Complementary clinical benefits of coronary-artery stenting and blockade of platelet glycoprotein IIb/IIIa receptors. Evaluation of Platelet IIb/IIIa Inhibition in Stenting Investigators.

BACKGROUND: Inhibition of the platelet glycoprotein IIb/IIIa receptor with the monoclonal-antibody fragment abciximab reduces the acute ischemic complications associated with percutaneous coronary revascularization, whereas coronary-stent implantation reduces restenosis. We conducted a trial to determine the efficacy of abciximab and stent implantation in improving long-term outcome. METHODS: A total of 2399 patients were randomly assigned to stent implantation and placebo, stent implantation and abciximab, or balloon angioplasty and abciximab. The patients were followed for six months. RESULTS: At six months, the incidence of the composite end point of death or myocardial infarction was 11.4 percent in the group that received a stent and placebo, as compared with 5.6 percent in the group that received a stent and abciximab (hazard ratio, 0.47; 95 percent confidence interval, 0.33 to 0.68; P<0.001) and 7.8 percent in the group assigned to balloon angioplasty and abciximab (hazard ratio, 0.67; 95 percent confidence interval, 0.49 to 0.92; P=0.01). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.70 (95 percent confidence interval, 0.48 to 1.04; P=0.07). The rate of repeated revascularization of the target vessel was 10.6 percent in the stent-plus-placebo group, as compared with 8.7 percent in the stent-plus-abciximab group (hazard ratio, 0.82; 95 percent confidence interval, 0.59 to 1.13; P=0.22) and 15.4 percent in the angioplasty-plus-abciximab group (hazard ratio, 1.49; 95 percent confidence interval, 1.13 to 1.97; P=0.005). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.55 (95 percent confidence interval, 0.41 to 0.74; P<0.001). Among patients with diabetes, the combination of abciximab and stenting was associated with a lower rate of repeated target-vessel revascularization (8.1 percent) than was stenting and placebo (16.6 percent, P=0.02) or angioplasty and abciximab (18.4 percent, P=0.008). CONCLUSIONS: For coronary revascularization, abciximab and stent implantation confer complementary long-term clinical benefits.     

Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. Stent versus Thrombolysis for Occluded Coronary Arteries in Patients with Acute Myocardial Infarction Study Investigators

BACKGROUND: Prevention of myocardial damage is the main goal of all reperfusion therapies in patients with acute myocardial infarction. The relative efficacy of various reperfusion strategies is under intensive investigation. We assessed whether coronary stenting combined with the blockade of platelet glycoprotein IIb/IIIa receptors produces a greater degree of myocardial salvage than fibrinolysis with an accelerated infusion of alteplase, a tissue plasminogen activator, in patients with acute myocardial infarction. METHODS: A total of 140 patients were enrolled in the randomized trial; 71 were assigned to receive a stent plus abciximab, and 69 to receive intravenous alteplase. The primary end point was the degree of myocardial salvage, determined by means of serial scintigraphic studies with technetium Tc 99m sestamibi. The secondary end point was a composite of death, reinfarction, and stroke within six months after randomization. RESULTS: In the group that received a stent plus abciximab, the median size of the final infarct was 14.3 percent of the left ventricle (25th and 75th percentiles, 6.8 and 24.5 percent), as compared with a median of 19.4 percent (25th and 75th percentiles, 7.9 and 34.2 percent) in the alteplase group (P=0.02). This difference was due to the larger salvage index (the percentage of the left ventricle that was salvaged, divided by the percentage that was compromised by the initial perfusion defect) in the stent group: 0.57 (25th and 75th percentiles, 0.35 and 0.69), as compared with 0.26 (25th and 75th percentiles, 0.09 and 0.61; P<0.001). The cumulative incidence of death, reinfarction, or stroke at six months was lower in the stent group than in the alteplase group (8.5 vs. 23.2 percent. P=0.02; relative risk, 0.34; 95 percent confidence interval, 0.13 to 0.88). CONCLUSIONS: In patients with acute myocardial infarction, coronary stenting plus abciximab leads to a greater degree of myocardial salvage and a better clinical outcome than does fibrinolysis with a tissue plasminogen activator.     

