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The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT).

OBJECTIVES: We attempted to compare the effect of an angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) on atherosclerotic events. BACKGROUND: Angiotensin-converting enzyme inhibitors and ARBs interrupt the renin-angiotensin system by distinct mechanisms. It is not clear whether ARBs reduce atherosclerotic events such as myocardial infarction (MI) like ACE inhibitors. This evidence gap may reflect the nature of the studies conducted, to date. Placebo-controlled studies enrolled cohorts at low risk of atherosclerotic events (e.g., patients with chronic heart failure, most treated with an ACE inhibitor). One of the main active controlled trials was confounded by a blood pressure difference between treatments. METHODS: We compared the effects of captopril, valsartan, and their combination on atherosclerotic events in 14,703 patients randomized in the Valsartan in Acute Myocardial Infarction Trial (VALIANT). RESULTS: The number of individuals adjudicated as having a fatal or non-fatal MI in the captopril group was 559 (total investigator reported events 798), 587 (796) in the valsartan group, and 554 (756) in the combination group; valsartan versus captopril, p = 0.651 (0.965); combination versus captopril, p = 0.187 (0.350). Overall, all atherosclerotic events examined occurred at a similar frequency in the captopril and valsartan groups. CONCLUSIONS: Angiotensin receptor blockers appear to be as effective as ACE inhibitors in reducing atherosclerotic events, even when used in addition to other secondary preventive treatments. These data, although not conclusive, also support the hypothesis that adding an ARB to an ACE inhibitor may have a small additional anti-infarction effect, a possibility that needs to be prospectively tested.

Aged↗

Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: final results from the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) trial.

OBJECTIVES: The purpose of this investigator-driven, prospective, randomized, double-blinded, placebo-controlled phase II study was to compare the effects of granulocyte colony-stimulating factor (G-CSF) on the improvement of myocardial function in patients undergoing delayed percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Experimental and early clinical studies suggest that transplantation of stem cells improves cardiac regeneration and neovascularization after acute myocardial infarction. Most investigators have utilized either a direct injection or intracoronary infusion of bone marrow-derived cells, but early cytokine-mediated mobilization of stem cells has been reported to show similar improvement in cardiac function. METHODS: Forty-four patients with late revascularized subacute STEMI were treated either with G-CSF or placebo over 5 days after successful PCI. Primary end points were change of global and regional myocardial function from baseline (1 week after PCI) to 3 months after PCI assessed by magnetic resonance imaging (MRI). Secondary end points consisted of characterization of mobilized stem cell populations, assessment of safety parameters up to 12 months including 6-month angiography, as well as myocardial perfusion assessed by MRI. RESULTS: Global myocardial function from baseline (1 week after PCI) to 3 months improved in both groups, but G-CSF was not superior to placebo (Delta(ejection fraction) 6.2 +/- 9.0 vs. 5.3 +/- 9.8%, p = 0.77). A slight but non-significant improvement of regional function occurred in both groups. Granulocyte colony-stimulating factor resulted in mobilization of endothelial progenitor cell populations and was well tolerated with a similar rate of target lesion revascularization from in-stent restenosis. In both groups major adverse cardiovascular events occurred in a comparable frequency. Granulocyte colony-stimulating factor resulted in significant improvement of myocardial perfusion 1 week and 1 month after PCI. CONCLUSIONS: Granulocyte colony-stimulating factor treatment after PCI in subacute STEMI is feasible and relatively safe. However, patients do not benefit from G-CSF when PCI is performed late. Granulocyte colony-stimulating factor results in improved myocardial perfusion of the infarcted area, which may reflect enhanced neovascularization.

Angioplasty, Balloon, Coronary↗

Effect of Terplex/VEGF-165 gene therapy on left ventricular function and structure following myocardial infarction. VEGF gene therapy for myocardial infarction.

