Treatment of Unstable Angina Pectoris (European Experience) Semi Sen,
MD,
Cem Uzbek,
MD,
Gunther Berg, MD, Roland Bach, Hermann Schieffer, MD
Unstable a&ma pectoris is used to describe accelerated angina, new onset of angina, or prolonged angina. The natural history of the angina varies according to clinical presentation. The l-year mortalBy rate ranges from 2% to nearly 40%. Specific therapy includes nitrates, p-adrenergic blockers, and/or calcium antagonists as well as antithrombotic therapy in the form of aspirin. Patients with severe angina at rest and STand T-wave changes should be admItted to a coronary care unit where full-dose heparin is adminIstered. Coronary angiography should be performed in individuals who fail to respond to the conventional therapy in order to evaluate other therapeutic options, including percutaneous transluminal coronary angloplasty (PTCA) and coronary bypass surgery. In some cases, especially in patients with intracoronary thrombus, thrombolytic therapy may be beneficial. (Am J Cardiol1991;6&47C-SlC)
MD,
Jan Dyckmans,
MD,
and
T
he term “unstable angina” is generally used to describe different clinical conditions, such as accelerated angina pectoris (with increase of severity and frequency of known chronic angina), new onset of angina, and prolonged angina associated with ST-segment and T-wave changes. The prognosis of patients with any of these clinical syndromes differs considerably, with the worst in the prolonged angina group. Therefore, the management of unstable angina, including the aggressiveness and timing of interventional techniques, initially depends on the clinical presentation. This report will first briefly discuss the treatment of unstable angina with antithrombotic drugs, antiischemic agents, and intervention techniques, and then will cover our experience with coronary interventions in the Department of Cardiology of the University of Saarland in Homburg/Saar. ARRTHROMBOTIC
THERAPY
Rupture of an atherosclerotic plaque with platelet aggregation and thrombus formation, as occurs in Q-wave and non-Q-wave infarction, plays a major role in unstable angina.’ Heparin and aspirin can prevent fatal and nonfatal myocardial infarction (MI).24 In a recently published study, ticlopidine, an inhibitor of platelet aggregation that is completely different from aspirin, also significantly reduced vascular death and nonfatal MI in patients with unstable angina.5 Antithrombotic therapy must be started in the early phase of unstable angina. ANRISCHEMIC
From the Medizinische Klinik der LJniversiW des Saarlandes, Innere Medizin III, HomburgiSaar, Germany. Address for reprints: Semi Sen, MD, Medizinische Universitgtsklinik, Innere Medizin III (Kardiologie), D-6650 Homburg/ Saar, Germany.
THERAPY
Beta-adrenergic blockers or calcium antagonists, in combination with nitrates, are widely used to treat unstable angina, despite the lack of data showing that antiischemic therapy reduces mortality or the rate of infarction. However, the beneficial effect of reducing ischemic episodes is clear-cut.&’ Available reports show that P-adrenergic blockers or calcium antagonists such as diltiazem and verapamil are equally effective in preventing ischemia
A SYMPOSIUM:
MECHANISMS
OF UNSTABLE
ANGINA
47c
and can be used as monotherapy.8,9 In addition, diltiazem reduced the reinfarction rate in patients with non-Q-wave infarction,” which is pathogenetically similar to unstable angina.‘l However, nifedipine as monotherapy should be avoided because of increased adverse cardiac events.7,‘z On the other hand, nifedipine is safe and effective as part of combination therapy when the symptoms are not controlled with P-adrenergic blockers.7,13,14
