(Circulation. 1995;91:2295-2298.)
© 1995 American Heart Association, Inc.
Articles |
Angiographic and Clinical Progression in Unstable Angina
From Clinical Observations to Clinical Trials
From the Department of Medicine, Montreal Heart Institute, Montreal, Quebec, Canada.
Correspondence to Pierre Théroux, MD, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, HIT 1C8, Canada.
Key Words: Editorials • angiography • angina • clinical trials
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Introduction |
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 Top Introduction Angiographic Anatomy of Culprit...Progression Versus Occlusion Pathophysiological Implications Clinical Events Role of Coronary Angioplasty...Matching End Points of...Outlook for the Future...References |
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Chen et al1 took advantage of a long waiting list for coronary angioplasty at their institution to describe the angiographic and clinical evolution of coronary lesions causing unstable angina. The study involved a small number of patients, with no controls. Patients enrolled were highly selected and treated unconventionally, at least by North American standards. The authors assessed lesion severity by quantitative coronary angiography and lesion morphology by conventional descriptors.
The data confirmed the many previous observations of complex lesions in unstable angina2 3 and emphasized their rapid progression.4 5 More importantly, they provided an opportunity to discuss new challenging concepts in unstable angina.
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Angiographic Anatomy of Culprit Coronary Lesions |
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TopIntroductionAngiographic Anatomy of Culprit...Progression Versus Occlusion Pathophysiological Implications Clinical Events Role of Coronary Angioplasty...Matching End Points of...Outlook for the Future...References |
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Although coronary angioscopic and endovascular ultrasound studies have stressed its limitations, angiography is the only widely used diagnostic test in clinical practice. Angiographic morphology has clear clinical implications to evaluate pathophysiology2 3 and prognosis6 7 and to orient treatment, including coronary angioplasty.8 Particularly relevant findings in addition to the conventional description of the severity and number of lesions are ulcerations, filling defects, eccentricity, and irregularities.2 7
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Progression Versus Occlusion |
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TopIntroductionAngiographic Anatomy of Culprit...Progression Versus Occlusion Pathophysiological Implications Clinical Events Role of Coronary Angioplasty...Matching End Points of...Outlook for the Future...References |
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Progression and progression to complete occlusion are usually considered at the same level of significance in angiographic studies of lesion evolution. The two findings, however, may correspond to different pathophysiological mechanisms.9 In the study by Chen et al,1 72% of patients with a coronary event showed progression. Of the 29 lesions that progressed, 69% progressed to complete occlusion. This progression was independent of conventional risk factors and of the extent of coronary disease. Progression was also the hallmark of culprit lesions, occurring in 25% of the 85 such lesions (with occlusion in 81%) compared with 8% of the 113 nonculprit lesions (with occlusion in 37%). Progression and progression to complete occlusion were more frequent in stenoses with initially greater than 50% lumen diameter reduction than in less severe stenoses.