BACKGROUND: We used a novel lipopolymeric gene delivery system, TeplexDNA, to transfect myocardium with plasmid vascular endothelial growth factor-165 (pVEGF) and evaluated the ability of pVEGF to preserve left ventricular function and structure after coronary ligation in a rabbit model. METHODS: New Zealand white rabbits underwent circumflex coronary ligation after direct intramyocardial injection of either Terplex alone or Terplex + 50 microg pVEGF-165. Serial echocardiography and histologic studies were performed (n = 12/group). Mortality did not differ between groups. The data is reported as the mean +/- standard deviation. RESULTS: Over the 21 days following coronary ligation, pVEGF-165-treated animals demonstrated significant improvement in fractional shortening (20-25%, p = 0.02), long axis two-dimensional ejection fraction (42-51%, p=0.02) and short axis m-mode ejection fraction (46-54%, p = 0.02). No significant improvements were noted in the control group. VEGF-treated animals had a 50% increase in peri-infarct vessel density and a trend towards a smaller infarct size (20% vs. 29%, p = 0.10). In animals receiving pVEGF-165, the diastolic ventricular area increased from 1.87 +/- 0.24 cm2 prior to ligation to 2.19 +/- 0.23 cm2 at 21 days following ligation, compared to an increase from 1.84 +/- 0.38 to 2.54 +/- 0.55 cm2 over the same period in control animals (p = 0.03). Similarly, the systolic ventricular area in VEGF-165 animals increased from 1.06 +/- 0.26 cm2 prior to ligation to 1.50 +/- 0.29 cm2 at 21 days following ligation, compared to an increase from 1.16 +/- 0.30 to 1.86 +/- 0.43 cm2 over the same period in the control animals (p = 0.04). CONCLUSION: TerplexDNA mediated delivery of plasmid VEGF administered at the time of coronary occlusion improves left ventricular function and reduces left ventricular dilation following myocardial infarction.

Animals↗

Early dobutamine echocardiography predicts improvement in regional and global left ventricular function after reperfused acute myocardial infarction without residual stenosis of the infarct-related artery.

BACKGROUND: The accuracy of dobutamine echocardiography (DE) early after reperfused acute myocardial infarction (AMI) without residual stenosis of the infarct-related artery is unknown. The objective of this study was to assess whether in reperfused AMI DE can predict early as well as late regional and global spontaneous functional recovery. METHODS: DE was performed in 157 patients (61 +/- 11 years; 33 women) 3 days after AMI treated with successful direct percutaneous transluminal coronary angioplasty (Thrombolysis in Myocardial Infarction flow grade 3, residual stenosis <30%). All patients underwent 2-dimensional echocardiography and coronary angiography at 1 month and 145 (92%) at 6 months. RESULTS: Patency and restenosis rate were similar between those who did and did not respond to DE. DE showed a high accuracy in predicting both early and late regional functional recovery (86% and 81%, respectively). DE accuracy in predicting early and late reversible dysfunction was also high on a patient-by-patient analysis (89% and 87%). In DE responders left ventricular ejection fraction increased from 44% +/- 9% at baseline to 57% +/- 9% at 6 months (P <.00005), whereas only a slight, although significant improvement was found in nonresponders (from 40% +/- 10% to 44% +/- 12%; P =.03). A significant correlation was found between the number of dobutamine-responder segments and the magnitude of their functional improvement at peak dobutamine and changes in ejection fraction (r =.72; P <.000001; r =.68, P <.000001, respectively). CONCLUSIONS: These data indicate that in patients with AMI in whom anterograde flow is fully restored without residual stenosis, DE can predict the recovery of regional function and whether a relevant change in ejection fraction will occur at early and late follow-up.

Angioplasty, Balloon, Coronary↗

Danish multicenter randomized study on fibrinolytic therapy versus acute coronary angioplasty in acute myocardial infarction: rationale and design of the DANish trial in Acute Myocardial Infarction-2 (DANAMI-2).

