Search PubMed⌕ Search

Biomedical subjects

E Ambrosioni

Publications and source records attributed to E Ambrosioni.

At least 37 records · Page 2Linked to original sources
PubMed1999

Efficacy and tolerability of moexipril and nitrendipine in postmenopausal women with hypertension. MADAM study group. Moexipril as Antihypertensive Drug After Menopause.

OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of the new angiotensin-converting enzyme (ACE) inhibitor moexipril and the calcium antagonist nitrendipine in postmenopausal women with mild to moderate hypertension. METHODS: After a 4-week placebo run-in period, 93 postmenopausal women (age range 44-70 years) with primary hypertension were randomized to receive moexipril 15 mg once daily or nitrendipine 20 mg once daily for 8 weeks. The mean sitting systolic (SSBP) and sitting diastolic blood pressures (SDBP) at baseline were 161.3/103.0 mmHg in the moexipril group, and 162.2/102.3 mmHg in the nitrendipine group. RESULTS: After the 8 weeks of treatment, the SSBP/SDBP reductions were -21.2/-15.2 mmHg in the moexipril group and -18.2/-13.6 mmHg in the nitrendipine group. Blood pressure responses were adequate in 82.2% of the moexipril-treated patients and in 80.9% in the nitrendipine-treated group. Adverse events were more frequent with nitrendipine than with moexipril. The most common adverse events in the nitrendipine group were headache (23.4%), flushing (21.3%) and ankle oedema (14.9%). In the moexipril group the most common adverse event was cough (8.9%). CONCLUSION: The results of the study suggest that moexipril and nitrendipine are equieffective in the given dosages. In the patient population of postmenopausal women, the ACE inhibitor moexipril appears to have an advantage over the calcium antagonist nitrendipine with regard to tolerability.

Aged↗
PubMed1999

Effects of the administration of an angiotensin-converting enzyme inhibitor during the acute phase of myocardial infarction in patients with arterial hypertension. SMILE Study Investigators. Survival of Myocardial Infarction Long-term Evaluation.

A positive history of arterial hypertension (HBP) is present in as many as 30% of patients with acute myocardial infarction (AMI) and their clinical outcome could be greatly improved by drugs enhancing blood pressure control and preserving ventricular function. The aim of the present study was to evaluate the importance of a history of HBP on the clinical efficacy of early treatment with the angiotensin-converting enzyme (ACE) inhibitor zofenopril in patients with anterior AMI. We summarize the results of a post-hoc analysis of data from the Survival of Myocardial Infarction Long-term Evaluation (SMILE) study, which randomly evaluated the efficacy of zofenopril given within 24 h of symptom onset to patients with anterior AMI not undergoing thrombolysis. Of 1441 patients who entered the study, 565 (39.2%) had a history of HBP. The mean follow-up time was 12 months and the main outcome measures were 6-week combined occurrence of death and severe congestive heart failure (CHF) and 1-year mortality. After 6-week of treatment with zofenopril the relative risk of death or severe CHF was 0.60 (95% confidence interval [CI]: 0.45-0.81; 2P < .05) in the hypertensive group and 0.89 (0.74-1.08; 2P = .62) for normotensive patients, whereas the 1-year risk of death was 0.61 (95% CI: 0.23,0.89; 2P < .05) and 0.77 (95% CI: 0.52-1.17; 2P = .22), respectively. The 6-week prevalence of mild-to-moderate CHF was also significantly reduced by zofenopril in the hypertensive population (14.1% v 9.4%; 2P < .05). The present data suggest that treatment with zofenopril started within 24 h of the onset of anterior AMI could be highly beneficial in patients with a history of HBP.

Adolescent↗
PubMed1999

The extent of regional wall motion abnormalities identifies patients at risk of extensive left ventricular remodeling: implications for the design of post myocardial infarction trials.

