A randomized, blinded, placebo-controlled trial of recombinant human tissue-type plasminogen activator in patients with unstable angina pectoris

Twenty-four patients with unstable angina pectoris, defined as chest pain at rest with transient ST segment deviation of at least 1 mm, were randomly assigned to blinded treatment with either placebo or intravenous recombinant human tissue-type plasminogen activator (rt-PA). Before randomization, all patients were treated with oral beta-blockers, calcium antagonists, nitrates, and continuous intravenous heparin for a monitoring period of 12 to 28 hr. After this monitoring period the 24 patients were randomly assigned to receive either placebo or 1.75 mg/kg intravenous rt-PA given over 12 hr at a rate of 0.75 mg/kg over 1 hr, 0.5 mg/kg over 4 hr, and 0.5 mg/kg over 7 hr. One patient, assigned to receive placebo, developed acute myocardial infarction after randomization but before receiving the study drug. Ischemic events were recorded during a hospital follow-up period of at least 4 days unless a further intervention was indicated or the coronary angiogram was normal. The follow-up period was 7 +/- 5 days (mean +/- SD) after the placebo infusion and 8 +/- 4 days after the infusion of rt-PA. Unstable angina pectoris persisted after the completion of the infusion in six of 11 patients receiving placebo and only one of 12 patients receiving rt-PA (p less than .03). Coronary angiography, performed 38 +/- 19 hr after the infusion, demonstrated subocclusive thrombus in eight of 11 patients receiving placebo but in none of 11 patients treated with rt-PA (p less than .002). One patient on rt-PA refused coronary angiography.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nitroglycerin infusion after percutaneous coronary intervention does not influence short- and long-term outcome--a prospective NAPI (Nitroglycerin Administration after Percutaneous Intervention) study

BACKGROUND: Although the benefit of nitroglycerin infusion in patients after elective coronary angioplasty has not been established, this regimen is routinely used in some centres. AIM: The Nitroglycerin Administration after Percutaneous Intervention (NAPI) study tested the efficacy of routine nitroglycerin infusion on the 1st day after percutaneous coronary intervention (PCI) in a double-blind randomised single-centre clinical trial. METHODS: We randomly assigned 200 patients scheduled for elective PCI to treatment with nitroglycerin (100 patients, age 58+/-6 years, infusion up to 100 microg/min) or placebo (100 patients, age 57+/-5 years, p=NS, NaCl 0.9%) for 12 hours after PCI. Patients with acute myocardial infarction, haemodynamic instability during PCI and known intolerance to nitrates were excluded. Patients who were randomised to the placebo group had the possibility to receive nitroglycerin infusion according to the attending physician's decision. Clinical endpoints (cardiac death, myocardial infarction, postprocedural chest pain, unstable angina and repeated PCI) were assessed in hospital and out of hospital with follow-up extended to 24 months. RESULTS: There were no differences during in-hospital stay between those receiving nitroglycerin and receiving placebo, regarding mortality (0 vs. 0%, NS), myocardial infarction (0 vs. 2%, NS), postprocedural chest pain (10 vs. 8%, NS) or repeated PCI (0 vs. 2%, NS). Similarly, 24-month follow-up also revealed no significant differences between those receiving nitroglycerin and placebo (mortality: 0 vs. 0%, NS; myocardial infarction: 4 vs. 4%, NS; repeated PCI: 10 vs. 8%, NS or CABG: 0 vs. 0%, NS). CONCLUSIONS: Routine use of intravenous nitroglycerin after elective PCI has no influence on in-hospital and long-term outcome, including cardiac death, myocardial infarction, postprocedural chest pain, unstable angina and repeated PCI.     

Haemodynamic effects of intravenous isosorbide dinitrate in congestive heart failure]

The effects of intravenous infusion of isosorbide dinitrate (ISDN) were evaluated in 22 patients with congestive heart failure. These patients did not receive vasodilator therapy before this study. Seven of these patients (two bolus groups of 5.0 mg and 7.5 mg each) were infused bolusly. The mean PA, PCWP and mean RA decreased for 5 min and, after 60 min, they were back to the original levels. The mean Ao had an accentuated change when the 7.5 mg bolus was injected, but, apart from that, changes were minimal. The CI changed little and upwardly. ISDN was infused continuously in 10 patients (two infusion groups of 5.0 mg/hr and 7.5 mg/hr each) whose mean PA, PCWP and mean RA decreased for 15 min and continued downwardly but mildly for 120 min. The mean Ao did not change much and the CI slightly increased. Five of the 22 patients (bolus+infusion group of 5.0 mg and 5.0 mg/hr) showed rapid response but the parameters only slightly changed. Since this group included severe heart failure patients, the results observed were milder. The response of all 5 groups receiving ISDN infusion were confirmed by the serum ISDN concentration curve. These results indicate that continuous infusions of 7.5 mg/hr ISDN or bolus infusions of 5.0 mg and infusion of 5.0 mg/hr improved haemodynamics in patients with congestive heart failure.     