BACKGROUND: Randomized trials have indicated that primary coronary angioplasty performed in patients admitted directly to highly-experienced angioplasty centers offers certain advantages over intravenous fibrinolytic therapy. However, the large majority of patients with acute myocardial infarction are submitted to hospitals without a catheterization laboratory. This means that additional transportation will be necessary for many patients if a strategy of acute coronary angioplasty is to be introduced as routine treatment. The delay of treatment caused by transportation might negate (part of) the benefits of primary angioplasty compared to fibrinolytic therapy given immediately at the local hospital. STUDY DESIGN: The DANish trial in Acute Myocardial Infarction-2 (DANAMI-2) is the first large-scale study to clarify, in a whole community, which of the 2 treatment strategies is best. A total of 1900 patients with ST-elevation myocardial infarction are to be randomized: 800 patients will be admitted to invasive hospitals and 1100 patients will be admitted to referral hospitals. Half of the 1100 patients admitted to referral hospitals will immediately be transferred to an invasive center to be treated with primary angioplasty. IMPLICATIONS: If acute transfer from a local hospital to an angioplasty center is the superior strategy, primary angioplasty should be offered to all patients as routine treatment on a community basis.

Angioplasty, Balloon, Coronary↗

Relationship between antecedent angina pectoris and short-term prognosis after thrombolytic therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group.

The relationship between preinfarction clinical status and short-term outcome was prospectively evaluated in 775 patients hospitalized with acute myocardial infarction after reperfusion therapy. It was anticipated that a history of angina preceding myocardial infarction by more than 7 days would be associated with more extensive underlying coronary artery disease and a more complicated in-hospital course. However, although this group did have a higher risk profile for coronary artery disease (hypertension 53.6% vs 37.2%; diabetes 22.5% vs 12.1%; hyperlipidemia 19.4% vs 9.8%; mean number of risk factors 2.2 vs 1.7, p = 0.0001), a higher incidence of multivessel disease (57.7% vs 39.6%, p less than 0.0001), worse baseline global left ventricular function (left ventricular ejection fraction 48.8% vs 51.3%, p = 0.03), and impaired function of the noninfarct zone (-0.05 vs +0.46 SD/chord, p = 0.002), the in-hospital course was less complicated than in the group without prior angina. Patients without antecedent angina had a higher rate of reocclusion of the infarct-related artery (13.6% vs 8.2%; p = 0.048). Although the difference did not reach statistical significance (7.2% vs 4.6%; p = 0.21), the in-hospital mortality rate was also higher in this group. These findings suggest that a history of prior angina is not necessarily associated with an unfavorable short-term prognosis after reperfusion therapy. This may be related to the greater prior use by this group of beta-adrenergic- and calcium channel-blocking agents (23.1% vs 8.5% and 20.7% vs 3.8%, respectively). It may also be related to the beneficial effects of collateral vessels, myocardial preconditioning, or differences in the native fibrinolytic system.

Aged↗

Angiographic and clinical characteristics associated with increased in-hospital mortality in elderly patients with acute myocardial infarction undergoing percutaneous intervention (a pooled analysis of the primary angioplasty in myocardial infarction trials).

Advanced age is associated with increased mortality in acute myocardial infarction (AMI) but the mechanism remains unclear. We performed a pooled analysis of 3,032 patients from the Primary Angioplasty in Myocardial Infarction (PAMI)-2, Stent-PAMI, and PAMI-No Surgery On Site trials to determine which clinical, hemodynamic, and angiographic characteristics in the elderly were associated with in-hospital death. There were 452 patients aged >/=75 years and 2,580 patients aged <75 years. Older patients had a lower number of risk factors for coronary artery disease but more comorbidities. Acute catheterization demonstrated more 3-vessel disease, higher left ventricular (LV) end-diastolic pressure, lower LV ejection fraction, and higher initial rates of Thrombolysis In Myocardial Infarction (TIMI) trial 2 or 3 flow. Elderly patients were equally likely to undergo percutaneous intervention but had a lower procedural success rate and lower rates of final TIMI 3 flow, and older patients were more likely to have post-AMI complications. In-hospital mortality was 10.2% and 1.8%, respectively (p = 0.001). Cardiac and noncardiac mortality was higher in elderly patients, and no significant differences in causes of death were identified. Multivariate analysis revealed that the strongest predictors of death were age >/=75 years, lower LV ejection fraction, lower final TIMI flow, higher Killip class, need for an intra-aortic balloon pump (IABP), and post-AMI stroke/transient ischemic attack, or significant arrhythmia. Despite avoiding thrombolysis, elderly patients remain at increased risk of bleeding, stroke, and other post-AMI complications, and death. Cardiac risk factor analysis and acute catheterization offer prognostic information but do not completely explain the mechanism of increased in-hospital mortality in the elderly.