sion in 9) who were unresponsive to the standard therapy, including full-dose intravenous heparin, underwent coronary angiography within 12 hours after admission to the intensive care unit. Fifteen patients had l-vessel disease, 10 had 2-vessel disease, and 6 had 3-vessel disease. Intracoronary thrombus was visualized in 13 patients (Figure 1). Percutaneous transluminal coronary angioplasty (PTCA) was performed in 17 of 18 patients without angiographic evidence of thrombus (1 patient had CORONARY INTERVENTIONS emergency surgery because of left main stenosis), Thrombolytic therapy: Since intracoronary and thrombus was detected in 6. All 19 patients thrombi are frequently detected in patients with with evidence of thrombi were treated with intraveunstable angina, investigators have become inter- nous rt-PA at a dose of 10 mg as a bolus, followed ested in the applicability of thrombolytic ther- by continuous infusion of 10 mgihr over 9 hours apy. 15-29Some have found only mild quantitative (Figure 1). Control angiography performed within and qualitative effects of thrombolytic therapy,23,25,2824 hours (n= 15) showed complete lysis of thrombi whereas others report symptomatic and clinical in lO.patients and partial lysis in 5. More imporimprovement.16’22’24’26 In a randomized, double- tantly, subsequent PTCA (n=5) was without any blind, placebo-controlled study of 24 patients with complications in 4 patients with complete thrombolunstable angina, defined as chest pain at rest with ysis and 1 patient with partial thrombolysis. One transient ST-segment deviation of at least 1 mm, other patient underwent coronary bypass surgery no coronary thrombi were found in patients treated electively. In the remaining 9 patients a substantial with recombinant tissue-type plasminogen activadecrease of stenosis was observed and there were tor (rt-PA) compared with 8 of 11 placebo-treated no indications for further coronary interventions. patients.22 Further, recurrent angina occurred in Coronary angioplasty: PTCA was initially atonly 1 actively treated patient compared with 6 in tempted only in those patients with l-vessel disease the placebo group. Nicklas et a127noted additional benefits of thrombolysis in combination with maxi- and in those with a single, proximal, noncalcified mal therapy. The benefit was limited, however, to lesion of a major epicardial coronary artery whose angina was relatively resistant to medical therapy. patients with angiographic evidence of intracoroRecently, increasing numbers of patients with unnary thrombus. A prospective study was performed in our institu- stable angina have undergone PTCA in many tion to determine whether thrombolysis in patients centers.31”6 The initial success rate of PTCA appears to be slightly lower and the acute complicawith unstable angina and evidence of intracoronary tion rate higher in unstable versus stable angina. thrombi would beneficially affect outcome.30ThirtyBetween January 1 and December 1, 1990, one patients (26 male and 5 female, mean age PTCA was performed in our center in 1,092 pa602 11 years) with intermittent electrocardiographic abnormalities during chest pain (ST depres- tients: 755 with stable angina and 337 with unstable sion in 17 patients, ST elevation in 10, and T inver- angina. Most of the patients with unstable angina ,-
CABG
I
17
Thrombus (+)
L
b
sten. (%) 74 +/- 20 LV-EF (%) 58 +I- 6
48c
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
Thrombus (+)
FIBRINOLYSIS (rt - PA) 19
68
NOVEMBER
4, 1991
FIGURE 1. The rate of intracoronary thrombus detected by urgent coronary angiography before and after percutaneous transluminal coronary angioplasty (PTCA) in 31 patients with unstable angina unresponsive to the conventional therapy. Sten = coronary stenosis; LV-EF = left ventricular ejection fraction; CAGG = coronary artery bypass graft; &PA = recombinant tissue-type plasminogen activator.
i
SA (n = 755) SVD (n) DVD (n) TVD (n) LVEF (%) lntraluminal filling defect (n)
272 274
(36%) (36%) (28%)
209
58 65
(9%)
DVD = double-vessel disease: TVD unstable angina; SVD = single-vessel NS = difference not srgnificant.