Intracoronary adenosine causes angina pectoris like pain--an inquiry into the nature of visceral pain

STUDY OBJECTIVE--The aim was to study the tentative role of adenosine as a messenger between myocardial ischaemia and angina pectoris. DESIGN--Adenosine was administered in serial doses of 0.1-20 mg either as an intravenous bolus, or intra-arterially over 10 s into the left coronary artery, the aorta and the iliac artery. Coronary sinus flow was determined by thermodilution. ECG was monitored continuously. The patient was not aware of which site or dose was used. After each injection, the start of, maximum, end, magnitude, and location of pain were noted. PATIENTS--Six patients with angina pectoris referred for coronary angiography entered the study. MEASUREMENTS AND RESULTS--After intracoronary adenosine injection in the absence of ischaemic ECG changes, a dose dependent degree of chest pain was experienced not different in quality or location from the patients' habitual angina pectoris. Adenosine into the aorta provoked pain in lower chest and upper abdomen, whereas injection into the iliac artery provoked pain in the ipsilateral leg. On intravenous injection equipotent doses of adenosine caused chest pain of the same degree and quality as after intracoronary injection. Immediately after intracoronary injection the coronary sinus blood flow started to increase, but the onset of chest pain was delayed. Onset of pain was earlier the higher the dose, the maximum dose resulting in onset after 18(SEM 2) s. Coronary sinus blood flow increased dose dependently after left coronary artery injection but following intravenous injection no further increase was seen beyond that induced by the lowest dose. CONCLUSIONS--We suggest that adenosine is an important messenger for the sensation of angina pectoris and the effect is not due to coronary steal leading to myocardial ischaemia.     

Comprehensive treatment plan for the prevention of primary ventricular fibrillation in acute myocardial infarction

This report of 1,165 cases of acute myocardial infarction outlines a method for preventing primary ventricular fibrillation In patients with this lesion. The plan of prevention begins in the emergency room, with every patient suspected of having myocardial Infarction receiving an intravenous bolus injection of lidocaine, 75 mg, followed by a 2 mg/min infusion controlled by an infusion pump. If administration of lidocaine is ineffective (19 percent of cases), procainamide is given intravenously in a dose of 100 mg every 5 minutes, repeated as necessary to a maximum of 1 g and followed by an infusion of 2 to 6 mg/min. Ventricular tachycardia is rapidly converted to sinus rhythm by either drug or electrical therapy. Monitoring by telemetry is continued after the patient's discharge from the coronary care unit. A new episode of sustained chest pain requires the reinstitution of prophylactic lidocaine therapy. Important precautions to control the toxic effects of these intravenous medications can be achieved in the community hospital where the nursing staff makes the decision to increase the dose of lidocaine or to substitute procainamide. There has been no recognized mortality from the use of these drugs as outlined. With this total system of care, the prevalence rate of primary ventricular fibrillation has been decreased from 6.5 percent (9 of 139 cases) to 0.3 percent (3 of 1,026 cases) and no deaths have occurred.     

Adenosine induced chest pain--a comparison between intracoronary bolus injection and steady state infusion.

OBJECTIVE: Adenosine may induce chest pain in at least two ways, either by direct stimulation of sensory afferents before actual ischaemia occurs or secondary to ischaemia. The aim was to study if the mechanism of pain induction may depend on the method of adenosine administration. METHODS: Increasing doses of adenosine were given to seven male patients with ischaemic heart disease referred for coronary angiography: first as a bolus intracoronary injection (2.5-50 mumol), second as a 1 ml.min-1 steady state infusion (0.01-20 mumol.min-1) and third as an intravenous steady state infusion (0.076-0.76 mumol.kg-1 x min-1). Pain, rate-pressure product, coronary sinus blood flow, and ECG were monitored. Lactate was analysed in coronary sinus and arterial blood. RESULTS: After intracoronary bolus injection there were no signs of myocardial ischaemia, whereas during intracoronary steady state infusion, and in spite of a lower, but definite, degree of pain, 5/7 patients showed myocardial lactate production and three patients showed ST depression. During the intravenous steady state infusion 6/6 patients showed ST depression. CONCLUSIONS: These findings suggest that when using adenosine for studies on the mechanisms of chest pain in patients with ischaemic heart disease it is preferable to use an intracoronary bolus injection technique rather than a steady state infusion, as the risk of inducing ischaemia with the latter model cannot be ignored.     