These results contrast with the findings of iterative angiographic studies in patients with stable angina.10 11 12 13 Follow-up in these studies usually extends for more than 1 year; progression is observed in 40% to 50% of patients but is generally of small magnitude (0.2 mm or 10% change in the initial severity of stenosis). Occlusion occurs in less than 10% of patients.13 Of interest, patients with a less severe stenosis (10% to 40% lumen diameter reduction) usually experience a clinical event in association with progression, whereas patients with more severe lesions progress without concomitant clinical symptoms. Also, modification of risk factors and of the lipid profile is usually more effective in delaying progression of less severe lesions.11 13
These striking differences between progression and occlusion suggest that the underlying pathophysiological mechanisms may differ and stress the importance of the thrombotic processes that cause occlusion and rapid progression.14
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Pathophysiological Implications |
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TopIntroductionAngiographic Anatomy of Culprit...Progression Versus Occlusion Pathophysiological Implications Clinical Events Role of Coronary Angioplasty...Matching End Points of...Outlook for the Future...References |
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Angiography was performed after the clinical event in the study by Chen et al,1 and the time course of progression before the event is not known. It could have been sudden occlusion by acute reactivation of an uncontrolled disease process, rapid progression in relation to the previously unstable state, or a combination of the two mechanisms, with rapid progression favoring acute occlusion. An active state of disease can lead to progression and to clinical events. Conversely, unstable angina can lead to an active state of the disease and rapid progression. There exist many evidences in the literature that both views are correct. Sudden plaque rupture can lead to acute thrombus formation and to myocardial infarction or unstable angina, depending on the severity of the obstruction to coronary blood flow and on the presence of collateral circulation, the latter probably influenced by the severity of the preexisting stenosis.14 From cholesterol-lowering clinical trials we have learned that progression is associated with a higher risk of a subsequent clinical event.12 13 One study further showed that the rapid progression observed in unstable angina was not confined to the culprit coronary lesion but also could involve other diseased or nondiseased coronary artery segments, suggesting that rapid atherosclerosis can indeed be present in these patients.4
The mechanisms for progression in unstable angina are intriguing. They can result from remodeling and organization of plaque hemorrhage or from repeated subclinical cycles of rupture, hemorrhage, and organization, as documented by histological studies.15 The mechanisms also can be more fundamental and related to the response-to-injury hypothesis of atherosclerosis.16 Platelets and leukocytes, principally monocytes, adhere early to the damaged endothelium. Local secretion of thromboxane, serotonin, and other vasoactive substances promotes further platelet aggregation and dynamic coronary vasoconstriction.17 Tissue factor expressed from the endothelium and from monocytes leads to local thrombin generation and fibrin deposition.18 Platelets, monocytes/macrophages, and endothelial cells secrete many mitogens.16 Platelet-derived growth factor (PDGF) is chemotactic for smooth muscle cells, macrophages, and neutrophils and mitogenic for medial smooth muscle and can induce both smooth muscle cell migration and proliferation. Macrophages and endothelial cells also secrete PDGF and other growth factors such as fibroblast growth factor and interleukin-1.16 The proliferative effect of these factors is facilitated by "progression factors" such as epidermal growth factor and transforming growth factor-ß secreted by platelets and macrophages. The mechanism of restenosis after coronary angioplasty is also likely to be related to similar mechanisms of platelet adhesion and cell transformation mediated by cytotoxines and growth factors.19
The correlation observed between frequency and severity of platelet aggregation and subsequent neointimal proliferation after endothelial injury stresses the importance of platelet deposition in subsequent progression.20
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Clinical Events |
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TopIntroductionAngiographic Anatomy of Culprit...Progression Versus Occlusion Pathophysiological Implications Clinical Events Role of Coronary Angioplasty...Matching End Points of...Outlook for the Future...References |
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The clinical outcome in the study by Chen et al1 was unfavorable despite rapid stabilization of the unstable clinical state, and 31% of patients experienced a coronary event within a few months. These events consisted in myocardial infarction in 5 patients and recurrent unstable angina in 21. This high event rate is puzzling considering the selection process, with inclusion of less than 10% of the total population of patients admitted for unstable angina; more than 50% of all patients had no angiography and 76% of the patients with angiography had either urgent balloon angioplasty or bypass surgery. The 85 enrolled patients were put on a waiting list for angioplasty because of rapid stabilization of their unstable state. The selection criteria for an urgent or deferred intervention are not known. They were either not adequate considering the high event rate during follow-up, or the clinical course of unstable angina is highly unpredictable. Some elements are useful in predicting higher risk, including more severe clinical presentation, non–Q-wave myocardial infarction, previous bypass surgery, ECG changes at admission or during pain, recurrent chest pain on treatment, more extensive coronary disease, and left ventricular dysfunction.21 The patients studied by Chen et al had ECG changes but no other apparent features of high risk. More particularly, they stabilized rapidly on medical therapy. Yet 14% had a coronary event within 2 to 5 months, another 8% between 5 and 9 months, and 9% between 9 and 14 months. This observation raises important questions on prognosis, optimal treatment, and the end points that should serve to evaluate success of treatment.
