Testing cardiovascular drug safety and efficacy in randomized trials

Circulation Research

Volumn 114, Issue 7, 2014, Pages 1156-1161

  Fitzgerald, Garret A ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

cholesterol; clinical trial; cyclooxygenase; niacin; rosiglitazone; thromboxane receptor

Indexed keywords

ACETYLSALICYLIC ACID; ALDOSTERONE; ALDOSTERONE SYNTHASE; BIOLOGICAL MARKER; CELECOXIB; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; DALCETRAPIB; HIGH DENSITY LIPOPROTEIN; IBUPROFEN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LUMIRACOXIB; NAPROXEN; NICOTINIC ACID; NONSTEROID ANTIINFLAMMATORY AGENT; ROFECOXIB; ROSIGLITAZONE; TERUTROBAN; TORCETRAPIB; VALDECOXIB;

ALDOSTERONE BLOOD LEVEL; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHRONIC ARTHRITIS; DRUG APPROVAL; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; DRUG SAFETY; ELEVATED BLOOD PRESSURE; ENZYME INHIBITION; GENETIC VARIABILITY; HEART DISEASE; HEART PROTECTION; HIGH RISK PATIENT; HUMAN; LIPOPROTEIN BLOOD LEVEL; MORTALITY; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POST TREATMENT SURVIVAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK BENEFIT ANALYSIS; TREATMENT OUTCOME; UPREGULATION;

CHOLESTEROL; CLINICAL TRIAL; CYCLOOXYGENASE; NIACIN; ROSIGLITAZONE; THROMBOXANE RECEPTOR;

CARDIOVASCULAR AGENTS; HUMANS; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84897517078     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.114.301809     Document Type: Review

References (44)

