The Big Idea: the coxib crisis Iron, aspirin and heart disease risk revisited
Open accessAbstract
Kuhn1 used the term ‘crisis’ for the chaotic situation provoked by an unresolved anomaly (i.e. a finding not explainable by a prevailing scientific paradigm). As a crisis evolves, the rules by which the old paradigm are applied to new findings become increasingly blurred. Kuhn's description of a paradigm in crisis1 applies accurately to recent discussions of the cardiovascular risks of the coxibs.2,3 Recognition of paradigm crises is problematic in all scientific fields; however, in medical science, failure to recognize and resolve an ongoing crisis can put lives at risk by delaying a necessary paradigm shift. There had been a ‘working paradigm’, reviewed by Antman et al.2 in a paper that aptly presents the current crisis. Their account of the ‘tsunami of events’ following withdrawal of rofecoxib in 2004 suggests an ongoing paradigm crisis. By the early 1990s, the prevailing paradigm involved ‘the recognition that there are two different cyclooxygenases (COXs), which ‘led to the straightforward view that COX-2 is responsible for the adverse pro-inflammatory effects of prostanoids and that non-specific COX inhibitors cause bleeding by inhibiting COX-1 in platelets’.2 The paradigm encouraged development of COX-2 selective inhibitors to isolate an assumed anti-inflammatory mechanism of aspirin from the mechanism causing haemorrhage. Which of the direct and indirect effects of long-term aspirin use is responsible for cardioprotection remains fundamentally a matter of speculation. There is no reliable proof that the mechanisms under most intense discussion are responsible for prevention of coronary events with regular use. The ‘working paradigm’2 has been overtaken by a paradigm crisis. The mechanism of benefit could be an unexpected effect of aspirin or it could be hidden within one of the known harmful effects of aspirin.
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Elevated iron stores can predispose to coronary artery disease and thence myocardial infarction.
“It is well known that elevated iron stores can predispose to coronary artery disease and thence myocardial infarction.”
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Cites
<i>The Structure of Scientific Revolutions</i>
Kuhn, T. S., & Schlegel, R. (1963) · Physics Today · doi:10.1063/1.3050879 · Cited by 35,538 · see citing works
The Structure of Scientific Revolutions.
Böhm, D., & Kühn, T. (1964) · The Philosophical Quarterly · doi:10.2307/2217783 · Cited by 9,193 · see citing works
Silverstein, F. E., Faich, G. A., Goldstein, J. L., Simon, L. S., Pincus, T., Whelton, A., Makuch, R., Eisen, G. M., Agrawal, N. M., Stenson, W. F., et al. (2000) · JAMA · doi:10.1001/jama.284.10.1247 · Cited by 3,144 · see citing works
IRON AND THE SEX DIFFERENCE IN HEART DISEASE RISK
Sullivan, J. (1981) · The Lancet · doi:10.1016/s0140-6736(81)92463-6 · Cited by 969 · see citing works
Self-citationAntman, E. M., Bennett, J. S., Daugherty, A., Furberg, C., Roberts, H., & Taubert, K. A. (2007) · Circulation · doi:10.1161/circulationaha.106.181424 · Cited by 804 · see citing works
The Structure of Scientific Revolutions 2nd edition
Kühn, T. (1970) · Science · Cited by 645 · see citing works
Baigent, C., Collins, R., Appleby, P., Parish, S., Sleight, P., & Peto, R. (1998) · BMJ · doi:10.1136/bmj.316.7141.1337 · Cited by 404 · see citing works
Cyclooxygenase Inhibition and Cardiovascular Risk
Antman, E. M., DeMets, D. L., & Loscalzo, J. (2005) · Circulation · doi:10.1161/circulationaha.105.568451 · Cited by 284 · see citing works
The iron paradigm of ischemic heart disease
Sullivan, J. L. (1989) · American Heart Journal · doi:10.1016/0002-8703(89)90887-9 · Cited by 241 · see citing works
Self-citationCritical Leg Ischaemia Prevention Study (CLIPS) Group (2007) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2006.01763.x · Cited by 202 · see citing works