BACKGROUND: The FAMIS (Fosinopril in Acute Myocardial Infarction Study) was a multicenter, placebo-controlled, double-blind trial designed to evaluate the safety and the efficacy of fosinopril in reducing left ventricular enlargement after acute anterior myocardial infarction. We evaluated the echocardiographic examinations performed during the trial in order to assess the trend of the remodeling process over time and to evaluate the role of infarct size in identifying patients at risk of progressive left ventricular dilation. METHODS: A complete echocardiographic examination was performed on admission, before discharge and three months later. Patients undergoing coronary bypass surgery or PTCA had a further examination prior to the procedure. The echocardiograms were analyzed at a central laboratory, and the end-diastolic and end-systolic left ventricular volumes were computed by using a modified Simpson's rule technique. Regional wall motion was evaluated using the centerline method, analyzing the left ventricular boundary along 100 chords perpendicular to the centerline constructed midway between the end-diastolic and the end-systolic contours. A quantitative infarct-size index was then computed according to the number of chords with a fractional shortening equal to or less than 5%. RESULTS: Left ventricular end-diastolic and end-systolic volume index significantly increased over time (p < 0.0001); as a result, the stroke volume increased (p < 0.0001) but the ejection fraction did not change. Patients were then divided according to the three-month infarct-size index. For both end-diastolic and end-systolic volume, not only did larger infarcts had higher volumes, but there was also a greater increase from baseline to 3 months. Moreover, larger infarcts had a lower ejection fraction, with a further reduction over the three months, while smaller infarcts had higher values and an increase over time. An infarct-size index of 25 or larger allowed prospective identification at the baseline examination of patients at risk of subsequent left ventricular dilation. CONCLUSIONS: In conclusion, patients at greatest risk of left ventricular dilation, namely those with larger infarct size, constitute a group that is worth considering for any therapeutic effort for reducing the remodeling process. These patients could in fact benefit from therapeutic strategies aimed at the reduction of left ventricular remodeling and should be studied in clinical trials.

Aged↗
PubMed1998

Evaluation of a weight-adjusted single-bolus plasminogen activator in patients with myocardial infarction: a double-blind, randomized angiographic trial of lanoteplase versus alteplase.

BACKGROUND: Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. METHODS AND RESULTS: InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P<0. 001). Similar results were observed at 90 minutes (26.1% to 57.1%, P<0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg lanoteplase compared with 71.4% with alteplase. Thus, at this dose, lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. CONCLUSIONS: Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg lanoteplase than alteplase. In this study, safety with lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.

Adolescent↗
PubMed1998

Short- and long-term effects of early fosinopril administration in patients with acute anterior myocardial infarction undergoing intravenous thrombolysis: results from the Fosinopril in Acute Myocardial Infarction Study. FAMIS Working Party.

BACKGROUND: Angiotensin-converting enzyme inhibitors are used in patients who have myocardial infarction with left ventricular (LV) dysfunction. Few data are available in patients whose LV function is within the normal range. METHODS AND RESULTS: The Fosinopril in Acute Myocardial Infarction Study was a 2-year, randomized, double-blind, placebo-controlled, multicenter study of 285 patients with anterior acute myocardial infarction and was designed to investigate the effects of the early (<9 hours) administration of fosinopril and thrombolysis on (1) changes in echocardiographically evaluated LV volumes at 3 months and (2) long-term occurrence of death and congestive heart failure. LV volumes were normal at baseline in more than 70% of patients and were comparable between groups both at baseline and after 3 months of treatment. Fosinopril-treated patients showed a 30% reduction in the 2-year combined prevalence of death or moderate-to-severe congestive heart failure (New York Heart Association class III-IV) despite having a worse clinical profile at baseline. The benefit of fosinopril was confirmed both in patients without congestive heart failure at admission and in those with ejection fraction >40% at baseline. Moreover, the incidence of significant ventricular arrhythmias was lower in the fosinopril group (0.8% vs 6.0%, p < 0.02). CONCLUSIONS: The results of the Fosinopril in Acute Myocardial Infarction Study suggest that early treatment with fosinopril can benefit patients with acute myocardial infarction in addition to a prevention of LV remodeling.

Aged↗
PubMed1998

Low-dose antihypertensive therapy with 1.5 mg sustained-release indapamide: results of randomised double-blind controlled studies. European study group.

