283
Views
1
CrossRef citations to date
0
Altmetric
Reviews

Emerging drugs for coronary artery disease. From past achievements and current needs to clinical promises

, & , MD PhD FESC FACC
Pages 203-233 | Published online: 13 Jan 2011

Bibliography

  • Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 2001;16(22):2746-53
  • Boden WE, O'Rourke RA, Teo KK, Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356(15):1503-16
  • Frye RL, August P, Brooks MM, A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med 2009;360(24):2503-15
  • Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol 2005;46(7):1225-8
  • Baigent C, Keech A, Kearney PM, Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366(9493):1267-78
  • Chapman MJ. Therapeutic elevation of HDL-cholesterol to prevent atherosclerosis and coronary heart disease. Pharmacol Ther 2006;111(3):893-908
  • Ridker PM, Danielson E, Fonseca FA, Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359(21):2195-207
  • Cannon CP, Braunwald E, McCabe CH, Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350(15):1495-504
  • LaRosa JC, Grundy SM, Waters DD, Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352(14):1425-35
  • Miller M, Cannon CP, Murphy SA, Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol 2008;51(7):724-30
  • Singh IM, Shishehbor MH, Ansell BJ. High-density lipoprotein as a therapeutic target: a systematic review. JAMA 2007;298(7):786-98
  • Wolfram RM, Brewer HB, Xue Z, Impact of low high-density lipoproteins on in-hospital events and one-year clinical outcomes in patients with non-ST-elevation myocardial infarction acute coronary syndrome treated with drug-eluting stent implantation. Am J Cardiol 2006;98(6):711-17
  • Castelli WP, Garrison RJ, Wilson PW, Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 1986;256(20):2835-8
  • Barter P, Gotto AM, LaRosa JC, HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007;357(13):1301-10
  • Brown BG, Zhao XQ. Nicotinic acid, alone and in combinations, for reduction of cardiovascular risk. Am J Cardiol 2008;101(8A):58B-62B
  • Nicholls SJ, Tuzcu EM, Sipahi I, Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA 2007;297(5):499-508
  • Nissen SE, Nicholls SJ, Sipahi I, Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 2006;295(13):1556-65
  • Taylor AJ, Lee HJ, Sullenberger LE. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin 2006;22(11):2243-50
  • Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 2006;6(7):508-19
  • Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med 1999;340(2):115-26
  • Segers D, Garcia-Garcia HM, Cheng C, A primer on the immune system in the pathogenesis and treatment of atherosclerosis. EuroIntervention 2008;4(3):378-90
  • Cook S, Togni M, Schaub MC, High heart rate: a cardiovascular risk factor? Eur Heart J 2006;27(20):2387-93
  • Diaz A, Bourassa MG, Guertin MC, Tardif JC. Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease. Eur Heart J 2005;26(10):967-74
  • Fox K, Borer JS, Camm AJ, Resting heart rate in cardiovascular disease. J Am Coll Cardiol 2007;50(9):823-30
  • Kannel WB, Kannel C, Paffenbarger RS Jr. Cupples LA. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J 1987;113(6):1489-94
  • Fox K, Ford I, Steg PG, Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet 2008;372(9641):817-21
  • Jost S, Nolte CW, Sturm M, How to standardize vasomotor tone in serial studies based on quantitation of coronary dimensions? Int J Card Imaging 1998;14(6):357-72
  • Kaski JC, Tousoulis D, Haider AW, Reactivity of eccentric and concentric coronary stenoses in patients with chronic stable angina. J Am Coll Cardiol 1991;17(3):627-33
  • McPherson DD, Sirna S, Collins SM, Can atherosclerotic coronary arteries vasodilate? An intraoperative high-frequency epicardial echocardiographic study. Am J Cardiol 1995;76(1):21-5
  • Yamagishi M, Nissen SE, Booth DC, Coronary reactivity to nitroglycerin: intravascular ultrasound evidence for the importance of plaque distribution. J Am Coll Cardiol 1995;25(1):224-30
  • Poss J, Werner C, Lorenz D, The renin inhibitor aliskiren upregulates pro-angiogenic cells and reduces atherogenesis in mice. Basic Res Cardiol 2010;105(6):725-35
  • Cuisset T, Frere C, Quilici J, Relationship between aspirin and clopidogrel responses in acute coronary syndrome and clinical predictors of non response. Thromb Res 2009;123(4):597-603
  • Francescone S, Halperin JL. ‘Triple therapy’ or triple threat? Balancing the risks of antithrombotic therapy for patients with atrial fibrillation and coronary stents. J Am Coll Cardiol 2008;51(8):826-7
  • Tadamura E, Mamede M, Kubo S, The effect of nitroglycerin on myocardial blood flow in various segments characterized by rest-redistribution thallium SPECT. J Nucl Med 2003;44(5):745-51
  • A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results. JAMA 1982;247(12):1707-14
  • A randomized trial of propranolol in patients with acute myocardial infarction. II. Morbidity results. JAMA 1983;250(20):2814-19
  • Quyyumi AA, Crake T, Wright CM, Medical treatment of patients with severe exertional and rest angina: double blind comparison of beta blocker, calcium antagonist, and nitrate. Br Heart J 1987;57(6):505-11
  • Dahlof B, Sever PS, Poulter NR, Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005;366(9489):895-906
  • Chahine RA, Feldman RL, Giles TD, Randomized placebo-controlled trial of amlodipine in vasospastic angina. Amlodipine Study 160 Group. J Am Coll Cardiol 1993;21(6):1365-70
  • Fox KM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003;362(9386):782-8
  • Yusuf S, Sleight P, Pogue J, Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342(3):145-53
  • Ferrari R, Bertrand ME, Remme WJ, Insight into ACE inhibition in the prevention of cardiac events in stable coronary artery disease: the EUROPA trial. Expert Rev Cardiovasc Ther 2007;5(6):1037-46
  • Dagenais GR, Pogue J, Fox K, Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. Lancet 2006;368(9535):581-8
  • Granger CB, McMurray JJ, Yusuf S, Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003;362(9386):772-6
  • Julius S, Kjeldsen SE, Weber M, Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004;363(9426):2022-31
  • Verma S, Strauss M. Angiotensin receptor blockers and myocardial infarction. BMJ 2004;329(7477):1248-9
  • Sipahi I, Debanne SM, Rowland DY, Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol 2010;11(7):627-36