Coronary angioplasty with or without stent implantation for acute myocardial infarction. Stent Primary Angioplasty in Myocardial Infarction Study Group

BACKGROUND: Coronary-stent implantation is frequently performed for treatment of acute myocardial infarction. However, few studies have compared stent implantation with primary angioplasty alone. METHODS: We designed a multicenter study to compare primary angioplasty with angioplasty accompanied by implantation of a heparin-coated Palmaz-Schatz stent. Patients with acute myocardial infarction underwent emergency catheterization and angioplasty. Those with vessels suitable for stenting were randomly assigned to undergo angioplasty with stenting (452 patients) or angioplasty alone (448 patients). RESULTS: The mean (+/-SD) minimal luminal diameter was larger after stenting than after angioplasty alone (2.56+/-0.44 mm vs. 2.12+/-0.45 mm, P<0.001), although fewer patients assigned to stenting had grade 3 blood flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) (89.4 percent, vs. 92.7 percent in the angioplasty group; P=0.10). After six months, fewer patients in the stent group than in the angioplasty group had angina (11.3 percent vs. 16.9 percent, P=0.02) or needed target-vessel revascularization because of ischemia (7.7 percent vs. 17.0 percent, P<0.001). In addition, the combined primary end point of death, reinfarction, disabling stroke, or target-vessel revascularization because of ischemia occurred in fewer patients in the stent group than in the angioplasty group (12.6 percent vs. 20.1 percent, P<0.01). The decrease in the combined end point was due entirely to the decreased need for target-vessel revascularization. The six-month mortality rates were 4.2 percent in the stent group and 2.7 percent in the angioplasty group (P=0.27). Angiographic follow-up at 6.5 months demonstrated a lower incidence of restenosis in the stent group than in the angioplasty group (20.3 percent vs. 33.5 percent, P<0.001). CONCLUSIONS: In patients with acute myocardial infarction, routine implantation of a stent has clinical benefits beyond those of primary coronary angioplasty alone.     

Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization.

BACKGROUND: In the setting of percutaneous coronary revascularization, agents in the class known as platelet glycoprotein IIb/IIIa inhibitors have significantly reduced the incidence of death or nonfatal myocardial infarction at 30 days. We assessed whether there are differences in safety or efficacy between two such inhibitors, tirofiban and abciximab. METHODS: Using a double-blind, double-dummy design at 149 hospitals in 18 countries, we randomly assigned patients to receive either tirofiban or abciximab before undergoing percutaneous coronary revascularization with the intent to perform stenting. The primary end point was a composite of death, nonfatal myocardial infarction, or urgent target-vessel revascularization at 30 days. The trial was designed and statistically powered to demonstrate the noninferiority of tirofiban as compared with abciximab. RESULTS: The primary end point occurred more frequently among the 2398 patients in the tirofiban group than among the 2411 patients in the abciximab group (7.6 percent vs. 6.0 percent; hazard ratio, 1.26; one-sided 95 percent confidence interval of 1.51, demonstrating lack of equivalence, and two-sided 95 percent confidence interval of 1.01 to 1.57, demonstrating the superiority of abciximab over tirofiban; P=0.038). The magnitude and the direction of the effect were similar for each component of the composite end point (hazard ratio for death, 1.21; hazard ratio for myocardial infarction, 1.27; and hazard ratio for urgent target-vessel revascularization, 1.26), and the difference in the incidence of myocardial infarction between the tirofiban group and the abciximab group was significant (6.9 percent and 5.4 percent, respectively; P=0.04). The relative benefit of abciximab was consistent regardless of age, sex, the presence or absence of diabetes, or the presence or absence of pretreatment with clopidogrel. There were no significant differences in the rates of major bleeding complications or transfusions, but tirofiban was associated with a lower rate of minor bleeding episodes and thrombocytopenia. CONCLUSIONS: Although the trial was intended to assess the noninferiority of tirofiban as compared with abciximab, the findings demonstrated that tirofiban offered less protection from major ischemic events than did abciximab.     

