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Biomedical subjects

A Avezum

Publications and source records attributed to A Avezum.

At least 19 recordsLinked to original sources
PubMed2006

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

Aged↗
PubMed2005

Management and outcomes of lower risk patients presenting with acute coronary syndromes in a multinational observational registry.

OBJECTIVE: To document patterns of risk stratification, management practices, and outcomes among patients with acute coronary syndromes (ACS) presenting without high risk features. PATIENTS: The study was based on 11,885 consecutive patients presenting with non-ST segment elevation ACS enrolled in GRACE (global registry of acute coronary events). Patients without dynamic ST segment changes, positive troponin (or other cardiac markers), or haemodynamic or arrhythmic instability were defined as being at lower risk. MAIN OUTCOME MEASURES: Management and outcomes were compared with high risk presentations. RESULTS: Of 11,885 patients presenting with unstable angina or non-ST segment elevation myocardial infarction, 4252 (36%) were regarded as being at lower risk. Functional testing for risk stratification was performed in 1163 of 4207 (28%) lower risk and 1531 of 7521 (20%) high risk patients (p < 0.0001). Coronary angiography was performed in 1930 of 4190 (46%) and 3860 of 7544 (51%), and echocardiography in 1692 of 4190 (40%) and 4348 of 7533 (58%) of lower risk and high risk patients, respectively (p < 0.0001 for both). Over one third of patients did not undergo further risk assessment with angiography or functional testing (2746 of 7437 (37%) high risk, 1499 of 4148 (36%) lower risk, not significant). Death occurring in hospital was more likely in the high risk cohort (41 of 4227 (1.0%) lower risk v 215 of 7586 (2.8%) high risk, p < 0.0001), whereas rates of recurrent angina during admission and readmission were similar in both groups (1354 of 4231 (32%) high risk, 2313 of 7587 (31%) lower risk, not significant). In the six months after discharge, death or myocardial infarction occurred in 79 of 3223 (2.5%) lower risk patients and 302 of 5451 (5.5%) high risk patients (p < 0.0001). CONCLUSIONS: Globally, further risk stratification after ACS presentation is suboptimal, regardless of presenting characteristics. Although in-hospital death and myocardial infarction are uncommon, recurrent ischaemia is encountered often in both groups. It remains to be seen whether better outcomes may be achieved with wider application of risk stratification and appropriately directed management strategies.

Acute Disease↗
PubMed2003

Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: findings from the global registry of acute coronary events (GRACE).

OBJECTIVE: To determine whether creatinine clearance at the time of hospital admission is an independent predictor of hospital mortality and adverse outcomes in patients with acute coronary syndromes (ACS). DESIGN: A prospective multicentre observational study, GRACE (global registry of acute coronary events), of patients with the full spectrum of ACS. SETTING: Ninety four hospitals of varying size and capability in 14 countries across four continents. PATIENTS: 11 774 patients hospitalised with ACS, including ST and non-ST segment elevation acute myocardial infarction and unstable angina. MAIN OUTCOME MEASURES: Demographic and clinical characteristics, medication use, and in-hospital outcomes were compared for patients with creatinine clearance rates of > 60 ml/min (normal and minimally impaired renal function), 30-60 ml/min (moderate renal dysfunction), and < 30 ml/min (severe renal dysfunction). RESULTS: Patients with moderate or severe renal dysfunction were older, were more likely to be women, and presented to participating hospitals with more comorbidities than those with normal or minimally impaired renal function. In comparison with patients with normal or minimally impaired renal function, patients with moderate renal dysfunction were twice as likely to die (odds ratio 2.09, 95% confidence interval 1.55 to 2.81) and those with severe renal dysfunction almost four times more likely to die (odds ratio 3.71, 95% confidence interval 2.57 to 5.37) after adjustment for other potentially confounding variables. The risk of major bleeding episodes increased as renal function worsened. CONCLUSION: In patients with ACS, creatinine clearance is an important independent predictor of hospital death and major bleeding. These data reinforce the importance of increased surveillance efforts and use of targeted intervention strategies in patients with acute coronary disease complicated by renal dysfunction.