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Role of Coronary Angioplasty |
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TopIntroductionAngiographic Anatomy of Culprit...Progression Versus Occlusion Pathophysiological Implications Clinical Events Role of Coronary Angioplasty...Matching End Points of...Outlook for the Future...References |
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The conclusion by Chen et al that earlier coronary angioplasty could prevent subsequent clinical events is premature. The single but large TIMI 3B study did not document a significant benefit of an early routine invasive strategy over an early conservative strategy with angioplasty performed when recurrent chest pain at rest or during an exercise test was documented.22 The patients with routine angioplasty required, however, less rehospitalization during the following month (7.8% versus 14.1% of patients). Similarly, bypass surgery did not improve long-term prognosis in randomized trials of surgical versus medical treatment.23 24 In the large Veterans Administration Cooperative Study, myocardial infarction occurred after 2 years in 11.7% of patients treated surgically and in 12.2% of patients treated medically; the less frequent need for rehospitalization observed early disappeared with time.25 Furthermore, balloon angioplasty performed during the more acute phase, although associated with a success rate approaching 90%, carries a two- to fourfold increase in risk of myocardial infarction, emergency surgery, in-hospital mortality, and need for repeat angioplasty compared with stable angina.26 27 28 29 The risk approximates 10% to 15% and extends through follow-up with more frequent recurrent symptoms and restenosis.26 27 28
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Matching End Points of Clinical Trials to Clinical Practice |
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TopIntroductionAngiographic Anatomy of Culprit...Progression Versus Occlusion Pathophysiological Implications Clinical Events Role of Coronary Angioplasty...Matching End Points of...Outlook for the Future...References |
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Most studies in unstable angina focus on death and myocardial infarction as outcome events based on clinical trials in acute myocardial infarction, on the robustness of these end points, and on objective criteria for their evaluation. Mortality in unstable angina is, however, presently less than 2% and is a consequence of myocardial infarction, meaning that treatment had already failed.30 31 32 33 Progression to complete occlusion and to myocardial infarction is a direct consequence of the disease process itself. The incidence of myocardial infarction has been reduced to 2% to 6% by actual antithrombotic therapy.30 31 32 33 34 Predictors of infarction, presumably marking an uncontrolled disease process, can be recognized. These are recurrent chest pain on treatment and ischemic ECG changes; they are observed in 15% to 20% of patients.22 30 32 33 34 They urge rapid coronary angiography to explore the possibility of an intervention procedure. Such a procedure is not, however, always possible or indicated and in practice is applied in approximately half the patients. Recurrence of ischemia requiring a more thorough investigation to prevent acute myocardial infarction is probably therefore a valid end point in clinical trials in unstable angina. The sample size required to document reduction in death, myocardial infarction, and recurrent ischemia is in the range of a few thousand patients. Considering death and myocardial infarction only, the sample size is more than 10 000 patients, questioning such design when other effective therapeutic options are available. Thrombotic complications related to interventions driven by symptoms belong to the unstable state and should generally be considered as true end points. As a consequence, outcome is preferably measured at hospital discharge or after a few weeks. A more comprehensive approach could include evaluation of angiographic progression in dilated and nondilated segments as suggested by the data of Chen et al1 on long-term outcome.
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Outlook for the Future |
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TopIntroductionAngiographic Anatomy of Culprit...Progression Versus Occlusion Pathophysiological Implications Clinical Events Role of Coronary Angioplasty...Matching End Points of...Outlook for the Future...References |
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A more fundamental goal in unstable angina is to control the acute disease process that leads to accelerated atherosclerosis. An antiplatelet regimen consisting of a combined thromboxane synthesis inhibitor and of a serotonin receptor antagonist given for 15 days attenuated the neointimal proliferation in an experimental model of endothelial injury at sites of coronary stenoses.20 Platelet aggregation now can be completely inhibited by drugs acting on the platelet membrane receptor glycoprotein IIb/IIIa. Blockage of the receptor may add benefit to aspirin and to heparin in unstable angina.35 This therapeutic approach, in the EPIC trial, reduced the abrupt closure rate in high-risk angioplasty by 35%,29 with sustained clinical benefits after 6 months.36 A recent trial also showed reduction in restenosis after angioplasty with trapidil, a competitive antagonist to the receptor of PDGF.37 The use of an HMG-CoA reductase inhibitor in the Scandinavian Simvastatin Survival Study (4S) reduced by 40% the rate of cardiac events in subsequent years in patients with a history of previous angina or myocardial infarction.38
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Footnotes |
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The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association, Inc.