OBJECTIVE: In accordance with international recommendations on the need to decrease doses of antihypertensive drugs, a low-dose (1.5 mg) sustained-release (SR) formulation of indapamide was developed to optimize the drug's efficacy : safety ratio. The aim of this work was to evaluate the benefit of a low-dose diuretic by consolidating the efficacy and safety results of two clinical trials with a similar design. PATIENTS AND METHODS: Clinical data were obtained in two European randomized double-blind studies with 690 mild to moderate hypertensive patients (95 mmHg < or = supine diastolic blood pressure < or = 114 mmHg using a mercury sphygmomanometer) treated respectively for 2 and 3 months, with a mean age of 53 and 57 years, 44 and 57% males, mean supine diastolic blood pressure of 100.6 and 102.5 mmHg and mean supine systolic blood pressure of 161.0 and 164.5 mmHg. RESULTS: The first study, a dose-finding study with indapamide SR at 1.5, 2 and 2.5 mg versus placebo and the immediate-release (IR) formulation of indapamide, showed that the 1.5 mg dosage of the new indapamide formulation had an improved antihypertensive efficacy : safety ratio. The second study confirmed the equivalence of blood pressure reductions with 1.5 mg indapamide SR and 2.5 mg indapamide IR, and better acceptability with 1.5 mg indapamide SR, particularly in the number of patients with serum potassium levels < 3.4 mmol/l, which was reduced by more than 50%. The long-term efficacy of 1.5 mg indapamide SR was observed through a 9-month open-treatment follow-up to the second study. CONCLUSION: The 1.5 mg SR formulation of indapamide has an improved antihypertensive efficacy : safety ratio, which is in accordance with international recommendations for the use of low-dose antihypertensive drugs and diuretics in first-line therapy of hypertension.

Adult↗
PubMed1998

Evidence-based medicine and ACE inhibition.

The use of angiotensin-converting enzyme (ACE) inhibitors has been generally beneficial in the treatment of many clinical conditions characterized by a significant degree of cardiovascular and renal involvement. Most of the available data on the benefits of ACE inhibitors have come from well-conducted large clinical trials that have provided much information supporting the use of ACE inhibitors, in agreement with the basic principles of evidence-based medicine. In particular, ACE inhibitors improve blood pressure control in patients with hypertension and have proved to be beneficial in patients with left ventricular (LV) systolic dysfunction and chronic congestive heart failure (CHF). Improved survival rates after the use of ACE inhibitors have been also demonstrated in patients with acute myocardial infarction (MI), whether or not the condition is complicated by acute CHF. More recently, some studies have demonstrated the ability of ACE inhibitors (particularly fosinopril) to prevent the long-term development of CHF in patients treated acutely during MI and without baseline LV dysfunction. ACE inhibitors appear to improve the long-term prognosis of patients with coronary artery disease (CAD) and to reduce the occurrence of re-infarction, as demonstrated in the Studies of Left Ventricular Dysfunction (SOLVD) trial and the Survival and Ventricular Enlargement study (SAVE). Finally, a protective role for ACE inhibitors has been reported even in diabetic hypertensive patients, in whom such agents can significantly reduce the occurrence of major cardiovascular events (CAD and stroke) with a pattern that is largely independent of blood pressure control and is not observed with the use of calcium antagonists. These data confirm the strong involvement of the renin-angiotensin system in the pathophysiology of vascular diseases and strongly support the role of ACE inhibitors as drugs for present and future therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Thromboxane antagonism and cough induced by angiotensin-converting-enzyme inhibitor.

BACKGROUND: The increased prostaglandin synthesis that might follow stimulation of the arachidonic acid cascade by angiotensin-converting-enzyme inhibition (ACE-I) has been suggested to underlie the appearance of cough on ACE-I treatment. We investigated whether the prostanoid thromboxane was involved. METHODS: Nine patients with essential hypertension who had cough after enalapril 20 mg once a day (coughers) were treated, while continuing the enalapril, in a double-blind crossover study with placebo or picotamide, 600 mg twice daily. Picotamide is a platelet antiaggregant that acts through both inhibition of thromboxane synthase and thromboxane-receptor antagonism. Thirteen hypertensive patients with no history of ACE-I-induced cough were also treated with enalapril and served as controls. Cough frequency was measured by a visual analogue scale and by a daily cough diary. 24 h urinary recovery of 11-dehydro-thromboxane-B2 and 6-keto-PGF1 alpha were measured to assess any changes in endoperoxide metabolism during the study periods. FINDINGS: 11-dehydro-thromboxane-B2 (TXB2) recovery was significantly reduced by picotamide, which led to the disappearance of cough in eight patients within 72 h. Picotamide urinary recovery data suggested incomplete absorption in the non-responder. At baseline and after rechallenge with enalapril, 11-dehydro-TXB2 excretion was in the same range in the controls and in the coughers, but the latter showed significantly lower excretion of 6-keto-PGF1 alpha, and their ratio of 11-dehydroTXB2 to 6-keto-PGF1 alpha was twice that of the controls (1.40 [95% CI 0.86-1.95] vs 0.61 [0.37-0.84]). INTERPRETATION: A thromboxane antagonist is effective in ACE-I-induced cough. An imbalance between thromboxane and prostacyclin may represent a marker of patients susceptible to ACE-I-induced cough.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Post acute myocardial infarction: the Fosinopril in Acute Myocardial Infarction Study (FAMIS).