  • Bangalore S, Kumar S, Kjeldsen SE, Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324 168 participants from randomised trials. Lancet Oncol 2010. [Epub ahead of print]
  • Violi F, Micheletta F, Iuliano L. MRC/BHF Heart Protection Study. Lancet 2002;360(9347):1782-3
  • Jukema JW, Bruschke AV, van Boven AJ, Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS). Circulation 1995;91(10):2528-40
  • Birjmohun RS, Hutten BA, Kastelein JJ, Stroes ES. Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials. J Am Coll Cardiol 2005;45(2):185-97
  • Altmann SW, Davis HR Jr, Zhu LJ, Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 2004;303(5661):1201-4
  • Mikhailidis DP, Sibbring GC, Ballantyne CM, Meta-analysis of the cholesterol-lowering effect of ezetimibe added to ongoing statin therapy. Curr Med Res Opin 2007;23(8):2009-26
  • Pandor A, Ara RM, Tumur I, Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med 2009;265(5):568-80
  • Villines TC, Stanek EJ, Devine PJ, The ARBITER 6-HALTS Trial (arterial biology for the investigation of the treatment effects of reducing cholesterol 6-HDL and LDL treatment strategies in atherosclerosis): final results and the impact of medication adherence, dose, and treatment duration. J Am Coll Cardiol 2010;55(24):2721-6
  • Charlton-Menys V, Durrington PN. Human cholesterol metabolism and therapeutic molecules. Exp Physiol 2008;93(1):27-42
  • Bays HE, Davidson M, Jones MR, Abby SL. Effects of colesevelam hydrochloride on low-density lipoprotein cholesterol and high-sensitivity C-reactive protein when added to statins in patients with hypercholesterolemia. Am J Cardiol 2006;97(8):1198-205
  • Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324(7329):71-86
  • Baigent C, Blackwell L, Collins R, Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373(9678):1849-60
  • Berger JS, Roncaglioni MC, Avanzini F, Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 2006;295(3):306-13
  • Bertrand ME, Legrand V, Boland J, Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study. Circulation 1998;98(16):1597-603
  • Urban P, Macaya C, Rupprecht HJ, Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high-risk patients: the multicenter aspirin and ticlopidine trial after intracoronary stenting (MATTIS). Circulation 1998;98(20):2126-32
  • Chen ZM, Jiang LX, Chen YP, Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366(9497):1607-21
  • Peters MJ, Heyderman RS, Faust S, Severe meningococcal disease is characterized by early neutrophil but not platelet activation and increased formation and consumption of platelet-neutrophil complexes. J Leukoc Biol 2003;73(6):722-30
  • Steinhubl SR, Berger PB, Mann JT III, Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;288(19):2411-20
  • Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. The EPIC Investigation. N Engl J Med 1994;330(14):956-61
  • Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. The RESTORE Investigators. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis. Circulation 1997;96(5):1445-53
  • Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. The PURSUIT Trial Investigators. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy. N Engl J Med 1998;339(7):436-43
  • Montalescot G, Barragan P, Wittenberg O, Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 2001;344(25):1895-1903
  • Roffi M, Chew DP, Mukherjee D, Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes. Circulation 2001;104(23):2767-71
  • A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. N Engl J Med 1998;338(21):1498-1505
  • Bijsterveld NR, Moons AH, Meijers JC, Rebound thrombin generation after heparin therapy in unstable angina. A randomized comparison between unfractionated and low-molecular-weight heparin. J Am Coll Cardiol 2002;39(5)811-17
  • Levine M, Gent M, Hirsh J, A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996;334(11):677-81
  • Kelton JG, Warkentin TE. Diagnosis of heparin-induced thrombocytopenia. Still a journey, not yet a destination. Am J Clin Pathol 1995;104(6):611-13
  • Yusuf S, Mehta SR, Chrolavicius S, Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA 2006;295(13):1519-30
  • Yusuf S, Mehta SR, Chrolavicius S, Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 2006;354(14):1464-76
  • Andreotti F, Testa L, Biondi-Zoccai GG, Crea F. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients. Eur Heart J 2006;27(5):519-26
  • Rothberg MB, Celestin C, Fiore LD, Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. Ann Intern Med 2005;143(4):241-50
  • Lewis GF, Rader DJ. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 2005;96(12):1221-32
  • von EA, Nofer JR, Assmann G. High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 2001;21(1):13-27
  • Kontush A, Chapman MJ. Antiatherogenic small, dense HDL–guardian angel of the arterial wall? Nat Clin Pract Cardiovasc Med 2006;3(3):144-53
  • Navab M, Ananthramaiah GM, Reddy ST, The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res 2004;45(6):993-1007
  • Mineo C, Deguchi H, Griffin JH, Shaul PW. Endothelial and antithrombotic actions of HDL. Circ Res 2006;98(11):1352-64
  • Yuhanna IS, Zhu Y, Cox BE, High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med 2001;7(7):853-7
  • Ohta T, Saku K, Takata K, Different effects of subclasses of HDL containing apoA-I but not apoA-II (LpA-I) on cholesterol esterification in plasma and net cholesterol efflux from foam cells. Arterioscler Thromb Vasc Biol 1995;15(7):956-62
  • Persegol L, Verges B, Foissac M, Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation. Diabetologia 2006;49(6):1380-6
  • Zheng L, Nukuna B, Brennan ML, Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease. J Clin Invest 2004;114(4):529-41
  • Tall AR. Plasma cholesteryl ester transfer protein. J Lipid Res 1993;34(8):1255-74
  • Koizumi J, Mabuchi H, Yoshimura A, Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia. Atherosclerosis 1985;58(1-3):175-86
  • Thompson A, Di AE, Sarwar N, Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 2008;299(23):2777-88
  • Altschul R, Hoffer A, Stephen JD. Influence of nicotinic acid on serum cholesterol in man. Arch Biochem 1955;54(2):558-9
  • Brown BG, Zhao XQ, Chait A, Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345(22):1583-92
  • Taylor AJ, Sullenberger LE, Lee HJ, Arterial biology for the investigation of the treatment effects of reducing cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation 2004;110(23):3512-17
