Relationship between blood pressure and cardiac events in patients with a healed myocardial infarction.

This study investigated the association between blood pressure (diastolic [DBP] and systolic [SBP]) and cardiac events in a total of 6,602 patients with a healed myocardial infarction (MI) (5,320 men, 1,282 women; mean age, 58.9+/-10.4 years), including in-patients and out-patients, from January 1986 to January 1999. The primary endpoints (cardiac events) were recurrent MI (fatal and non-fatal), death from congestive heart failure, or sudden death. The total number of cardiac events was 195 (3.0%) and the incidences of the 3 cardiac events were compared among the 3 DBP groups (DBP low group, <70 mmHg; DBP middle group, 70-89 mmHg; DBP high group, > or =90 mmHg). There were some significant differences in the characteristics of patients among the 3 groups, but no significant difference in cardiac death and total mortality was found among the 3 groups. Cardiac events occurred in 59 of 1,780 patients (3.3%, 33.9/1,000 person years) in the DBP low group, tended to be reduced in number in the DBP middle group (87 of 3,549 patients 2.5%, 21.4/1,000 person years) and were slightly increased in number in the DBP high group (24 of 642 patients 3.7%, 35.2/1,000 person years). Although this correlation between BP and cardiac events appears to be J-shaped, because there is no statistically significant difference in the rate of cardiac events among the 3 groups, we conclude that DBP does not influence the occurrence of cardiac events. The prevalence of cardiac events tended to be greater with a SBP less than 120 mmHg.

Continuous long-term dosing with oral slow-release isosorbide dinitrate does not reduce incidence of cardiac events in patients with healed myocardial infarction.

BACKGROUND: In the short term, isosorbide dinitrate (ISDN) is considered to be therapeutically effective. The long-term effects of treatment with slow-release ISDN are less clear. HYPOTHESIS: The study was undertaken to investigate the effects of continuous, long-term dosing with oral slow-release ISDN on the incidence of cardiac events in patients with healed myocardial infarction (MI). The study was carried out in accordance with the intention-to-treat principle. METHODS: In all, 1.102 in- and outpatients, of either gender, with healed MI were randomly divided into groups treated with ISDN (n = 470) and not treated with ISDN (n = 632). Patients in the ISDN group received a continuous regimen of 20 mg of oral, long-acting ISDN three times a day, after meals. The mean observation period was 15.0 +/- 18.5 months. The primary endpoints were nonfatal and fatal recurrent MI, death from congestive heart failure, and sudden death. RESULTS: There were no significant differences in the baseline characteristics of the patients in the ISDN and no-treatment groups; nevertheless, significantly more patients in the ISDN group experienced cardiac events. In the ISDN group, 35 patients (7.4%) experienced cardiac events during the observation period, versus only 28 patients (4.4%) in the no-treatment group (p < 0.05; odds ratio 1.74; 95% confidence interval 1.04-2.90). CONCLUSION: Continuous long-term dosing with oral, slow-release ISDN does not reduce and probably increases the incidence of cardiac events among patients with healed MI.

Protective effect of PEG-SOD against early coronary reperfusion injury assessed in reperfused and non-reperfused ischaemic areas of the same heart.