Aged↗

Persistent negative T waves in the infarct-related leads as an independent predictor of poor long-term prognosis after acute myocardial infarction.

This study sought to determine the long-term prognostic significance of persistent or transient negative T waves in infarct-related leads. After acute myocardial infarction (AMI), QRS and T wave alterations may resolve. No clinical study has investigated the prognostic importance of persistent versus transient negative T waves. We studied 147 consecutive patients with first AMI and >/=2 negative T waves in the infarct-related leads on the electrocardiogram. One hundred twenty patients developed Q waves. Patients were followed clinically for 60 +/- 21 months. T-wave normalization was observed early (before hospital discharge) in 34 patients and late (at 4 +/- 1 months) in 65. Thirty patients had Q-wave regression. Adverse outcome occurred in 57 patients. There were 23 hard events (cardiac death in 12 patients and nonfatal AMI in 11). Patients with early or late T-wave normalization had similar event-free survival curves that diverged rapidly from that of patients with persistent negative T waves, who had a worse outcome (p <0.0001). Patients with or without Q-wave regression had similar survival curves. Using multivariate Cox regression analysis, higher end-systolic volume (hazard ratio [HR] 1.01, p = 0.007), the presence of multivessel disease (HR 3.33, p = 0.009), and persistent negative T waves (HR 2.92, p = 0.024) predicted hard events. Persistent negative T waves 4 months after first AMI were independently associated with a worse outcome, whereas Q-wave regression has no long-term prognostic importance.

Adult↗

Reduction of infarct size by the early use of intravenous timolol in acute myocardial infarction. International Collaborative Study Group.

One hundred forty-four patients admitted to the hospital within 4 hours after the onset of symptoms of suspected acute myocardial infarction (AMI) were randomly assigned to either intravenous timolol treatment or to matching placebo. Infarct evolution was assessed by continuous vectorcardiography and CK release. Timolol reduced myocardial ischemia and infarct size as measured by an accelerated reduction in ST-vector magnitude, a significant reduction in maximal cumulative CK release (29.5%) and significantly smaller changes in QRS-vector parameters (20 to 25%). Furthermore, the predicted CK release and maximal QRS-vector change for a given initial ST-vector magnitude was significantly reduced by timolol. The drug regimen also caused a significant reduction in pain and the need for analgesic medication.

Administration, Oral↗

Usefulness of fibrinogenolytic and procoagulant markers during thrombolytic therapy in predicting clinical outcomes in acute myocardial infarction. TIMI-5 Investigators. Thrombolysis in Myocardial Infarction.

Thrombin activity is increased in the setting of acute myocardial infarction (AMI) and has been shown to increase further after the administration of thrombolytic therapy for acute infarction. This increase in thrombin activity may play an important role in the 15% to 25% rate of failure to achieve initial reperfusion and in the 5% to 15% rate of early reocclusion after initially successful thrombolysis. To investigate potential mechanisms of thrombin formation in vivo, to understand better the balance of coagulation and fibrinolysis during treatment with recombinant tissue-type plasminogen activator (rt-PA), and to investigate the role of hemostatic markers as predictors of clinical events, we measured 3 markers of procoagulant activity: fibrinopeptide A (FPA), thrombin-antithrombin III complexes (TAT), and prothrombin fragment 1.2 (F1.2), and a marker of fibrinogenolytic activity (B beta 1-42) in patients enrolled in the Thrombolysis in Myocardial Infarction (TIMI)-5 study. This trial was a randomized, dose-ranging, pilot trial of hirudin versus heparin as adjunctive antithrombotic therapy with rt-PA administered to patients with AMI. Correlation of markers at 1 hour with clinical outcomes revealed that increased FPA and TAT levels were associated with increased mortality and TIMI grades 0, 1, or 2 flow at 90 minutes; increased F1.2 levels were associated with TIMI grade 0 or 1 flow at 90 minutes; and increased levels of all 3 procoagulant markers were associated with hemorrhagic events. Late (12 to 24 hours) increases in F1.2, TAT, and B beta 1-42 may be predictive of recurrent ischemia. These results suggest that selected markers of procoagulant and fibrinogenolytic activity may be useful in predicting clinical outcomes in patients treated with thrombolytic therapy for AMI.

