RESUMO
BACKGROUND: Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). Use of sulfhydryl ACE-inhibitors (ACEIs), such as zofenopril or captopril, plus xanthine oxidase inhibitors (XOIs), may potentially result in enhanced antioxidant effects and improved survival. OBJECTIVE: We verified the benefit of such combination in a randomly stratified sample of 525 of the 3630 post-AMI patients of the four randomized prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies. METHODS: One hundred sixty-five (31.4%) patients were treated with XOIs (79 under zofenopril, 86 placebo, lisinopril or ramipril), whereas 360 were not (192 zofenopril, 168 placebo or other ACEIs). In these four groups, we separately estimated the 1-year combined risk of major cardiovascular events (MACE, death or hospitalization for cardiovascular causes). RESULTS: MACE occurred in 10.1% of patients receiving zofenopril + XOIs, in 18.6% receiving placebo or other ACEIs + XOIs, in 13.5% receiving zofenopril without XOIs and in 22.0% receiving placebo or other ACEIs, but no XOIs (p = 0.034 across groups). Rate of survival free from MACE was significantly larger under treatment with zofenopril + XOIs than with other ACEIs with no XOIs [hazard ratio: 2.29 (1.06-4.91), p = 0.034]. A non-significant trend for superiority of zofenopril + XOIs combination was observed vs. zofenopril alone [1.19 (0.54-2.64), p = 0.669] or vs. placebo or other ACEIs + XOIs [1.82 (0.78-4.26), p = 0.169]. CONCLUSIONS: Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an urate lowering drug with antioxidant activity and an ACEI, with best effects observed with zofenopril.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/análogos & derivados , Inibidores Enzimáticos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Xantina Oxidase/antagonistas & inibidores , Idoso , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Captopril/efeitos adversos , Captopril/uso terapêutico , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Lisinopril/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Intervalo Livre de Progressão , Estudos Prospectivos , Ramipril/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
In the Survival of Myocardial Infarction Long-term Evaluation (SMILE) 1, 3, and 4 studies, early administration of zofenopril in acute myocardial infarction showed to be prognostically beneficial versus placebo or ramipril. The SMILE-2 showed that both zofenopril and lisinopril are safe and showed no significant differences in the incidence of major cardiovascular (CV) complications. In this pooled analysis of individual data of the SMILE studies, we evaluated whether the superior efficacy of zofenopril is maintained also in patients with ≥1 CV risk factor (CV+, n = 2962) as compared to CV- (n = 668). The primary study end point was set to 1-year combined occurrence of death or hospitalization for CV causes. The risk of CV events was significantly reduced with zofenopril versus placebo either in the CV+ (-37%; hazard ratio: 0.63; 95% confidence interval: 0.51-0.78; P = 0.0001) or in the CV- group (-55%; hazard ratio: 0.45; 0.26-0.78; P = 0.004). Also, the other angiotensin-converting enzyme inhibitors reduced the risk of major CV outcomes, though the reduction was not statistically significant versus placebo (CV+: 0.78; 0.58-1.05; P = 0.107; CV-: 0.71; 0.36-1.41; P = 0.334). The benefit was larger in patients treated with zofenopril than other angiotensin-converting enzyme inhibitors, with a statistically significant difference for CV+ (0.79; 0.63-0.99; P = 0.039) versus CV- (0.62; 0.37-1.06; P = 0.081). In conclusion, zofenopril administered to patients after acute myocardial infarction has a positive impact on prognosis, regardless of the patient's CV risk profile.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/análogos & derivados , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Idoso , Captopril/uso terapêutico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
The SMILE-4 study showed that in patients with left ventricular dysfunction (LVD) after acute myocardial infarction, early treatment with zofenopril plus acetyl salicylic acid is associated with an improved 1-year survival, free from death or hospitalization for cardiovascular (CV) causes, as compared to ramipril plus acetyl salicylic acid. We now report CV outcomes during a 5-year follow-up of the patients of the SMILE-4 study. Three hundred eighty-six of the 518 patients completing the study (51.2%) could be tracked after the study end and 265 could be included in the analysis. During the 5.5 (±2.1) years of follow-up, the primary endpoint occurred in 27.8% of patients originally randomized and treated with zofenopril and in 43.8% of patients treated with ramipril [odds ratio (OR) and 95% confidence interval, 0.65 (0.43-0.98), P = 0.041]. Such a result was achieved through a significantly larger reduction in CV hospitalization under zofenopril [OR: 0.61 (0.37-0.99), P = 0.047], whereas reduction in mortality rate with zofenopril did not achieve statistical significance versus ramipril [OR: 0.75 (0.36-1.59), P = 0.459]. These results were in line with those achieved during the initial 1-year follow-up. Benefits of early treatment of patients with LVD after acute myocardial infarction with zofenopril are sustained over many years as compared to ramipril.