  • Kearney PM, Blackwell L, Collins R, Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371(9607):117-25
  • Vogt A, Kassner U, Hostalek U, Steinhagen-Thiessen E. Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study. Curr Med Res Opin 2006;22(2):417-25
  • Morrow JD, Awad JA, Oates JA, Roberts LJ. Identification of skin as a major site of prostaglandin D2 release following oral administration of niacin in humans. J Invest Dermatol 1992;98(5):812-15
  • Dean BJ, Chang S, Silva Elipe MV, Metabolism of MK-0524, a prostaglandin D2 receptor 1 antagonist, in microsomes and hepatocytes from preclinical species and humans. Drug Metab Dispos 2007;35(2):283-92
  • Sturino CF, O'Neill G, Lachance N, Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocy clopenta[b]indol-3-yl]-acetic acid (MK-0524). J Med Chem 2007;50(4):794-806
  • Maccubbin D, Bays HE, Olsson AG, Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia. Int J Clin Pract 2008;62(12):1959-70
  • Staels B, Fruchart JC. Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes 2005;54(8):2460-70
  • Tardif JC, Gregoire J, L'Allier PL, Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 2007;297(15):1675-82
  • Roma P, Gregg RE, Meng MS, In vivo metabolism of a mutant form of apolipoprotein A-I, apo A-IMilano, associated with familial hypoalphalipoproteinemia. J Clin Invest 1993;91(4):1445-52
  • Sirtori CR, Calabresi L, Franceschini G, Cardiovascular status of carriers of the apolipoprotein A-I(Milano) mutant: the Limone sul Garda study. Circulation 2001;103(15):1949-54
  • Chiesa G, Sirtori CR. Recombinant apolipoprotein A-I(Milano): a novel agent for the induction of regression of atherosclerotic plaques. Ann Med 2003;35(4):267-73
  • Shah PK, Yano J, Reyes O, High-dose recombinant apolipoprotein A-I(milano) mobilizes tissue cholesterol and rapidly reduces plaque lipid and macrophage content in apolipoprotein e-deficient mice. Potential implications for acute plaque stabilization. Circulation 2001;103(25):3047-50
  • Ibanez B, Vilahur G, Cimmino G, Rapid change in plaque size, composition, and molecular footprint after recombinant apolipoprotein A-I Milano (ETC-216) administration: magnetic resonance imaging study in an experimental model of atherosclerosis. J Am Coll Cardiol 2008;51(11):1104-9
  • Ivandic B, Castellani LW, Wang XP, Role of group II secretory phospholipase A2 in atherosclerosis: 1. Increased atherogenesis and altered lipoproteins in transgenic mice expressing group IIa phospholipase A2. Arterioscler Thromb Vasc Biol 1999;19(5):1284-90
  • Burke JE, Dennis EA. Phospholipase A2 biochemistry. Cardiovasc Drugs Ther 2009;23(1):49-59
  • Stafforini DM. Biology of platelet-activating factor acetylhydrolase (PAF-AH, lipoprotein associated phospholipase A2). Cardiovasc Drugs Ther 2009;23(1):73-83
  • Zalewski A, Macphee C. Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target. Arterioscler Thromb Vasc Biol 2005;25(5):923-31
  • Mangin EL Jr, Kugiyama K, Nguy JH, Effects of lysolipids and oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta. Circ Res 1993;72(1):161-6
  • Elinder LS, Dumitrescu A, Larsson P, Expression of phospholipase A2 isoforms in human normal and atherosclerotic arterial wall. Arterioscler Thromb Vasc Biol 1997;17(10):2257-63
  • Marathe GK, Harrison KA, Murphy RC, Bioactive phospholipid oxidation products. Free Radic Biol Med 2000;28(12):1762-70
  • Stocker R. Molecular mechanisms underlying the antiatherosclerotic and antidiabetic effects of probucol, succinobucol, and other probucol analogues. Curr Opin Lipidol 2009;20(3):227-35
  • Ferns GA, Forster L, Stewart-Lee A, Probucol inhibits mononuclear cell adhesion to vascular endothelium in the cholesterol-fed rabbit. Atherosclerosis 1993;100(2):171-81
  • Wu BJ, Di GN, Beck K, Probucol [4,4′-[(1-methylethylidene)bis(thio)]bis-[2,6-bis(1,1-dimethylethyl)phenol ]] inhibits compensatory remodeling and promotes lumen loss associated with atherosclerosis in apolipoprotein E-deficient mice. J Pharmacol Exp Ther 2007;321(2):477-84
  • Walldius G, Erikson U, Olsson AG, The effect of probucol on femoral atherosclerosis: the Probucol Quantitative Regression Swedish Trial (PQRST). Am J Cardiol 1994;74(9):875-83
  • Barnhart JW, Wagner ER, Jackson RL. The synthesis, metabolism, and biological activity of probucol and its analogs. In: Witiak DT, Newman HAI, Feller DR, editors, Antilipidemic drugs. Elsevier, Amsterdam; 1993. p. 227-98
  • Guo J, Massaeli H, Li W, Identification of IKr and its trafficking disruption induced by probucol in cultured neonatal rat cardiomyocytes. J Pharmacol Exp Ther 2007;321(3):911-20
  • Meng CQ, Somers PK, Rachita CL, Novel phenolic antioxidants as multifunctional inhibitors of inducible VCAM-1 expression for use in atherosclerosis. Bioorg Med Chem Lett 2002;12(18):2545-8
  • DiFrancesco D. Funny channels in the control of cardiac rhythm and mode of action of selective blockers. Pharmacol Res 2006;53(5):399-406
  • Tardif JC, Ford I, Tendera M, Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J 2005;26(23):2529-36
  • Ruzyllo W, Tendera M, Ford I, Fox KM. Antianginal efficacy and safety of ivabradine compared with amlodipine in patients with stable effort angina pectoris: a 3-month randomised, double-blind, multicentre, noninferiority trial. Drugs 2007;67(3):393-405
  • Somlyo AP, Somlyo AV. Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol 2000;522 Pt 2:177-85
  • Uehata M, Ishizaki T, Satoh H, Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 1997;389(6654):990-4
  • Dong M, Yan BP, Liao JK, Rho-kinase inhibition: a novel therapeutic target for the treatment of cardiovascular diseases. Drug Discov Today 2010;15(15-16):622-9
  • Belardinelli L, Shyrock JC, Fraser H. The mechanism of ranolazine action to reduce ischemia-induced diastolic dysfunction. Eur Heart J 2006;8(Suppl A):A10-13
  • Antzelevitch C, Belardinelli L, Zygmunt AC, Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 2004;110(8):904-10
  • Campbell DJ. Interpretation of plasma renin concentration in patients receiving aliskiren therapy. Hypertension 2008;51(1):15-18
  • Melnyk RA, Tam J, Boie Y, Renin and prorenin activate pathways implicated in organ damage in human mesangial cells independent of angiotensin II production. Am J Nephrol 2009;30(3):232-43
  • Nguyen G, Delarue F, Burckle C, Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest 2002;109(11):1417-27
  • FitzGerald GA. Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists. Am J Cardiol 1991;68(7):11B-15B
