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M L Simoons

Publications and source records attributed to M L Simoons.

At least 55 records · Page 3Linked to original sources
PubMed1998

Risk factors for in-hospital nonhemorrhagic stroke in patients with acute myocardial infarction treated with thrombolysis: results from GUSTO-I.

BACKGROUND: Nonhemorrhagic stroke occurs in 0.1% to 1.3% of patients with acute myocardial infarction who are treated with thrombolysis, with substantial associated mortality and morbidity. Little is known about the risk factors for its occurrence. METHODS AND RESULTS: We studied the 247 patients with nonhemorrhagic stroke who were randomly assigned to one of four thrombolytic regimens within 6 hours of symptom onset in the GUSTO-I trial. We assessed the univariable and multivariable baseline risk factors for nonhemorrhagic stroke and created a scoring nomogram from the baseline multivariable modeling. We used time-dependent Cox modeling to determine multivariable in-hospital predictors of nonhemorrhagic stroke. Baseline and in-hospital predictors were then combined to determine the overall predictors of nonhemorrhagic stroke. Of the 247 patients, 42 (17%) died and another 98 (40%) were disabled by 30-day follow-up. Older age was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by higher heart rate, history of stroke or transient ischemic attack, diabetes, previous angina, and history of hypertension. These factors remained statistically significant predictors in the combined model, along with worse Killip class, coronary angiography, bypass surgery, and atrial fibrillation/flutter. CONCLUSIONS: Nonhemorrhagic stroke is a serious event in patients with acute myocardial infarction who are treated with thrombolytic, antithrombin, and antiplatelet therapy. We developed a simple nomogram that can predict the risk of nonhemorrhagic stroke on the basis of baseline clinical characteristics. Prophylactic anticoagulation may be an important treatment strategy for patients with high probability for nonhemorrhagic stroke, but further study is needed.

Age Factors↗
PubMed1998

Non-Q-wave versus Q-wave myocardial infarction after thrombolytic therapy: angiographic and prognostic insights from the global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries-I angiographic substudy. GUSTO-I Angiographic Investigators.

BACKGROUND: Although the stratification of patients with myocardial infarction into ECG subsets based on the presence or absence of new Q waves has important clinical and prognostic utility, systematic evaluation of the impact of thrombolytic therapy on the subsequent development and prognosis of non-Q-wave infarction has been limited to date. METHODS AND RESULTS: We examined 12-lead ECG, coronary anatomy, left ventricular function, and mortality among 2046 patients with ST-segment elevation infarction from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries angiographic subset to gain further insight into the pathophysiology and prognosis of Q- versus non-Q-wave infarction in the thrombolytic era. Non-Q-wave infarction developed in 409 patients (20%) after thrombolytic therapy. Compared with Q-wave patients, non-Q-wave patients were more likely to present with lesser ST-segment elevation in a nonanterior location. The infarct-related artery in non-Q-wave patients was more likely to be nonanterior (67% versus 58%, P=.012) and distally located (33% versus 39%, P=.021). Early (90-minute, 77% versus 65%, P=.001) and complete (54% versus 44%, P<.001) infarct-related artery patency was greater among the non-Q-wave group. Non-Q-wave patients had better global (ejection fraction, 66% versus 57%; P<.0001) and regional left ventricular function (10 versus 24 abnormal chords, P=.0001). In-hospital, 30-day, 1-year, and 2-year (6.3% versus 10.1%, P=.02) mortality rates were lower among non-Q-wave patients. CONCLUSIONS: The excellent prognosis among the subgroup of patients who develop non-Q-wave infarction after thrombolysis is related to early, complete, and sustained infarct-related artery patency with resultant limitation of left ventricular infarction and dysfunction.

Aged↗
PubMed1998

Rationale and clinical evidence for the use of GP IIb/IIIa inhibitors in acute coronary syndromes.

Platelet glycoprotein (GP) IIb/IIIa blockade has the potential to advance treatment of acute coronary syndromes, both as a primary pharmacologic approach and an adjunct to interventional treatment strategies. The benefits of GP IIb/IIIa inhibition with the chimeric monoclonal antibody abciximab in preventing ischemic complications of interventional treatment have been well defined in patients with unstable angina. In the future, major therapeutic applications for this class of agents may include the stabilization of patients with unstable angina and potentially as single medical therapy, as several recently completed trials have suggested. Evidence also is accumulating on the use of GP IIb/IIIa blockade as adjunctive therapy in fibrinolytic approaches to treatment of acute myocardial infarction. Several ongoing trials are evaluating the safety and efficacy of this novel strategy. This article reflects a distillation of the views and consensus regarding the prospective use of GP IIb/IIIa inhibitors in patients with acute coronary syndromes expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997. This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation.