Adult↗
PubMed2002

Management of acute coronary syndromes. Variations in practice and outcome; findings from the Global Registry of Acute Coronary Events (GRACE).

AIMS: Despite advances in the treatment of acute coronary syndromes based on randomized trial data and published guidelines, the extent to which such treatments are applied in practice remains uncertain. Data from clinical trials derive from selected geographical areas and in highly selected populations of patients, and hence may not reflect the overall population. The aim of the study was to investigate variations in hospital management and outcome using unselected data collected in the prospective Global Registry of Acute Coronary Events (GRACE). METHODS AND RESULTS: The 95 hospitals in GRACE were organized into 18 population-based clusters in 14 countries. Information was recorded about patient management and outcome during hospitalization and after discharge. Data on treatments administered were analysed by baseline condition, hospital type, by the presence or absence of a catheterization laboratory, and by geographical region. Of 11543 patients, 44% had an admission diagnosis of unstable angina, 36% presented with myocardial infarction, 9% were admitted to rule out a myocardial infarction, 7% had chest pain and 4% were hospitalized for 'other cardiac' and 'non-cardiac' diagnoses. Of the total GRACE population 38% had a final diagnosis of unstable angina, 30% ST-segment elevation myocardial infarction, 25% non-ST-segment elevation myocardial infarction, and 7% of 'other cardiac' and 'non-cardiac' final diagnoses. The event rates for hospital death or reinfarction were six and 2% for non-ST-segment elevation myocardial infarction, seven and 3% for ST-segment elevation myocardial infarction, and 3% hospital death for unstable angina. The use of aspirin was similar across all hospital types and geographical regions. In contrast, the use of percutaneous coronary intervention and glycoprotein IIb/IIIa inhibitors was higher (P<0.0001) in teaching hospitals and hospitals with catheterization laboratories and was also higher in the United States. At discharge a higher percentage (P<0.0001) of patients received angiotensin-converting enzyme inhibitors in hospitals without catheterization laboratories. The use of statins was lower in non-teaching hospitals and in centres without a catheterization laboratory. CONCLUSIONS: The GRACE study reveals substantial differences in the management of patients based on hospital type and geographical location. Further analyses will determine whether such variations translate into differences in longer term outcomes. GRACE provides a multinational reference for the implementation of therapies of proven efficacy.

Acute Disease↗
PubMed1999

Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators.

BACKGROUND: We investigated the effects of candesartan (an angiotensin II antagonist) alone, enalapril alone, and their combination on exercise tolerance, ventricular function, quality of life (QOL), neurohormone levels, and tolerability in congestive heart failure (CHF). METHODS AND RESULTS: Seven hundred sixty-eight patients in New York Heart Association functional class (NYHA-FC) II to IV with ejection fraction (EF) <0.40 and a 6-minute walk distance (6MWD) <500 m received either candesartan (4, 8, or 16 mg), candesartan (4 or 8 mg) plus 20 mg of enalapril, or 20 mg of enalapril for 43 weeks. There were no differences among groups with regard to 6MWD, NYHA-FC, or QOL. EF increased (P=NS) more with candesartan-plus-enalapril therapy (0.025+/-0.004) than with candesartan alone (0.015+/-0.004) or enalapril alone(0.015+/-0.005). End-diastolic (EDV) and end-systolic (ESV) volumes increased less with combination therapy (EDV 8+/-4 mL; ESV 1+/-4 mL; P<0.01) than with candesartan alone (EDV 27+/-4 mL; ESV 18+/-3 mL) or enalapril alone (EDV 23+/-7 mL; ESV 14+/-6 mL). Blood pressure decreased with combination therapy (6+/-1/4+/-1 mm Hg) compared with candesartan or enalapril alone (P<0.05). Aldosterone decreased (P<0.05) with combination therapy (23.2+/-5.3 pg/mL) at 17 but not 43 weeks compared with candesartan (0.7+/-7.8 pg/mL) or enalapril (-0.8+/-11. 3 pg/mL). Brain natriuretic peptide decreased with combination therapy (5.8+/-2.7 pmol/L; P<0.01) compared with candesartan (4. 4+/-3.8 pmol/L) and enalapril alone (4.0+/-5.0 pmol/L). CONCLUSIONS: Candesartan alone was as effective, safe, and tolerable as enalapril. The combination of candesartan and enalapril was more beneficial for preventing left ventricular remodeling than either candesartan or enalapril alone.