  • Barter PJ, Caulfield M, Eriksson M, Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357(21):2109-22
  • Bots ML, Visseren FL, Evans GW, Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet 2007;370(9582):153-60
  • Davidson MH, McKenney JM, Shear CL, Revkin JH. Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels. J Am Coll Cardiol 2006;48(9):1774-81
  • Kastelein JJ, van Leuven SI, Burgess L, Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med 2007;356(16):1620-30
  • McKenney JM, Davidson MH, Shear CL, Revkin JH. Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels on a background of atorvastatin. J Am Coll Cardiol 2006;48(9):1782-90
  • Nissen SE, Tardif JC, Nicholls SJ, Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med 2007;356(13):1304-16
  • de HW, de Vries-van der Weij, van der Hoorn JW, Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin. Circulation 2008;117(19):2515-22
  • de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation 2002;105(18):2159-65
  • Krishna R, Anderson MS, Bergman AJ, Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies. Lancet 2007;370(9603):1907-14
  • Forrest MJ, Bloomfield D, Briscoe RJ, Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br J Pharmacol 2008;154(7):1465-73
  • Clark RW, Ruggeri RB, Cunningham D, Bamberger MJ. Description of the torcetrapib series of cholesteryl ester transfer protein inhibitors, including mechanism of action. J Lipid Res 2006;47(3):537-52
  • Stein EA, Stroes ES, Steiner G, Safety and tolerability of dalcetrapib. Am J Cardiol 2009;104(1):82-91
  • Thomas LJ, Hammond RA, Forsberg EM, Co-administration of a CpG adjuvant (VaxImmune, CPG 7909) with CETP vaccines increased immunogenicity in rabbits and mice. Hum Vaccin 2009;5(2):79-84
  • Hermann F, Enseleit F, Spieker LE, Cholesterylestertransfer protein inhibition and endothelial function in type II hyperlipidemia. Thromb Res 2009;123(3):460-5
  • A study of the effect of RO4607381 on atherosclerotic plaque in patients with coronary heart disease. National Institutes of Health/Clinicaltrials gov/identifier:NCT00655473. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00655473?term=RO4607381&rank=5 [30 September 2010]
  • A study of RO4607381 in stable coronary heart disease patients with recent acute coronary syndrome. National Institutes of Health/Clinicaltrials gov/identifier:NCT00658515. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00658515?term=NCT00658515&rank=1 [30 September 2010]
  • Schwartz GG, Olsson AG, Ballantyne CM, Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. Am Heart J 2009;158(6):896-901
  • Study to assess the tolerability and efficacy of anacetrapib in patients with coronary heart disease (CHD) or CHD risk-equivalent disease (DEFINE). National Institutes of Health/Clinicaltrials gov/identifier:NCT00685776. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00685776?term=anacetrapib&rank=1 [30 September 2010]
  • Cannon CP, Dansky HM, Davidson M, Design of the DEFINE trial: determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib. Am Heart J 2009;158(4):513-19
  • Taylor AJ, Villines TC, Stanek EJ, Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009;361(22):2113-22
  • Sorrentino SA, Besler C, Rohrer L, Endothelial-vasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy. Circulation 2010;121(1):110-22
  • Maccubbin D, Koren MJ, Davidson M, Flushing profile of extended-release niacin/laropiprant versus gradually titrated niacin extended-release in patients with dyslipidemia with and without ischemic cardiovascular disease. Am J Cardiol 2009;104(1):74-81
  • Paolini JF, Mitchel YB, Reyes R, Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia. Am J Cardiol 2008;101(5):625-30
  • Brown BG, Boden WE. Niacin plus statin to prevent vascular events. National Institutes of Health/Clinicaltrials gov/identifier:NCT00120289. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00120289?term=NCT00120289&rank=1
  • Armitage J, Baigent C, Chen Z, Landray M. Treatment of HDL to reduce the incidence of vascular events HPS2-THRIVE. National Institutes of Health/Clinicaltrials gov/identifier:NCT00461630.Available from: http://clinicaltrials.gov/ct2/show/NCT00461630?term=NCT00461630&rank=1
  • Saad MF, Greco S, Osei K, Ragaglitazar improves glycemic control and lipid profile in type 2 diabetic subjects: a 12-week, double-blind, placebo-controlled dose-ranging study with an open pioglitazone arm. Diabetes Care 2004;27(6):1324-9
  • Skrumsager BK, Nielsen KK, Muller M, Ragaglitazar: the pharmacokinetics, pharmacodynamics, and tolerability of a novel dual PPAR alpha and gamma agonist in healthy subjects and patients with type 2 diabetes. J Clin Pharmacol 2003;43(11):1244-56
  • Buse JB, Rubin CJ, Frederich R, Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with type 2 diabetes. Clin Ther 2005;27(8):1181-95
  • Kendall DM, Rubin CJ, Mohideen P, Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a double-blind, randomized, pioglitazone-comparative study. Diabetes Care 2006;29(5):1016-23
  • Nissen SE, Wolski K, Topol EJ. Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus. JAMA 2005;294(20):2581-6
  • Goldstein BJ, Rosenstock J, Anzalone D, Effect of tesaglitazar, a dual PPAR alpha/gamma agonist, on glucose and lipid abnormalities in patients with type 2 diabetes: a 12-week dose-ranging trial. Curr Med Res Opin 2006;22(12):2575-90
  • Ratner RE, Parikh S, Tou C. Efficacy, safety and tolerability of tesaglitazar when added to the therapeutic regimen of poorly controlled insulin-treated patients with type 2 diabetes. Diab Vasc Dis Res 2007;4(3):214-21
  • Wilding JP, Gause-Nilsson I, Persson A. Tesaglitazar, as add-on therapy to sulphonylurea, dose-dependently improves glucose and lipid abnormalities in patients with type 2 diabetes. Diab Vasc Dis Res 2007;4(3):194-203
  • Henry RR, Lincoff AM, Mudaliar S, Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study. Lancet 2009;374(9684):126-35
  • A study with aleglitazar in patients with a recent acute coronary syndrome and type II diabetes mellitus. National Institutes of Health/Clinicaltrials gov/identifier:NCT01042769. Available from: http://clinicaltrials.gov/ct2/show/NCT01042769?term=aleglitazar&rank=5
  • Nanjee MN, Cooke CJ, Garvin R, Intravenous apoA-I/lecithin discs increase pre-beta-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans. J Lipid Res 2001;42(10):1586-93