Acute Disease↗
PubMed1998

Costs and effects in therapy for acute coronary syndromes: the case of abciximab in high-risk patients undergoing percutaneous transluminal coronary angioplasty in the EPIC study. Evaluation of 7E3 for the Prevention of Ischemic Complications.

Cost-effectiveness analyses are routinely performed to determine whether the additional cost of a novel therapy is balanced by additional effectiveness. The definitions of costs and effects involve a variety of assumptions, both in general economic terms and with regard to the specific medical setting under consideration. Similarly, differing criteria for acceptability of cost-effectiveness estimates can be used to generate different conclusions regarding cost-effectiveness. The issues and problems inherent in economic evaluation are discussed by an analysis of findings with the platelet glycoprotein IIb/IIIa inhibitor abciximab in the EPIC (Evaluation of 7E3 for the Prevention of Ischemic Complications) study in high-risk patients undergoing percutaneous transluminal coronary angioplasty.

Abciximab↗
PubMed1998

Unstable angina: good long-term outcome after a complicated early course.

OBJECTIVES: This study was performed to investigate the long-term outcome of patients with unstable angina within subgroups of the Braunwald classification. BACKGROUND: Long-term follow-up studies of patients with unstable angina are rare and date from more than two decades ago. This study was performed to establish the prognosis of different subgroups of patients with unstable angina (Braunwald criteria) during a 7-year follow-up period. METHODS: We registered a well defined group of 417 consecutive patients, admitted to the hospital for suspected unstable angina. The definite diagnosis was unstable angina in 282 patients (68%) and evolving myocardial infarction in 26; in 109 patients (26%), the symptoms were attributed to other or nonspecific causes. Patients with definite unstable angina were subclassified according to the Braunwald classification. Survival, survival without infarction and survival without infarction or intervention were determined for each class. RESULTS: After a median follow-up period of 94 months, the mortality rate in the first year was 6% and 2% to 3% in the following years. The frequency of revascularization was 47% in the first year, and that for myocardial infarction was 11% in the first year and 1% to 3% thereafter. The Braunwald classification appeared to be appropriate for risk stratification in the first year. However, at 7 years the event rates in all classes were similar. In particular, the Braunwald classification had no long-term impact on mortality or infarction rates. However, patients with acute angina at rest or postinfarction angina and patients with extensive anginal treatment had high intervention rates. CONCLUSIONS: To our knowledge, this study is the first to demonstrate that despite a complicated course during the first year, current management results in good long-term outcome in patients with unstable angina.

Adult↗
PubMed1998

The Cardiac Infarction Injury Score as a predictor for long-term mortality in survivors of a myocardial infarction.

AIMS: The Cardiac Infarction Injury Score (CIIS) is an electrocardiographic classification system that was developed as a diagnostic tool to assess the extent of cardiac injury in acute myocardial infarction. We investigated the prognostic value of the CIIS in post-myocardial infarction patients. METHODS AND RESULTS: The prognostic values of the CIIS for total and cardiac mortality was assessed in a large series (n = 3395) of patients who were enrolled in the ASPECT trial. Standard 12-lead electrocardiograms, recorded prior to hospital discharge were coded according to the CIIS and the Minnesota Code. Mean CIIS was 26 (range--8 to 59). After adjustment for other baseline characteristics, the CIIS was directly related to the risk of total mortality and cardiac mortality. At one-year follow-up the relative risks of CIIS > or = 40, CIIS 30-40 and CIIS 20-30 were significantly higher than in those with a CIIS < 20. The relative risks were, respectively, 2.3 (1.2-4.4), 2.2 (1.3-3.9) and 1.6 (0.9-2.9). At 3 year follow-up, the relative risks were, respectively, 2.1 (1.4-3.2), 1.7 (1.2-2.4) and 1.5 (1.0-2.1). The relative risks for total mortality were similar. When patients with major ECG abnormalities, as defined by the Minnesota code, were excluded, the associations were still significant in the CIIS classes 30-40 and > 40. CONCLUSION: The CIIS ECG scoring system is an important predictor for long-term cardiac mortality in post myocardial infarction patients. It can easily be automated and is efficient for classifying cardiac injury in epidemiological studies.

Adult↗
PubMed1998

Heart rate variability index in congestive heart failure: relation to clinical variables and prognosis.