UA (n = 337) 124 119 94 57 83
(37%) 135%) (28%) (25%)
P Value
NS NS NS NS 406. 21. Forrester JS, Litvak F, Grundfest W, Hickley A. A perspectiveof coronary diseaseseenthrough the arteries of living man.Circu[atin 1987;75:505-513. 22. Gold HK, Johns JA, Lembach RC, Yasuda T, Grossbard E, Zusman R, Collen D. A randomized,blinded, placebo-controUedtrial of recombinanthuman tissue-type plasminogen activator in patients with unstable angina pectoris. REFERENCES i. Fuster F, Badiion L, Cohen M, Ambrose JA, Badimon JJ, Chesebro J. Cimu[ation1987;75:1192-1199. Insightsinto the pathogen&s of acute ischemicsyndromes.Cirru&on 1988;77: 22. Ambrose JA, Monsen CH, Borrico S, Sherman W, Cohen M, Gorlm R, Fuster V. Quantitative and qualitative effects of intracoronary streptokinasein 121?-1220. unstableanginaand non-Qwave infarction. JAm Co11Cardiol1987;9:1156-1165. 2. Telford AM, Wilson C. Trial of heparin versus atenolol in prevention of myocardial infarction in intermediate coronary syndrome.Lancet 1981;1225- 24. Gotoh K, Mmamino T, Katoh 0, Hamano Y, Fukui S,Hori M, Kusuoka H, Mishima M, Inoue M, KamadaT. The role of intracoronary thrombusin unstable 1228. angina: angiographicassessmentand thrombolytic therapy during ongoing angi3. Thdroux P, Ouimet H, McCans J, Iatour JG, Joly P, Levy G, Pelletier E, nal attacks.Circulation 1988;77:52&-534. Juneau M, StasiakJ, deGuise P, Pelletier GB, Rier D, Waters DD. Aspirin, heparin,or both to treat acuteunstableangina.N&g~JMed 1988;319:1105-1111. 25. DeZwaan C, B&r FW, JanssenHG De&art HB, Vermeer F, Wellens HJJ. Effects of thrombolytic therapy in unstable angina: clinical and angiographic 4. Lewis HD, Davis JW, Archibald DG, Steinke WE, SmithermanTC, Doherty JE, SchnaperHW, LeWmter MM, Linares E, PougetJM, SabharwalSC,Chesler results. JAm Co11Cardioi 1988;12:301-309. E, DeMots H. Protective effectsof aspirin againstacutemyocardialinfarction and 26. Schreiber TL, Ma&a G, McNuhy A, Bunnell P, Kikel M, Mier DH, Devereux RB, Tenney R, Cowley M, Zola B. Urokinase plus heparin versus death in men with unstableangina.NEnglJMed 1983;309:396403. aspirin in unstable angina and non-Q-wave myocardial infarction. Am J Can&J 5. BalsanoF, Rizon P, Violi F, Scrutinio D, CiiieUo C, Aguglia F, PasotiC, Rudelli C. Antiplatelet treatment with ticlopidme in unstableangina.Circulation 1989;64%4@844. 27. NicklasJM, Top01EJ, Kander N, O’NeiU WW, Walton JA Ellis SG,Gorman 1990;82:17-26. L, Pitt B. Randomized,double-blind,placebo-controlledtrial of tissueplasmino&Kaplan K, Davison R, Parker M, Przybylek J, Teagarden JR, Iesch M. Intravenous nitroglycerin for the treatment of angina at rest unresponsiveto gen activator in unstableangina.JAm Co11CardioJ 1989;13:434441. 22. Williams DO, Top01EJ, Calii RM, Roberts R, Mancini J, JoelsonJM, Ellis standardnitrate therapy. Am JCardioi 1983;51:694698. 7. Holland Interuniversity Nifedipineimetoprolol Trial (HINT) ResearchGroup. SG, Kleiman NS. Intravenous recombinant tissue-typeplasminogenactivator in Early treatment of unstable angina in the coronary care unit. A randomised patientswith unstableanginapectoris.Ctiulation 1990;82:376383. double-blind, placebo controlled comparison of recurrent ischemia in patients 29. Rehr R, DisciascioG, Vetrovec G, Cowley M. Angiographic morphologyof coronary artery stenosesin prolonged rest angina: evidence of intracoronary treated with nifedipme or metoprolol or both. BrHeartJ 19&6;56:4C%413. thrombosis.JAm Co11Cam’ioJ1989;14:1429-1437. 