Aged↗
PubMed1999

The Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry in patients with unstable angina.

Clinical approaches to the prevention of the potentially catastrophic consequences of coronary ischemic phenomena such as unstable angina and suspected non-Q-wave myocardial infarction (MI) differ across the world. In addition to prevailing physician beliefs in different societies, the level of access to catheterization laboratories largely determines whether an interventionist or conservative strategy is adopted. The Organization to Assess Strategies for Ischemic Syndromes (OASIS)--a prospective registry of approximately 8,000 patients with acute myocardial ischemia with no ST elevation, treated in 95 hospitals across 6 countries--furnished a unique window into regional differences in clinical management and the frequency and timing of invasive procedures (i.e., angiography, percutaneous transluminal coronary angioplasty [PTCA], and coronary artery bypass graft [CABG] surgery), as well as the outcomes of these trends. At 6 months after symptom onset, patients in the United States and Brazil, where the catheterization laboratory facilities are more accessible, underwent significantly (p <0.001) more angiography (69.4%), PTCA (23.6%), and CABG (25.2%) than in Canada and Australia, where the corresponding rates were 48.4%, 17.0%, and 16.8% (p <0.001), respectively; and in Hungary and Poland, where the respective rates were 23.5%, 5.8%, and 10.9% (p <0.001). This relatively aggressive approach led at 6 months to a more substantial decrease in refractory angina in the United States and Brazil than in Canada and Australia (20.4% vs 13.9%; p <0.001), but no improvement in rates of cardiovascular mortality and MI (10.5% versus 10.5%; p = 0.36). There was a significant (p < or = 0.012) increase in stroke, (1.9% vs 1.3%; p = 0.010) and major bleeding (1.9% vs 1.1%; p = 0.009) events. Furthermore, an inverse correlation emerged between baseline cardiovascular risk status and frequency of angiography and PTCA interventions preferentially for low-risk compared with high-risk patients. In concert with findings from other recent randomized trials, the OASIS Registry data suggest that although there are fewer hospital readmissions for unstable angina, there is a trend toward increased rates of death, MI, and stroke. These data urge a cautious approach to the use of invasive procedures in patients with unstable angina unless future trials demonstrate a clear benefit with an aggressive approach.

Adrenergic beta-Antagonists↗
PubMed1999

Why do we need randomized and epidemiological studies on cardiovascular disease? Evidence-based cardiology VII.

Over the last two decades the results of randomized clinical studies, which are powerful aids for correctly assessing therapeutical strategies, have consolidated cardiological practice. In addition, scientifically interesting hypotheses have been generated through the results of epidemiological studies. Properly conducted randomized studies without systematic errors and with statistical power adequate for demonstrating moderate and reasonable benefits in relevant clinical outcomes have provided reliable and strong results altering clinical practice, thus providing adequate treatment for patients with cardiovascular disease (CVD). The dissemination and use of evidence-based medicine in treating coronary artery disease (CAD), heart failure (HF), and in prevention will prevent hundreds of thousands of deaths annually in developed and developing countries. CVD is responsible for approximately 12 million deaths annually throughout the world, and approximately 60% of these deaths occur in developing countries. During recent years, an increase in mortality and morbidity rates due to CVD has occurred in developing countries. This increase is an indication that an epidemiological (demographic, economical, and health-related) transition is taking place in developing countries and this transition implies a global epidemic of CVD, which will require wide-ranging and globally effective strategies for prevention. The identification of conventional and emerging risk factors for CVD, as well as their management in high-risk individuals, has contributed to the decrease in the mortality rate due to CVD. Through a national collaboration, several multi-center and multinational randomized and epidemiological studies have been carried out throughout Brazil, thus contributing not only to a generalized scientific growth in different Brazilian hospitals but also to the consolidation of an increasingly evidence-based clinical practice.

