Lei J, Sturkenboom M
BACKGROUND: & Aims: Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin increases risk of upper gastrointestinal bleeding (UGIB). Guidelines suggest that certain drug combinations be avoided, yet little is known about the magnitude of their interactions. We estimated the risk for UGIB during concomitant use of non-selective (ns)NSAIDs, selective inhibitors of cyclooxygenase 2 (COX2 inhibitors), and low-dose aspirin with other drugs.
METHODS: We performed case series analysis of data from 114,835 patients with UGIB (930,888 person-years follow-up), identified from 7 population-based healthcare databases (approximately 20 million individuals). Each patient served as their own control. Drug exposure was determined based on prescriptions of nsNSAIDs, COX2 inhibitors, or low-dose aspirin, alone and in combination with other drugs that affect risk for UGIB. We measured relative risk (incidence rate ratio [IRR] during drug exposure vs non-exposure) and excess risk due to concomitant drug exposure (relative excess risk due to interaction [RERI]).
RESULTS: Monotherapy with nsNSAIDs increased risk for diagnosis of UGIB (IRR, 4.3), to a greater extent than monotherapy with COX2 inhibitors (IRR, 2.9) or low-dose aspirin (IRR, 3.1). Combination therapy generally increased risk for UGIB; concomitant nsNSAID and steroid therapies increased the IRR to the greatest extent (12.8), and also produced the greatest excess risk (RERI, 5.5). Concomitant use of nsNSAIDs and aldosterone antagonists produced an IRR for UGIB of 11.0 (RERI, 4.5). Excess risk from concomitant use of nsNSAIDs with serotonin re-uptake inhibitors (SSRIs) was 1.6, whereas that from use of COX2 inhibitors with SSRI was 1.9, and that for use of low-dose aspirin with SSRI was 0.5. Excess risk for concomitant use of nsNSAIDs with anticoagulants was 2.4, for COX2 inhibitors with anticoagulants was 0.1, and for low-dose aspirin with anticoagulants was 1.9.
CONCLUSIONS: Based on a case series analysis, concomitant use of nsNSAIDs, COX2 inhibitors, or low-dose aspirin with SSRIs significantly increases risk for UGIB diagnosis. Concomitant use of nsNSAIDs or low-dose aspirin, but not COX2 inhibitors, with steroids, aldosterone antagonists, or anticoagulants produces significant excess risk for UGIB.
PMID: 24937265 [PubMed - as supplied by publisher]