8. Theroux P, TaeymansY, Morissette D, BoschX, Pelletier GB, Waters DD. A 30. Berg G, SenS,DyckmansJ, &bek C, Miiller M, Schieffer H. Fibrinolytische randomized study comparing propranolol and diltiaaem in the treatment of Therapie bei instabilerAngina pectoris:Effect einer prolongierten r&PA-Infusion unstableangina.JAm Co11CardtiJ1985;5:717-722. (abstr). Ztirdti11990;79(supp11):52. 9. Parodi 0, Simonetti I, Michelassi C, CarpeggianiC, Biagini A, L’Abbate A, Maseri A Comparisonof verapamil and propranolol therapy for anginapectoris 31. Meyer J, Schmitz H, Kiesslich T, Erbel R, Krebs W, Schulz W, Bardos P, at rest: a randomized, multiple-crossover,controlled trial in the coronary care Minale C, Messmer BJ. Percutaneous transbuninal coronary angioplasty in patientswith stableand unstableanginapectoris:analysisof early and late results. unit. Am J CardbJ1986;57:899-906. l0. Gibson RS, Baden WE, Theroux P, StraussHD, Pratt CM, GheorghiadeM, Am Heart J 1983;106:973-979. 32. Faxon DP, Detre KM, McCabe CH, Fisher L, Holmes DR, Cowley MJ, CaponeRJ, Crawford MH SchlantRC, Kleiger RE, Young PM, SchechtmanK, Pertyman MB, Roberts R, and the Dihiazem Reinfarction Study Group. Bourassa MG, Van Raden M, Ryan TJ. Role of percutaneous transhuninal coronary angioplastyin the treatment of unstableangina. Am J CardbJ1983;53: Diltiazem and reinfarction in patients with non-Q-wave myocardial infarction. Resultsof a double-blind, randomized,multicenter trial. NEngl Jhfed 1986315: 131c-135c. 33. Steffenino G, Meier B, Finci L, Rutishauser W. Follow up results of 423429. treatment of unstableanginaby coronary angioplasty.BrHeati J 1987;57:416419. ll.Ambrose JA, Hjemdalr-Monsen CE, Borrico S, Gorlm R, Fuster V. Angiographicdemonstrationof a commonlii between unstableanginapectoris 24. De Feyter PJ,SuryapranataH, SemtysPW, Beatt K Van Domburg R, Van Den Brand M, Tijssen JJ, Azar AJ, Hugenholtz PG. Coronary angioplastyfor and non-Q wave acutemyocardialinfarction. Am JCardioJ 1988;61:2@-%!7. 12. Muller JE, Turi ZG, Pearle DL, SchneiderJF, SerfasDH, Morrison J, Stone unstable angina: immediate and late results in 200 consecutivepatients with PH, Rude IX& Rosner B, Sobel BE, Tate C, SchemerE, Roberts R, Hennekens identification of risk factors for unfavorable early and late outcome.JAm Co11 CH, Braunwald E. Nifedipine and conventional therapy for unstable angina.A Cardiol1988;12:324-333. randomized,double-blind comparison.Circulation 1984;69:728739. 35. Rupprecht HJ, Brennecke R, Kottmeyer M, Bernhard G, Erbel R, Pop T, Meyer J. Short and long-term outcome after PTCA in patients with stable and l2. Gerstenblith G, Ouyang P, AchutI SC, Bulkley BH, Becker LC, Mellits ED, unstableangina.Ew Heart J 1990;11:964-973. BaugbmanKL, WeissJL, Flalrerty JT, Kallman CH, Llewellyn M, Weisfeld ML. !%c
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 68
NOVEMBER 4, 1991
38. Shawl FA, Velasco CE, Goldbamn TS, Forman MB. Effect of coronary angioplasty on electrcuxrdiographic changesin patients with unstable angina secondaryto left anterior descendingcoronary artery disease.JAm Coil Cardiol 1990,16:325-331. 37. Setbi Gg Copcland JG, Goldman S, Moritz T, Zadina K, Henderson WG. Implications of preoperative administration of aspirin in patients undergoing coronary artery bypassgrafting. JAm Coil Cardial 1990;15:15-20. 38. Mabin T& Holmes DR, Smith HC, Vliestra RF,, Bove AA, Reeder GS,
Chesebro JH, Breanahan JF, Orszulak TA. Intracoronary thrombus: role in coronaryocclusioncomplicatingpercutaneoustransluminalcoronary angioplasty. JAm Co11Cardiol1985;5:19%XI2.
