Early Administration Of Zofenopril Research Articles

Efficacy of zofenopril in combination with amlodipine in patients with acute myocardial infarction: a pooled individual patient data analysis of four randomized, double-blind, controlled, prospective studies

Objective: In the four SMILE (Survival of Myocardial Infarction Long-Term Evaluation) studies, early administration of zofenopril in acute myocardial infarction (AMI) showed beneficial effects as compared to placebo and other angiotensin converting enzyme inhibitors (ACEIs). This study investigated whether the concomitant administration of the dihydropyridine calcium channel-blocker amlodipine may improve zofenopril efficacy to prevent cardiovascular events in post-AMI patients.Methods: This was a post-hoc analysis of pooled individual patient data from the four large randomized SMILE studies. The primary endpoint was the 1-year combined occurrence of death or hospitalization for cardiovascular causes.Results: In total, 3488 patients were considered, 303 (8.7%) treated with concomitant amlodipine. Baseline systolic blood pressure and prevalence of metabolic syndrome were higher in amlodipine treated patients. The 1-year occurrence of major cardiovascular outcomes was significantly reduced in patients receiving concomitant treatment with amlodipine (hazard ratio, HR = 0.66; and 95% confidence interval, CI = 0.44–0.98; p = .039). After accounting for treatment with amlodipine, the risk of cardiovascular events was significantly reduced with zofenopril compared to placebo (HR = 0.78; 95% CI = 0.63–0.97; p = .026]. Among ACEI-treated patients, the zofenopril plus amlodipine combination reduced the risk of cardiovascular events by 38%, compared to the combination of other ACEIs plus amlodipine [HR = 0.76; 95% CI = 0.61–0.94); p = .013). The prognostic benefit of concomitant treatment with zofenopril plus amlodipine was independent from blood pressure lowering.Conclusions: Zofenopril had a positive impact on prognosis in post-AMI patients, compared to other ACEIs. Concomitant administration of amlodipine may help to reduce the risk of cardiovascular events at 1 year.

Efficacy of zofenopril in combination with thiazide diuretics in patients with acute myocardial infarction: a pooled individual data analysis of four randomized, double-blind, controlled, prospective studies.

BackgroundIn the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) studies, early administration of zofenopril after acute myocardial infarction (AMI) was prognostically beneficial as compared to placebo and other angiotensin-converting enzyme inhibitors (ACEIs), such as lisinopril and ramipril. Here, we investigated whether zofenopril efficacy could be affected by a concomitant use of thiazide diuretics (TDs).MethodsThis was a post hoc analysis of pooled individual patient data from the SMILE studies. Patients treated with other diuretics than TDs were excluded. The primary study endpoint was the 1-year combined occurrence of death or hospitalization for CV causes, with or without TD.ResultsAmong 2,995 patients, 263 (8.8%) were treated with a combination including a TD (TD+), whereas 2,732 (91.2%) were not treated with any diuretic (TD−). Proportions of subjects who were treated with TD were equally distributed (p=0.774) within the placebo, zofenopril, and other ACEIs groups. The 1-year risk of major cardiovascular events was similar in TD+ (18.3%) and TD− (16.8%) patients (hazard ratio [HR] 1.04; 95% CI 0.74–1.45; p=0.838). After stratifying per concomitant treatment and TD, the 1-year risk of CV events was significantly lower with zofenopril than with placebo (HR 0.70; 95% CI 0.55–0.88; p=0.002) and other ACEIs (HR 0.58; 95% CI 0.46–0.74; p=0.0001). Treatment with ACEIs and TD as concomitant therapy was associated with a larger blood pressure (BP) reduction (p=0.0001 for systolic BP and p=0.045 for diastolic BP).ConclusionIn post AMI patients, zofenopril maintained its positive impact on prognosis compared to placebo or other ACEIs, regardless concomitant TD administration. In this setting, TD shows advantages in managing the most difficult hypertensive patients.