OBJECTIVE: In order to investigate the salvage of ischaemic myocardium by polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), we compared reperfused and non-reperfused regions in the same canine heart and measured regional myocardial blood flow (RMBF) and myocardial CPK during coronary occlusion and reperfusion using non-radioactive, coloured microspheres. METHODS AND RESULTS: The chests of 17 mongrel dogs were opened under anaesthesia, and the left circumflex coronary artery was occluded for 90 min and then reperfused for 5 min. During this procedure, polystyrene microspheres of different colours were infused at four different times: prior to occlusion (orange), 10 min (red) and 90 min (blue) after occlusion, and 5 min after reperfusion (yellow). Thereafter, the heart was excised, cut in slices along the left circumflex coronary artery, and flow rates at the various times were assessed as a function of microsphere counts. In the control group (n=9), there are significant differences in the myocardial CPK level between reperfused and non-reperfused areas. The myocardial CPK level in reperfused area was significantly reduced compared to non-reperfused area in the outer layers (54 +/- 8 IU/g vs. 74 +/- 9 IU/g, P < 0.05), and also reduced in the inner layers (59 +/- 9 IU/g vs. 74 +/- 13 IU/g), however, it was not significantly different. In the PEG-SOD group (n=8), there was no significant difference in the myocardial CPK level between reperfused and non-reperfused areas in both inner and outer layers (inner layers; 68 +/- 11 IU/g vs. 68 +/- 6 IU/g, outer layer; 69 +/- 17 IU/g vs. 67 +/- 18 IU/g), indicating a significant protective effect of PEG-SOD. In the control group, transmural necrosis of the reperfused areas was 22.4 +/- 10.0%, which showed no significant difference compared with non-reperfused areas (23.1 +/- 9.9%). In the PEG-SOD group, transmural necrosis of the reperfused areas by TTC staining was 8.1 +/- 8.1%, which showed no significant difference compared with non-reperfused areas (8.5 +/- 7.1%). CONCLUSIONS: PEG-SOD prevents infarct extension during early coronary reperfusion.

Suppression of cell proliferation by tissue plasminogen activator during the early phase after balloon injury minimizes intimal hyperplasia in hypercholesterolemic rabbits.

Thrombus formation is a key component of the pathogenesis of restenosis after arterial balloon injury. The purpose of this study was to determine whether intimal hyperplasia could be attenuated by infusion of recombinant tissue plasminogen activator (tPA). Forty-two Kurosawa and Kusanagi hypercholesterolemic rabbits were divided into tPA (n = 20) and control (n = 22) groups, the former receiving 7 days of continuous tPA infusion (0.6 mg/kg/day) via ear veins. The walls of the common iliac arteries were injured using 2.5-mm balloon catheters and then examined histologically 7, 14, 21, and 28 days later. Cell proliferation was assessed by immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), and transforming growth factor (TGF)-beta immunohistochemistry was carried out to estimate cell proliferation and differentiation. It was observed that 28 days after balloon injury, intimal cross-sectional areas in the tPA group were significantly smaller than in controls (0.11 +/- 0.03 mm2 vs. 0.57 +/- 0.08 mm2, p < 0.01), as were ratios of the cross-sectional areas of the intima and media (0.21 +/- 0.07 vs. 1.06 +/- 0.18, p < 0.05). In addition, the numbers of PCNA-positive medial cells were significantly lower (0.06 +/- 0.01 vs. 0.36 +/- 0.08, p < 0.05) and TGF-beta-positive vessel wall areas were significantly smaller in tPA-treated animals 7 days after balloon injury (0.47 +/- 0.28% vs. 4.55 +/- 1.44%, p < 0.05). Thus infusion of tPA after arterial balloon injury appears to decrease medial cell proliferation and suppress intimal hyperplasia.

tPA via infusion catheters followed by continuous IV infusion for 3 days prevents intimal hyperplasia after balloon injury.

A rabbit model was used to examine the effects of tissue plasminogen activator (tPA) on development of intimal hyperplasia following balloon injury. Thirty-two hereditary hypercholesterolemic (KHC) rabbits underwent percutaneous transluminal coronary artery balloon catheterization and injury to the common iliac artery, after which they were divided into four groups: untreated (control); Dispatch catheterized-30 minutes local saline delivery [D(+)-tPA(-)]; D(+)-30 minutes local tPA delivery (0.6 mg/kg) [D(+)-tPA(30 min)]; and D(+)-30 minutes local tPA + 3 days intravenous infusion (0.6 mg/kg/24 h) [(D(+)-tPA(30 min + 3 d)]. Twenty-eight days later, the intimal cross-sectional areas of all three Dispatch catheterized groups were significantly smaller than those of control groups, as were the intimal/medial area ratios. Moreover, the intima/media ratios of the D(+)-tPA(30 min + 3 d) group were significantly smaller than those of the D(+)-tPA(-) group. Thus, local delivery of tPA via Dispatch catheters followed by continuous intravenous infusion of tPA for 3 days prevented intimal hyperplasia after angioplasty.

beta-blockers reduce the incidence of cardiac events in post-myocardial infarction patients.