39. SuryapranataH, De Fqter PJ, Semys PW. Coronary angioplastyin patients with unstableanginapectoris: is there a role for thrombolysis?JAm Co11Cardiol 1988;12:69A-77A. 40. Grill HP, Brinker JA. Nonacute thrombolytic therapy: an adjunctto coronary angioplastywith large intravascularthrombi. Am HeartJ 1989;118:662-666.
A SYMPOSIUM: MECHANISMS OF UNSTABLE ANGINA
!%c
MD,
Cem Uzbek,
MD,
Gunther Berg, MD, Roland Bach, Hermann Schieffer, MD
Unstable a&ma pectoris is used to describe accelerated angina, new onset of angina, or prolonged angina. The natural history of the angina varies according to clinical presentation. The l-year mortalBy rate ranges from 2% to nearly 40%. Specific therapy includes nitrates, p-adrenergic blockers, and/or calcium antagonists as well as antithrombotic therapy in the form of aspirin. Patients with severe angina at rest and STand T-wave changes should be admItted to a coronary care unit where full-dose heparin is adminIstered. Coronary angiography should be performed in individuals who fail to respond to the conventional therapy in order to evaluate other therapeutic options, including percutaneous transluminal coronary angloplasty (PTCA) and coronary bypass surgery. In some cases, especially in patients with intracoronary thrombus, thrombolytic therapy may be beneficial. (Am J Cardiol1991;6&47C-SlC)
MD,
Jan Dyckmans,
MD,
and
T
he term “unstable angina” is generally used to describe different clinical conditions, such as accelerated angina pectoris (with increase of severity and frequency of known chronic angina), new onset of angina, and prolonged angina associated with ST-segment and T-wave changes. The prognosis of patients with any of these clinical syndromes differs considerably, with the worst in the prolonged angina group. Therefore, the management of unstable angina, including the aggressiveness and timing of interventional techniques, initially depends on the clinical presentation. This report will first briefly discuss the treatment of unstable angina with antithrombotic drugs, antiischemic agents, and intervention techniques, and then will cover our experience with coronary interventions in the Department of Cardiology of the University of Saarland in Homburg/Saar. ARRTHROMBOTIC
THERAPY
Rupture of an atherosclerotic plaque with platelet aggregation and thrombus formation, as occurs in Q-wave and non-Q-wave infarction, plays a major role in unstable angina.’ Heparin and aspirin can prevent fatal and nonfatal myocardial infarction (MI).24 In a recently published study, ticlopidine, an inhibitor of platelet aggregation that is completely different from aspirin, also significantly reduced vascular death and nonfatal MI in patients with unstable angina.5 Antithrombotic therapy must be started in the early phase of unstable angina. ANRISCHEMIC
From the Medizinische Klinik der LJniversiW des Saarlandes, Innere Medizin III, HomburgiSaar, Germany. Address for reprints: Semi Sen, MD, Medizinische Universitgtsklinik, Innere Medizin III (Kardiologie), D-6650 Homburg/ Saar, Germany.