A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty

Patients presenting within four hours of the onset of acute myocardial infarction were randomly assigned to receive 80 to 100 mg of recombinant human-tissue plasminogen activator (t-PA) intravenously over a period of three hours (n = 72) or placebo (n = 66). Administration of the study drug was followed by coronary arteriography, and candidates for percutaneous transluminal coronary angioplasty were randomly assigned either to undergo angioplasty on the third hospital day (n = 42) or not to undergo angioplasty during the 10-day study period (n = 43). The patency rates of the infarct-related arteries were 66 percent in the t-PA group and 24 percent in the placebo group. No fatal or intracerebral hemorrhages occurred, and episodes of bleeding requiring transfusion were observed in 7.6 percent of the placebo group and 9.8 percent of the t-PA group. As compared with the use of placebo, administration of t-PA was associated with a higher mean (+/- SEM) ejection fraction on the 10th hospital day (53.2 +/- 2.0 vs. 46.4 +/- 2.0 percent, P less than 0.02), an improved ejection fraction during the study period (+3.6 +/- 1.3 vs. -4.7 +/- 1.3 percentage points, P less than 0.0001), and a reduction in the prevalence of congestive heart failure from 33 to 14 percent (P less than 0.01). Angioplasty improved the response of the ejection fraction to exercise (+8.1 +/- 1.4 vs. +1.2 +/- 2.2 percentage points, P less than 0.02) and reduced the incidence of postinfarction angina from 19 to 5 percent (P less than 0.05), but did not influence the ejection fraction at rest. These data support an approach to the treatment of acute myocardial infarction that includes early intravenous administration of t-PA and deferred cardiac catheterization and coronary angioplasty.     

Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II)

BACKGROUND. Long-term administration of angiotensin-converting--enzyme (ACE) inhibitors has been shown to improve survival in patients with symptomatic left ventricular failure and to attenuate left ventricular dilatation in patients with myocardial infarction. We studied whether mortality could be reduced during the 6 months after an acute myocardial infarction with use of the ACE inhibitor enalapril. METHODS. At 103 Scandinavian centers patients with acute myocardial infarctions and blood pressure above 100/60 mm Hg were randomly assigned to treatment with either enalapril or placebo, in addition to conventional therapy. Therapy was initiated with an intravenous infusion of enalapril (enalaprilat) within 24 hours after the onset of chest pain, followed by administration of oral enalapril. RESULTS. Of the 6090 patients enrolled, 3046 were assigned to placebo and 3044 to enalapril. The life-table mortality rates in the two groups at one and six months were not significantly different (6.3 and 10.2 percent in the placebo group vs. 7.2 and 11.0 percent in the enalapril group, P = 0.26). The relative risk of death in the enalapril group was 1.10 (95 percent confidence interval, 0.93 to 1.29). Death due to progressive heart failure occurred in 104 patients (3.4 percent) in the placebo group and 132 (4.3 percent) in the enalapril group (P = 0.06). Therapy had to be changed because of worsening heart failure in 30 percent of the placebo group and 27 percent of the enalapril group (P less than 0.006). Early hypotension (systolic pressure less than 90 mm Hg or diastolic pressure less than 50 mm Hg) occurred in 12 percent of the enalapril group and 3 percent of the placebo group (P less than 0.001). CONCLUSIONS. Enalapril therapy started within 24 hours of the onset of acute myocardial infarction does not improve survival during the 180 days after infarction.     

Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators.

BACKGROUND: In patients with refractory unstable angina, the platelet glycoprotein IIb/IIIa-receptor antibody abciximab reduces the incidence of cardiac events before and during coronary angioplasty. We investigated whether serum troponin T levels identify patients most likely to benefit from therapy with this drug. METHODS: Among 1265 patients with unstable angina who were enrolled in the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) trial, serum samples drawn at the time of randomization to abciximab or placebo were available from 890 patients; we used these samples for the determination of troponin T and creatine kinase MB levels. Patients with postinfarction angina were not included. RESULTS: Serum troponin T levels at the time of study entry were elevated (above 0.1 ng per milliliter) in 275 patients (30.9 percent). Among patients receiving placebo, the risk of death or nonfatal myocardial infarction was related to troponin T levels. The six-month cumulative event rate was 23.9 percent among patients with elevated troponin T levels, as compared with 7.5 percent among patients without elevated troponin T levels (P<0.001). Among patients treated with abciximab, the respective six-month event rates were 9.5 percent for patients with elevated troponin T levels and 9.4 percent for those without elevated levels. As compared with placebo, the relative risk of death or nonfatal myocardial infarction associated with treatment with abciximab in patients with elevated troponin T levels was 0.32 (95 percent confidence interval, 0.14 to 0.62; P=0.002). The lower event rates in patients receiving abciximab were attributable to a reduction in the rate of myocardial infarction (odds ratio, 0.23; 95 percent confidence interval, 0.12 to 0.49; P<0.001). In patients without elevated troponin T levels, there was no benefit of treatment with respect to the relative risk of death or myocardial infarction at six months (odds ratio, 1.26; 95 percent confidence interval, 0.74 to 2.31; P=0.47). CONCLUSIONS: The serum troponin T level, which is considered to be a surrogate marker for thrombus formation, identifies a high-risk subgroup of patients with refractory unstable angina suitable for coronary angioplasty who will particularly benefit from antiplatelet treatment with abciximab.     