Cardioprotective role of zofenopril in hypertensive patients with acute myocardial infarction: a pooled individual data analysis of the SMILE studies

Purpose: The four SMILE studies demonstrated that early administration of zofenopril following acute myocardial infarction is prognostically beneficial compared to placebo or other angiotensin-converting enzyme (ACE) inhibitors. In the present retrospective pooled analysis of individual SMILE studies, we evaluated the efficacy of zofenopril on cardiovascular (CV) outcomes in 1880 hypertensive and 1662 normotensive patients.Materials and methods: Four hundred and forty-nine hypertensives and 486 normotensives were treated with placebo, 980 and 786 with zofenopril 30–60 mg daily, 252 and 259 with lisinopril 5–10 mg daily, 199 and 131 with ramipril 10 mg daily, for 6 to 48 weeks.Results: The 1-year risk of death or hospitalization for CV causes was significantly reduced with zofenopril and lisinopril vs. placebo in both hypertensive (HR: 0.65; 95%CI: 0.48–0.86; p = .003 and .60, .36–.99; p = .049, respectively) and normotensive patients (0.56, 0.42–0.75; p = .0001 and .51, .28–.90; p = .020), whereas this was not the case for ramipril (hypertensives: 1.02, 0.69–1.52; p = .918; normotensives: 0.91, 0.59–1.41; p = .670). Zofenopril significantly reduced the risk of CV outcomes vs. the other two ACE-inhibitors pooled together in hypertensive (0.76; 0.58–0.99; p = .045), but not in normotensive patients (0.77; 0.55–1.10; p = .150).Conclusions: In cardiac patients of the SMILE studies with arterial hypertension treatment with the ACE-inhibitor zofenopril was beneficial in reducing the 1-year risk of CV events as compared to placebo and ramipril. An efficacy similar to that of zofenopril was observed with lisinopril.

Abstract 9850: Cardioprotective Role of Zofenopril in Hypertensive Patients With Acute Myocardial Infarction: A Pooled Individual Data Analysis of Four Randomized, Double-blind, Controlled, Prospective Studies

Introduction: the SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies demonstrated that early administration of zofenopril following acute myocardial infarction (AMI) is prognostically beneficial compared to placebo or other angiotensin-converting enzyme inhibitors (ACE-inhibitors). Hypothesis: In the present meta-analysis of individual data of four SMILE studies we evaluated the cumulative efficacy of zofenopril on cardiovascular (CV) morbidity and mortality in the subgroup of hypertensive patients. Methods: 1880 (53.1%) of the 3542 patients had a positive history for hypertension. 449 hypertensives and 486 normotensives were treated with placebo (SMILE 1 and 3), 980 and 786 with zofenopril 30-60 mg/die (all four studies), 451 and 390 with lisinopril 5-10 mg/die (SMILE 2) or ramipril 10 mg/die (SMILE 4). Treatment was continued for 6 to 48 weeks. For the purpose of this pooled analysis the primary study endpoint was set to 1-year combined occurrence of death or hospitalization for CV causes. Results: the risk of CV events was significantly reduced by 35% with zofenopril vs. placebo [HR: 0.65; 95% CI: 0.49-0.86; p=0.003) in hypertensive patients and by 41% in normotensive patients (0.59; 0.44-0.79; p=0.0001). The other ACE-inhibitors reduced CV morbidity and mortality as well, though the reduction (-17%) was not statistically significant vs. placebo either in hypertensives (0.83; 0.57-1.21; p=0.338) or normotensives (reduction: -24%; HR: 0.76; 0.50-1.15; p=0.194). Treatment with zofenopril of hypertensive and normotensive patients was associated with a non-statistically significant reduction in the risk of CV outcomes as compared to the other ACE-inhibitors (hypertensives: 0.78; 0.60-1.01; p=0.062; normotensives: 0.77; 0.55-1.10; p=0.1509. Conclusions: in high-risk cardiac patients with arterial hypertension, zofenopril treatment is associated with a clinically relevant reduction in long-term CV morbidity and mortality, compared to placebo, with an efficacy similar to that of other ACE-inhibitors, such as lisinopril and ramipril.