AIM: To evaluate the clinical and prognostic value of the heart rate variability index in patients with congestive heart failure. METHODS: Sixty-four patients with chronic congestive heart failure and sinus rhythm underwent clinical assessment, 24-h ambulatory electrocardiography and echocardiography. Patients were followed for 6 to 30 months. Cardiac death or heart transplantation constituted the primary end-point of the study. RESULTS: The heart rate variability index was related to left ventricular ejection fraction (r=0.29, P=0.02) and New York Heart Association class (P=0.01). Patients with a restrictive left ventricular filling pattern had a lower heart rate variability index compared to patients with a non-restrictive pattern (26+/-11 vs 33+/-9 units, P=0.01). Patients who died (n=11) or underwent heart transplantation (n=4) had a lower heart rate variability index compared to survivors (21+/-10 vs 33+/-9 units, P<0.0001). In multivariate survival analysis, a reduced heart rate variability index was related to survival independent of parameters of left ventricular function. CONCLUSION: The heart rate variability index provides independent information on clinical status and prognosis in patients with chronic congestive heart failure.

Aged↗
PubMed1998

Reperfusion therapy for acute myocardial infarction. Which strategy for which patient?

Several modes of reperfusion therapy for evolving myocardial infarction (MI) have been developed, which differ in terms of effectiveness, complexity and costs. Reperfusion resources are often restricted by budgetary or logistical circumstances. To arrive at an equitable distribution of treatment options, physicians should therefore consider which treatment to apply in which patient. Two major questions which arise in this respect are discussed here: what is the treatment effect in an individual patients, and what is an equitable resource allocation? Currently, the most relevant treatment options are: streptokinase (1.5MU over 1h), reteplase (2 boluses of 10MU), alteplase (tissue plasminogen activator; t-PA) [100mg over 1.5 hours] and immediate angioplasty. In combination with aspirin, streptokinase leads to an almost 40% mortality reduction at 1 month compared with placebo [from 13.2 to 8.0%; Second International Study of Infarct Survival (ISIS-2) trial]. The Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-1) study demonstrated a further mortality reduction by early combination therapy of aspirin, intravenous heparin and alteplase vs aspirin, heparin (either intravenous or subcutaneous) plus streptokinase (from 7.3 to 6.3%). The clinical effects of reteplase fall somewhere between those of streptokinase and alteplase. Combined analysis of the angioplasty trials suggests that angioplasty is superior to thrombolysis, especially in patients with a high cerebral bleeding risk. The noticed gradient of efficacy runs parallel to a gradient of costs and complexity: streptokinase is the least costly treatment option while direct angioplasty is the most expensive and complex. Subgroup analyses indicate that there are neither apparent deviations in the relative effect of reperfusion therapy as compared to control treatment, nor in the additional effect of more intensive therapy (alteplase) upon 'standard' therapy (streptokinase). Consequently, the absolute number of deaths avoided by reperfusion therapy appears to be greatest in those groups with a high mortality risk without therapy. There is one major exception: in patients treated early after symptom onset a much greater relative mortality reduction is observed than in those treated later. Owing to the higher mortality risk, the life expectancy of a patient with MI is shorter than that of an 'average' person of the same community and the same age. Since mortality reduction of reperfusion therapy is maintained at long term follow-up, part of this potential loss can be regained. This 're-gain of lost years' is judged to be the ultimate treatment effect in an individual patient. An equitable treatment allocation should be such that patients who will benefit most will receive the most effective therapy, while patients with similar expected benefit will be offered the same mode of therapy. The conclusion is that treatment guidelines or protocols can be very useful in clinical practice, especially if rapid decision making is of vital importance.

Angioplasty↗
PubMed1998

Rationale and clinical evidence for the use of GP IIb/IIIa inhibitors in acute coronary syndromes.

Platelet glycoprotein (GP) IIb/IIIa blockade has the potential to advance treatment of acute coronary syndromes, both as a primary pharmacologic approach and an adjunct to interventional treatment strategies. The benefits of GP IIb/IIIa inhibition with the chimeric monoclonal antibody abciximab in preventing ischemic complications of interventional treatment have been well defined in patients with unstable angina. In the future, major therapeutic applications for this class of agents may include the stabilization of patients with unstable angina and potentially as single medical therapy, as several recently completed trials have suggested. Evidence also is accumulating on the use of GP IIb/IIIa blockade as adjunctive therapy in fibrinolytic approaches to treatment of acute myocardial infarction. Several ongoing trials are evaluating the safety and efficacy of this novel strategy. This article reflects a distillation of the views and consensus regarding the prospective use of GP IIb/IIIa inhibitors in patients with acute coronary syndromes expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997. This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation.