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References |
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TopIntroductionAngiographic Anatomy of Culprit...Progression Versus Occlusion Pathophysiological Implications Clinical Events Role of Coronary Angioplasty...Matching End Points of...Outlook for the Future...References |
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1. Chen L, Chester MR, Redwood S, Huang J, Leatham E, Kaski JC. Angiographic stenosis progression and coronary events in patients with `stabilized' unstable angina. Circulation. 1995;91:2319-2324.
2. Ambrose JA, Winters SL, Stern A, Eng A, Teicholtz LE, Gorlin R, Fuster V. Angiographic morphology and the pathogenesis of unstable angina pectoris. J Am Coll Cardiol. 1985;5:609-616. [Abstract]
3.
Levin D, Gardiner D. Complex and simple
coronary artery stenoses: a new way to interpret coronary angiograms
based on morphologic features of lesions. Radiology. 1987;164:675-680.
4. Moise A, Théroux P, Taeymans Y, Descoings B, Lespérance J, Waters D, Pelletier GB, Bourassa MG. Unstable angina and progression of coronary atherosclerosis. N Engl J Med. 1983;309:685-689. [Abstract]
5. Ambrose JA, Winters SL, Arora RR, Eng A, Riccio A, Gorlin R, Fuster V. Angiographic evolution of coronary morphology in unstable angina. J Am Coll Cardiol. 1986;7:472-478. [Abstract]
6. Williams AE, Freeman MR, Chisholm RJ, Patt NL, Armstrong PW. Angiographic morphology in unstable angina pectoris. Am J Cardiol. 1988;62:1024-1027. [Medline] [Order article via Infotrieve]
7. Lespérance J, Théroux P, Hudon G, Waters D. A new look at coronary angiography: plaque morphology as a help to diagnosis and to evaluate prognosis. Int J Card Imaging. 1994;10:75-94. [Medline] [Order article via Infotrieve]
8. Davies SW, Marchant B, Lyons JP, Timmis AD, Rothman MT, Layton CA, Balcon R. Coronary lesion morphology in acute myocardial infarction: demonstration of early remodeling after streptokinase treatment. J Am Coll Cardiol. 1990;15:1079-1086.
9. Moise A, Lespérance J, Théroux P, Taeymans Y, Goulet C, Bourassa MG. Clinical and angiographic predictors of new total coronary occlusion in coronary disease: analysis of 313 nonoperated patients. Am J Cardiol. 1984;54:1176-1181. [Medline] [Order article via Infotrieve]
10.
Singh AN. Progression of coronary
atherosclerosis: clues to pathogenesis from serial coronary
angiography. Br Heart J. 1984;52:451-461.
11. Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, Zhao XQ, Bisson BD, Fitzpatrick VF, Dodge HT. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323:1289-1298. [Abstract]
12. Buchwald H, Varco RL, Matts JP, Long JM, Fitch LL, Campbell GS, Pearce MB, Yellin AE, Edmiston WA, Smink RD, Sawin HS, Campos CT, Hansen BJ, Tuna N, Karnegis JN, Sanmarco ME, Amplatz K, Castaneda-Zuniga WR, Hunter DW, Bissett JK, Weber FJ, Stevenson JW, Leon AS, Chalmers TC. Effect of partial ileal bypass on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia: report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med. 1990;323:946-955. [Abstract]
13.