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Aspirina/administração & dosagem , Captopril/análogos & derivados , Intervenção Médica Precoce , Infarto do Miocárdio/complicações , Ramipril/administração & dosagem , Disfunção Ventricular Esquerda/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Aspirina/efeitos adversos , Captopril/administração & dosagem , Captopril/efeitos adversos , Distribuição de Qui-Quadrado , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Ramipril/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Sístole , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
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.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/análogos & derivados , Hipertensão/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Captopril/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Nonadherence to antihypertensive treatment is a common problem in cardiovascular prevention and may influence prognosis. We explored predictors of adherence to antihypertensive treatment and the association of adherence with acute cardiovascular events. METHODS AND RESULTS: Using data obtained from 400 Italian primary care physicians providing information to the Health Search/Thales Database, we selected 18,806 newly diagnosed hypertensive patients >or=35 years of age during the years 2000 to 2001. Subjects included were newly treated for hypertension and initially free of cardiovascular diseases. Patient adherence was subdivided a priori into 3 categories-high (proportion of days covered, >or=80%), intermediate (proportion of days covered, 40% to 79%), and low (proportion of days covered, Assuntos
Anti-Hipertensivos/uso terapêutico
, Doenças Cardiovasculares/prevenção & controle
, Hipertensão/tratamento farmacológico
, Hipertensão/psicologia
, Cooperação do Paciente
, Idoso
, Doenças Cardiovasculares/epidemiologia
, Doenças Cardiovasculares/etiologia
, Estudos de Coortes
, Bases de Dados Factuais
, Complicações do Diabetes
, Quimioterapia Combinada
, Dislipidemias/complicações
, Feminino
, Humanos
, Hipertensão/complicações
, Incidência
, Masculino
, Pessoa de Meia-Idade
, Obesidade/complicações
RESUMO
OBJECTIVES: Renal abnormalities are strongly associated with cardiac damage in essential hypertension. Detection of preclinical cardiac and renal abnormalities is a key clinical step in hypertension management. This study investigated the relationship between ECG abnormalities and microalbuminuria (MAU) in hypertensive patients without overt cardiovascular disease. This relationship, in fact, has never been extensively studied. METHODS: The study population was that of Italy-Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease, a large observational study including 4121 hypertensive patients in Italy. Patients with overt cardiovascular diseases were excluded from the present analysis. ECGs were centrally read and urinary albumin/creatinine ratio was carefully assessed. Chronic kidney disease was defined by the presence of albuminuria or by a reduction of glomerular filtration rate. RESULTS: The presence of ECG abnormalities was significantly and directly associated with chronic kidney disease [odds ratio (OR) 1.66, 95% confidence interval (CI) 1.32-2.07, P<0.001], particularly with MAU (OR 1.81, 95% CI 1.39-2.36, P<0.001). Main selected ECG abnormalities were also significantly associated with MAU [rhythm abnormalities (OR 2.94, 95% CI 1.77-4.88, P<0.001), intraventricular conduction defects (OR 1.95, 95% CI 1.32- 2.87, P<0.01), ventricular repolarization alterations (OR 1.84, 95% CI 1.26-2.70, P<0.01) and left-axis deviation (OR 1.87, 95% CI 1.26-2.79, P<0.01)]. After adjustment for confounders, an abnormal ECG and all the main ECG abnormalities remained significantly associated with MAU. CONCLUSION: This is the first large and systematic analysis of the relationship between detailed ECG abnormalities and MAU/chronic kidney disease in hypertensive patients without overt cardiovascular diseases. We report a significant and independent relationship between the presence of ECG abnormalities and renal damage in a preclinical stage of hypertension. Identification of ECG abnormalities in hypertension should prompt physicians to careful detection for renal damage, also in order to achieve an accurate risk stratification.