  • Safety and Efficacy of APL180 in Healthy Volunteers and Patients With Coronary Heart Disease (CHD). National Institutes of Health/Clinicaltrials gov/identifier:NCT00568594. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00568594?term=HDL+infusion&rank=3
  • Shakib S. Safety, Tolerability and pharmacokinetics of CSL112 in healthy volunteers. National Institutes of Health/Clinicaltrials gov/identifier:NCT01129661. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01129661?term=HDL+infusion&rank=6
  • Nissen SE, Tsunoda T, Tuzcu EM, Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 2003;290(17):2292-300
  • Nicholls SJ, Tuzcu EM, Sipahi I, Relationship between atheroma regression and change in lumen size after infusion of apolipoprotein A-I Milano. J Am Coll Cardiol 2006;47(5):992-7
  • Tardif JC. Effect of CER-001 on atherosclerosis in ACS patients – efficacy and safety: The CHI SQUARE Trial. National institutes of Health/Clinicaltrials gov/identifier:NCT01201837. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01201837?term=HDL+infusion&rank=1
  • Rosenson RS, Hislop C, McConnell D, Effects of 1-H-indole-3-glyoxamide (A-002) on concentration of secretory phospholipase A2 (PLASMA study): a phase II double-blind, randomised, placebo-controlled trial. Lancet 2009;373(9664):649-58
  • PLASMA 2 Trial: Examination of once daily (QD) dosing of A-002 in subjects with stable coronary artery disease. National Institutes of Health/Clinicaltrials gov/identifier:NCT00525954. Available from: http://clinicaltrials.gov/ct2/show/NCT00525954?term=NCT00525954&rank=1 [30 September 2010]
  • FRANCIS-ACS Trial: A study of the safety and efficacy of A 002 in subjects with acute coronary syndromes. National Institutes of Health/Clinicaltrials gov/identifier:NCT00743925. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00743925?term=varespladib&rank=1
  • VISTA-16 Trial: evaluation of safety and efficacy of short-term A-002 treatment in subjects with acute coronary syndrome. National Institutes of Health/Clinicaltrials gov/identifier:NCT01130246. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01130246?term=varespladib&rank=3
  • Dzavik V. sPLA2 inhibition to decrease enzyme release after PCI trial (SPIDER-PCI). National Institutes of Health/Clinicaltrials gov/identifier:NCT00533039. Available from: http://clinicaltrials.gov/ct2/show/NCT00533039?term=NCT00533039&rank=1 [30 September 2010]
  • Mohler ER III, Ballantyne CM, Davidson MH, The effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 2008;51(17):1632-41
  • Serruys PW, Garcia-Garcia HM, Buszman P, Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation 2008;118(11):1172-82
  • The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY). National Institutes of Health/Clinicaltrials gov/identifier:NCT00799903. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00799903?term=Darapladib&rank=7
  • The Stabilization Of pLaques usIng Darapladib-Thrombolysis In Myocardial Infarction 52 Trial (SOLID-TIMI 52). National Institutes of Health/Clinicaltrials gov/identifier:NCT01000727. Availabe from: http://www.clinicaltrials.gov/ct2/show/NCT01000727?term=Darapladib&rank=8
  • Lerman A. Lp-PLA2, Progenitor Cells and Coronary Atherosclerosis in Humans AIM III. National Institutes of Health/Clinicaltrials gov/identifier:NCT01067339. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01067339?term=Darapladib&rank=9 [10 April 2010]
  • Tardif JC, Gregoire J, Schwartz L, Effects of AGI-1067 and probucol after percutaneous coronary interventions. Circulation 2003;107(4):552-8
  • Kunsch C, Luchoomun J, Grey JY, Selective inhibition of endothelial and monocyte redox-sensitive genes by AGI-1067: a novel antioxidant and anti-inflammatory agent. J Pharmacol Exp Ther 2004;308(3):820-9
  • Luyendyk JP, Piper JD, Tencati M, A novel class of antioxidants inhibit LPS induction of tissue factor by selective inhibition of the activation of ASK1 and MAP kinases. Arterioscler Thromb Vasc Biol 2007;27(8):1857-63
  • Tardif JC, Gregoire J, L'Allier PL, Effects of the antioxidant succinobucol (AGI-1067) on human atherosclerosis in a randomized clinical trial. Atherosclerosis 2008;197(1):480-6
  • Tardif JC, McMurray JJ, Klug E, Effects of succinobucol (AGI-1067) after an acute coronary syndrome: a randomised, double-blind, placebo-controlled trial. Lancet 2008;371(9626):1761-8
  • Borer JS, Fox K, Jaillon P, Lerebours G. Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial. Circulation 2003;107(6):817-23
  • Fox K, Ferrari R, Tendera M, Rationale and design of a randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction: the morBidity-mortality EvAlUaTion of the I(f) inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction (BEAUTIFUL) study. Am Heart J 2006;152(5):860-6
  • Fox K, Ford I, Steg PG, Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J 2009;30(19):2337-45
  • Ferrari R. A step further with Ivabradine: SIGNIfY (Study assessInG the morbidity-mortality beNefits of the If inhibitor ivabradine in patients with coronarY artery disease). Eur Heart J Suppl 2009;11(Suppl.):D19-27
  • Tardif JC, Ponikowski P, Kahan T. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur Heart J 2009;30(5):540-8
  • Swedberg K, Komajda M, Bohm M, Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2010;376(9744):875-85
  • Custodis F, Baumhakel M, Schlimmer N, Heart rate reduction by ivabradine reduces oxidative stress, improves endothelial function, and prevents atherosclerosis in apolipoprotein E-deficient mice. Circulation 2008;117(18):2377-87
  • Effects of the Ivabradine on reduction of Inflammatory markers in patients with acute coronary syndrome. National Institutes of Health/Clinicaltrials gov/identifier:NCT00815100. Available from: http://clinicaltrials.gov/ct2/show/NCT00815100?term=Ivabradine&rank=1 [30 September 2010]
  • Hiroki J, Fukumoto Y, Shimokawa H, Inhibition of Rho-kinase by fasudil preventing anginal attacks associated with spastic angina: a case report. J Cardiol 2004;44(4):161-4
  • Vicari RM, Chaitman B, Keefe D, Efficacy and safety of fasudil in patients with stable angina: a double-blind, placebo-controlled, phase 2 trial. J Am Coll Cardiol 2005;46(10):1803-11
  • Otsuka T, Ibuki C, Suzuki T, Vasodilatory effect of subsequent administration of fasudil, a rho-kinase inhibitor, surpasses that of nitroglycerin at the concentric coronary stenosis in patients with stable angina pectoris. Circ J 2006;70(4):402-8