Localized intracoronary gamma-radiation therapy to inhibit the recurrence of restenosis after stenting

BACKGROUND: Although the frequency of restenosis after coronary angioplasty is reduced by stenting, when restenosis develops within a stent, the risk of subsequent restenosis is greater than 50 percent. We report on a multicenter, double-blind, randomized trial of intracoronary radiation therapy for the treatment of in-stent restenosis. METHODS: Of 252 eligible patients in whom in-stent restenosis had developed, 131 were randomly assigned to receive an indwelling intracoronary ribbon containing a sealed source of iridium-192, and 121 were assigned to receive a similar-appearing nonradioactive ribbon (placebo). RESULTS: The primary end point, a composite of death, myocardial infarction, and the need for repeated revascularization of the target lesion during nine months of follow-up, occurred in 53 patients assigned to placebo (43.8 percent) and 37 patients assigned to iridium-192 (28.2 percent, P=0.02). However, the reduction in the incidence of major adverse cardiac events was determined solely by a diminished need for revascularization of the target lesion, not by reductions in the incidence of death or myocardial infarction. Late thrombosis occurred in 5.3 percent of the iridium-192 group, as compared with 0.8 percent of the placebo group (P=0.07), resulting in more late myocardial infarctions in the iridium-192 group (9.9 percent vs. 4.1 percent, P=0.09). Late thrombosis occurred in irradiated patients only after the discontinuation of oral antiplatelet therapy (with ticlopidine or clopidogrel) and only in patients who had received new stents at the time of radiation treatment. CONCLUSIONS: Intracoronary irradiation with iridium-192 resulted in lower rates of clinical and angiographic restenosis, although it was also associated with a higher rate of late thrombosis, resulting in an increased risk of myocardial infarction. If the problem of late thrombosis within the stent can be overcome, intracoronary irradiation with iridium-192 may become a useful approach to the treatment of in-stent restenosis.     

Multiple complex coronary plaques in patients with acute myocardial infarction

BACKGROUND: Acute myocardial infarction is believed to be caused by rupture of an unstable coronary-artery plaque that appears as a single lesion on angiography. However, plaque instability might be caused by pathophysiologic processes, such as inflammation, that exert adverse effects throughout the coronary vasculature and that therefore result in multiple unstable lesions. METHODS: To document the presence of multiple unstable plaques in patients with acute myocardial infarction and determine their influence on outcome, we analyzed angiograms from 253 patients for complex coronary plaques characterized by thrombus, ulceration, plaque irregularity, and impaired flow. RESULTS: Single complex coronary plaques were identified in 153 patients (60.5 percent) and multiple complex plaques in the other 100 patients (39.5 percent). As compared with patients with single complex plaques, those with multiple complex plaques were less likely to undergo primary angioplasty (86.0 percent vs. 94.8 percent, P = 0.03) and more commonly required urgent bypass surgery (27.0 percent vs. 5.2 percent, P < or = 0.001). During the year after myocardial infarction, the presence of multiple complex plaques was associated with an increased incidence of recurrent acute coronary syndromes (19.0 percent vs. 2.6 percent, P < or = 0.001); repeated angioplasty (32.0 percent vs. 12.4 percent, P < or = 0.001), particularly of non-infarct-related lesions (17.0 percent vs. 4.6 percent, P < or = 0.001); and coronary-artery bypass graft surgery (35.0 percent vs. 11.1 percent, P < or = 0.001). CONCLUSIONS: Patients with acute myocardial infarction may harbor multiple complex coronary plaques that are associated with adverse clinical outcomes. Plaque instability may be due to a widespread process throughout the coronary vessels, which may have implications for the management of acute ischemic heart disease.     