Role of adenosine in pathogenesis of anginal pain

The intravenous infusion of adenosine provokes anginalike chest pain. To establish its origin, an intracoronary infusion of increasing adenosine concentrations was given in 22 patients with stable angina pectoris. During adenosine infusion, 20 patients had chest pain without electrocardiographic signs of ischemia. They all reported that the chest pain was similar to their usual anginal pain. In 10 of the 22 patients adenosine was also infused into the right atrium, but it never produced symptoms at the doses that had provoked chest pain during intracoronary infusion. In seven other patients, the intracoronary adenosine infusion was repeated after intravenous administration of aminophylline, an antagonist of adenosine P1-receptors. Aminophylline decreased the severity of adenosine-induced chest pain (assessed with a visual analog scale) from 42 +/- 22 to 23 +/- 17 mm (p less than 0.002). In the remaining five of the 22 patients, monitoring of blood oxygen saturation in the coronary sinus during intracoronary adenosine administration showed that maximum coronary vasodilation was achieved at doses lower than those responsible for chest pain. A single-blind, placebo-controlled, randomized trial of the effect of aminophylline on exercise-induced chest pain was also performed in 20 other patients with stable angina. Aminophylline, compared with placebo, decreased the severity of chest pain at peak exercise from 67 +/- 21 to 51 +/- 23 mm (p less than 0.02), despite the achievement of a similar degree of ST-segment depression. Finally, the effect of intravenous adenosine was compared in 10 patients with predominantly painful myocardial ischemia and in 10 patients with predominantly silent ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intravenous injection of isosorbide dinitrate on the cardiovascular system

An assessment of the acute hemodynamic effect of intravenous isosorbide dinitrate (ISDN) was performed with a Mikro-tip angiocatheter in 10 patients during the diagnostic cardiac catheterization. Both left ventricular (LV) systolic pressure (SP) and end-diastolic pressure (EDP) were decreased by 2 mg of ISDN. Cardiac index, stroke work index and heart rate did not change significantly, and neither systemic vascular resistance nor pulmonary arteriolar resistance was reduced. Isovolumic phase and ejection phase indices of contractility were not altered. End-diastolic stress, an accurate index of preload, was reduced significantly (47.0 +/- 27.6 to 28.7 +/- 24.6 g/cm2, p less than 0.01), and mid-systolic stress, an index of afterload, was also reduced (371 +/- 102 to 332 +/- 85 g/cm2, p less than 0.05). No undesirable side effects were noted during this study. We concluded that bolus intravenous (IV) ISDN safely reduced both preload and afterload. As 2 mg of IV ISDN had no significant change on SVR, a larger dose of ISDN bolus injection might be needed for a significant arterial vasodilating effect. Bolus IV ISDN seems to be very effective in cases in which rapid reduction of LV filling pressure is mandatory.     

Ergonovine testing in a coronary care unit

This study describes the results of ergonovine testing in 100 consecutive patients who underwent this procedure in a coronary care unit. All patients had recently undergone coronary arteriography. A bolus injection of ergonovine was administered at 5 minute intervals in the following doses (mg): 0.0125, 0.025, 0.05, 0.1, 0.2, 0.3 and 0.4. The criterion for a positive test was the appearance of S-T elevation greater than 1 mm. The test was positive in all 17 patients known to have variant angina and in 18 (40 percent) of 45 patients who had a history of chest pain judged strongly suggestive of variant angina but who had no electrocardiogram recorded during pain. Of 38 patients with a history of chest pain classified as not entirely typical of variant angina, only 1 (2.6 percent) had a positive test.Of the 64 patients with a negative ergonovine test, 47 had chest pain and 25 had nausea but none had more serious complications. Ventricular arrhythmia accompanied S-T elevation in 18 of the 36 patients with a positive test but occurred in only 4 of the 64 with a negative test (p < 0.0005). No patient needed treatment with antiarrhythmic drugs. Four of the 36 patients with a positive test had serious complications: severe translent hypotension (2 patients), recurrent episodes of angina with S-T elevation (1 patient) and a subendocardial infarction (1 patient). Thus, ergonovine testing is useful in patients with a typical clinical history of variant angina but without an electrocardiogram recorded during pain. in this study, a small but definite incidence of serious complications occurred during a positive test.     