Abciximab↗
PubMed1998

Costs and effects in therapy for acute coronary syndromes: the case of abciximab in high-risk patients undergoing percutaneous transluminal coronary angioplasty in the EPIC study. Evaluation of 7E3 for the Prevention of Ischemic Complications.

Cost-effectiveness analyses are routinely performed to determine whether the additional cost of a novel therapy is balanced by additional effectiveness. The definitions of costs and effects involve a variety of assumptions, both in general economic terms and with regard to the specific medical setting under consideration. Similarly, differing criteria for acceptability of cost-effectiveness estimates can be used to generate different conclusions regarding cost-effectiveness. The issues and problems inherent in economic evaluation are discussed by an analysis of findings with the platelet glycoprotein IIb/IIIa inhibitor abciximab in the EPIC (Evaluation of 7E3 for the Prevention of Ischemic Complications) study in high-risk patients undergoing percutaneous transluminal coronary angioplasty.

Abciximab↗
PubMed1998

The European trial on reduction of cardiac events with perindopril in stable coronary artery disease (EUROPA).

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have an accepted place in the treatment of hypertension and heart failure. However, at present they have no specific role in the prevention or treatment of coronary artery disease: evidence from animal experiments and some of the large ACE inhibitor cardiac studies makes this effect well worth testing. OBJECTIVE: The objective of EUROPA is to assess the effects of perindopril (an ACE inhibitor) on outcome in patients with stable coronary artery disease, but no clinical heart failure. METHODS: This is a double-blind, placebo-controlled, multicentre study with a duration of 3.5 years. It is proposed to recruit 10500 patients from 24 countries in Europe. The primary end-point is a combined one: total mortality, non-fatal acute myocardial infarction, unstable angina pectoris and cardiac arrest with successful resuscitation are included; the outcome is studied in patients with proven coronary artery disease and no clinical heart failure. Secondary end-points consist of these events individually calculated. The first patient was recruited in October 1997, and it is planned to finish recruitment by the end of 1998.

Adolescent↗
PubMed1998

EUROPA substudies, confirmation of pathophysiological concepts. European trial on reduction of cardiac events with perindopril in stable coronary artery disease.

In patients with coronary disease, ACE inhibitors may improve endothelial function in the coronary arteries as well as peripheral arteries, and may have anti-proliferative effects which might result in retardation of progression of coronary artery disease. In order to verify these pathophysiological concepts, a series of substudies will be conducted as part of the EUROPA programme. Angiographic and intravascular ultrasound examination of coronary arteries will be performed in approximately 400 patients before and after 3 years' treatment with either perindopril or placebo, in order to assess progression and possible regression of coronary lesions. B-mode ultrasonography of the brachial artery will be used as a model for changes in the coronary arteries, to assess endothelial function in response to ischaemia (reactive hyperaemia) and to vasoconstriction (cold pressor test). Three hundred patients will be investigated before and at different intervals after initiation of study treatment. In addition genetic characterization will be performed of patients participating in EUROPA in order to assess whether specific genotypes do respond more or less favourably to perindopril. In addition, the effect of perindopril will be investigated in patients with diabetes type II, since ACE inhibition in such patients may improve microvascular function and renal function. Integration of these substudies, as well as detailed analysis of other specific subgroups in EUROPA, will help us understand the effects of treatment with perindopril in patients with stable coronary artery disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Comparison of peak serum C-reactive protein and hydroxybutyrate dehydrogenase levels in patients with acute myocardial infarction treated with alteplase and streptokinase.

Peak serum C-reactive protein concentrations were measured in 146 patients randomized to receive streptokinase, alteplase, or a combination of streptokinase and alteplase in the GUSTO-I trial. Those receiving alteplase treatment had lower values than those receiving streptokinase or the combination treatment. Irrespective of treatment, complete reperfusion of the infarct-related artery (TIMI grade 3 flow) was associated with low peak serum C-reactive protein values.

Aged↗
PubMed1997

Difference in countries' use of resources and clinical outcome for patients with cardiogenic shock after myocardial infarction: results from the GUSTO trial.