The capacity of beta-blockers to prevent cardiac events in post-myocardial infarction (MI) patients was investigated. Among 1,483 study participants, a beta-blocker was included in the therapeutic regimens of 833 (beta-blocker group) and was omitted from the regimens of 650 (control group). The incidence of cardiac events (recurrent MI, sudden death and death by congestive heart failure) during a follow up period of 17.4 +/- 20.9 months was retrospectively compared between the two groups. Cardiac events occurred in 27 (3.2%) members of the beta-blocker group and in 44 (6.8%) controls, which represents a significant decline in the incidence of cardiac events among patients administered beta-blockers (p < 0.01, odds ratio 0.46, 95 % confidence intervals 0.28-0.75). Subgroup and multivariate analyses showed beta-blockers to be as efficacious in Japanese post-MI patients as was previously shown in Western patients. While these findings are compelling, it is clear that confirmation in a large, multicenter, placebo - controlled, randomized clinical trial, analogous to those that have been carried out in Western countries, is necessary.

[Drug treatment for secondary prevention of myocardial infarction].

The effects of drug treatment on cardiac events for 11 years from January 1986 to December 1996 were investigated in 1,483 patients with myocardial infarction, 1,164 men and 319 women (mean age 60.1 +/- 11.2 years), followed up for 17.4 +/- 20.9 months. Seventy-one patients (4.8%, 33 cases per 1,000 person-year) had cardiac events (recurrent myocardial infarction, sudden death and death by congestive heart failure). Multivariate analysis showed treatment with cholesterol lowering agents and beta-blockers reduced cardiac events, whereas administration of antiarrhythmic agents increased cardiac events. Univariate analysis showed that the incidence of cardiac events was 2.2% in patients treated with cholesterol lowering agents but 6.2% in patients without treatment, showing a significant difference (p < 0.01). The incidence was 3.2% for patients treated with beta-blockers and 6.8% for those without (p < 0.01), showing that beta-blockers were also effective to reduce cardiac events. Antiplatelet agents were also effective (3.7% vs 7.1%, p < 0.01). Calcium antagonists, angiotensin converting enzyme inhibitors and warfarin were not effective. Nitrates (6.0% vs 3.1%, p < 0.01) and antiarrhythmic agents (13.7% vs 3.6%, p < 0.01) increased the incidence of cardiac events. A placebo-controlled, double blind, large clinical multicenter study is required to confirm these results.

Retrospective analysis showing less cardiac events in post-myocardial infarction patients treated with metoprolol. Secondary Prevention Group.

This analysis was carried out to clarify the capacity of metoprolol to prevent cardiac events in Japanese post-myocardial infarction patients during a follow-up period of 16.3 months. Cardiac events occurred in 44 of 650 patients treated without beta-blockers (6.8%) and in 13 of 432 patients treated with metoprolol (3.0%), which represents a significant decline in the incidence of cardiac events among patients receiving metoprolol (p<0.01, odds ratio 0.43, 95% confidence interval 0.23-0.80). Because this was a retrospective analysis, there were unavoidable differences in the backgrounds of the patients in the 2 groups. Subgroup analyses, each focusing on a specific patient characteristic, were therefore performed. These showed that metoprolol effectively reduced cardiac events in many subgroups. Furthermore, multivariate analysis carried out to exclude any modification based on the differences in patient background confirmed metoprolol to be effective in reducing subsequent cardiac events in post-myocardial infarction patients. A large, randomized, placebo-controlled clinical trial needs to be performed in the Japanese population to confirm the present result.

Prevention of coronary arterial renarrowing by continuous 3-day infusion of tissue plasminogen activator after successful percutaneous transluminal coronary angioplasty: a randomized, double-blind, placebo-controlled study.