Cardiology↗
PubMed1998

Variations between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina or myocardial infarction without initial ST elevation. OASIS (Organisation to Assess Strategies for Ischaemic Syndromes) Registry Investigators.

BACKGROUND: There are wide variations between countries in the use of invasive cardiac catheterisation and revascularisation procedures for patients with acute ischaemic syndromes. We studied the relation between rates of such procedures and rates of cardiovascular death, myocardial infarction, stroke, refractory angina, and major bleeding in a prospective, registry-based study in six countries with widely varying intervention rates. METHODS: 7987 consecutive patients presenting with unstable angina or suspected myocardial infarction without ST-segment elevation were recruited prospectively from 95 hospitals in six countries and followed up for 6 months. FINDINGS: The rates of all procedures were highest in patients in Brazil and the USA, intermediate in Canada and Australia, and lowest in Hungary and Poland. There were no significant differences in rates of cardiovascular death or myocardial infarction among these countries (4.7% overall [range 3.7-5.6] at 7 days; 11% overall [9-12] at 6 months). For the countries with the highest rates of invasive procedures (59%) versus the rest (21%) there was no difference in rate of cardiovascular death or myocardial infarction (adjusted odds ratio 0.88 at 7 days and 1.0 at 6 months). Rates of stroke were higher in Brazil and the USA than in the countries with lower intervention rates (adjusted odds ratio at 7 days 3.0, p=0.012; at 6 months 1.8, p=0.004) but rates of refractory angina at 7 days (0.7, p<0.001) and readmission for unstable angina at 6 months were lower (0.70, 0.63; both p<0.001). Comparison of results for hospitals without cardiac-catheterisation facilities and for those with such facilities gave adjusted odds ratios for cardiovascular death, myocardial infarction, or stroke at 6 months of 0.83 (10.6% vs 12.5%, p=0.05) and for refractory angina of 1.25 (19.3% vs 16.1%, p=0.09). INTERPRETATION: Higher rates of invasive and revascularisation procedures were associated with lower rates of refractory angina or readmission for unstable angina, no apparent reduction in cardiovascular death or myocardial infarction, but with higher rates of stroke. Randomised trials should assess the relative impact of conservative and more aggressive approaches to invasive cardiac procedures and revascularisations in patients with unstable angina.

Aged↗
PubMed1998

Beta-blocker therapy for congestive heart failure: a systemic overview and critical appraisal of the published trials.

OBJECTIVE: To evaluate the effect of beta-blockers on mortality and morbidity, and to provide an appraisal of the reliability of the available data. DATA SOURCES: MEDLINE search for trials of beta-blockers for congestive heart failure (CHF). STUDY SELECTION: All randomized trials of beta-blockers versus placebo, or greater than one month's duration, in patients with CHF. Eighteen published trials involving 2986 patients were selected. DATA EXTRACTION: Independently by two authors. DATA SYNTHESIS: The Yusuf-Peto method for combining data was used. Data were available on mortality in 2841 patients (95%), on hospitalization for heart failure in 1514 (51%) and on heart transplantation in 2330 (79%). There was a lower rate of death in the active treatment group (131 of 1606) [8.2] versus 155 of 1235 [12.6%]; OR = 72; 99% CI 0.51 to 1.00), a lower rate of hospitalization for heart failure (137 of 756 [18.1%] versus 218 of 758 [28.7%]; OR = 0.54; 99% CI 0.39 to 0.74) and a trend towards a lower proportion of patients receiving heart transplantation (15 of 1354 [l.1%] versus 26 of 976 [2.7%]; OR = 0.45; 99% CI 0.20 to 1.03). Ventricular function improved; however, there was no effect on exercise duration. Although the effects on mortality were nominally statistically significant, the use of formal methods of interim monitoring adapted for meta-analyses suggests that substantially more patients still need to be studied in large scales trials to provide reliable and conclusive evidence. CONCLUSIONS: While the available data on the use of beta-blockers in CHF appear to be promising, they are neither complete nor robust. The routine use of beta-blockers in patients with heart failure should wait the results of ongoing studies.