THERAPY
Beta-adrenergic blockers or calcium antagonists, in combination with nitrates, are widely used to treat unstable angina, despite the lack of data showing that antiischemic therapy reduces mortality or the rate of infarction. However, the beneficial effect of reducing ischemic episodes is clear-cut.&’ Available reports show that P-adrenergic blockers or calcium antagonists such as diltiazem and verapamil are equally effective in preventing ischemia
A SYMPOSIUM:
MECHANISMS
OF UNSTABLE
ANGINA
47c
and can be used as monotherapy.8,9 In addition, diltiazem reduced the reinfarction rate in patients with non-Q-wave infarction,” which is pathogenetically similar to unstable angina.‘l However, nifedipine as monotherapy should be avoided because of increased adverse cardiac events.7,‘z On the other hand, nifedipine is safe and effective as part of combination therapy when the symptoms are not controlled with P-adrenergic blockers.7,13,14
sion in 9) who were unresponsive to the standard therapy, including full-dose intravenous heparin, underwent coronary angiography within 12 hours after admission to the intensive care unit. Fifteen patients had l-vessel disease, 10 had 2-vessel disease, and 6 had 3-vessel disease. Intracoronary thrombus was visualized in 13 patients (Figure 1). Percutaneous transluminal coronary angioplasty (PTCA) was performed in 17 of 18 patients without angiographic evidence of thrombus (1 patient had CORONARY INTERVENTIONS emergency surgery because of left main stenosis), Thrombolytic therapy: Since intracoronary and thrombus was detected in 6. All 19 patients thrombi are frequently detected in patients with with evidence of thrombi were treated with intraveunstable angina, investigators have become inter- nous rt-PA at a dose of 10 mg as a bolus, followed ested in the applicability of thrombolytic ther- by continuous infusion of 10 mgihr over 9 hours apy. 15-29Some have found only mild quantitative (Figure 1). Control angiography performed within and qualitative effects of thrombolytic therapy,23,25,2824 hours (n= 15) showed complete lysis of thrombi whereas others report symptomatic and clinical in lO.patients and partial lysis in 5. More imporimprovement.16’22’24’26 In a randomized, double- tantly, subsequent PTCA (n=5) was without any blind, placebo-controlled study of 24 patients with complications in 4 patients with complete thrombolunstable angina, defined as chest pain at rest with ysis and 1 patient with partial thrombolysis. One transient ST-segment deviation of at least 1 mm, other patient underwent coronary bypass surgery no coronary thrombi were found in patients treated electively. In the remaining 9 patients a substantial with recombinant tissue-type plasminogen activadecrease of stenosis was observed and there were tor (rt-PA) compared with 8 of 11 placebo-treated no indications for further coronary interventions. patients.22 Further, recurrent angina occurred in Coronary angioplasty: PTCA was initially atonly 1 actively treated patient compared with 6 in tempted only in those patients with l-vessel disease the placebo group. Nicklas et a127noted additional benefits of thrombolysis in combination with maxi- and in those with a single, proximal, noncalcified mal therapy. The benefit was limited, however, to lesion of a major epicardial coronary artery whose angina was relatively resistant to medical therapy. patients with angiographic evidence of intracoroRecently, increasing numbers of patients with unnary thrombus. A prospective study was performed in our institu- stable angina have undergone PTCA in many tion to determine whether thrombolysis in patients centers.31”6 The initial success rate of PTCA appears to be slightly lower and the acute complicawith unstable angina and evidence of intracoronary tion rate higher in unstable versus stable angina. thrombi would beneficially affect outcome.30ThirtyBetween January 1 and December 1, 1990, one patients (26 male and 5 female, mean age PTCA was performed in our center in 1,092 pa602 11 years) with intermittent electrocardiographic abnormalities during chest pain (ST depres- tients: 755 with stable angina and 337 with unstable sion in 17 patients, ST elevation in 10, and T inver- angina. Most of the patients with unstable angina ,-
CABG
I
17
Thrombus (+)
L
b
sten. (%) 74 +/- 20 LV-EF (%) 58 +I- 6
48c
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
Thrombus (+)
FIBRINOLYSIS (rt - PA) 19
68
NOVEMBER
4, 1991
FIGURE 1. The rate of intracoronary thrombus detected by urgent coronary angiography before and after percutaneous transluminal coronary angioplasty (PTCA) in 31 patients with unstable angina unresponsive to the conventional therapy. Sten = coronary stenosis; LV-EF = left ventricular ejection fraction; CAGG = coronary artery bypass graft; &PA = recombinant tissue-type plasminogen activator.