Assuntos
Albuminúria/etiologia , Arritmias Cardíacas/etiologia , Eletrocardiografia , Hipertensão/complicações , Insuficiência Renal Crônica/etiologia , Idoso , Albuminúria/epidemiologia , Arritmias Cardíacas/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/epidemiologiaAssuntos
Hipertensão/terapia , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Encefalopatias/diagnóstico , Encefalopatias/etiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/prevenção & controle , Anticoncepcionais Orais/efeitos adversos , Atenção à Saúde , Complicações do Diabetes/complicações , Dieta , Interações Medicamentosas , Quimioterapia Combinada , Ecocardiografia , Eletrocardiografia , Exercício Físico/fisiologia , Feminino , Cardiopatias/prevenção & controle , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Hiperglicemia/prevenção & controle , Hipertensão/diagnóstico , Hipertensão Induzida pela Gravidez/diagnóstico , Masculino , Informática Médica , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Assistência Perioperatória/métodos , Exame Físico/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Gravidez , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/etiologia , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Medição de Risco , Fatores de Risco , Comportamento de Redução do Risco , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/prevenção & controle , Apneia Obstrutiva do Sono/complicações , Abandono do Hábito de Fumar , Redução de Peso , Adulto JovemRESUMO
OBJECTIVE: To evaluate the clinical efficacy of the early administration of zofenopril in a group of patients with and without metabolic syndrome (MS+ and MS-) and anterior myocardial infarction enrolled in the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study. METHODS: Patients were randomized double-blind to zofenopril (n=719) or placebo (n=699) for 6 weeks. The primary end point was the effect of treatment on the 6-week combined occurrence of death and severe congestive heart failure. The secondary end point was the 1-year mortality rate. RESULTS: Of the 1418 patients included in this post-hoc analysis, 686 (48.3%) had MS. After 6 weeks of treatment zofenopril significantly reduced the incidence of all-cause death and severe congestive failure (risk reduction: 69%, 95% CI: 7-78; 2p=0.002) in MS+ patients. This was the case for 1-year mortality, too (29%, 95% CI: 4-41; 2p=0.048). Zofenopril was effective also in MS- patients but the amount of relative risk reduction was less than in MS+ for both the primary (-11%; 2p=0.61) and secondary endpoint (-19%; 2p=0.025). CONCLUSIONS: Results of this post-hoc analysis of the SMILE Study demonstrate the striking benefit of early administration of zofenopril in MS+ patients with acute anterior myocardial infarction.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/análogos & derivados , Síndrome Metabólica/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Idoso , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Captopril/administração & dosagem , Captopril/uso terapêutico , Comorbidade , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Incidência , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologiaRESUMO
BACKGROUND: Metabolic syndrome is a highly prevalent condition in the Italian population. This study assesses the feasibility and efficacy of a multifactorial approach for primary prevention of cardiovascular disease risk assessment in patients with metabolic syndrome in the daily clinical practice setting. METHODS: 726 patients were enrolled (males : females = 7 : 3), their ages ranging from 26 to 70 years, with metabolic syndrome and cardiovascular death risk ≥5%, computed by means of the European Systematic COronary Risk Evaluation (SCORE) algorithm. The first phase (3 months) consisted of an improvement in lifestyle and, if necessary, the initial administration of an antihypertensive therapy (valsartan 160 mg/day for patients with blood pressure ≥140/90 mmHg and ≥130/80 mmHg for diabetic patients). During phase 2 (6 months), patients with systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg (≥130/80 mmHg for diabetic patients) were administered valsartan 160 mg/day + hydrochlorothiazide 12.5 mg/day combined; those with total cholesterol levels ≥190 mg/dL (≥175 mg/dL for diabetic patients) started treatment with fluvastatin 80 mg prolonged release (XL), as prescribed in the guidelines. A control group was approached with another conventional treatment. RESULTS: After 9 months of monitoring, the SBP dropped by 27 mmHg in the valsartan-treated patients and by 11 mmHg in the control group, while the DBP dropped by 12 mmHg in the former group and 2 mmHg in the latter. Total cholesterolaemia was reduced by 47 mg/dL in patients undergoing fluvastatin and valsartan therapy, by 19 mg/dL in those treated with valsartan only and by 33 mg/dL in those administered another conventional treatment. Relative risk reduction observed after 9 months, compared with the beginning of the study, was almost 48% in the valsartan/valsartan + fluvastatin group, versus 28% observed with the other conventional treatment. The reduction of risk at 60 years of age was an average of 39% at 3 months and 48% at 9 months, compared with the beginning of the study. Therapeutic success was accomplished with 78% of the patients treated with valsartan/valsartan + fluvastatin, compared with 47% of patients in the conventional therapy group. CONCLUSION: The present study demonstrated that the normalization of the main cardiovascular risk factors in patients with metabolic syndrome may be easily achieved in standard clinical practice settings, by leading an adequate lifestyle and, if necessary, the administration of antihypertensive and/or lipid-lowering monotherapy at the usual doses.