  • Otsuka T, Ibuki C, Suzuki T, Administration of the Rho-kinase inhibitor, fasudil, following nitroglycerin additionally dilates the site of coronary spasm in patients with vasospastic angina. Coron Artery Dis 2008;19(2):105-10
  • Nohria A, Grunert ME, Rikitake Y, Rho kinase inhibition improves endothelial function in human subjects with coronary artery disease. Circ Res 2006;99(12):1426-32
  • Creager MA. The effect of Fasudil on vascular function in humans. National Institutes of Health/Clinicaltrials gov/identifier:NCT00120718. Availabe from: http://clinicaltrials.gov/ct2/show/NCT00120718?term=NCT00120718&rank=1 [30 September 2010]
  • Chaitman BR, Skettino SL, Parker JO, Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol 2004;43(8):1375-82
  • Chaitman BR, Pepine CJ, Parker JO, Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA 2004;291(3):309-16
  • Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA 2007;297(16):1775-83
  • Stone PH, Gratsiansky NA, Blokhin A, Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol 2006;48(3):566-75
  • Keating GM. Ranolazine: a review of its use in chronic stable angina pectoris. Drugs 2008;68(17):2483-503
  • Koren MJ, Crager MR, Sweeney M. Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: the Ranolazine Open Label Experience (ROLE). J Am Coll Cardiol 2007;49(10):1027-34
  • Thomas G, Weiss RJ. Study the Effects of Ranolazine on myocardial perfusion assessed by serial quantitative exercise SPECT imaging. National Institutes of Health/Clinicaltrials gov/identifier:NCT01221272. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01221272?term=ranolazine&rank=1 [30 September 2010]
  • Rajagopalan S. Aleskiren effect on plaque progression using 3-dimensional magnetic resonance imaging (3D MRI) (ALPINE). National Institutes of Health/Clinicaltrials gov/identifier:NCT01123629. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01123629?term=aliskerin&rank=1 [30 September 2010]
  • Safety and Efficacy of Aliskiren on the Progression of Atherosclerosis in Coronary Artery Disease Patients (AQUARIUS). National Institutes of Health/Clinicaltrials gov/identifier:NCT00853827. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00853827?term=aliskiren&rank=87
  • Braunwald E; TIMI study group. Efficacy and safety of aliskiren and valsartan versus placebo in patients stabilized following an acute coronary syndrome. National Institutes of Health/Clinicaltrials gov/identifier:NCT00409578. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00409578?term=aliskiren&rank=20
  • Lerman A. The effect of Tekturna on endothelial function and endothelial progenitor cells in patients with early atherosclerosis. National Institutes of Health/Clinicaltrials gov/identifier:NCT01067326. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01067326?term=aliskiren&rank=32
  • Safety and Efficacy of Aliskiren in Post Myocardial Infarction Patients (ASPIRE). National Institutes of Health/Clinicaltrials gov/identifier:NCT00414609. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00414609?term=aliskiren&rank=70
  • Costa J, Ferro JM, Matias-Guiu J, Triflusal for preventing serious vascular events in people at high risk. 2005;(3):CD004296
  • Michelson AD, Frelinger AL III, Braunwald E, Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial. Eur Heart J 2009;30(14):1753-63
  • Wiviott SD, Braunwald E, McCabe CH, Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357(20):2001-15
  • Montalescot G, Wiviott SD, Braunwald E, Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009;373(9665):723-31
  • Wallentin L, Becker RC, Budaj A, Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361(11):1045-57
  • Wijns W, Kolh P, Danchin N, Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2010;31(20):2501-55
  • Bhatt DL, Harrington RA. A Clinical Trial to Demonstrate the Efficacy of Cangrelor (PCI). National Institutes of Health/Clinicaltrials gov/identifier:NCT00305162. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00305162?term=NCT00305162&rank=1
  • Harrington RA, Stone GW, McNulty S, Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009;361(24):2318-29
  • Bhatt DL, Lincoff AM, Gibson CM, Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009;361(24):2330-41
  • Topol EJ. Maintenance of platelet inhibition with cangrelor (Bridge). National Institutes of Health/Clinicaltrials gov/identifier:NCT00767507. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00767507?term=NCT00767507&rank=1 [30 September 2010]
  • Berger JS, Roe MT, Gibson CM, Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: the Early Rapid ReversAl of platelet thromboSis with intravenous Elinogrel before PCI to optimize reperfusion in acute Myocardial Infarction (ERASE MI) pilot trial. Am Heart J 2009;158(6):998-1004
  • Leonardi S, Rao SV, Harrington RA, Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor, versus clopidogrel to eVAluate Tolerability and Efficacy in nonurgent Percutaneous Coronary Interventions patients (INNOVATE-PCI). Am Heart J 2010;160(1):65-72
  • The thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRA*CER) trial: study design and rationale. Am Heart J 2009;158(3):327-34
  • Morrow DA, Scirica BM, Fox KA, Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the thrombin-receptor antagonist in secondary prevention of atherothrombotic ischemic events (TRA 2 degrees P)-TIMI 50 trial. Am Heart J 2009;158(3):335-41
  • A Double-Blind Study of E5555 in Japanese Subjects With Coronary Artery Disease. National Institutes of Health/Clinicaltrials gov/identifier:NCT00540670. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00540670?term=NCT00540670&rank=1 [30 September 2010]
  • A Double-Blind Study of E5555 in Japanese Patients With Acute Coronary Syndrome. National Institutes of Health/Clinicaltrials gov/identifier:NCT00619164. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00619164?term=NCT00619164&rank=1 [30 September 2010]
  • Goto S, Ogawa H, Takeuchi M, Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease. Eur Heart J 2010;31(21):2601-13
  • Viles-Gonzalez JF, Fuster V, Corti R, Atherosclerosis regression and TP receptor inhibition: effect of S18886 on plaque size and composition – a magnetic resonance imaging study. Eur Heart J 2005;26(15):1557-61
  • Hennerici MG. Rationale and design of the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic Attack (PERFORM) Study. Cerebrovasc Dis 2009;(Suppl 3):28-32