Antithrombin III↗

Usefulness of ST-segment depression in non-infarct-related electrocardiographic leads in predicting prognosis after thrombolytic therapy for acute myocardial infarction.

This study investigated both the in-hospital and long-term prognostic significance of ST-segment depression in non-infarct-related leads in patients who received thrombolytic therapy after acute myocardial infarction (AMI). We evaluated 221 consecutive patients who were admitted with their first AMI and underwent thrombolysis. Patients were followed for an average of 31 months and were classified into 3 groups: group 1 included 51 patients with persistent ST-segment depression, group 2 had 97 patients with transient ST-segment depression, and group 3 consisted of 73 patients without ST-segment depression (absent). Group 1 had significantly worse long-term survival during follow up by Kaplan-Meier analysis (55%) versus group 2 (81%) and group 3 (94%) (p = 0.0004) and higher event rates. This prognostic significance seemed to be maintained in both the anterior and inferior wall AMI groups. Multivariate analysis, using the Cox model, showed that Killip class, in-hospital left ventricular ejection fraction, and the persistence of ST-segment depression on the predischarge electrocardiogram (group 1) were independent predictors of survival. ST-segment depression in non-infarct-related leads on the predischarge electrocardiogram is an independent risk factor for worse long-term survival after anterior as well as inferior AMI treated with thrombolytic therapy.

Disease-Free Survival↗

Prospective validation of a composite end point in thrombolytic trials of acute myocardial infarction (TIMI 4 and 5). Thrombosis In Myocardial Infarction.

Although the use of composite end points in clinical trials has increased in recent years, few data are available on the validity of such an approach. In the Thrombolysis In Myocardial Infarction (TIMI) 4 and 5 trials, we set out to validate prospectively the nonfatal components of the "unsatisfactory outcome" end point. This end point consisted of the in-hospital occurrence or observation of new-onset severe congestive heart failure/shock, left ventricular ejection fraction <40% (or <30% for patients with prior myocardial infarction), reinfarction, reocclusion by sestamibi perfusion imaging, TIMI flow grade <2 at 90 minutes or 18 to 36 hours, intracranial hemorrhage, major spontaneous hemorrhage, or anaphylaxis. Among 576 patients in TIMI 4 and 5 with 1-year follow-up, a nonfatal unsatisfactory outcome end point was reached in hospital in 45% of patients. Compared with patients without such an end point, patients with an end point had a relative risk of 1-year mortality of 2.5 (95% confidence interval 1.4 to 5.6, p = 0.001). For individual components, new-onset severe congestive heart failure/shock had a relative risk of 4.6 (p = 0.001), left ventricular ejection fraction <40% had a relative risk of 3.5 (p = 0.006), recurrent myocardial infarction had a relative risk of 2.2 (p = 0.047), and TIMI flow grade <2 at 90 minutes had a relative risk of 2.2 (p = 0.005). Our findings show that these nonfatal in-hospital end points and the composite end point are associated with an increased risk of 1-year mortality and as such are valid predictive survival markers for use in clinical trials.

Aged↗

Effect of early captopril treatment on blood adrenaline levels in acute myocardial infarction (the substudy of ISIS-4). International Study of Infarct Survival-4.

Of patients with acute myocardial infarction eligible for the International Study of Infarct Survival-4, randomized to captopril (n = 30) or placebo (n = 33), the captopril group had a significant decrease in blood adrenaline on day 3 compared with baseline values. Results suggest that suppression of sympathetic activity contributes to the beneficial effects of treatment with angiotensin-converting enzyme inhibitors in the early phase of acute myocardial infarction.

Aldosterone↗

Direct angioplasty and stenting of the infarct-related artery in acute myocardial infarction.

This study provides the incidence of in-hospital and 1-month recurrent ischemia in 118 patients with acute myocardial infarction when an aggressive direct angioplasty strategy was performed, including stenting of the infarct artery. Coronary stenting in acute myocardial infarction is feasible, and acute and 1-month angiographic results after stenting seem superior to those after standard angioplasty alone.