BACKGROUND: Use of aggressive and invasive interventions is more common in the USA than in other countries. We have compared use of resources for patients with cardiogenic shock after myocardial infarction in the USA and in other countries, and assessed the association between use of resources and clinical outcomes. METHODS: We analysed data for patients with cardiogenic shock after myocardial infarction who were enrolled in the GUSTO-I trial (1891 treated in the USA, 1081 treated in other countries). Patients were randomly assigned combinations of streptokinase, heparin, and accelerated tissue-plasminogen activator (t-PA), then decisions about further interventions were left to the discretion of the attending physician. The interventions included in our analysis were: pulmonary-artery catheterisation, cardiac catheterisation, intravenous inotropic agents, ventilatory support, intra-aortic balloon counterpulsation (IABP), percutaneous transluminal coronary angioplasty (PTCA), and coronary bypass graft surgery (CABG). The primary outcome measure was death from any cause at 30 days of follow-up. FINDINGS: Patients who were treated in the USA were significantly younger than those treated elsewhere (median 68 [IQR 59-75] vs 70 [62-76], p < 0.001), a smaller proportion had anterior infarction (49 vs 53%, p < 0.001), and they had a shorter time to treatment (mean 3.1 vs 3.3 h, p < 0.001). Aggressive diagnostic and therapeutic procedures were used more commonly in the USA than in the other countries: cardiac catheterisation (58 vs 23%); IABP (35 vs 7%); right-heart catheterisation (57 vs 22%); and ventilatory support (54 vs 38%). 483 (26%) of the patients treated in the USA underwent PTCA, compared with 82 (8%) patients in other countries. Patients who underwent revascularisation had better survival in all countries. Adjusted 30-day mortality was significantly lower among patients treated in the USA than among those treated elsewhere (50 vs 66%, p < 0.001). The difference in mortality remained at 1 year-56% of patients treated in the USA died versus 70% of patients treated elsewhere (hazard ratio 0.69 [95% CI 0.63-0.75], p < 0.001). INTERPRETATION: 30-day and 1-year mortality was significantly lower among patients treated in the USA than among those treated in other countries. This difference in mortality may be due to the greater use of invasive diagnostic and therapeutic interventions in the USA.

Aged↗
PubMed1997

Selection of thrombolytic therapy for individual patients: development of a clinical model. GUSTO-I Investigators.

We developed a logistic regression model with data from the GUSTO-I trial to predict mortality rate differences in individual patients who received accelerated tissue plasminogen activator (TPA) versus streptokinase treatment for acute myocardial infarction. A nomogram was developed from a reduced version of this model that approximated the underlying risk of patients treated with streptokinase, and thus the benefit of TPA. The 30-day mortality rate with accelerated TPA was 0.063 versus 0.073 with streptokinase and subcutaneously administered heparin and 0.074 with streptokinase and intravenously administered heparin. No baseline patient characteristics were significantly associated with a different relative effect of TPA. Older patients and those with anterior infarction, higher Killip classification (except Killip class IV), lower blood pressure, and increased heart rate had the greatest absolute benefit with accelerated TPA. Patients with acute myocardial infarction who had more high-risk characteristics derived a greater absolute benefit from treatment with accelerated TPA versus streptokinase.

Age Factors↗
PubMed1997

Thrombolysis-induced coronary reperfusion causes acute and massive interstitial release of cardiac muscle cell proteins.

OBJECTIVE: Reperfusion of the infarct-related artery in patients with acute myocardial infarction limits infarct size, but also causes accelerated release into plasma of cardiac tissue proteins. The latter effect could reflect either enhanced protein washout from the heart or abrupt disruption of myocyte membranes. The present study indicates that the latter mechanism prevails. METHODS: In 26 patients, patency of the infarct-related artery was determined by coronary angiography 90 min and 5-7 days after thrombolytic treatment. Continuous electrocardiography was performed during the first 24 h after admission. Cumulative release of myoglobin (Mb) and creatine kinase (CK) into plasma was calculated from frequently sampled plasma concentrations. RESULTS: In patients with a patent infarct-related artery after 90 min, onset of a rapid (> 50%) decrease in ST-vector magnitude coincided with an equally rapid increase in QRS-vector magnitude, and with a sudden onset of release into plasma of Mb as well as CK. In these patients, a maximal initial release rate was observed and cumulative release conformed closely to a simple model for sudden interstitial liberation of proteins. In contrast, protein release started more gradually and could not be fitted to this model, in patients with persistent occlusion of the infarct-related artery at 90 min and absence of ST-vector normalisation. CONCLUSIONS: Previous studies have demonstrated significant myocardial salvage by timely reperfusion therapy. Nevertheless, this study indicates that the moment of recanalisation of the infarct-related artery coincides with sudden and massive disruption of myocyte membranes. Attenuation of this effect, if possible, could further improve the benefits of reperfusion therapy.

Adult↗