{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:10:55Z","timestamp":1790485855551,"version":"4.1.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Large clinical trials compared distinct nonsteroidal anti-inflammatory drugs in terms of their risk of adverse cardiovascular events. However, whether pharmacologically equipotent doses were used, that is, whether a similar degree of COX (cyclooxygenase)-2 inhibition was achieved, was not considered. We compared drug target inhibition and blood pressure (BP) response to celecoxib and naproxen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Sixteen healthy participants were treated with celecoxib (200 mg\/d), naproxen (500 mg\/d), or placebo for 7 days in a double-blind, crossover design. The degree of COX inhibition was assessed ex vivo using established whole blood assays and in vivo by quantifying urinary metabolites of thromboxane A\n                      <jats:sub>2<\/jats:sub>\n                      (COX-1) and prostacyclin (COX-2). Ambulatory BP was measured throughout the final dosing interval.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Both nonsteroidal anti-inflammatory drugs inhibited COX-2 activity relative to placebo, but naproxen inhibited COX-2 activity to a greater degree (62.9\u00b121.7%) than celecoxib (35.7\u00b125.2%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05). Similarly, naproxen treatment inhibited prostacyclin formation in vivo (48.0\u00b124.9%) to a greater degree than celecoxib (26.7\u00b124.6%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05). Naproxen significantly increased BP compared with celecoxib (mean arterial pressure, +2.5 [95% CI, 1.5\u20133.5] mm\u2009Hg; systolic BP, +4.0 [95% CI, 2.9\u20135.1] mm\u2009Hg; and diastolic BP, +1.8 [95% CI, 0.8\u20132.8] mm\u2009Hg;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05 for all). The difference in systolic BP relative to placebo was associated with the degree of COX-2 inhibition (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Future studies should consider pharmacokinetic and pharmacodynamic properties, as well as patient-specific factors that may modulate the cardiovascular risk of nonsteroidal anti-inflammatory drug use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT02502006.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/hypertensionaha.124.25516","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T10:00:15Z","timestamp":1767002415000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Degree of Cyclooxygenase-2 Inhibition Modulates Blood Pressure Response"],"prefix":"10.1161","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9918-9170","authenticated-orcid":true,"given":"Katherine N.","family":"Theken","sequence":"first","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (K.N.T., S.G., C.S., S.F., N.F.L., D.S., G.R.G., G.A.F., T.G.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."},{"name":"Department of Oral and Maxillofacial Surgery and Pharmacology, School of Dental Medicine (K.N.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumita","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (K.N.T., S.G., C.S., S.F., N.F.L., D.S., G.R.G., G.A.F., T.G.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5145-3681","authenticated-orcid":true,"given":"Carsten","family":"Skarke","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (K.N.T., S.G., C.S., S.F., N.F.L., D.S., G.R.G., G.A.F., T.G.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."},{"name":"Department of Medicine (C.S., G.A.F.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Fries","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (K.N.T., S.G., C.S., S.F., N.F.L., D.S., G.R.G., G.A.F., T.G.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."},{"name":"Center for Translational Medicine (S.F.), School of Medicine OWL, Bielefeld University, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3965-5624","authenticated-orcid":true,"given":"Nicholas F.","family":"Lahens","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (K.N.T., S.G., C.S., S.F., N.F.L., D.S., G.R.G., G.A.F., T.G.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1972-8865","authenticated-orcid":true,"given":"Dimitra","family":"Sarantopoulou","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (K.N.T., S.G., C.S., S.F., N.F.L., D.S., G.R.G., G.A.F., T.G.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."},{"name":"Now with National Institute on Aging, National Institutes of Health, Baltimore, MD (D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-7658","authenticated-orcid":true,"given":"Gregory R.","family":"Grant","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (K.N.T., S.G., C.S., S.F., N.F.L., D.S., G.R.G., G.A.F., T.G.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."},{"name":"Department of Genetics (G.R.G.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5885-6819","authenticated-orcid":true,"given":"Garret A.","family":"FitzGerald","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (K.N.T., S.G., C.S., S.F., N.F.L., D.S., G.R.G., G.A.F., T.G.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."},{"name":"Department of Medicine (C.S., G.A.F.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8569-8396","authenticated-orcid":true,"given":"Tilo","family":"Grosser","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (K.N.T., S.G., C.S., S.F., N.F.L., D.S., G.R.G., G.A.F., T.G.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."},{"name":"Department of Translational Pharmacology (T.G.), School of Medicine OWL, Bielefeld University, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","volume-title":"Pain Management and the Intersection of Pain and Opioid Use Disorder","author":"National Academies of Sciences Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse","year":"2017","unstructured":"National Academies of Sciences Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse. Pain management and the opioid epidemic: balancing societal and individual benefits and risks of prescription opioid use. In: Phillips JK, Ford MA, Bonnie RJ, eds. Pain Management and the Intersection of Pain and Opioid Use Disorder. National Academies Press (US); 2017."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan0088"},{"key":"e_1_3_3_4_2","volume-title":"Medical Expenditure Panel Survey","author":"Stagnitti MN","year":"2009","unstructured":"Stagnitti MN. Trends in outpatient prescription analgesics utilization and expenditures for the U.S. civilian noninstitutionalized population, 1996 and 2006. Statistical brief #235. Medical Expenditure Panel Survey. 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