Aged↗

Usefulness of antioxidant vitamins in suspected acute myocardial infarction (the Indian experiment of infarct survival-3)

In a randomized, double-blind, placebo-controlled trial, the effects of combined treatment with the antioxidant vitamins A (50,000 IU/day), vitamin C (1,000 mg/day), vitamin E (400 mg/day), and beta-carotene (25 mg/day) were compared for 28 days in 63 (intervention group) and 62 (placebo group) patients with suspected acute myocardial infarction. After treatment with antioxidants, the mean infarct size (creatine kinase and creatine kinase-MB gram equivalents) was significantly less in the antioxidant group than in the placebo group. Serum glutamic-oxaloacetic transaminase decreased by 45.6 IU/dl in the antioxidant group versus 25.8 IU/dl in the placebo group (p < 0.02). Cardiac enzyme lactate dehydrogenase increased slightly (88.6 IU/dl) in the antioxidant group compared with that in the placebo group (166.5 IU/dl) (p < 0.01). QRS score in the electrocardiogram was significantly less in the antioxidant than in the placebo group. The following levels increased in the antioxidant group versus the placebo group, respectively: plasma levels of vitamin E increased by 8.8 and 2.2 mumol/L (p < 0.01), vitamin C increased by 12.6 and 4.2 mumol/L (p < 0.01), beta-carotene increased by 0.28 and 0.06 mumol/L (p < 0.01), and vitamin A increased by 0.36 and 0.12 mumol/L (p < 0.01). Serum lipid peroxides decreased by 1.22 pmol/ml in antioxidant versus 0.22 pmol/ml in the placebo group (p < 0.01). Angina pectoris, total arrhythmias, and poor left ventricular function occurred less often in the antioxidant group. Cardiac end points were significantly less in the antioxidant group (20.6% vs 30.6%, respectively). These results suggest that combined treatment with antioxidant vitamins A, E, C, and beta-carotene in patients with recent acute myocardial infarction may be protective against cardiac necrosis and oxidative stress, and could be beneficial in preventing complications and cardiac event rate in such patients.

Adult↗

Invasive versus conservative strategies in unstable angina and non-Q-wave myocardial infarction following treatment with tirofiban: rationale and study design of the international TACTICS-TIMI 18 Trial. Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy. Thrombolysis In Myocardial Infarction.

In the management of unstable angina and non-Q-wave acute myocardial infarction (AMI), there is considerable debate regarding the use of invasive strategy versus conservative strategy. The Thrombolysis In Myocardial Infarction (TIMI) III B trial found similar clinical outcomes for the 2 strategies, but the Veterans Administration Non-Q-Wave Infarction Strategies in-Hospital trial found a higher mortality with the invasive strategy. Both these trials were conducted before platelet glycoprotein IIb/IIIa inhibition and coronary stenting, both of which improve clinical outcome. Thus, there is a need to reexamine the question of which management strategy is optimal in the current era of platelet glycoprotein IIb/IIIa inhibition and new coronary interventions. The Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS-TIMI 18) trial is an international, multicenter, randomized trial that is evaluating the clinical efficacy of early invasive and early conservative treatment strategies in patients with unstable angina or non-Q-wave AMI treated with tirofiban, heparin, and aspirin. Patients are randomized to an invasive strategy, involving cardiac catheterization within 4 to 48 hours and revascularization with angioplasty or bypass surgery if feasible, versus a conservative strategy, where patients are referred for catheterization only for recurrent pain at rest or provokable ischemia. The primary end point is death, MI, or rehospitalization for acute coronary syndromes through a 6-month follow-up. The trial is also testing the "troponin hypothesis," that baseline troponins T and I will be useful in selecting an optimal management strategy.

Adolescent↗

Effects of aspirin and trapidil on cardiovascular events after acute myocardial infarction. Japanese Antiplatelets Myocardial Infarction Study (JAMIS) Investigators.