Vascular injury resulting from percutaneous transluminal coronary angioplasty (PTCA) and subsequent thrombus formation are important factors in the pathogenesis of coronary arterial restenosis. The present study was undertaken to determine whether infusions of tissue plasminogen activator (tPA), beginning immediately after PTCA, would decrease the renarrowing of the coronary arterial lumen. Patients were randomized and divided into two groups: one group (15 patients, 16 lesions) received continuous, 3-day, intravenous infusions of tPA (0.25 mg/kg/day in 0.9% saline), beginning immediately after successful PTCA, while the other group (17 patients, 17 lesions) received saline alone. Coronary angiography was performed before, immediately after, 24 hours after, and 3 months after PTCA. Coronary stenosis (%), reference diameters, and minimum luminal diameters were measured by quantitative coronary angiography. The incidence of restenosis tended to be lower in the tPA group than in the placebo group (tPA group, 13%; placebo group, 41%; NS), although diameter stenoses before and immediately after PTCA were not significantly different in the two groups. Three months later, however, diameter stenoses were significantly smaller in the tPA group (35.6 +/- 13.3 vs 47.7 +/- 18.9%; P<0.05). Thus, intravenous tPA infusion beginning immediately after successful PTCA may inhibit renarrowing of the coronary arterial lumen.

Percutaneous transluminal coronary angioplasty performed 24-48 hours after the onset of acute myocardial infarction improves chronic-phase left ventricular regional wall motion.

The authors investigated the capacity of percutaneous transluminal coronary angioplasty (PTCA) performed 24-48 hours after the onset of acute myocardial infarction (AMI) to improve regional left ventricular wall motion. Twenty-four patients were divided into two groups: a PTCA group who received successful PTCA (14 cases) and a non-PTCA group (10 cases) who did not receive PTCA. Left ventricular end-diastolic volume (LVEDV) increased significantly (p<0.01) from 57+/-14 mL/m2 during the acute phase to 83+/-16 mL/m2 during the chronic phase in the non-PTCA group, whereas no significant change in LVEDV was seen in the PTCA group (69+/-26 vs. 76+/-16 mL/m2). In addition, in patients with 99% stenosis/thrombolysis in myocardial infarction (TIMI) grade 3 flow, increases in regional left ventricular wall motion (delta(sd)/chord) at the infarcted site between the acute and chronic phases were significantly greater in the PTCA group than in the non-PTCA group (2.49+/-1.05 vs. 0.67+/-0.65, p<0.01). PTCA performed 24-48 hours after the onset of AMI improved wall motion at the infarcted site.

Intermittent nitrate therapy for prior myocardial infaraction does not induce rebound angina nor reduce cardiac events.

OBJECTIVE: Long-term nitrate therapy for ischemic heart disease may cause drug tolerance which diminishes its beneficial effects; consequently, intermittent administration of nitrates is recommended. With this regimen, however, the potential occurrence of rebound angina during the nitrate-free intervals is a source of concern. SUBJECTS AND METHODS: We carried out a retrospective study of 606 patients to determine whether rebound angina occurred when conventional continuous nitrate administration was replaced by intermittent administration as part of a long-term therapy protocol for prior myocardial infarction. The subjects were receiving treatment for myocardial infarction and included 293 patients treated with nitrates (Nitrate group) and 313 patients who were not (No-nitrate group). The former included 186 patients who received intermittent nitrate administration (Intermittent group) and 107 patients who received continuous administration (Continuous group). The mean period of observation was 4.3 +/- 1.6 months. RESULTS: There were no cases of rebound angina in the Intermittent group. Cardiac events occurred in one case in the No-nitrate group (0.3%), in 4 cases in the Continuous group (3.7%) and in 2 cases in the Intermittent group (1.1%). The incidence of cardiac events was thus significantly increased in the Continuous group compared to the No-nitrate group (p < 0.05; odds ratio 9.06; 95% CI 1.41-58.28). The Intermittent group did not significantly differ from the No-nitrate group in the incidence of cardiac events. CONCLUSION: It is concluded that intermittent administration of nitrates does not cause rebound angina and is therefore safe. A randomized controlled trial is needed to find the long-term effect on cardiac events.

Chronic use of continuous dosing of long-term nitrates does not prevent cardiac events in patients with severe acute myocardial infarction.