  • Gresele P, Deckmyn H, Arnout J, Characterization of N,N'-bis(3-picolyl)-4-methoxy-isophtalamide (picotamide) as a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist in human platelets. Thromb Haemost 1989;61(3):479-84
  • Buccellati C, Ciceri P, Ballerio R, Evaluation of the effects of anti-thromboxane agents in platelet-vessel wall interaction. Eur J Pharmacol 2002;443(1-3):133-41
  • Balsano F, Violi F. Effect of picotamide on the clinical progression of peripheral vascular disease. A double-blind placebo-controlled study. The ADEP Group. Circulation 1993;87(5):1563-9
  • Neri Serneri GG, Coccheri S, Marubini E, Violi F. Picotamide, a combined inhibitor of thromboxane A2 synthase and receptor, reduces 2-year mortality in diabetics with peripheral arterial disease: the DAVID study. Eur Heart J 2004;25(20):1845-52
  • Douglas JS Jr, Holmes DR Jr, Kereiakes DJ, Coronary stent restenosis in patients treated with cilostazol. Circulation 2005;112(18):2826-32
  • Tsuchikane E, Fukuhara A, Kobayashi T, Impact of cilostazol on restenosis after percutaneous coronary balloon angioplasty. Circulation 1999;100(1):21-6
  • Zafar MU, Ibanez B, Choi BG, A new oral antiplatelet agent with potent antithrombotic properties: comparison of DZ-697b with clopidogrel a randomised phase I study. Thromb Haemost 2010;103(1):205-12
  • Maluenda G, Lemesle G, Collins SD, The clinical significance of hematocrit values before and after percutaneous coronary intervention. Am Heart J 2009;158(6):1024-30
  • Marmur JD, Poludasu S, Agarwal A, Bolus-only platelet glycoprotein IIb-IIIa inhibition during percutaneous coronary intervention. J Invasive Cardiol 2006;18(11):521-6
  • A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb investigators. N Engl J Med 1996;335(11):775-82
  • Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularisation procedures in patients with acute myocardial ischaemia without ST elevation: a randomised trial. Organisation to Assess Strategies for Ischemic Syndromes (OASIS-2) Investigators. Lancet 1999;353(9151):429-38
  • Antman EM. Hirudin in acute myocardial infarction. Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9B trial. Circulation 1996;94(5)911-21
  • Jang IK, Brown DF, Giugliano RP, A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with novastan and TPA (MINT) study. J Am Coll Cardiol 1999;33(7):1879-85
  • Stone GW, McLaurin BT, Cox DA, Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006;355(21):2203-16
  • Stone GW, Witzenbichler B, Guagliumi G, Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008;358(21):2218-30
  • Dangas G, Mehran R, Guagliumi G, Role of clopidogrel loading dose in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty: results from the HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trial. J Am Coll Cardiol 2009;54(15):1438-46
  • Lincoff AM, Bittl JA, Harrington RA, Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA 2003;289(7):853-63
  • Albers GW, Diener HC, Frison L, Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005;293(6):690-8
  • Olsson SB. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 2003;362(9397):1691-8
  • Connolly SJ, Ezekowitz MD, Yusuf S, Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361(12):1139-51
  • Schulman S, Kearon C, Kakkar AK, Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009;361(24):2342-52
  • Bousser MG, Bouthier J, Buller HR, Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet 2008;371(9609):315-21
  • Paty I, Trellu M, Destors JM, Reversibility of the anti-FXa activity of idrabiotaparinux (biotinylated idraparinux) by intravenous avidin infusion. J Thromb Haemost 2010;8(4):722-9
  • Bioequipotency Study of SSR126517E and Idraparinux in Patients With Deep Venous Thrombosis of the Lower Limbs (EQUINOX). National Institutes of Health/Clinicaltrials gov/identifier:NCT00311090. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00311090?term=NCT00311090&rank=1 [30 September 2010]
  • Evaluation of Weekly Subcutaneous Biotinylated Idraparinux Versus Oral Adjusted-dose Warfarin to Prevent Stroke and Systemic Thromboembolic Events in Patients With Atrial Fibrillation (BOREALIS-AF). National Institutes of Health/Clinicaltrials gov/identifier:NCT00580216. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00580216?term=NCT00580216&rank=1 [30 September 2010]
  • Cohen M, Bhatt DL, Alexander JH, Randomized, double-blind, dose-ranging study of otamixaban, a novel, parenteral, short-acting direct factor Xa inhibitor, in percutaneous coronary intervention: the SEPIA-PCI trial. Circulation 2007;115(20):2642-51
  • Sabatine MS, Antman EM, Widimsky P, Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-ACS1 TIMI 42): a randomised, double-blind, active-controlled, phase 2 trial. Lancet 2009;374(9692):787-95
  • Effect of Otamixaban versus unfractionated heparin + eptifibatide in patients with unstable angina/non ST elevation myocardial infarction undergoing early invasive strategy (TAO). National Institutes of Health/Clinicaltrials gov/identifier:NCT01076764. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01076764?term=NCT01076764&rank=1 [30 September 2010]
  • Fisher WD, Turpie AG. Evaluation of AVE5026 as compared to placebo for the extended prophylaxis of venous thromboembolism in patients having undergone hip fracture surgery (SAVE-HIP3). National Institutes of Health/Clinicaltrials gov/identifier:NCT00709904. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00709904?term=NCT00709904&rank=1 [30 September 2010]
  • Lassen MR, Turpie AG. Evaluation of AVE5026 as compared to enoxaparin for the prevention of thromboembolism in patients undergoing elective knee replacement surgery (SAVE-KNEE). National Institutes of Health/Clinicaltrials gov/identifier:NCT00718224. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00718224?term=NCT00718224&rank=1 [30 September 2010]
  • Mouret P, Turpie AG. Evaluation of AVE5026 as compared to enoxaparin for the prevention of thromboembolism in patients undergoing total hip replacement surgery (SAVE-HIP1). National Institutes of Health/Clinicaltrials gov/identifier:NCT00697099. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00697099?term=NCT00697099&rank=1 [30 September 2010]
  • Turpie AG, Lassen MR, Davidson BL, Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009;373(9676):1673-80
  • Mega JL, Braunwald E, Mohanavelu S, Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet 2009;374(9683):29-38