RESUMO
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.
Assuntos
Anlodipino , Captopril/análogos & derivados , Infarto do Miocárdio , Idoso , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Captopril/administração & dosagem , Captopril/efeitos adversos , Análise de Dados , Método Duplo-Cego , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Prognóstico , Tempo para o Tratamento , Resultado do TratamentoRESUMO
BACKGROUND: In 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). METHODS: This 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. RESULTS: Among 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). CONCLUSION: In 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.
RESUMO
Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical efficacy and safety have been described in the four randomized controlled trials of the SMILE program, which globally enrolled more than 3600 patients in post-acute myocardial infarction (AMI) setting. The SMILE-4 study specifically selected patients with left ventricular dysfunction at admission, and compared the effects of zofenopril or ramipril in combination with acetylsalicylic acid (ASA). Zofenopril demonstrated its superiority over ramipril in reducing the combined occurrence of death or hospitalization for cardiovascular causes both in the overall population included in the original study and in subgroups of patients at highest risk, namely hypertensive and diabetic subjects. The effects of the early treatment with zofenopril were sustained over time, and, after 5 years of follow-up, zofenopril increased the survival likelihood and reduced the hospitalization rate. Compared to ramipril, zofenopril was cost-effective with a number to treat of 13 and an incremental cost-effectiveness ratio (ICER) of 2125.45 euros for any additional event prevented. Furthermore, in real-world settings, zofenopril decreased the risk of death in patients with heart failure, particularly in men, and in subjects older than 76 years or with ejection fraction lower than 54%. These results support the early use of zofenopril immediately after AMI, even in the presence of comorbidities, and its maintenance over time to reduce the risk of heart failure. FUNDING: Menarini International Operations Luxembourg S.A.
Assuntos
Captopril/análogos & derivados , Insuficiência Cardíaca , Infarto do Miocárdio , Ramipril/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Método Duplo-Cego , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: The aim of the study was to investigate the cardioprotective effects of the angiotensin-converting enzyme inhibitor zofenopril in post-myocardial infarction (MI) patients with preserved left ventricular function (LVF). METHODS: Three hundred forty-nine post-MI patients with preserved LVF (LV ejection fraction >40%) were treated for 6 months with zofenopril 30 to 60 mg (n = 177) or placebo (n = 172) according to a double-blind, randomized study design. The primary end point of the study was the combined occurrence of significant ST-T abnormalities on ambulatory electrocardiography (ECG), ECG abnormalities or symptoms of angina during standard exercise test, recurrence of MI, and need for revascularization procedures for angina. RESULTS: The primary end point occurred in 20.3% of zofenopril-treated and 35.9% of placebo-treated patients (P = .001), despite no differences in blood pressure control, LVF, and concomitant therapy. ST-T depression during ambulatory ECG occurred in 22.7% of patients treated with placebo and 10.7% of those undergoing ACE-inhibition treatment (P = .027). ST-T depression in response to exercise test occurred in 14.2% and 26.7% of patients treated with zofenopril or placebo, respectively, (P = .024), with a lower proportion of zofenopril-treated patients who complained of anginal pain (4.7 vs 14.3%; P = .017), significant ST depression (14.2 vs 26.7%; P = .024), and major ventricular arrhythmias (3.8 vs 10.5%; P = .048). The rate of major cardiovascular events was reduced in patients treated with ACE inhibitor, with a lower rate of development and progression of congestive heart failure. CONCLUSIONS: The results of the SMILE-ISCHEMIA study support the cardioprotective role of zofenopril when given to patients with normal LVF after acute MI.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/análogos & derivados , Coração/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Idoso , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Captopril/administração & dosagem , Captopril/farmacologia , Captopril/uso terapêutico , Método Duplo-Cego , Eletrocardiografia Ambulatorial , Teste de Esforço , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Função Ventricular EsquerdaRESUMO
OBJECTIVE: A previous analysis of the ForLife study demonstrated a high estimated risk of stroke, poor blood pressure control and higher cardiovascular risk. Data from a subsequent visit within 6 months, to evaluate the impact of systematic stroke risk assessment, are reported. METHODS: Between February and July 2003, 1800 general practitioners (GPs) recruited a total of 12,792 (7512 untreated and 5280 treated) patients with hypertension. Blood pressure values were assessed in the whole study population, and for different demographic and clinical features in two visits within 6 months. The data were recorded into a Framingham-based stroke risk score and computed using a risk calculator. RESULTS: Between the two visits the percentage of patients with controlled blood pressure (< 140/90 mmHg) increased substantially in all subgroups, being greater in patients who were not treated at baseline. Among initially treated patients, the greater control of blood pressure involved both diastolic and systolic values. The percentage of patients with diabetes whose blood pressure levels were less than 130/80 mmHg also increased at the second visit. Between the two visits the estimated stroke risk score showed a reduction, with a significant shift of patients from high to intermediate and low-risk categories. This reduction involved all subgroups, including patients with diabetes and left ventricular hypertrophy. CONCLUSION: The present large-scale observational study demonstrates that the assessment of stroke risk and increased awareness of stroke risk factors by GPs is associated with improved blood pressure control, reduced cardiovascular risk profile and a prompt reduction in the 10-year estimated risk of stroke.