This study was performed to investigate the effects of the chronic use of continuous, not eccentric, dosing of nitrates on cardiac events in patients with severe acute myocardial infarction. A total of 1,303 patients with healed myocardial infarction were divided into two groups: treatment with nitrates or nontreatment. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure and sudden death. Among the 725 patients treated with nitrates, 45 patients (6.2%) experienced cardiac events during the observation period, whereas only 17 of the 578 patients treated without nitrates (2.9%) had cardiac events. This difference was statistically significant (p < 0.01; odds ratio 2.18, 95% confidence interval 1.24-3.86). In Killip class II-IV patients, the incidence of cardiac events in patients with nitrates was significantly greater than in patients without nitrates (18.8 vs. 3.5%, p < 0.05). The chronic use of continuous, not eccentric, dosing of nitrates did not prevent cardiac events in patients with severe acute myocardial infarction.

Prevention of left ventricular remodeling by percutaneous transluminal coronary angioplasty performed 24 hours after the onset of acute myocardial infarction.

It remains controversial whether percutaneous transluminal coronary angioplasty (PTCA) performed 24 hours after the onset of acute myocardial infarction (AMI) in coronary arteries with 99% stenosis is useful in preserving left ventricular function. We investigated the effectiveness of PTCA in preventing left ventricular remodeling when it was performed 24 hours after the onset of AMI in infarct-related coronary arteries (IRCAs) having 99% stenosis and thrombolysis in myocardial infarction (TIMI) grade 3 flow. The subjects were 19 patients with AMI (anterior wall, 9 patients; inferior wall, 7 patients; and non-Q, 3 patients) who, within 24 hours of the onset of AMI, underwent coronary angiography and left ventriculography during the acute and/ or chronic phases. The patients were divided into a PTCA group, comprised of patients in whom PTCA was successfully performed 24 hours after the onset of AMI (n = 10), and a non-PTCA group (n = 9). The non-PCTA group included patients who were successfully reperfused by thrombolysis and did not include patients who had spontaneous reperfusion or reperfusion after PTCA. In the non-PTCA group, the left ventricular end-diastolic volume (mean +/- SD) was significantly increased in the chronic phase (86 +/- 23 mL/m(2)) as compared with the acute phase (67 +/- 13 mL/m(2)), whereas in the PTCA group no significant difference was observed between end-diastolic volumes in the acute and chronic phases (67 +/- 26 and 68 +/- 13 mL/m(2), respectively). Left ventricular remodeling is prevented by PTCA when it is performed 24 hours after the onset of AMI in IRCAs with 99% stenosis and TIMI grade 3 flow.

Incidence of cancer in postmyocardial infarction patients treated with short-acting nifedipine and diltiazem. Secondary Prevention Group.

BACKGROUND: Recent reports suggest a possible link between nifedipine (but not diltiazem) and an increased risk of cancer in patients being treated with calcium antagonists. METHODS: A total of 1054 postmyocardial infarction patients were divided randomly into those being treated with calcium antagonists (n = 566 [nifedipine, 425 patients and diltiazem, 141 patients]) and controls (no calcium antagonist; n = 488). The patients were followed for 26.3 months, and the incidences of cardiac events as well as cancer were compared among the 3 groups. RESULTS: Thirteen patients (2.7%) in the control group developed cancer, whereas 15 patients in the nifedipine group (3.5%; odds ratio, 1.34; 95% confidence interval [95% CI], 0.63-2.85) and 3 patients in the diltiazem group (2.1%; odds ratio, 0.89; 95% CI, 0.27-2.93) developed cancer. CONCLUSIONS: Diltiazem appears to present no increased risk of cancer. The incidence of cancer was slightly higher in the patients receiving nifedipine than in those not being treated with a calcium antagonist, which is consistent with earlier reports; however, this increase was not statistically significant.

Increased coronary vasomotor tone in acute myocardial infarction patients with spontaneous coronary recanalization.