  • An efficacy and safety study for rivaroxaban in patients with acute coronary syndrome. National Institutes of Health/Clinicaltrials gov/identifier:NCT00809965. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00809965?term=NCT00809965&rank=1 [30 September 2010]
  • Once – daily oral direct factor Xa inhibitor rivaroxaban in the long-term prevention of recurrent symptomatic venous thromboembolism in patients with symptomatic deep-vein thrombosis or pulmonary embolism. The Einstein-Extension Study. National Institutes of Health/Clinicaltrials gov/identifier:NCT00439725. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00439725?term=NCT00439725&rank=1 [30 September 2010]
  • Randomized, Double-Blind Study Comparing Once Daily Oral Rivaroxaban With Adjusted-Dose Oral Warfarin for the Prevention of Stroke in Subjects With Non-Valvular Atrial Fibrillation. National Institutes of Health/Clinicaltrials gov/identifier:NCT00403767. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00403767?term=NCT00403767&rank=1 [30 September 2010]
  • Lassen MR, Raskob GE, Gallus A, Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med 2009;361(6):594-604
  • Lassen MR, Raskob GE, Gallus A, Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 2010;375(9717):807-15
  • Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation (ARISTOTLE). National Institutes of Health/Clinicaltrials gov/identifier:NCT00461630. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00412984?term=NCT00412984&rank=1 [30 September 2010]
  • Phase III Acute Coronary Syndrome (APPRAISE-2). National Institutes of Health/Clinicaltrials gov/identifier:NCT00831441. Available from: http://clinicaltrials.gov/ct2/show/NCT00831441?term=NCT00831441&rank=1
  • A Study to Assess the Safety of a Potential New Drug in Comparison to the Standard Practice of Dosing With Warfarin for Non-valvular Atrial Fibrillation. National Institutes of Health/Clinicaltrials gov/identifier:NCT00504556. Available from: http://clinicaltrials.gov/ct2/show/NCT00504556?term=NCT00504556&rank=1
  • Fuji T. A Phase 2b Study of DU-176b, Prevention of Venous Thromboembolism in Patients After Total Hip Arthroplasty. National Institutes of Health/Clinicaltrials gov/identifier:NCT01203098. Available from: http://clinicaltrials.gov/ct2/show/NCT01203098?term=NCT01203098&rank=1
  • Fuji T. A Study of DU-176b, Prevention of Venous Thromboembolism in Patients After Total Hip Arthroplasty. National Institutes of Health/Clinicaltrials gov/identifier:NCT01181167. Available from: http://clinicaltrials.gov/ct2/show/NCT01181167?term=NCT01181167&rank=1
  • TIMI study group. Global Study to Assess the Safety and Effectiveness of DU-176b vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation (EngageAFTIMI48). National Institutes of Health/Clinicaltrials gov/identifier:NCT00781391. Available from: http://clinicaltrials.gov/ct2/show/NCT00781391?term=NCT00781391&rank=1
  • Lassen MR, Dahl O, Mismetti P, SR123781A: a new once-daily synthetic oligosaccharide anticoagulant for thromboprophylaxis after total hip replacement surgery: the DRIVE (Dose Ranging Study in Elective Total Hip Replacement Surgery) study. J Am Coll Cardiol 2008;51(15):1498-504
  • Agnelli G, Haas S, Ginsberg JS, A phase II study of the oral factor Xa inhibitor LY517717 for the prevention of venous thromboembolism after hip or knee replacement. J Thromb Haemost 2007;5(4):746-53
  • Turpie AG, Bauer KA, Davidson BL, A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). J Thromb Haemost 2009;101(1):68-76
  • Study Evaluating Safety, Tolerability and Efficacy of YM150 in Subjects With Acute Coronary Syndromes (RUBY-1). National Institutes of Health/Clinicaltrials gov/identifier:NCT00994292. Available from: http://clinicaltrials.gov/ct2/show/NCT00994292?term=YM150&rank=4
  • Losordo DW, Schatz RA, White CJ, Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation 2007;115(25):3165-72
  • van RJ, Bax JJ, Beeres SL, Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA 2009;301(19):1997-2004
  • Flint OP, Masters BA, Gregg RE, Durham SK. Inhibition of cholesterol synthesis by squalene synthase inhibitors does not induce myotoxicity in vitro. Toxicol Appl Pharmacol 1997;145(1):91-8
  • Tavridou A, Kaklamanis L, Megaritis G, Pharmacological characterization in vitro of EP2306 and EP2302, potent inhibitors of squalene synthase and lipid biosynthesis. Eur J Pharmacol 2006;535(1-3):34-42
  • Cuchel M, Bloedon LT, Szapary PO, Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 2007;356(2):148-56
  • Crooke RM, Graham MJ, Lemonidis KM, An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis. J Lipid Res 2005;46(5):872-84
  • Akdim F, Stroes ES, Kastelein JJ. Antisense apolipoprotein B therapy: where do we stand? Curr Opin Lipidol 2007;18(4):397-400
  • Akdim F, Stroes ES, Sijbrands EJ, Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy. J Am Coll Cardiol 2010;55(15):1611-18
  • Giugliano RP, Wiviott SD, Stone PH, Recombinant nematode anticoagulant protein c2 in patients with non-ST-segment elevation acute coronary syndrome: the ANTHEM-TIMI-32 trial. J Am Coll Cardiol 2007;49(25):2398-407
  • Chan MY, Cohen MG, Dyke CK, Phase 1b randomized study of antidote-controlled modulation of factor IXa activity in patients with stable coronary artery disease. Circulation 2008;117(22):2865-74
  • Hagedorn I, Schmidbauer S, Pleines I, Factor XIIa inhibitor recombinant human albumin Infestin-4 abolishes occlusive arterial thrombus formation without affecting bleeding. Circulation 2010;121(13):1510-17
  • Matthay MA. Severe sepsis – a new treatment with both anticoagulant and antiinflammatory properties. N Engl J Med 2001;344(10):759-62
  • Study to Look at the Effects of ART-123 on Patients With Sepsis and Disseminated Intravascular Coagulation (DIC). National Institutes of Health/Clinicaltrials gov/identifier:NCT01090115. Available from: http://clinicaltrials.gov/ct2/show/NCT01090115?term=NCT01090115&rank=1
  • Kearon C, Comp P, Douketis J, Dose-response study of recombinant human soluble thrombomodulin (ART-123) in the prevention of venous thromboembolism after total hip replacement. J Thromb Haemost 2005;3(5):962-8
  • Cannon CP, Giugliano RP, Blazing MA, Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J 2008;156(5):826-32
  • Sharma M, Ansari MT, Abou-Setta AM, Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. Ann Intern Med 2009;151(9):622-30

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.