Many studies have clearly documented the beneficial effects of angiotensin converting enzyme (ACE) inhibitors in patients with acute myocardial infarction (AMI). The Fosinopril in Acute Myocardial Infarction Study (FAMIS) was a 2-year randomized, double-blind, placebo-controlled multicenter study investigating the hemodynamic and clinical effects of early (< 9 h from onset of symptoms) administration of fosinopril in 285 patients with anterior AMI undergoing thrombolysis within 6 h of symptom onset. The objective of the study was twofold: 1) to estimate changes in left ventricular (LV) volumes and function over 3 months by a series of echocardiographic evaluations, and 2) to clinically assess mortality and the occurrence of congestive heart failure (CHF) over 2 years. LV volumes measured at baseline (24 to 48 h from symptom onset) were within the normal range in over two-thirds of randomized patients, and the changes in volume were comparable after 3 months of treatment with either fosinopril or placebo. However, fosinopril-treated patients showed a 30% reduction in the 2-year incidence of death or moderate-to-severe CHF (P = .04) despite having a worst prognostic profile at baseline. This benefit of fosinopril was confirmed in the subgroup of patients without CHF on admission, who showed a 34.1% reduction in the 2-year occurrence of CHF (P = .05) and a 29.1% reduction in death or CHF (P = .04). The results of the FAMIS study suggest that early treatment with fosinopril, in conjunction with thrombolysis, can significantly delay the development of CHF in patients with AMI, acting through mechanisms independent of fosinopril's impact on LV remodeling.

Adolescent↗
PubMed1997

From the monitoring of severe to a survey of mild adverse effects of current antihypertensive therapy: the hidden side of the iceberg. The Scientific Committee of the Italian Pharmacoepidemiology Survey on Antihypertensive Therapy.

One of the most important causes of the unsatisfactory results of antihypertensive therapy in current medical practice is the difficulty in evaluating individual tolerability to the various antihypertensive agents. The methods commonly used, i.e. assessment in controlled studies of limited duration, or notification to pharmacovigilance authorities, clearly underestimate the problem. In order to obtain more correct information on antihypertensive practice, an Italian pharmacoepidemiological study has recently been planned, and the results of a pilot phase of this study are reported here.

Antihypertensive Agents↗
PubMed1996

Effects of the early administration of zofenopril on onset and progression of congestive heart failure in patients with anterior wall acute myocardial infarction. The SMILE Study Investigators. Survival of Myocardial Infarction Long-term Evaluation.

Chronic congestive heart failure (CHF) is a common disease responsible for a high mortality and morbidity whose clinical course can be improved by angiotensin-converting-enzyme (ACE) inhibition. However, limited data are available on the effects of ACE inhibitors on the onset and progression of CHF in patients with acute myocardial infarction (AMI). The present study was performed as a substudy of the Survival of Myocardial Infarction Long-term Evaluation trial and involved 1,146 patients with anterior wall AMI not undergoing thrombolysis with the exclusion of patients with prior history or clinical signs of CHF on admission. Patients were randomly allocated to treatment with zofenopril (7.5 to 30 mg twice daily) or placebo for a cumulative period of 6 weeks. The prevalence of CHF, either mild to moderate or severe, has been the main objective and has been evaluated 6 weeks and 1 year after AMI. The overall prevalence of CHF was not reduced by zofenopril after both 6 weeks and 12 months. Conversely the prevalence of severe CHF (1.6% vs 2.6%: risk reduction 55.5%; 95% confidence interval 9 to 63; p = 0.0325) and the combined occurrence of death or severe CHF (4.8% vs 8.2%: risk reduction 59%; 95% confidence interval 11 to 71; p = 0.024) were reduced after 6 weeks of treatment with zofenopril. Moreover, the percentage of patients experiencing a deterioration to severe CHF after 1 year was significantly reduced with zofenopril (11.0% vs 24.3%; p = 0.001). In conclusion, the early administration of zofenopril to patients with AMI attenuates the progression of the clinical symptoms of CHF and its clinical consequences, suggesting that ACE inhibitors should be regarded as a suitable strategy for the prevention and treatment of CHF in patients with AMI.