Adrenergic beta-Antagonists↗
PubMed1997

Combination neurohormonal blockade with ACE inhibitors, angiotensin II antagonists and beta-blockers in patients with congestive heart failure: design of the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study.

BACKGROUND: The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study is a trial of combination neurohormonal blockade using an angiotensin II antagonist (candesartan), an angiotensin-converting enzyme inhibitor (enalapril) and a beta-blocker (metoprolol) in patients with congestive heart failure (CHF). OBJECTIVES: Primary objectives of stage I are to determine the efficacy (via the 6 min walk test) and safety of candesartan alone, and in combination with enalapril, versus enalapril alone. Secondary objectives are to determine the effect of the above combinations on neurohormones, ventricular function, quality of life and symptoms. Stage II objectives are similar, evaluating the effect of the addition of metoprolol or placebo to the above medication(s). DESIGN: Randomized, two-stage trial consisting of a three-way comparison (stage I), followed by a 3 x 2 partial factorial design (stage II). SETTING: Sixty out-patient clinics in five countries. PATIENTS: Patients with symptoms of CHF (New York Heart Association functional classes II to IV), ejection fraction less than 40% and 6 min walk distance of 500 m or less. INTERVENTIONS: In stage I, 770 patients are randomized to receive candesartan alone, enalapril alone, or candesartan plus enalapril. After five months (end of stage I), patients are assessed for eligibility to be randomized in stage II. Those who are not candidates for randomization to beta-blocker or placebo are followed on their stage I medications until the end of the study. In stage II, patients are randomized to receive metoprolol or placebo for a further six months in addition to their stage I medications. Endpoints are measured at baseline, end of stage I (week 20) and end of stage II (week 46). STUDY STATUS: The study has recently completed follow-up in both stages. The findings from this study will be used to design a large scale mortality study that will help further define the role of neurohormonal blockade in patients with CHF.

Adrenergic beta-Antagonists↗
PubMed1996

Treatment for acute myocardial infarction. Overview of randomized clinical trials.

This review summarizes the results of several pharmacological interventions that have been evaluated in the management of acute myocardial infarction. Of these, thrombolytic therapy, aspirin, beta-blockers and angiotensin converting enzyme inhibitors have all been proven to reduce mortality risk and the latter three classes of drugs have also been shown to reduce morbidity. Routine use of heparin or nitrates is not recommended although they may be useful in specific circumstances such as post-infarction angina or large infarcts. Drugs that have as yet not been shown to have a role in the routine management of acute myocardial infarction include Class I antiarrhythmic agents, magnesium and calcium antagonists. Management of patients with acute myocardial infarction can now be appropriately based on the evidence generated from well conducted randomized clinical trials and appropriate therapeutic choices based on such information can be expected to reduce their morbidity and mortality risks.

Evaluation Studies as Topic↗
PubMed1994

Recent advances and future directions in myocardial infarction.

Cardiovascular disease is the leading cause of death in most industrialised countries and is a major source of health care expenditure worldwide. Identification and management of risk factors for the development of coronary heart disease (CHD) have enormous potential for improving health and reducing health care costs. There is evidence that the reduction in deaths from CHD has occurred earlier and to a greater extent in countries with aggressive policies of cardiovascular risk factor intervention. Likewise, the treatment of patients presenting with acute myocardial infarction (MI) should be aimed at both extending event-free survival and improving the quality of life. This review focuses on recent advances and future directions in the understanding of risk factor modification before an MI (prevention), treatment of MI including thrombolysis and primary percutaneous transluminal coronary angioplasty, and the subsequent management of patients after MI.

Angioplasty, Balloon, Coronary↗