The effect of warfarin on mortality and reinfarction after myocardial infarction

BACKGROUND AND METHODS. The use of oral anticoagulation in the long-term treatment of survivors of acute myocardial infarction has been highly controversial. We therefore randomly assigned 1214 patients who had recovered from acute myocardial infarction (mean interval from the onset of symptoms to randomization, 27 days) to treatment with warfarin (607 patients) or placebo (607 patients) for an average of 37 months (range, 24 to 63). RESULTS. At the end of the treatment period, there had been 123 deaths in the placebo group and 94 in the warfarin group--a reduction in risk of 24 percent (95 percent confidence interval, 4 to 44 percent; P = 0.027). A total of 124 patients in the placebo group had reinfarctions, as compared with 82 in the warfarin group--a reduction of 34 percent (95 percent confidence interval, 19 to 54 percent; P = 0.0007). Furthermore, we observed a reduction of 55 percent (95 percent confidence interval, 30 to 77 percent) in the number of total cerebrovascular accidents in the warfarin group as compared with the placebo group (44 vs. 20; P = 0.0015). Serious bleeding was noted in 0.6 percent of the warfarin-treated patients per year. CONCLUSIONS. Long-term therapy with warfarin has an important beneficial effect after myocardial infarction and can be recommended in the treatment of patients who survive the acute phase.     

Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation

BACKGROUND: Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients. METHODS: We randomly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) (6259 patients) or placebo (6303 patients) in addition to aspirin for 3 to 12 months. RESULTS: The first primary outcome--a composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke--occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group (relative risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence interval, 0.72 to 0.90; P<0.001). The second primary outcome--the first primary outcome or refractory ischemia--occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group (relative risk, 0.86; 95 percent confidence interval, 0.79 to 0.94; P<0.001). The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization procedures were also significantly lower with clopidogrel. There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group (3.7 percent vs. 2.7 percent; relative risk, 1.38; P=0.001), but there were not significantly more patients with episodes of life-threatening bleeding (2.2 percent [corrected] vs. 1.8 percent; P=0.13) or hemorrhagic strokes (0.1 percent vs. 0.1 percent). CONCLUSIONS: The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel.     

Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb Investigators.

BACKGROUND: Studies have reported that women with acute myocardial infarction have in-hospital and long-term outcomes that are worse than those of men. METHODS: To assess sex-based differences in presentation and outcome, we examined data from the Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb study, which enrolled 12,142 patients (3662 women and 8480 men) with acute coronary syndromes, including infarction with ST-segment elevation, infarction with no ST-segment elevation, and unstable angina. RESULTS: Overall, the women were older than the men, and had significantly higher rates of diabetes, hypertension, and prior congestive heart failure. They had significantly lower rates of prior myocardial infarction and were less likely ever to have smoked. A smaller percentage of women than men had infarction with ST elevation (27.2 percent vs. 37.0 percent, P<0.001), and of the patients who presented with no ST elevation (those with myocardial infarction or unstable angina), fewer women than men had myocardial infarction (36.6 percent vs. 47.6 percent, P<0.001). Women had more complications than men during hospitalization and a higher mortality rate at 30 days (6.0 percent vs. 4.0 percent, P<0.001) but had similar rates of reinfarction at 30 days after presentation. However, there was a significant interaction between sex and the type of coronary syndrome at presentation (P=0.001). After stratification according to coronary syndrome and adjustment for base-line variables, there was a nonsignificant trend toward an increased risk of death or reinfarction among women as compared with men only in the group with infarction and ST elevation (odds ratio, 1.27; 95 percent confidence interval, 0.98 to 1.63; P=0.07). Among patients with unstable angina, female sex was associated with an independent protective effect (odds ratio for infarction or death, 0.65; 95 percent confidence interval, 0.49 to 0.87; P=0.003). CONCLUSIONS: Women and men with acute coronary syndromes had different clinical profiles, presentation, and outcomes. These differences could not be entirely accounted for by differences in base-line characteristics and may reflect pathophysiologic and anatomical differences between men and women.     

