Pharmacoepidemiological Studies Advance The Information From Randomized Trials Investigating Nsaid Associated Cardiovascular Risk

Patricia McGettigan, David A Henry

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Meta-analyses of randomised trials generated estimates of cardiovascular risk with non-steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Objectives: To update estimates of cardiovascular risks associated with NSAIDs prescribed in general populations. Methods: Systematic review and meta-analysis of community-based controlled observational studies published 2000–2010. We pooled adjusted relative risk (RR) estimates for cardiovascular events with individual NSAIDs, in different doses, in populations with low and high cardiovascular risk. NSAIDs were compared in pair-wise analyses generating relative relative risks (RRR). Results: Eligible studies: 28 case-control (184,946 cardiovascular events); 23 cohort (>2.3 million individuals). Of extensively-studied drugs, RR was increased at low doses with rofecoxib (less than diclofenac 1.3 (1.1, 1.5), celecoxib 1.4 (1.2, 1.6), RR day, >1200 mg/day, RR 1.8 (1.4, 2.3). Naproxen was risk-neutral. Etoricoxib, RR 2.1 (1.5, 2.9), etodolac, 1.6 (1.3, 1.9), indomethacin 1.3 (1.2, 1.4), and meloxicam 1.2 (1.1, 1.3) had elevated risks. In pair-wise comparisons, etoricoxib had significantly higher risk than ibuprofen (RRR 1.68; 99%CI 1.1, 2.5) and naproxen (1.75; 1.2, 2.6). Naproxen had lower RRR than ibuprofen (0.92; 0.87, 0.99). Relative risks were constant irrespective of background cardiovascular risk. Conclusions: Etodolac, indomethacin and meloxicam have received little scrutiny in randomized studies. The pharmacoepidemiological data suggest they increase cardiovascular risk. Etoricoxib concerns are reinforced. Extensive data on diclofenac augment anxiety about its safety; it is available without prescription in several countries but is associated with increased risk even at low doses. Neither high nor low doses of naproxen appear to increase risk giving it an apparent advantage over other NSAIDs.
Original languageUndefined
Article numberO8
Pages (from-to)25
JournalBasic and Clinical Pharmacology and Toxicology
Volume109
Issue numberS1
DOIs
Publication statusPublished - 2011
Externally publishedYes

Cite this

@article{14b708e2087e4604aac19ac2eb6d18cc,
title = "Pharmacoepidemiological Studies Advance The Information From Randomized Trials Investigating Nsaid Associated Cardiovascular Risk",
abstract = "Background: Meta-analyses of randomised trials generated estimates of cardiovascular risk with non-steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Objectives: To update estimates of cardiovascular risks associated with NSAIDs prescribed in general populations. Methods: Systematic review and meta-analysis of community-based controlled observational studies published 2000–2010. We pooled adjusted relative risk (RR) estimates for cardiovascular events with individual NSAIDs, in different doses, in populations with low and high cardiovascular risk. NSAIDs were compared in pair-wise analyses generating relative relative risks (RRR). Results: Eligible studies: 28 case-control (184,946 cardiovascular events); 23 cohort (>2.3 million individuals). Of extensively-studied drugs, RR was increased at low doses with rofecoxib (less than diclofenac 1.3 (1.1, 1.5), celecoxib 1.4 (1.2, 1.6), RR day, >1200 mg/day, RR 1.8 (1.4, 2.3). Naproxen was risk-neutral. Etoricoxib, RR 2.1 (1.5, 2.9), etodolac, 1.6 (1.3, 1.9), indomethacin 1.3 (1.2, 1.4), and meloxicam 1.2 (1.1, 1.3) had elevated risks. In pair-wise comparisons, etoricoxib had significantly higher risk than ibuprofen (RRR 1.68; 99{\%}CI 1.1, 2.5) and naproxen (1.75; 1.2, 2.6). Naproxen had lower RRR than ibuprofen (0.92; 0.87, 0.99). Relative risks were constant irrespective of background cardiovascular risk. Conclusions: Etodolac, indomethacin and meloxicam have received little scrutiny in randomized studies. The pharmacoepidemiological data suggest they increase cardiovascular risk. Etoricoxib concerns are reinforced. Extensive data on diclofenac augment anxiety about its safety; it is available without prescription in several countries but is associated with increased risk even at low doses. Neither high nor low doses of naproxen appear to increase risk giving it an apparent advantage over other NSAIDs.",
author = "Patricia McGettigan and Henry, {David A}",
year = "2011",
doi = "10.1111/j.1742-7843.2011.00731.x",
language = "Undefined",
volume = "109",
pages = "25",
journal = "Pharmacology and Toxicology",
issn = "0901-9928",
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Pharmacoepidemiological Studies Advance The Information From Randomized Trials Investigating Nsaid Associated Cardiovascular Risk. / McGettigan, Patricia; Henry, David A.