1. Horwitz RI, Abell JE, Christian JB, Wivel AE. Right answers, wrong questions in clinical research. Sci Transl Med. 2014;6:221fs5.
2. Urban TJ, Goldstein DB. Pharmacogenetics at 50: genomic personalization comes of age. Sci Transl Med. 2014;6:220ps1.
3. Fries S, Grosser T, Price TS, Lawson JA, Kapoor S, DeMarco S, Pletcher MT, Wiltshire T, FitzGerald GA. Marked interindividual variability in the response to selective inhibitors of cyclooxygenase-2. Gastroenterology. 2006;130:55-64.
4. van der Leeuw J, Ridker PM, van der Graf Y, Visseren FL. Personalized CVD prevention by applying individualized prediction [published online ahead of print February 9, 2014]. Eur Heart J. doi: 10.1093/eurheartj/ehu004. Accessed March 9, 2014.
5. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ; VIGOR Study Group. 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, 2 p following 1528.
6. Schnitzer TJ, Burmester GR, Mysler E, Hochberg MC, Doherty M, Ehrsam E, Gitton X, Krammer G, Mellein B, Matchaba P, Gimona A, Hawkey CJ; TARGET Study Group. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet. 2004;364:665-674.
7. Silverstein, F.E., et al. 2000. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS Study: a randomized controlled trial. JAMA. 284:1247-1255.
8. Nussmeier NA, Whelton AA, Brown MT, Langford RM, Hoeft A, Parlow JL, Boyce SW, Verburg KM. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med. 2005;352:1081-1091.
9. Masferrer JL, Reddy ST, Zweifel BS, Seibert K, Needleman P, Gilbert RS, Herschman HR. In vivo glucocorticoids regulate cyclooxygenase-2 but not cyclooxygenase-1 in peritoneal macrophages. J Pharmacol Exp Ther. 1994;270:1340-1344.
10. McAdam BF, Mardini IA, Habib A, Burke A, Lawson JA, Kapoor S, FitzGerald GA. Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammation. J Clin Invest. 2000;105:1473-1482.
11. Crofford LJ, Wilder RL, Ristimäki AP, Sano H, Remmers EF, Epps HR, Hla T. Cyclooxygenase-1 and-2 expression in rheumatoid synovial tissues. Effects of interleukin-1 beta, phorbol ester, and corticosteroids. J Clin Invest. 1994;93:1095-1101.
12. Grosser T, Fries S, FitzGerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest. 2006;116:4-15.
13. Catella-Lawson F, Reilly MP, Kapoor SC, Cucchiara AJ, DeMarco S, Tournier B, Vyas SN, FitzGerald GA. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345:1809-1817.
14. Patrono C, García Rodríguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med. 2005;353:2373-2383.
15. Grosser T, Yu Y, Fitzgerald GA. Emotion recollected in tranquility: lessons learned from the COX-2 saga. Annu Rev Med. 2010;61:17-33.
16. Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J, Merhi A, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769-779.
17. MacDonald TM, Mackenzie IS, Wei L, Hawkey CJ, Ford I, and the SCOT Study Group Collaborators. Methodology of a large prospective, randomised, open, blinded endpoint streamlined safety study of celecoxib versus traditional non-steroidal anti-inflammatory drugs in patients with osteoarthritis or rheumatoid arthritis: protocol of the standard care versus celecoxib outcome trial (SCOT). BMJ Open 2013;3:e002295. doi:10.1136/bmjopen-2012-002295.
18. February 10-11, 2014, Joint Meeting of the Arthritis Advisory Committee (AAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM)-Webcast Recording. http://www.fda.gov/downloads/AdvisoryCommittees/ CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM384901.pdf. Accessed March 9, 2014.
19. Nissen SE Analyses of cancer data from three ezetimibe trials. N Engl J Med. 2009;360:86-87.
20. Califf RM, Lokhnygina Y, Cannon CP, Stepanavage ME, McCabe CH, Musliner TA, Pasternak RC, Blazing MA, Giugliano RP, Harrington RA, Braunwald E. An update on the IMProved reduction of outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) design. Am Heart J. 2010;159:705-709.
21. Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014;32:40-51.
22. Skarke C, FitzGerald GA. Training translators for smart drug discovery. Sci Transl Med. 2010;2:26cm12.
23. Bousser MG, Amarenco P, Chamorro A, Fisher M, Ford I, Fox KM, Hennerici MG, Mattle HP, Rothwell PM, de Cordoüe A, Fratacci MD; PERFORM Study Investigators. Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial. Lancet. 2011;377:2013-2022.
24. Audoly LP, Rocca B, Fabre JE, Koller BH, Thomas D, Loeb AL, Coffman TM, FitzGerald GA. Cardiovascular responses to the isoprostanes iPF(2alpha)-III and iPE(2)-III are mediated via the thromboxane A(2) receptor in vivo. Circulation. 2000;101:2833-2840.
25. FitzGerald GA, Oates JA, Hawiger J, Maas RL, Roberts LJ 2nd, Lawson JA, Brash AR. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest. 1983;71:676-688.
26. Reilly MP, Delanty N, Roy L, Rokach J, Callaghan PO, Crean P, Lawson JA, FitzGerald GA. Increased formation of the isoprostanes IPF2alpha-I and 8-epi-prostaglandin F2alpha in acute coronary angioplasty: evidence for oxidant stress during coronary reperfusion in humans. Circulation. 1997;96:3314-3320.
27. van Kooten F, Ciabattoni G, Patrono C, Dippel DW, Koudstaal PJ. Platelet activation and lipid peroxidation in patients with acute ischemic stroke. Stroke. 1997;28:1557-1563.
28. Voight BF, Peloso GM, Orho-Melander M, et al. Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study. Lancet. 2012;380:572-580.
29. Tanne JH. Pfizer stops clinical trials of heart drug. BMJ. 2006;333:1237.
30. Rader DJ, deGoma EM. Future of cholesteryl ester transfer protein inhibitors. Annu Rev Med. 2014;65:385-403.
31. Rosenson RS, Hurt-Camejo E. Phospholipase A2 enzymes and the risk of atherosclerosis. Eur Heart J. 2012;33:2899-2909.
32. The AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: baseline characteristics of study participants. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH) trial. Am Heart J. 2011;161(3):538-543.
33. Song WL, FitzGerald GA. Niacin, an old drug with a new twist. J Lipid Res. 2013;54:2586-2594.
34. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457-2471.
35. Mahaffey KW, Hafley G, Dickerson S, Burns S, Tourt-Uhlig S, White J, Newby LK, Komajda M, McMurray J, Bigelow R, Home PD, Lopes RD. Results of a reevaluation of cardiovascular outcomes in the RECORD trial. Am Heart J. 2013;166:240-249.e1.
36. Djulbegovic B, Hozo I, Ioannidis JP. Improving the drug development process: more not less randomized trials. JAMA. 2014;311:355-356.
37. Seok J, Warren HS, Cuenca AG, et al.; Inflammation and Host Response to Injury, Large Scale Collaborative Research Program. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA. 2013;110:3507-3512.
38. Krauth D, Anglemyer A, Philipps R, Bero L. Nonindustry-sponsored preclinical studies on statins yield greater efficacy estimates than industry-sponsored studies: a meta-analysis. PLoS Biol. 2014.;12:e1001770. doi:10.1371/journal.pbio.1001770.
39. Ramsey BW, Davies J, McElvaney NG, et al.; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365:1663-1672.
40. Vertex Announces Results of Phase 3 Study of Ivacaftor in People with CF who have the R117H Mutation. http://investors.vrtx.com/releasedetail. cfm?ReleaseID=814799. Accessed March 9, 2014.
41. Zerhouni EA. Turning the titanic. Sci Transl Med. 2014;6:221ed2.
42. FitzGerald GA. Can intellectual property save drug development? Science. 2012;338(6106):483-484.
43. Ehrenreich H, Weissenborn K, Prange H, et al.; EPO Stroke Trial Group. Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke. 2009;40:e647-e656.
44. Cao Y. Erythropoietin in cancer: a dilemma in risk therapy. Trends Endocrinol Metab. 2013;24:190-199.