Medical versus surgical treatment of unstable angina

Unstable angina is an important symptom of coronary artery disease. Two general clinical presentations may occur: (1) stable angina with a recent increase in severity or angina of recent onset, or (2) acute coronary insufficiency or angina at rest with chest pain resembling that of acute infarction. The risk of death or infarction is greater in patients who have recurrent chest pain and ST-T wave abnormalities despite hospital treatment. In patients without electrocardiographic or serum enzyme evidence of a completed infarct, coronary arteriography and bypass graft surgery can be performed with an acceptably low mortality rate. Surgical treatment provides better symptomatic relief than medical management in many patients, but the significant incidence of perioperative infarction makes it difficult to determine if surgery prevents infarction. Some studies indicate that surgery improves survival in subgroups, but data from large scale randomized studies will be needed to answer this question securely. Patients with disease of the left main coronary artery should probably have surgical treatment.Medical treatment will relieve symptoms in most patients with unstable angina and on a long-term basis may obviate the need for surgery. A preliminary period of intensive medical treatment before surgery may be advantageous since there is little evidence that survival rates are improved by treating unstable angina as an acute surgical emergency.     

在急诊科设立胸痛中心对胸痛患者诊疗时间的影响

目的在急诊科设立胸痛中心并研究其对急性胸痛患者诊疗时间的影响。方法在急诊科设立急性胸痛中心,每周开诊3d,时间随机确定,其余时间由急诊科按常规流程对胸痛患者进行诊疗,由研究者对急性胸痛患者的病因和诊疗时间进行注册登记。结果2006年1月至2007年12月因急性非创伤性胸痛就诊北京军区总医院急诊科或胸痛中心的患者共696例,心源性胸痛244例（35％）,包括急性心肌梗死141例（20％）,不稳定型心绞痛81例（12％）,稳定型心绞痛17例（2．4％）,主动脉夹层2例（0．3％）,急性肺栓塞3例（0．4％）;非心源性胸痛452例（65％）,呼吸系统41例（6％）,消化系统70例（10％）,胸膜骨骼肌肉41例（6％）,神经精神或其他299例（42％）。经胸痛中心诊治的胸痛患者的诊疗时间与常规诊疗流程相比都有所缩短。急性心肌梗死（70．1±31．7）min vs（115±40．5）min（P〈0．01）;不稳定型心绞痛（228±54）min vs（264±78）min（P=0．02）;非心源性胸痛（108±66）min vs （126±96）min（P=0．03）。结论急性胸痛患者的病因中,心源性者占35％,以急性心肌梗死和不稳定型心绞痛为主;非心源性者占65％。胸痛中心模式能显著缩短急性胸痛患者的诊疗时间。     

Usefulness of massive oral nicorandil in a patient with variant angina refractory to conventional treatment

A 67-year-old man, who was previously diagnosed with vasospastic angina and treated with standard therapy, was admitted to our hospital because of recurrent chest pain refractory to sublingual nitroglycerin. Admission electrocardiography revealed ST segment elevation in II, III and aV(F), and his symptoms were relieved by intravenous bolus administration of nicorandil. He was diagnosed to have active variant angina, and remained symptomatic even after treatment with calcium antagonists and nitrates at optimal doses. Intravenous bolus administration of nicorandil was consistently effective to relieve his symptoms. Anginal attack was finally prevented by massive oral nicorandil in addition to conventional treatment.     

112例不稳定型心绞痛患者介入治疗的临床评价

目的 探讨不稳定型心绞痛患者介入治疗的安全性及临床效果。方法 不稳定型心绞痛112例．反复发作时即行冠状动脉造影,明确病变后对“罪犯”血管行经皮冠状动脉介入治疗,术后残余狭窄小于10％,前向血流按心肌梗死溶栓治疗临床实验（thrombolysisinmyocardialinfarction,TIMI）血流分级3级为手术成功;随访6月,分析即时及远期效果。结果 手术成功率100％,所有病例均随访6月,其中,17例（15％）患者在经皮冠状动脉介入术后3-6个月再发心绞痛,发作时心电图或平板负荷试验提示心肌缺血,此17例均再次冠状动脉造影提示“罪犯”血管支架内再狭窄,再次行经皮冠状动脉介入术。其余病例术后6个月内未再发心绞痛。随访期间无1例再发心肌梗死或死亡。结论 早期介入治疗不稳定型心绞痛患者是有效的治疗方法,手术成功率及安全性高,近期和远期临床效果满意。     