Effectiveness of drug-eluting stents versus bare-metal stents in large coronary arteries in patients with acute myocardial infarction

This study compared clinical outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in large coronary arteries in patients with acute myocardial infarction (MI). A total of 985 patients who underwent single-vessel percutaneous coronary intervention (PCI) in large coronary arteries (≥ 3.5 mm) in lesions < 25 mm were divided into DES group (n = 841) and BMS group (n = 144). Clinical outcomes during 12 months were compared. In-hospital outcome was similar between the groups. At six months, death/MI rate was not different. However, DES group had significantly lower rates of target-lesion revascularization (TLR) (1.7% vs 5.6%, P = 0.021), target-vessel revascularization (TVR) (2.2% vs 5.6%, P = 0.032), and total major adverse cardiac events (MACE) (3.4% vs 11.9%, P = 0.025). At 12 months, the rates of TLR and TVR remained lower in the DES group (2.5% vs 5.9%, P = 0.032 and 5.9% vs 3.1%, P = 0.041), but the rates of death/MI and total MACE were not statistically different. The use of DES in large vessels in the setting of acute MI is associated with lower need for repeat revascularization compared to BMS without compromising the overall safety over the course of one-year follow-up.     

Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction

In a double-blind trial of streptokinase for acute myocardial infarction, 219 consecutive patients presenting with infarction within four hours (mean, 3.0 +/- 0.8) of the onset of chest pain were randomly assigned to treatment with streptokinase (1.5 million units) or placebo, given intravenously over 30 minutes. The primary end point of the study was left ventricular function in patients with first infarctions. Patients who could undergo beta-blockade also received intravenous propranolol. Heparin (for 48 hours) and a combination of low-dose aspirin and dipyridamole were administered to both groups until cineangiography was performed at three weeks. In the patients with first infarctions treated with streptokinase, the left ventricular ejection fraction was 6 percentage points higher (streptokinase vs. placebo, 59 +/- 10.5 vs. 53 +/- 13.5 percent; P less than 0.005), with benefit to patients with either anterior infarction (57 +/- 11.9 vs. 49 +/- 15.9 percent; P less than 0.05) or inferior infarction (60 +/- 9.1 vs. 55 +/- 11.3 percent; P less than 0.05). Left ventricular function was improved regardless of whether concomitant propranolol was given. Survival (at 30 days) was improved with streptokinase: 2 deaths occurred among 79 patients who received this drug, as compared with 12 deaths among 93 patients who received placebo (2.5 vs. 12.9 percent, P = 0.012). Rates of reinfarction (streptokinase vs. placebo, 3 vs. 1 percent) and requirements for surgery or angioplasty (7 vs. 5 percent) were similar in the two groups. We conclude that administration of intravenous streptokinase (1.5 million units) to patients with a first myocardial infarction results in improved left ventricular function and short-term survival.     

Long-term treatment with a platelet glycoprotein-receptor antagonist after percutaneous coronary revascularization. EXCITE Trial Investigators. Evaluation of Oral Xemilofiban in Controlling Thrombotic Events

BACKGROUND: When administered intravenously at the time of percutaneous coronary revascularization, glycoprotein IIb/IIIa receptor antagonists decrease the incidence of death and nonfatal myocardial infarction and the need for urgent revascularization. We hypothesized that long-term administration of oral glycoprotein IIb/IIIa antagonists, which block the aggregation of platelets, might stabilize intravascular plaque and prevent additional ischemic cardiac events. METHODS: We conducted a prospective, double-blind trial in which 7232 patients were randomly assigned to receive 20 mg of oral xemilofiban or placebo 30 to 90 minutes before undergoing percutaneous coronary revascularization, with maintenance doses of 10 or 20 mg of xemilofiban or placebo administered three times daily for up to 182 days. There were two primary composite end points: one was death, nonfatal myocardial infarction, or urgent revascularization at 182 days, and the other was death or nonfatal myocardial infarction at 182 days. RESULTS: Death, myocardial infarction, or urgent revascularization occurred within 182 days in 324 patients who received placebo (Kaplan-Meier cumulative event rate, 13.5 percent), 332 who received 10 mg of xemilofiban (13.9 percent, P=0.82 for the comparison with placebo), and 306 who received 20 mg of xemilofiban (12.7 percent, P=0.36 for the comparison with placebo). The incidence of death or myocardial infarction was also similar in all three groups. Clinically significant hemorrhagic complications and thrombocytopenia were infrequent. CONCLUSIONS: The administration of the glycoprotein IIb/IIIa antagonist xemilofiban before percutaneous coronary revascularization and for up to six months thereafter does not significantly reduce the incidence of important clinical end points.     