Waters D, Higginson L, Gladstone P, Kimball B, Le May
M, Boccuzzi SJ, Lespérance J, CCAIT Study Group. Effects
of monotherapy with an HMG-CoA reductase inhibitor on the progression
of coronary atherosclerosis as assessed by serial quantitative
angiography: the Canadian Coronary Atherosclerosis Intervention Trial
(CCAIT). Circulation. 1994;89:959-968.
14. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med. 1992;326:310-318. [Medline] [Order article via Infotrieve]
15.
Falk E. Unstable angina with fatal outcome:
dynamic coronary thrombosis leading to infarction and/or sudden death:
autopsy evidence of recurrent mural thrombosis with peripheral
embolization culminating in total vascular occlusion.
Circulation. 1985;71:699-708.
16. Ross R. The pathogenesis of atherosclerosis. N Engl J Med. 1986;314:488-500. [Medline] [Order article via Infotrieve]
17.
Willerson JT, Golino P, Eidt J, Campbell WB, Buja LM.
Specific platelet mediators and unstable coronary artery
lesions: experimental evidence and potential clinical
implications. Circulation. 1989;80:198-205.
18.
Annex BH, Denning SM, Channon KM, Sketch MH, Stack RS,
Morrissey JH, Peters KG. Differential expression of tissue
factor protein in directional atherectomy specimens from patients with
stable and unstable coronary syndromes.
Circulation. 1995;91:619-622.
19.
Liu MW, Roubin GS, King SB III. Restenosis after
coronary angioplasty: potential biologic determinants and role of
intimal hyperplasia. Circulation. 1989;79:1374-1387.
20.
Willerson JT, Yao SK, McNatt J, Benedict CR, Anderson
HV, Golino P, Murphree SS, Buja LM. Frequency and severity of
cyclic flow alternations and platelet aggregation predict the severity
of neointimal proliferation following experimental coronary
stenosis and endothelial injury. Proc Natl Acad Sci
U S A. 1991;88:10624-10628.
21. Théroux P, Waters D. Diagnosis and management of unstable angina. In: Schlant RC, Alexander RW, O'Rourke RA, Roberts R, Sonnenblick EH, eds. Hurst's The Heart. 8th ed. New York, NY: McGraw-Hill Inc; 1994:1083-1106.
22.
TIMI 3B Investigators. Effects of tissue
plasminogen activator and a comparison of early invasive and
conservative strategies in unstable angina and non–Q-wave myocardial
infarction. Circulation. 1994;89:1545-1556.
23. Russell RO, Moraski RE, Kouchoukos N, Karp R, Mantle JA, Rogers WJ, Rackley CE, Resnekov L, Falicov RE, Al-Sadir J, Brooks H, Anagnostopoulos CE, Lamberti J, Wolk M, Gay W, Killip T, Rosati RA, Oldham HN Jr, Wagner GS, Peter RH, Conti CR, Curry RO, Daicoff G, Becker LC, Plotnick G, Gott VL, Brawley RK, Donahoo JS, Ross RS, Hutter AM Jr, DeSanctis RW, Gold HK, Leinbach RC, Buckley MJ, Austen WG, Biddle TL, Yu PN, DeWeese JA, Schroeder J, Stinson D, Silverman J, Kaplan EM, Gilbert JP, Newell JB, Frommer PL, Mock MB. Unstable angina pectoris: National Cooperative Study Group to compare surgical and medical therapy, II: in-hospital experience and initial follow-up results in patients with one, two and three vessel disease. Am J Cardiol. 1978;42:838-848.
24. Luchi RJ, Scott SM, Deupree RH, Principal Investigators and Associates of Veterans Administration Cooperative Study No. 28. Comparison of medical and surgical treatment for unstable angina pectoris. N Engl J Med. 1987;316:977-984. [Abstract]
25.
Booth DC, Deupree RH, Hultgren HN, DeMaria AN, Scott
SM, Luchi RJ, Investigators of Veterans Affairs Cooperative Study No.