i
SA (n = 755) SVD (n) DVD (n) TVD (n) LVEF (%) lntraluminal filling defect (n)
272 274
(36%) (36%) (28%)
209
58 65
(9%)
DVD = double-vessel disease: TVD unstable angina; SVD = single-vessel NS = difference not srgnificant.
UA (n = 337) 124 119 94 57 83
(37%) 135%) (28%) (25%)
P Value
NS NS NS NS 406. 21. Forrester JS, Litvak F, Grundfest W, Hickley A. A perspectiveof coronary diseaseseenthrough the arteries of living man.Circu[atin 1987;75:505-513. 22. Gold HK, Johns JA, Lembach RC, Yasuda T, Grossbard E, Zusman R, Collen D. A randomized,blinded, placebo-controUedtrial of recombinanthuman tissue-type plasminogen activator in patients with unstable angina pectoris. REFERENCES i. Fuster F, Badiion L, Cohen M, Ambrose JA, Badimon JJ, Chesebro J. Cimu[ation1987;75:1192-1199. Insightsinto the pathogen&s of acute ischemicsyndromes.Cirru&on 1988;77: 22. Ambrose JA, Monsen CH, Borrico S, Sherman W, Cohen M, Gorlm R, Fuster V. Quantitative and qualitative effects of intracoronary streptokinasein 121?-1220. unstableanginaand non-Qwave infarction. JAm Co11Cardiol1987;9:1156-1165. 2. Telford AM, Wilson C. Trial of heparin versus atenolol in prevention of myocardial infarction in intermediate coronary syndrome.Lancet 1981;1225- 24. Gotoh K, Mmamino T, Katoh 0, Hamano Y, Fukui S,Hori M, Kusuoka H, Mishima M, Inoue M, KamadaT. The role of intracoronary thrombusin unstable 1228. angina: angiographicassessmentand thrombolytic therapy during ongoing angi3. Thdroux P, Ouimet H, McCans J, Iatour JG, Joly P, Levy G, Pelletier E, nal attacks.Circulation 1988;77:52&-534. Juneau M, StasiakJ, deGuise P, Pelletier GB, Rier D, Waters DD. Aspirin, heparin,or both to treat acuteunstableangina.N&g~JMed 1988;319:1105-1111. 25. DeZwaan C, B&r FW, JanssenHG De&art HB, Vermeer F, Wellens HJJ. Effects of thrombolytic therapy in unstable angina: clinical and angiographic 4. Lewis HD, Davis JW, Archibald DG, Steinke WE, SmithermanTC, Doherty JE, SchnaperHW, LeWmter MM, Linares E, PougetJM, SabharwalSC,Chesler results. JAm Co11Cardioi 1988;12:301-309. E, DeMots H. Protective effectsof aspirin againstacutemyocardialinfarction and 26. Schreiber TL, Ma&a G, McNuhy A, Bunnell P, Kikel M, Mier DH, Devereux RB, Tenney R, Cowley M, Zola B. Urokinase plus heparin versus death in men with unstableangina.NEnglJMed 1983;309:396403. aspirin in unstable angina and non-Q-wave myocardial infarction. Am J Can&J 5. BalsanoF, Rizon P, Violi F, Scrutinio D, CiiieUo C, Aguglia F, PasotiC, Rudelli C. Antiplatelet treatment with ticlopidme in unstableangina.Circulation 1989;64%4@844. 27. NicklasJM, Top01EJ, Kander N, O’NeiU WW, Walton JA Ellis SG,Gorman 1990;82:17-26. L, Pitt B. Randomized,double-blind,placebo-controlledtrial of tissueplasmino&Kaplan K, Davison R, Parker M, Przybylek J, Teagarden JR, Iesch M. Intravenous nitroglycerin for the treatment of angina at rest unresponsiveto gen activator in unstableangina.JAm Co11CardioJ 1989;13:434441. 