To clarify the role of coronary spasm or dynamic coronary obstruction in the development of acute myocardial infarction (AMI) with spontaneous recanalization (SR), symptoms in 296 patients with AMI admitted within 24 h after the onset of chest pain were analyzed just before and after onset, and coronary angiograms were analyzed soon after onset. Patients were divided into 3 groups according to the initial angiographic findings in the infarct-related coronary artery (IRCA): group 1 comprised 172 patients with total occlusion (TIMI O); group 2 comprised 57 patients with subtotal occlusion (TIMI 1,2); and group 3 comprised 67 patients with SR (TIMI 3). The incidence of SR was 20.3% at 0-4 h after onset, 22.2% at 4-6 h, 19.7% at 6-12 h, 24.0% at 12-24 h, and 36.0% at 24 h or later. The incidence of SR did not increase significantly as time elapsed. The incidence of angina at rest and variable-threshold angina before the onset of infarction was only 16.2% in group 1, but was significantly higher in groups 2 (64.3%) and 3 (61.9%). The incidence of intermittent chest pain at onset in group 1 (8.4%) was significantly lower than in groups 2 (54.5%) and 3 (38.8%). Vasodilation of the proximal normal segment adjacent to the stenotic site of the IRCA induced by intracoronary nitroglycerin was significantly higher in groups 2 (11.7 +/- 1.2%) and 3 (20.7 +/- 2.6%) than in group 1 (4.0 +/- 0.6%). These results suggest that coronary spasm or dynamic obstruction may be involved in the pathogenesis of thrombus formation or coronary obstruction causing AMI in many Japanese patients.

Short-acting nifedipine and diltiazem do not reduce the incidence of cardiac events in patients with healed myocardial infarction. Secondary Prevention Group.

BACKGROUND: The administration of calcium antagonists to patients with healed myocardial infarction is a controversial treatment. This study was conducted to elucidate the effect of short-acting nifedipine and diltiazem on cardiac events in patients with healed myocardial infarction. METHODS AND RESULTS: A controlled clinical open trial of 1115 patients with healed myocardial infarction was carried out between 1986 and 1994. The patients included 595 who received no calcium antagonist, 341 who received short-acting nifedipine 30 mg/d, and 179 who received short-acting diltiazem 90 mg/d. The primary end points were cardiac events, which were defined as fatal or nonfatal recurrent myocardial infarction; death from congestive heart failure; sudden death; and hospitalization because of worsening angina, congestive heart failure, or premature ventricular contractions. Cardiac events occurred in 51 patients (8.6%) in the no-calcium-antagonist group and 54 (10.4%) in the calcium-antagonist group (odds ratio, 1.24; 95% CI, 0.83 to 1.85), demonstrating that the calcium antagonists did not reduce the incidence of cardiac events. Subgroup analysis revealed no beneficial effects of these drugs for reducing cardiac events in patients with such complications as hypertension or angina pectoris. CONCLUSIONS: This study showed that use of short-acting nifedipine and diltiazem in this postmyocardial infarction population was associated with a 24% higher cardiac event rate, but this strong adverse trend did not reach statistical significance.

[Prevention of cardiac events by beta-blocking agents in elderly patients after myocardial infarction].

We retrospectively analyzed the effect of beta-blocking agents on the incidence of cardiac events in elderly patients who had had myocardial infarction. A total of 1169 patients who had had a myocardial infarction (age, 60.2 +/- 11.4 years) were followed for a mean of 18.0 +/- 19.7 months and the incidence of cardiac events (fatal or nonfatal myocardial infarction, sudden cardiac death, and death due to congestive heart failure) was computed. There were 21 cardiac events in 653 patients who received beta-blocking agents (3.2%) and 39 events in 516 patients who did not receive beta-blocking agents (7.6%, p < 0.01). Among patients less than 50 years old, the incidences of cardiac events were 4.1% in those who received beta-blocking agents and 7.6% in those who did not; among those 50 to 59 years old the incidences were 3.0% and 7.5%, respectively; among those 60 to 69 years old they were 4.3% and 6.0%, respectively; and among those 70 years old or older they were 0.8% and 11.4%, respectively (p < 0.01). We found that beta-blocking agents prevented cardiac events both in elderly and in younger patients after myocardial infarction.

Aspirin plus either dipyridamole or ticlopidine is effective in preventing recurrent myocardial infarction. Secondary Prevention Group.