Relief of refractory angina with continuous intravenous infusion of nitroglycerin

Seventy-five patients with chest pain due to prolonged myocardial ischemia (group I, n=45) or acute myocardial infaction (group II, n=30) were treated with continuous intravenous infusion of nitroglycerin. Pain relief was achieved immediately or after titration in 40 of 45 group I patients and 22 of 30 group II patients. Of the 29 group I patients who received narcotic analgesics for pain relief prior to the nitroglycerin infusion, 20 experienced a decrease in narcotics required for pain relief while intravenously receiving nitroglycerin. Twenty-four of 28 group I patients and 14 of 19 group II patients who had angina refractory to multiple doses of sublingual nitroglycerin received relief with intravenous administration of nitroglycerin. This data suggests that intravenous administration of nitroglycerin is useful, adjunctive therapy for chest pain even when refractory to multiple doses of sublingual nitroglycerin.     

Negative inotropic effect of lidocaine in patients with coronary arterial disease and normal subjects.

The effect of administration of lidocaine on left ventricular performance was studied using systolic time intervals in nine normal subjects, eight patients with stable angina, and 15 patients with acute myocardial infarction. The greatest response in systolic time intervals occurred at three minutes after intravenous injection of lidocaine (100 mg), with values returning to baseline at 10 to 15 minutes. Administration of lidocaine produced a significant prolongation of the preejection period (PEP) corrected for heart rate in all groups and a prolongation of the ratio of PEP to left ventricular ejection time (PEP/LVET) in patients with angina. The group with acute myocardial infarction exhibited a hyperadrenergic state, as shown by a short baseline QS2I. The QS I was lengthened by administration of lidocaine in all groups, but this was more profound in those with acute myocardial infarction. These changes in systolic time intervals were still present at two hours after injection in six patients with acute myocardial infarction in whom an infusion of lidocaine followed the initial bolus. The effect of administering lidocaine after intravenous injection of propranolol (5 mg) was also studied in six normal subjects. Although propranolol therapy along prolonged the PEP/LVET, a further significant prolongation followed subsequent injection of lidocaine.     

Lower threshold for adenosine-induced chest pain in patients with angina and normal coronary angiograms.

OBJECTIVE--To investigate whether patients with angina-like chest pain and normal coronary angiograms are more sensitive to adenosine as an inducer of chest pain. DESIGN--Increasing doses of adenosine were given in a single blind study as intravenous bolus injections. Chest pain and the electrocardiographic findings were noted. PATIENTS--Eight patients with angina-like chest pain but no coronary stenoses (group A), nine patients with angina and coronary stenoses (group B), and 16 healthy volunteers (group C). RESULTS--In the absence of ischaemic signs on the electrocardiogram adenosine provoked angina-like pain in all patients in groups A and B. The pain was located in the chest, and its quality and location were described as being no different from the patient's habitual angina. In group C, 14 of 16 subjects reported chest pain. The lowest dose resulting in chest pain was lower in group A (0.9 (0.6) mg) than in group B (3.1 (1.5)mg) (p < 0.005) and in group C (6.2 (3.7) mg) (p < 0.005). The maximum tolerable dose was lower in group A (4.7 (2.1) mg) than in group B (9.2 (3.8) mg) (p < 0.05) and in group C (12.0 (4.1) mg) (p < 0.005). CONCLUSIONS--Patients with angina-like chest pain and normal coronary angiograms have a low pain threshold and low tolerance to pain induced by adenosine.     

Chest pain in clinical practice: impact of routine troponin determination on clinical manifestations and care