Assuntos
Hipertensão/complicações , Acidente Vascular Cerebral/prevenção & controle , Idoso , Pressão Sanguínea , Complicações do Diabetes/etiologia , Complicações do Diabetes/prevenção & controle , Medicina de Família e Comunidade , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/complicações , Itália , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/etiologiaRESUMO
OBJECTIVES: To investigate the possible interactions between serum cholesterol levels and the renin-angiotensin system on the development of stable hypertension in subjects with high-normal blood pressure (BP). BACKGROUND: Hypercholesterolemia increases angiotensin-II type 1 (AT1) receptor density and pressor responsiveness to angiotensin II, and has been reported to contribute to the development of hypertension. The effects of elevated serum cholesterol levels on BP control might be exaggerated by concomitant activation of the renin-angiotensin system, and their combination might contribute to the development of stable hypertension. METHODS: We investigated the relationship between serum cholesterol levels, plasma renin activity (PRA) and the long-term development of hypertension in 66 young (age < 45 years) patients with high-normal BP and elevated (> 200 mg/dl, n = 46: HC) or normal (=200 mg/dl, n = 20: NC) serum cholesterol levels and in 20 normotensive, normocholesterolemic controls (C). The main outcome measure was the prospective evaluation of the 15-year incidence of stable hypertension in the different populations. RESULTS: New-onset hypertension was higher in patients with high-normal BP and HC when compared to NC patients [relative risk (RR) = 1.9; 95% confidence interval (CI), 1.1-4.3, P < 0.001] and control subjects (RR = 3.1; 95% CI = 1.4-5.3, P < 0.001). High PRA increased the overall rate of hypertension in both HC and NC. The interaction between HC and PRA was more evident in patients with borderline high cholesterol levels (200-240 mg/dl) where the adjusted relative risk of new onset of hypertension was 2.17 (95% CI 1.2-3.74; P < 0.05) in high PRA subjects and 1.17 (95% CI 0.67-2.23; P = 0.87) in subjects with normal PRA. CONCLUSION: We support the hypothesis that the presence of hypercholesterolemia can promote the development of stable hypertension through its interaction with the circulating renin-angiotensin system in patients with high-normal blood pressure.
Assuntos
Colesterol/sangue , Hipertensão/etiologia , Hipertensão/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Adulto , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Hipercolesterolemia/complicações , Hipertensão/sangue , Masculino , Renina/sangue , Fatores de RiscoRESUMO
BACKGROUND: Blood pressure (BP) control is reported to be poor in hypertensive patients worldwide. OBJECTIVE: BP levels, the rate of BP control, prevalence of risk factors and total cardiovascular risk were assessed in a large cohort of hypertensive patients, derived from recent surveys performed in Italy. METHODS: Fifteen studies on hypertension, performed in different clinical settings (general population, general clinical practice, specialist outpatient clinics and hypertension centres) over the past decade were considered. RESULTS: The overall sample included 52 715 hypertensive patients (26 315 men and 26 410 women, mean age 57.3 +/- 6.9 years). Despite the high percentage of patients on stable antihypertensive treatment (n = 36 556, 69%), mean systolic and diastolic BP levels were 147.8 +/- 8.5 and 89.5 +/- 5.2 mmHg, respectively. On the basis of the nature of the study (population surveys or clinical referrals), systolic BP levels were consistently higher than the normality threshold in both settings (142.6 +/- 12.4/84.8 +/- 3.7 mmHg and 150.4 +/- 4.6/91.9 +/- 4.1 mmHg, respectively). The BP stratification could be assessed in 40 829 individuals: 4.5% had optimal, 9.2% normal and 8.3% high-normal BP levels, however, the large majority were in grade 1 (39%) or grades 2-3 (32.6%) hypertension. In the overall sample, 55.9% of hypertensive patients had hypercholesterolemia, 28.7% were smokers, 36.4% were overweight or obese and 15.0% had diabetes mellitus. Cardiovascular risk stratification was assessed in 37 813 hypertensives: 23.2% had low, 33.9% moderate, 30.2% high and 12.7% very high added risk. CONCLUSION: Our analysis demonstrates the persistence of poor BP control and high prevalence of risk factors, supporting the need for more effective, comprehensive and urgent actions to improve the clinical management of hypertension.