The efficacy of combining antiplatelet agents with low doses of aspirin to prevent cardiac events in patients with myocardial infarction was examined. A total of 1,083 patients with prior myocardial infarction were randomly divided into those who were (618) and were not (465) treated with antiplatelet agents, and observed for 12.5 +/- 18.5 months. Those treated with antiplatelet agents included 113 patients treated with aspirin (50 mg) plus dipyridamole (150 mg/day), 253 treated with aspirin (50 mg) plus ticlopidine (200 mg/day), and 252 treated with only 1 of the 3 antiplatelet agents. Cardiac events, including fatal or nonfatal recurrent myocardial infarction, death by congestive heart failure, and sudden death, occurred in 34 patients (7.3%) in the nontreatment group and in 19 patients (3.1%; p < 0.01) in the treatment group; odds ratio 0.40, 95% confidence interval 0.23-0.71. There were only 2 cardiac events (1.8%) in the aspirin + dipyridamole group (p < 0.05 vs nontreatment group: odds ratio 0.28: 0.08-1.03), and 5 such events (2.0%) in the aspirin + ticlopidine group (p < 0.01; odds ratio 0.28: 0.11-0.69). Subgroup analysis to exclude differences in the patients' background confirmed the efficacy of these antiplatelet agents. We conclude that combined treatment with low doses of aspirin plus either dipyridamole or ticlopidine is effective in preventing cardiac events in patients who have had prior myocardial infarction.

Recombinant tissue plasminogen activator prevents intimal hyperplasia after balloon angioplasty in hypercholesterolemic rabbits.

The purpose of this study was to clarify whether continuous infusion of recombinant tissue plasminogen activator (rtPA) prevents intimal hyperplasia at the site of arterial injury. Forty-three Kurosawa and Kusanagi hypercholesterolemic (KHC) rabbits which underwent balloon angioplasty of the right common iliac artery were randomly divided into 2 groups; rtPA for 7 days (n = 29) and untreated (n = 14). The former group was subdivided into a high-dose group (n = 15) (2 mg/kg per day continuously for 7 days after 3 mg/kg for 4h) and a low-dose group (n = 14) (0.6 mg/kg per day for 7 days after 0.6 mg/kg for 4 h). Balloon angioplasty was performed with a 2.5-mm balloon (3 x 60-sec, 6-atm inflations at 60-sec intervals) 1 h after the initiation of rtPA infusion via an ear vein. The iliac arteries of the rabbits were histologically studied at 28 days. The cross-sectional areas of the intima, media, and adventitia were calculated at the site of intimal hyperplasia. The intimal cross-sectional area was 0.07 +/- 0.11 (mean +/- SD) mm2 for the high-dose rtPA group and 0.11 +/- 0.07 mm2 for the low-dose rtPA group, and both of these values were significantly less than that for the control group (0.57 +/- 0.21 mm2 p < 0.01). The ratio of the intimal to medial cross-sectional area was significantly (p < 0.01) lower for the rtPA groups than for the control group (high-dose rtPA; 0.10 +/- 0.13, low-dose rtPA; 0.21 +/- 0.19, control; 1.25 +/- 0.55). In conclusion, continuous infusion of rtPA for 7 days prevented intimal hyperplasia after balloon injury.

Long-term nitrate treatment increases cardiac events in patients with healed myocardial infarction. Secondary Prevention Group.

BACKGROUND: Nitrates dilate coronary arteries, ameliorate myocardial ischemia, minimize left ventricular remodeling, and reduce mortality in patients with acute myocardial infarction. However, the effects of long-term treatment with nitrates on cardiac events in patients with healed myocardial infarction are not known. METHODS AND RESULTS: A total of 1,002 patients with healed myocardial infarction (789 male and 213 female) were randomly divided into 2 groups: treatment with nitrates or nontreatment. The mean observation period was 18.0 +/- 19.9 months. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. Baseline characteristics of the 2 groups were also compared to determine any effects on outcome. Among the 621 cases treated with nitrates, 41 cases (6.6%) experienced cardiac events during the observation period, whereas only 12 of the 381 cases that were not treated with nitrates (3.1%) had cardiac events. This difference was statistically significant (p < 0.05; odds ratio 2.17; 95% confidence interval 1.13-4.19). There were no differences in the incidence of noncardiac death or being lost to follow-up between the 2 groups. Although the precise mechanism of this increase in the occurrence of cardiac events by long-term treatment with nitrates is not clear, nitrate tolerance with possible rebound and neurohormonal effects may be involved. CONCLUSION: Long-term treatment with nitrates increased cardiac events in patients with healed myocardial infarction.