Reduction of Iron Stores and Cardiovascular Outcomes in Patients With Peripheral Arterial Disease
Zacharski, L. R., Chow, B. K., Howes, P. S., Shamayeva, G., Baron, J. A., Dalman, R. L., Malenka, D. J., Ozaki, C. K., & Lavori, P. W. (2007) · JAMA · doi:10.1001/jama.297.6.603 · Cited by 180 · see citing works
Arthritis Medicines and Cardiovascular Events—“House of Coxibs”
Topol, E. J. (2005) · JAMA · doi:10.1001/jama.293.3.366 · Cited by 113 · see citing works
Body iron stores and their determinants in healthy postmenopausal US women
Liu, J.-M., Hankinson, S. E., Stampfer, M. J., Rifai, N., Willett, W. C., & Ma, J. (2003) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/78.6.1160 · Cited by 102 · see citing works
Sullivan, J. L. (2004) · Journal of Laboratory and Clinical Medicine · doi:10.1016/j.lab.2004.10.006 · Cited by 82 · see citing works
Self-citationCannon, C. P., Curtis, S., Bolognese, J. A., & Laine, L. (2006) · American Heart Journal · doi:10.1016/j.ahj.2006.05.024 · Cited by 68 · see citing works
Aspirin intake and the use of serum ferritin as a measure of iron status
Fleming, D. J., Jacques, P. F., Massaro, J. M., D’Agostino, R. B., Wilson, P. W. F., & Wood, R. J. (2001) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/74.2.219 · Cited by 66 · see citing works
Milman, N. T., Ovesen, L., Byg, K., & Graudal, N. A. (1999) · Annals of Hematology · doi:10.1007/s002770050537 · Cited by 65 · see citing works
Lapenna, D., Pierdomenico, S. D., Ciofani, G., Ucchino, S., Neri, M., Giamberardino, M. A., & CUCCURULLO, F. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.11.014 · Cited by 58 · see citing works
Stored Iron and Vascular Reactivity
Sullivan, J. L. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000174124.20147.22 · Cited by 41 · see citing works
Self-citationEffect of Helicobacter pylori infection and low‐dose aspirin use on iron stores in the elderly
Kaffes, A. J., Cullen, J. S., Mitchell, H. M., & Katelaris, P. (2003) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.2003.03089.x · Cited by 25 · see citing works
Iron, Aspirin, and Heart Disease Risk
Sullivan, J. L. (1982) · JAMA · doi:10.1001/jama.1982.03320310015002 · Cited by 11 · see citing works
Self-citationNEJM “failed its readers” by delay in publishing its concerns about VIGOR trial
Dobson, R. (2006) · BMJ · doi:10.1136/bmj.333.7559.116-f · Cited by 7 · see citing works
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Kell, D. B. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-2 · Cited by 554 · see citing works
Aspirin-associated iron loss as an anticancer mechanism
Mascitelli, L., Pezzetta, F., & Sullivan, J. L. (2009) · Medical Hypotheses · doi:10.1016/j.mehy.2009.07.047 · Cited by 14 · see citing works
Self-citationKatyayani, K., Raizada, M. S., Raina, S., Sharma, R., & Yadav, R. (2022) · International Journal of Noncommunicable Diseases · doi:10.4103/jncd.jncd_34_22 · Cited by 1 · see citing works
- Authors
- Sullivan, J. L.
- Affiliations
- University of Central Florida (US)
- Corresponding author
- Sullivan, Jerome L
- Venue
- Journal of the Royal Society of Medicine
- Publisher
- SAGE Publications
- Published
- 2007-07
- Volume
- 100
- Issue
- 7
- Pages
- 346-349
- ISSN
- 0141-0768 (ISSN-L)
- 1758-1095
- PMC
- PMC1905876
- OpenAlex
- W2150242329
- Cited by
- 3
- References
- 22
- Citations by year
- 2022: 1
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of the Royal Society of Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Journal of International Crisis and Risk Communication Research (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- COX-2 inhibitors, COX-2 selective inhibitors, aspirin, cardiovascular risk, paradigm crisis, cyclooxygenase, cardioprotection mechanisms, iron, prostanoids
- MeSH terms
- Iron Deficiencies, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Heart Diseases, Humans, Risk Factors, Cyclooxygenase 2 Inhibitors
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