INTRODUCTION AND OBJECTIVES. To study the significance of chest pain in the clinical practice of a Spanish hospital and to evaluate the impact of routine troponin determination. METHODS: In our institution, routine serial measurements of troponins I and T were made in the evaluation of chest pain in 2000. We compared the results obtained in 1999 for all patients who visited the emergency room for chest pain and the patients who were hospitalized. We recorded the diagnosis at discharge, duration of the hospital stay, and associated costs. RESULTS: In 2000, 1,820 patients with chest pain visited the emergency department, which was equivalent to 1.9% of visits and 7.5 cases per 1,000 people and year: 43% of these patients were hospitalized for suspected acute coronary syndrome as compared to 49% in 1999 (-12%; p > 0.001). Among the patients admitted, 28% were discharged with a diagnosis of non-ischemic chest pain. Troponin determinations were associated with a lower probability of admission due to unstable angina (11.5 vs 16.0%; -28%; p < 0.001) and non-ischemic chest pain (12.1 vs 14.5%; -16%; p < 0.05), and an increase in diagnoses of non-Q wave acute myocardial infarction (3.4% vs 1.8%; +89%; p < 0.01). Non-ST elevation acute coronary syndrome ACS required 3,751 days of hospitalization and 1,003,420 euros of cost, and troponin determinations were associated with a reduction in hospital stays of 832 days (-18.2%) and 185,100 euros (-15.6%). CONCLUSION: Chest pain had a high incidence, 7.5, and generates high costs in hospital admissions. The routine use of serial troponin determinations was associated with a reduction in hospital admissions due to unstable angina and non-ischemic chest pain, and costs.     

Clinical presentation and functional prognosis in syndrome X.

OBJECTIVES--To assess the effect of clinical presentation on functional prognosis in patients with syndrome X. DESIGN--A prospective study. Patients with syndrome X presenting with unstable angina and stable angina were followed up with a questionnaire to examine their functional state. PATIENTS--41 patients with syndrome X and unstable angina and 41 patients with syndrome X and stable angina. Syndrome X was defined as typical anginal chest pain, a positive exercise test, and normal coronary angiogram. SETTING--Regional cardiothoracic centre. RESULTS--The mean follow up time was 36 (range 20-51) months for the unstable angina group and 35 (range 19-51) months for the stable angina group. No patient was lost to follow up in either group. At follow up 28 patients in the unstable angina group were pain free compared with 15 patients in the stable angina group (p = 0.008). Seven patients in the unstable angina group had further hospital admission with chest pain after the cardiac catheterisation compared wtih 12 patients in the stable angina group (NS). Seven patients in the unstable angina group believed that they had heart disease compared with 27 in the stable angina group (p < 0.001). 26 patients in the unstable angina group but only eight patients in the stable angina group were unlimited in their physical activity (p < 0.001). 12 patients in the unstable angina group compared with 27 patients in the stable angina group were unable to work normally because of chest pain (p < 0.001). The mean (SD) duration of symptoms before cardiac catheterisation was 7.9 (4.7) months in the unstable angina group and 13.4 (5.6) months in the stable angina group (p < 0.001). 10 patients in the unstable angina group and 24 patients in the stable angina group still attended hospital outpatient clinics because of chest pain (p = 0.004). 16 patients in the unstable angina group and 29 patients in the stable angina group were still taking regular antianginal medication (p < 0.001). CONCLUSIONS--Patients with syndrome X who present with unstable angina have a significantly better functional prognosis than those presenting with symptoms of stable angina. This may reflect differences in underlying pathophysiological mechanisms.     

Effect of intravenous metoprolol before hospital admission on chest pain in suspected acute myocardial infarction

BACKGROUND: The aim of this study was to describe the effect of intravenous metoprolol on the intensity of chest pain before hospital admission in patients with suspected acute myocardial infarction AMI). METHODS AND RESULTS: Two hundred sixty-two patients with acute chest pain and suspected AMI were randomly assigned before hospital admission to either 5 mg morphine plus metoprolol 5 mg x 3 intravenously or 5 mg morphine plus intravenous placebo. Chest pain was evaluated on a 10-grade scale before and for 60 minutes after intravenous injection. One hundred thirty-four patients were randomly assigned to metoprolol and 128 to placebo. Among all patients randomized to metoprolol, the mean chest pain score was reduced by 3.0 +/- 1.9 arbitrary units AU) from before to after intravenous injection compared with 2.6 +/- 2.1 AU for placebo not significant). Among patients with an initially confirmed or strong suspicion of AMI, the corresponding figures were 3.1 +/- 1.8 AU for metoprolol and 2.2 +/- 1.6 AU for placebo P =.02). Among patients with only a vague or moderate suspicion of AMI, there was no difference. The treatment was well tolerated. CONCLUSIONS: When all patients were included in the analyses, there was no significant difference with regard to reduction of chest pain in the patients randomly assigned to metoprolol compared with placebo. A retrospective subgroup analysis indicated a beneficial effect of metoprolol among patients with an initially strong suspicion of or confirmed AMI. Further investigations are warranted to confirm this finding.