经静脉心肌超声造影对心肌梗死患者自体骨髓单个核细胞移植后心肌微循环的评价

目的利用经静脉心肌超声造影（IMCE）观察心肌梗死患者自体骨髓单个核细胞移植术前后心肌微循环的变化。方法40例急性心肌梗死患者在病情稳定后7～10d,行延迟经皮冠状动脉成形术（PCI）。随机分成骨髓细胞移植组（20例）和对照组（20例）,观察术前、术后1月、术后6月左心室舒张末内径（LVDd）,左室射血分数（LVEF）和术前及术后1个月的IMCE,测量平台期的心肌显像增大强度A,曲线上升平均斜率β及A与β之积在手术前后的变化。结果移植组LVEF由术前的（37.26±4.21）1月后上升到（54.42±5.26）（P〈0.05）;而对照组差异不显著（38.86±4.63对40.28±4.56）（P〉0.05）。LVDd移植组术后6月与术前比较差异不显著（50.23±3.42对52.48±3.26）（P〉0.05）;而对照组（50.96±2.68对64.31±3.28）（P〈0.05）心脏有扩大趋势。IMCE示手术后相关心肌节段的A、β及A.β均较术前显著增加。其中A.β（dB/s）移植组由术前的2.37±0.16（dB/s）增加到术后的15.60±0.24（dB/s）;较对照组（2.06±0.12至7.98±0.23）增加更为明显（P〈0.05）,示急性心肌梗死延迟PCI术后梗死相关节段心肌血流灌注速度和灌注量均有增加,自体骨髓单个核细胞移植组增加更明显。结论自体骨髓单个核细胞移植可改善梗死区心肌微循环,明显增加心肌血流量。     

A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction

We compared the efficacy of immediate coronary angioplasty after acute myocardial infarction with that of elective angioplasty at 7 to 10 days in patients treated initially with intravenous tissue plasminogen activator. The plasminogen activator (150 mg) was administered 2.95 +/- 1.1 hours after the onset of symptoms, to 386 patients with acute myocardial infarction. Ninety minutes later, patency of the coronary artery serving the area of the infarct was demonstrated by coronary angiography in 288 patients (75 percent). Bleeding problems were frequently encountered, as evidenced by an average drop in hematocrit of 11.7 +/- 6.5 points from base line to nadir and by a need for transfusion not related to bypass surgery in 70 patients (18 percent). After successful thrombolysis, 197 patients with a patent but severely stenotic vessel suitable for angioplasty were randomly assigned to immediate angioplasty (n = 99) or, if indicated 7 to 10 days after infarction, to deferred (elective) angioplasty (n = 98). The incidence of reocclusion was similar in the two groups: 11 percent in the group assigned to immediate angioplasty and 13 percent in the group assigned to elective angioplasty. Neither group had a significant improvement in global left ventricular function, and regional wall motion in the infarct zone improved to a similar extent in the two groups. In the elective-angioplasty group, the rate of crossover to emergency angioplasty for recurrent ischemia was 16 percent (whereas 5 percent of the immediate-angioplasty group required emergency repeated angioplasty; P = 0.01). In 14 percent of the patients in the elective group, the stenosis was substantially reduced by the time of the seven-day follow-up angiography, obviating the need for angioplasty. We conclude that in patients with initially successful thrombolysis and suitable coronary-artery anatomy, immediate angioplasty offers no clear advantage over delayed elective angioplasty.     