22. Williams DO, Top01EJ, Calii RM, Roberts R, Mancini J, JoelsonJM, Ellis standardnitrate therapy. Am JCardioi 1983;51:694698. 7. Holland Interuniversity Nifedipineimetoprolol Trial (HINT) ResearchGroup. SG, Kleiman NS. Intravenous recombinant tissue-typeplasminogenactivator in Early treatment of unstable angina in the coronary care unit. A randomised patientswith unstableanginapectoris.Ctiulation 1990;82:376383. double-blind, placebo controlled comparison of recurrent ischemia in patients 29. Rehr R, DisciascioG, Vetrovec G, Cowley M. Angiographic morphologyof coronary artery stenosesin prolonged rest angina: evidence of intracoronary treated with nifedipme or metoprolol or both. BrHeartJ 19&6;56:4C%413. thrombosis.JAm Co11Cam’ioJ1989;14:1429-1437. 8. Theroux P, TaeymansY, Morissette D, BoschX, Pelletier GB, Waters DD. A 30. Berg G, SenS,DyckmansJ, &bek C, Miiller M, Schieffer H. Fibrinolytische randomized study comparing propranolol and diltiaaem in the treatment of Therapie bei instabilerAngina pectoris:Effect einer prolongierten r&PA-Infusion unstableangina.JAm Co11CardtiJ1985;5:717-722. (abstr). Ztirdti11990;79(supp11):52. 9. Parodi 0, Simonetti I, Michelassi C, CarpeggianiC, Biagini A, L’Abbate A, Maseri A Comparisonof verapamil and propranolol therapy for anginapectoris 31. Meyer J, Schmitz H, Kiesslich T, Erbel R, Krebs W, Schulz W, Bardos P, at rest: a randomized, multiple-crossover,controlled trial in the coronary care Minale C, Messmer BJ. Percutaneous transbuninal coronary angioplasty in patientswith stableand unstableanginapectoris:analysisof early and late results. unit. Am J CardbJ1986;57:899-906. l0. Gibson RS, Baden WE, Theroux P, StraussHD, Pratt CM, GheorghiadeM, Am Heart J 1983;106:973-979. 32. Faxon DP, Detre KM, McCabe CH, Fisher L, Holmes DR, Cowley MJ, CaponeRJ, Crawford MH SchlantRC, Kleiger RE, Young PM, SchechtmanK, Pertyman MB, Roberts R, and the Dihiazem Reinfarction Study Group. Bourassa MG, Van Raden M, Ryan TJ. Role of percutaneous transhuninal coronary angioplastyin the treatment of unstableangina. Am J CardbJ1983;53: Diltiazem and reinfarction in patients with non-Q-wave myocardial infarction. Resultsof a double-blind, randomized,multicenter trial. NEngl Jhfed 1986315: 131c-135c. 33. Steffenino G, Meier B, Finci L, Rutishauser W. Follow up results of 423429. treatment of unstableanginaby coronary angioplasty.BrHeati J 1987;57:416419. ll.Ambrose JA, Hjemdalr-Monsen CE, Borrico S, Gorlm R, Fuster V. Angiographicdemonstrationof a commonlii between unstableanginapectoris 24. De Feyter PJ,SuryapranataH, SemtysPW, Beatt K Van Domburg R, Van Den Brand M, Tijssen JJ, Azar AJ, Hugenholtz PG. Coronary angioplastyfor and non-Q wave acutemyocardialinfarction. Am JCardioJ 1988;61:2@-%!7. 12. 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A SYMPOSIUM: MECHANISMS OF UNSTABLE ANGINA
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