28. Quality of life after bypass surgery for unstable angina:
5-year follow-up results of a Veterans Affairs Cooperative
Study. Circulation. 1991;83:87-95.
26. de Feyter PJ, Serruys PW. Percutaneous transluminal coronary angioplasty for unstable angina. In: Topol EJ, ed. Textbook of Interventional Cardiology. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1994:274-291.
27.
Bauters C, Lablanche JM, McFadden EP, Bertrand ME.
Repeat percutaneous coronary angioplasty: clinical and
angiographic follow-up in patients with stable or unstable angina
pectoris. Eur Heart J. 1993;14:235-239.
28. Myler RK, Shaw RE, Stertzer SH, Bashour TT, Ryan C, Hecht HS, Cumberland DC. Unstable angina and coronary angioplasty. Circulation. 1990;82(suppl II):II-88-II-95.
29.
EPIC Investigators. Use of a monoclonal antibody
directed against the platelet glycoprotein IIb/IIIa receptor in
high-risk coronary angioplasty. N Engl J Med. 1994;330:956-961.
30. Théroux P, Ouimet H, McCans J, Latour JG, Joly P, Lévy G, Pelletier E, Juneau M, Stasiak J, de Guise P, Pelletier GB, Rinzler D, Waters DD. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988;319:1105-1111. [Abstract]
31. RISC Study Group. Risk of myocardial infarction and death during treatment with aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet. 1990;336:827-830. [Medline] [Order article via Infotrieve]
32.
Théroux P, Waters D, Qiu S, McCans J, de Guise P,
Juneau M. Aspirin versus heparin to prevent myocardial
infarction during the acute phase of unstable angina.
Circulation. 1994;88:2045-2048.
33. ECLA 3. Clinical predictors of in-hospital prognosis in unstable angina. Circulation. 1993;88(suppl I):I-608. Abstract.
34.
Cohen M, Adams PC, Parry G, Antithrombotic Therapy in
Acute Coronary Syndrome Research Group. Combination
antithrombotic therapy in unstable rest angina and non–Q-wave
infarction in nonprior aspirin users.
Circulation. 1994;89:81-88.
35. Théroux P, Kouz S, Knudtson ML, Kells C, Nasmith J, Roy L, Dalle Ave S, Steiner B, Xiao Z, Rapold HJ. A randomized double-blind controlled trial with the nonpeptidic platelet GP IIb/IIIa antagonist RO 44-9883 in unstable angina. Circulation. 1994;90(suppl I):I-232. Abstract.
36. Topol EJ, Califf RM, Weisman HF, Ellis SG, Tcheng JE, Worley S, Ivanhoe R, George BS, Fintel D, Weston M, Sigmon K, Anderson KM, Lee KL, Willerson JT, EPIC Investigators. Randomized trial of coronary intervention with antibody against IIb/IIIa integrin for reduction of clinical restenosis: results at six months. Lancet. 1994;343:881-886. [Medline] [Order article via Infotrieve]
37.
Maresta A, Balducelli M, Cantini L, Casari A, Chioin R,
Fabbri M, Fontanelli A, Monici Preti PA, Repetto S, De Servi S, Varani
E, STARC Investigators. Trapidil (triazolopyrimidine), a
platelet-derived growth antagonist, reduces restenosis after
percutaneous transluminal angioplasty.
Circulation. 1994;90:2710-2715.
38. The Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383-1389. [Medline] [Order article via Infotrieve]
39. Hamm CW, Ravkilde J, Gerhardt W, Jorsgensen P, Peheim E, Ljungdahl L, Goldmann B, Katus HA. The prognostic value of serum troponin-T in unstable angina. N Engl J Med. 1992;327:146-150. [Abstract]
40.
Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi
AG, Pepys MB, Maseri A. The prognostic value of C-reactive
protein and serum amyloid A protein in severe unstable angina.
N Engl J Med. 1994;331:417-424.
41. Théroux P, Waters D, Lam J, Juneau M, McCans J. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med. 1992;327:141-145.[Abstract]
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