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Objective: The SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies demonstrated that early administration of zofenopril following acute myocardial infarction (AMI) is prognostically beneficial compared to placebo or other angiotensin-converting enzyme inhibitors (ACE-inhibitors). In the present meta-analysis of individual data of four SMILE studies we evaluated the cumulative efficacy of zofenopril on cardiovascular (CV) morbidity and mortality in the subgroup of hypertensive patients. Design and method: 1880 (53.1%) of the 3542 patients had a positive history for hypertension. 449 hypertensives and 486 normotensives were treated with placebo (SMILE 1 and 3), 980 and 786 with zofenopril 30–60 mg/die (all four studies), 451 and 390 with lisinopril 5–10 mg/die (SMILE 2) or ramipril 10 mg/die (SMILE 4). Treatment was continued for 6 to 48 weeks. For the purpose of this pooled analysis the primary study endpoint was set to 1-year combined occurrence of death or hospitalization for CV causes. Results: The risk of CV events was significantly reduced by 35% with zofenopril vs. placebo [HR: 0.65; 95% CI: 0.49–0.86; p = 0.003) in hypertensive patients and by 41% in normotensive patients (0.59; 0.44–0.79; p = 0.0001). The other ACE-inhibitors reduced CV morbidity and mortality as well, though the reduction (−17%) was not statistically significant vs. placebo either in hypertensives (0.83; 0.57–1.21; p = 0.338) or normotensives (reduction: −24%; HR: 0.76; 0.50–1.15; p = 0.194). Treatment with zofenopril of hypertensive and normotensive patients was associated with a non-statistically significant reduction in the risk of CV outcomes as compared to the other ACE-inhibitors (hypertensives: 0.78; 0.60–1.01; p = 0.062; normotensives: 0.77; 0.55–1.10; p = 0.1509). Conclusions: In high-risk cardiac patients with arterial hypertension, zofenopril treatment is associated with a clinically relevant reduction in long-term CV morbidity and mortality, compared to placebo, with an efficacy similar to that of other ACE-inhibitors, such as lisinopril and ramipril.

Defining the Role of Zofenopril in the Management of Hypertension and Ischemic Heart Disorders

Zofenopril is a specific ACE inhibitor with antihypertensive, remarkable antioxidant, and cardioprotective properties, including the ability to improve endothelial function and protect against ischemia. These beneficial properties of zofenopril are believed to be due primarily to the presence of a sulfhydryl group and the highly lipophilic nature of the agent. As a potent, long-acting ACE inhibitor with tissue selectivity, it is a useful agent for the treatment of a number of cardiovascular diseases. ACE inhibitors block the renin-angiotensin-aldosterone system (RAAS) and are recommended in the management of hypertension with associated risk factors because of their renoprotective and cardioprotective effects. There is a robust body of comparative data supporting zofenopril as an effective and well tolerated ACE inhibitor for treating hypertension. Hypertensive patients frequently require combination therapy to adequately control BP. ACE inhibitors combined with a diuretic make a very effective combination, as a result of the synergistic mechanisms of these two drug classes that allow good efficacy and favorable tolerability at low doses. The combination of zofenopril and hydrochlorothiazide is effective and superior to monotherapy with either agent. Clinical studies have demonstrated that early administration of zofenopril in patients with acute myocardial infarction is effective and well tolerated for reducing the incidence of major cardiovascular events in at-risk patients, and it is believed that much of the benefit is a result of the primary cardioprotective effect of zofenopril.

A review of the angiotensin-converting enzyme inhibitor, zofenopril, in the treatment of cardiovascular diseases

Based on preclinical and clinical findings, zofenopril appears to be an angiotensin-converting enzyme (ACE) inhibitor with high potency, significant tissue selectivity and a long duration of action. Its ancillary properties, such as antioxidant activity and cardiovascular (CV) protection, make this drug potentially suitable for the treatment, and possibly prevention, of several CV diseases. There is a large body of evidence that support a complex interaction between ACE inhibitors and CV disease. A review of the preclinical profile of zofenopril clearly suggest that such interaction can be even more complex and could involve some drug-specific properties directly involved in the definition of the overall clinical profile of zofenopril as emerged from randomised clinical trials. In particular, zofenopril combines the feature of an effective ACE inhibitor, with plasma and tissue activity, along with that of an antioxidant compound, and both these characteristics can contribute to its capacity of controlling hypertension and improving the prognosis of patients with coronary artery disease. The results of The Survival of Myocardial Infarction Long term Evaluation (SMILE) trials have demonstrated that the early administration of zofenopril to patients with acute myocardial infarction is associated with a significant reduction in the 6-week occurrence of major CV events (death and congestive heart failure) in high-risk patients with anterior non-thrombolysed myocardial infarction, and this effect is enhanced in some higher-risk subgroups of patients, such as those with a history of diabetes or arterial hypertension.