Adolescent↗
PubMed1996

Clinical aspects of ACE inhibition in patients with acute myocardial infarction.

The purpose of the present article was to review the current evidence on the use of angiotensin-converting enzyme (ACE) inhibitors in acute myocardial infarction (MI). This article is based on published information as well as on our personal experience derived from an extensive analysis of the SMILE study. All the randomized trials have been included irrespective of the primary endpoint, and the results are presented in terms of either hemodynamic or clinical benefit. Short- and long-term treatment with ACE inhibitors in patients with acute MI results in a significant reduction in mortality, which is more evident in high risk patients (i.e., patients with left ventricular dysfunction, congestive heart failure on admission, or anterior myocardial infarction). Development and progression of congestive heart failure after myocardial infarction was significantly reduced by ACE inhibition, which also reduced the rate of reinfarction, the need for revascularization procedures, as well as the occurrence of ventricular arrhythmias, probably through a mechanism involving some drug-dependent effects. In conclusion, the available data strongly support a wide benefit associated with the use of ACE inhibitors in patients with high-risk acute MI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Cost-effectiveness calculations from trials.

EFFECTIVENESS OF ANTIHYPERTENSIVE THERAPY: Data on the effectiveness of antihypertensive therapy derived from the results of large clinical trials are of great importance, but also have a number of significant flaws and probably underestimate the real effectiveness of treatment. In the next few years much more information is likely to become available on the effects of the newer classes of drugs and thus evaluations of cost-effectiveness will have fewer limitations than at present. ECONOMIC VALUE OF SAVING A LIFE: Today, in every country worldwide, priority should be given to determining the economic cost of avoiding the morbidity and mortality caused by hypertension. Each society must decide the price per life-year gained that it is willing to pay. This is the most difficult task of all, since the economic value of saving a life is not easily evaluable.

Antihypertensive Agents↗
PubMed1996

A risk-benefit assessment of ACE inhibitor therapy post-myocardial infarction.

The use of ACE inhibitors in patients with myocardial infarction (MI) has been the subject of several studies conducted during recent years. These studies have demonstrated the capacity of these agents to improve both survival and morbidity of patients with MI. However, the use of ACE inhibitors in patients with MI has been shown to reduce blood pressure (BP) and so could jeopardise the ischaemic myocardium. A significant reduction in systemic BP has been demonstrated by all the studies of ACE inhibitors in patients with MI, but no relationship has been found between the occurrence of hypotension and a worse clinical outcome. An increased risk of death has been observed exclusively in association with severe and sudden hypotension, the occurrence of which can be largely prevented by the administration of the ACE inhibitor according to an increasing dose-titration scheme. Conversely, a certain degree of long term BP reduction could result in some beneficial effect in patients with MI and contribute to the lower incidence of re-infarction observed in patients with acute MI undergoing long term treatment with captopril. Since the renin-angiotensin system is strictly related to kidney function, its blockade by an ACE inhibitor could result in some degree of renal dysfunction, particularly in patients with MI and impaired ventricular function. The available results from large-scale studies suggest that abnormalities in kidney function (namely an increase in serum creatinine) are observed in 0.9 to 2.4% of patients with MI who, nevertheless, experience some benefit from treatment with ACE inhibitors. Interestingly, the administration of ACE inhibitors does not seem to further compromise severely impaired renal function, and may also represent a useful tool for the treatment of patients with renal dysfunction associated with MI. The use of ACE inhibitors in patients with MI is associated with a satisfactory clinical and laboratory safety profile. The occurrence of significant adverse effects seems to be very low and mainly attributable to a rather modest prevalence of cough (2.4 to 6.8%). Discontinuation of treatment because of biochemical and haematological abnormalities has been observed in less than 1% of treated patients. Thus, the beneficial effects of ACE inhibitor treatment seem to outweigh safety concerns, thereby reinforcing the role of ACE inhibition as a suitable therapeutic strategy in the treatment of patients with MI.

Angiotensin-Converting Enzyme Inhibitors↗