In: Basic and Clinical Pharmacology and Toxicology, Vol. 109, No. S1, O8, 2011, p. 25.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Pharmacoepidemiological Studies Advance The Information From Randomized Trials Investigating Nsaid Associated Cardiovascular Risk

AU - McGettigan, Patricia

AU - Henry, David A

PY - 2011

Y1 - 2011

N2 - Background: Meta-analyses of randomised trials generated estimates of cardiovascular risk with non-steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Objectives: To update estimates of cardiovascular risks associated with NSAIDs prescribed in general populations. Methods: Systematic review and meta-analysis of community-based controlled observational studies published 2000–2010. We pooled adjusted relative risk (RR) estimates for cardiovascular events with individual NSAIDs, in different doses, in populations with low and high cardiovascular risk. NSAIDs were compared in pair-wise analyses generating relative relative risks (RRR). Results: Eligible studies: 28 case-control (184,946 cardiovascular events); 23 cohort (>2.3 million individuals). Of extensively-studied drugs, RR was increased at low doses with rofecoxib (less than diclofenac 1.3 (1.1, 1.5), celecoxib 1.4 (1.2, 1.6), RR day, >1200 mg/day, RR 1.8 (1.4, 2.3). Naproxen was risk-neutral. Etoricoxib, RR 2.1 (1.5, 2.9), etodolac, 1.6 (1.3, 1.9), indomethacin 1.3 (1.2, 1.4), and meloxicam 1.2 (1.1, 1.3) had elevated risks. In pair-wise comparisons, etoricoxib had significantly higher risk than ibuprofen (RRR 1.68; 99%CI 1.1, 2.5) and naproxen (1.75; 1.2, 2.6). Naproxen had lower RRR than ibuprofen (0.92; 0.87, 0.99). Relative risks were constant irrespective of background cardiovascular risk. Conclusions: Etodolac, indomethacin and meloxicam have received little scrutiny in randomized studies. The pharmacoepidemiological data suggest they increase cardiovascular risk. Etoricoxib concerns are reinforced. Extensive data on diclofenac augment anxiety about its safety; it is available without prescription in several countries but is associated with increased risk even at low doses. Neither high nor low doses of naproxen appear to increase risk giving it an apparent advantage over other NSAIDs.

AB - Background: Meta-analyses of randomised trials generated estimates of cardiovascular risk with non-steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Objectives: To update estimates of cardiovascular risks associated with NSAIDs prescribed in general populations. Methods: Systematic review and meta-analysis of community-based controlled observational studies published 2000–2010. We pooled adjusted relative risk (RR) estimates for cardiovascular events with individual NSAIDs, in different doses, in populations with low and high cardiovascular risk. NSAIDs were compared in pair-wise analyses generating relative relative risks (RRR). Results: Eligible studies: 28 case-control (184,946 cardiovascular events); 23 cohort (>2.3 million individuals). Of extensively-studied drugs, RR was increased at low doses with rofecoxib (less than diclofenac 1.3 (1.1, 1.5), celecoxib 1.4 (1.2, 1.6), RR day, >1200 mg/day, RR 1.8 (1.4, 2.3). Naproxen was risk-neutral. Etoricoxib, RR 2.1 (1.5, 2.9), etodolac, 1.6 (1.3, 1.9), indomethacin 1.3 (1.2, 1.4), and meloxicam 1.2 (1.1, 1.3) had elevated risks. In pair-wise comparisons, etoricoxib had significantly higher risk than ibuprofen (RRR 1.68; 99%CI 1.1, 2.5) and naproxen (1.75; 1.2, 2.6). Naproxen had lower RRR than ibuprofen (0.92; 0.87, 0.99). Relative risks were constant irrespective of background cardiovascular risk. Conclusions: Etodolac, indomethacin and meloxicam have received little scrutiny in randomized studies. The pharmacoepidemiological data suggest they increase cardiovascular risk. Etoricoxib concerns are reinforced. Extensive data on diclofenac augment anxiety about its safety; it is available without prescription in several countries but is associated with increased risk even at low doses. Neither high nor low doses of naproxen appear to increase risk giving it an apparent advantage over other NSAIDs.

U2 - 10.1111/j.1742-7843.2011.00731.x

DO - 10.1111/j.1742-7843.2011.00731.x

M3 - Article

VL - 109

SP - 25

JO - Pharmacology and Toxicology

JF - Pharmacology and Toxicology

SN - 0901-9928

IS - S1

M1 - O8

ER -