Pravastatin therapy and the risk of stroke

BACKGROUND: Several epidemiologic studies have concluded that there is no relation between total cholesterol levels and the risk of stroke. In some studies that classified strokes according to cause, there was an association between increasing cholesterol levels and the risk of ischemic stroke and a possible association between low cholesterol levels and the risk of hemorrhagic stroke. Recent reviews of trials of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have suggested that these agents may reduce the risk of stroke. METHODS: In a double-blind trial (the Long-Term Intervention with Pravastatin in Ischaemic Disease study), we compared the effects of pravastatin on mortality due to coronary heart disease (the primary end point) with the effects of placebo among 9014 patients with a history of myocardial infarction or unstable angina and a total cholesterol level of 155 to 271 mg per deciliter (4.0 to 7.0 mmol per liter). Our goal in the present study was to assess effects on stroke from any cause and nonhemorrhagic stroke, which were secondary end points. RESULTS: There were 419 strokes among 373 patients over a follow-up period of six years. A total of 309 strokes were classified as ischemic, 31 as hemorrhagic, and 79 as of unknown type. Among the patients given placebo, the risk of stroke was 4.5 percent, as compared with 3.7 percent among those given pravastatin (relative reduction in risk, 19 percent; 95 percent confidence interval, 0 to 34 percent; P=0.05). Non-hemorrhagic stroke occurred in 4.4 percent of the patients given placebo, as compared with 3.4 percent of those given pravastatin (reduction in risk, 23 percent; 95 percent confidence interval, 5 to 38 percent; P=0.02). Pravastatin had no effect on hemorrhagic stroke (incidence, 0.2 percent in the placebo group vs. 0.4 percent in the pravastatin group; P=0.28). CONCLUSIONS: Pravastatin has a moderate effect in reducing the risk of stroke from any cause and the risk of nonhemorrhagic stroke in patients with previous myocardial infarction or unstable angina.     

Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock.

BACKGROUND: The leading cause of death in patients hospitalized for acute myocardial infarction is cardiogenic shock. We conducted a randomized trial to evaluate early revascularization in patients with cardiogenic shock. METHODS: Patients with shock due to left ventricular failure complicating myocardial infarction were randomly assigned to emergency revascularization (152 patients) or initial medical stabilization (150 patients). Revascularization was accomplished by either coronary-artery bypass grafting or angioplasty. Intraaortic balloon counterpulsation was performed in 86 percent of the patients in both groups. The primary end point was mortality from all causes at 30 days. Six-month survival was a secondary end point. RESULTS: The mean age of the patients was 66+/-10 years, 32 percent were women and 55 percent were transferred from other hospitals. The median time to the onset of shock was 5.6 hours after infarction, and most infarcts were anterior in location. Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography, and 87 percent underwent revascularization; only 2.7 percent of the patients assigned to medical therapy crossed over to early revascularization without clinical indication. Overall mortality at 30 days did not differ significantly between the revascularization and medical-therapy groups (46.7 percent and 56.0 percent, respectively; difference, -9.3 percent; 95 percent confidence interval for the difference, -20.5 to 1.9 percent; P=0.11). Six-month mortality was lower in the revascularization group than in the medical-therapy group (50.3 percent vs. 63.1 percent, P=0.027). CONCLUSIONS: In patients with cardiogenic shock, emergency revascularization did not significantly reduce overall mortality at 30 days. However, after six months there was a significant survival benefit. Early revascularization should be strongly considered for patients with acute myocardial infarction complicated by cardiogenic shock.     

Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease

BACKGROUND: The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease. METHODS: A total of 1205 patients were randomly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year. The costs of hospital resources used were also determined. RESULTS: At one year, there was no significant difference between the two groups in terms of the rates of death, stroke, or myocardial infarction. Among patients who survived without a stroke or a myocardial infarction, 16.8 percent of those in the stenting group underwent a second revascularization, as compared with 3.5 percent of those in the surgery group. The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery (P<0.001 by the log-rank test). The costs for the initial procedure were $4,212 less for patients assigned to stenting than for those assigned to bypass surgery, but this difference was reduced during follow-up because of the increased need for repeated revascularization; after one year, the net difference in favor of stenting was estimated to be $2,973 per patient. CONCLUSION: As measured one year after the procedure, coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death, stroke, and myocardial infarction. However, stenting is associated with a greater need for repeated revascularization.