Aspirin therapy confers conclusive net benefits in the acute phase of evolving myocardial infarction, but no clear evidence of benefit from the long-term use of aspirin after acute myocardial infarction (AMI) has been shown in any single study. This multicenter study, the Japanese Antiplatelets Myocardial Infarction Study, was performed to find out whether aspirin or trapidil would improve clinical outcome compared with no antiplatelets in postinfarction patients. The study was a multicenter, open-label, randomized controlled trial of aspirin 81 mg/day, trapidil 300 mg/day, and no antiplatelets in patients with AMI admitted within 1 month from the onset of symptoms. Seven hundred twenty-three patients were enrolled at 70 hospitals in 18 prefectures of Japan; 250 were randomly assigned to treatment with 81 mg aspirin (aspirin group), 243 to that with trapidil (trapidil group), and 230 were not given antiplatelet agents. The mean follow-up period was 475 days. This study demonstrated that long-term use of aspirin at the dose of 81 mg/day reduced the incidence of recurrent AMI compared with the group receiving no antiplatelets after AMI (p = 0.0045) and that trapidil also reduced the occurrence of reinfarction compared with the group receiving no antiplatelets, but the difference was not significant (p = 0.0810). The incidence of cardiovascular events including cardiovascular death, reinfarction, uncontrolled unstable angina requiring admission to hospital, and nonfatal ischemic stroke was reduced in the group receiving 300 mg trapidil daily compared with the group receiving no antiplatelets (p = 0.0039). The use of aspirin 81 mg/day provided almost no benefit over no antiplatelets therapy in the incidence of cardiovascular events. In conclusion, low-dose aspirin (81 mg) effectively prevented recurrent AMI in postinfarction patients after thrombolysis or coronary angioplasty when used over a long term. Furthermore, the long-term use of trapidil resulted in a significant reduction in the incidence of cardiovascular events.

Aged↗

Primary percutaneous transluminal coronary angioplasty for acute myocardial infarction in patients not included in randomized studies. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

Patients with acute myocardial infarction included in randomized trials comparing primary percutaneous transluminal coronary angioplasty (pPTCA) with thrombolysis represent a special subgroup of patients with a low event rate. Patients excluded from these trials represent a variety of different subgroups, with different patient characteristics and possibly different clinical event rates. Primary PTCA was performed in 491 consecutive patients with acute myocardial infarction in the prospective multicenter observational Maximal Individual Therapy in Acute Myocardial Infarction trial. They were divided into the following groups: group I, patients fulfilling the inclusion criteria of the randomized trials (284 of 491, 58%); group II, patients not included in these trials (207 of 491, 42%). Of group II the following subgroups were defined: group IIa, patients in cardiogenic shock (20 of 491, 4.1%); group IIb, patients with a left bundle branch block (12 of 491, 2,4%); group IIc, patients with contraindications for thrombolysis (42 of 491, 8.6%); group IId, patients with a nondiagnostic first electrocardiogram (95 of 491, 19.3%); group IIe, patients with a prehospital delay of > 12 hours (72 of 491, 14.7%); group IIf, patients with an unknown prehospital delay (30 of 491, 6.1%). A comparison of groups I and II showed similar baseline characteristics but a higher clinical event rate during hospitalization was seen in group II: combined end point of death, reinfarction, heart failure equal to or greater than NYHA class III, any stroke or postinfarction angina, 26.6% versus 18%; p = 0.022. Hospital deaths were nearly twice as high in these patients, without reaching statistical significance (10.6% vs 6%; p = 0.06). The subgroups of group II showed quite different rates of clinical events. In-hospital death rates were: IIa, 40% (8 of 20); IIb, 8% (1 of 12); IIc, 12% (5 of 42); IId, 5% (5 of 95); IIe, 6% (4 of 72); and IIf, 13% (4 of 30). The incidence of the combined end point was 60% (12 of 20) in IIa, 33% (4 of 12) in IIb, 29% (12 of 42) in IIc, 16% (15 of 95) in IId, 26% (19 of 72) in IIe, and 33% (10 of 30) in IIf. Thus, in clinical practice, about half of the patients treated with pPTCA would not have been included in randomized trials comparing pPTCA with thrombolysis. These patients represent a population at higher risk for in hospital clinical events. However, they do represent very different nonhomogenous subgroups with different clinical event rates.

Aged↗