Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?

doi:10.3390/ijms20174262

Review

. 2019 Aug 30;20(17):4262.

doi: 10.3390/ijms20174262.

Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?

Shanzana Khan^{1

2}, Karen L Andrews^{3

4}, Jaye P F Chin-Dusting^{3

4}

Affiliations

¹ Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia. shanzana.khan@monash.edu.
² Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia. shanzana.khan@monash.edu.
³ Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia.
⁴ Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.

PMID: 31480335
PMCID: PMC6747368
DOI: 10.3390/ijms20174262

Review

Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?

Shanzana Khan et al. Int J Mol Sci. 2019.

. 2019 Aug 30;20(17):4262.

doi: 10.3390/ijms20174262.

Authors

Shanzana Khan^{1

2}, Karen L Andrews^{3

4}, Jaye P F Chin-Dusting^{3

4}

Affiliations

¹ Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia. shanzana.khan@monash.edu.
² Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia. shanzana.khan@monash.edu.
³ Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia.
⁴ Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.

PMID: 31480335
PMCID: PMC6747368
DOI: 10.3390/ijms20174262

Abstract

Cyclo-oxygenase (COX) inhibitors are among the most commonly used drugs in the western world for their anti-inflammatory and analgesic effects. However, they are also well-known to increase the risk of coronary events. This area is of renewed significance given alarming new evidence suggesting this effect can occur even with acute usage. This contrasts with the well-established usage of aspirin as a mainstay for cardiovascular prophylaxis, as well as overwhelming evidence that COX inhibition induces vasodilation and is protective for vascular function. Here, we present an updated review of the preclinical and clinical literature regarding the cardiotoxicity of COX inhibitors. While studies to date have focussed on the role of COX in influencing renal and vascular function, we suggest an interaction between prostanoids and T cells may be a novel factor, mediating elevated cardiovascular disease risk with NSAID use.

Keywords: T cells; adaptive immunity; coronary disease; cyclo-oxygenase; immune-mediated hypertension; prostanoids; vascular dysfunction.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
COX inhibition decreases or increases BP through inhibition of renal COX-1 or COX-2 respectively. However, the overwhelming effect of COX inhibition in the vasculature is vasodilatory. Finally, we have shown systemic COX inhibition may increase BP through activation of T cells and promotion of their infiltration into cardiovascular organs.

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References

1. Qi Z., Hao C.M., Langenbach R.I., Breyer R.M., Redha R., Morrow J.D., Breyer M.D. Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II. J. Clin. Investig. 2002;110:61–69. doi: 10.1172/JCI0214752. - DOI - PMC - PubMed
1. Bally M., Dendukuri N., Rich B., Nadeau L., Helin-Salmivaara A., Garbe E., Brophy J.M. Risk of acute myocardial infarction with NSAIDs in real world use: Bayesian meta-analysis of individual patient data. BMJ. 2017;357:j1909. doi: 10.1136/bmj.j1909. - DOI - PMC - PubMed
1. Khan S.I., Shihata W.A., Andrews K.L., Lee M.K.S., Moore X.L., Jefferis A.M., Vinh A., Gaspari T., Dragoljevic D., Jennings G.L., et al. Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat. FASEB J. 2019;33:1510–1521. doi: 10.1096/fj.201701498RR. - DOI - PubMed
1. Guzik T.J., Hoch N.E., Brown K.A., McCann L.A., Rahman A., Dikalov S., Goronzy J., Weyand C., Harrison D.G. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J. Exp. Med. 2007;204:2449–2460. doi: 10.1084/jem.20070657. - DOI - PMC - PubMed
1. Bombardier C., Laine L., Reicin A., Shapiro D., Burgos-Vargas R., Davis B., Day R., Ferraz M.B., Hawkey C.J., Hochberg M.C., et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N. Engl. J. Med. 2000;343:1520–1528. doi: 10.1056/NEJM200011233432103. - DOI - PubMed

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[1] Qi Z., Hao C.M., Langenbach R.I., Breyer R.M., Redha R., Morrow J.D., Breyer M.D. Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II. J. Clin. Investig. 2002;110:61–69. doi: 10.1172/JCI0214752. - DOI - PMC - PubMed

[2] Qi Z., Hao C.M., Langenbach R.I., Breyer R.M., Redha R., Morrow J.D., Breyer M.D. Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II. J. Clin. Investig. 2002;110:61–69. doi: 10.1172/JCI0214752. - DOI - PMC - PubMed

[3] Bally M., Dendukuri N., Rich B., Nadeau L., Helin-Salmivaara A., Garbe E., Brophy J.M. Risk of acute myocardial infarction with NSAIDs in real world use: Bayesian meta-analysis of individual patient data. BMJ. 2017;357:j1909. doi: 10.1136/bmj.j1909. - DOI - PMC - PubMed

[4] Bally M., Dendukuri N., Rich B., Nadeau L., Helin-Salmivaara A., Garbe E., Brophy J.M. Risk of acute myocardial infarction with NSAIDs in real world use: Bayesian meta-analysis of individual patient data. BMJ. 2017;357:j1909. doi: 10.1136/bmj.j1909. - DOI - PMC - PubMed

[5] Khan S.I., Shihata W.A., Andrews K.L., Lee M.K.S., Moore X.L., Jefferis A.M., Vinh A., Gaspari T., Dragoljevic D., Jennings G.L., et al. Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat. FASEB J. 2019;33:1510–1521. doi: 10.1096/fj.201701498RR. - DOI - PubMed

[6] Khan S.I., Shihata W.A., Andrews K.L., Lee M.K.S., Moore X.L., Jefferis A.M., Vinh A., Gaspari T., Dragoljevic D., Jennings G.L., et al. Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat. FASEB J. 2019;33:1510–1521. doi: 10.1096/fj.201701498RR. - DOI - PubMed

[7] Guzik T.J., Hoch N.E., Brown K.A., McCann L.A., Rahman A., Dikalov S., Goronzy J., Weyand C., Harrison D.G. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J. Exp. Med. 2007;204:2449–2460. doi: 10.1084/jem.20070657. - DOI - PMC - PubMed

[8] Guzik T.J., Hoch N.E., Brown K.A., McCann L.A., Rahman A., Dikalov S., Goronzy J., Weyand C., Harrison D.G. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J. Exp. Med. 2007;204:2449–2460. doi: 10.1084/jem.20070657. - DOI - PMC - PubMed

[9] Bombardier C., Laine L., Reicin A., Shapiro D., Burgos-Vargas R., Davis B., Day R., Ferraz M.B., Hawkey C.J., Hochberg M.C., et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N. Engl. J. Med. 2000;343:1520–1528. doi: 10.1056/NEJM200011233432103. - DOI - PubMed

[10] Bombardier C., Laine L., Reicin A., Shapiro D., Burgos-Vargas R., Davis B., Day R., Ferraz M.B., Hawkey C.J., Hochberg M.C., et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N. Engl. J. Med. 2000;343:1520–1528. doi: 10.1056/NEJM200011233432103. - DOI - PubMed

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Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?

Affiliations

Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?

Authors

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Abstract

Conflict of interest statement

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Abstract

Conflict of interest statement

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