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Inquéritos Epidemiológicos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Idoso , Pressão Sanguínea/fisiologia , Estudos de Coortes , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: A number of patients with chronic heart failure (CHF) have diastolic but not systolic dysfunction. This occurs particularly in the elderly and in hypertension, but the prevalence of diastolic dysfunction in elderly hypertensives without CHF has never been investigated systematically. METHODS AND RESULTS: The Assessment of PRevalence Observational Study of Diastolic Dysfunction (APROS-diadys) project was a cross-sectional observational study on elderly (age >/= 65 years) hypertensives without systolic dysfunction [left ventricular ejection fraction (LVEF) >/= 45%] consecutively attending hospital outpatient clinics in Italy, in order to establish the prevalence of echocardiographic signs of diastolic dysfunction according to various criteria, and to correlate them with a number of demographic and clinical characteristics. Primary criteria for diastolic dysfunction was an E/A ratio (ratio between transmitral peak velocities of E and A waves) < 0.7 or > 1.5 on echocardiographic Doppler examination. Secondary criteria were: E/A < 0.5 and deceleration time (DT) > 280 ms, or isovolumic relaxation time (IVRT) > 105 ms or pulmonary vein (PV) peak systolic/peak diastolic flow (S/D) ratio > 2.5 or PV atrial retrograde flow (PV A) > 35 cm/s. Throughout Italy, 27 447 patients were screened in 107 clinics, with 24 141 excluded according to protocol. Among the remaining 3336 patients, 754 (22.6%) had signs of CHF. After exclusion of 37 protocol violators, 2545 patients (49.0% men, mean age 70.3 years, 95.4% under antihypertensive treatment) were studied ultrasonographically. Diastolic dysfunction (primary criteria) was found in 649 (25.8%) patients. Multiple logistic regression analysis found age, gender, left ventricular mass, systolic and pulse pressures and midwall shortening fraction as significant covariates. Using secondary criteria, the prevalence of diastolic dysfunction was higher (45.6%), mostly because of IVRT > 105 ms or PVA flow > 35 cm/s. CONCLUSION: CHF and diastolic dysfunction are highly prevalent in elderly hypertensives attending hospital clinics.
Assuntos
Diástole/fisiologia , Hipertensão/complicações , Hipertensão/fisiopatologia , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Estudos Transversais , Teste de Esforço , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/tratamento farmacológico , Itália/epidemiologia , Masculino , Disfunção Ventricular Esquerda/epidemiologiaRESUMO
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.
Assuntos
Captopril/análogos & derivados , Hipertensão/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Captopril/administração & dosagem , Captopril/uso terapêutico , Esquema de Medicação , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: No data are available on the clinical efficacy of the early administration (<24 hours from onset of chest pain) of angiotensin-converting enzyme inhibitors in non-thrombolysed patients with non-ST-elevation myocardial infarction (NSTEMI). We have addressed this issue in a subgroup of NSTEMI patients enrolled in the SMILE trial. METHODS: Of the overall population of 1556 patients, 526 (33.8%) had an anterior wall NSTEMI, defined as an ST elevation <1 mm or an ST depression in at least two contiguous precordial leads with or without new abnormal Q waves. No patient of the SMILE Study received thrombolytic therapy or was reperfused. Patients were randomized, double-blind, to zofenopril (n = 253) or placebo (n = 273) for 6 weeks. The primary end point was the effect of treatment on the 6-week combined occurrence of death and severe congestive heart failure (CHF). Secondary end points included the evaluation of the 6-week rate of severe CHF as well as the 1-year mortality rate. RESULTS: After 6 weeks of treatment, zofenopril significantly reduced both the incidence of the primary end point (risk reduction 65%, 95% CI 20-80, 2P = .003) and the 6-week incidence of severe CHF (84%, 95% CI 33-97, 2P = .006) in NSTEMI patients. One-year mortality was also significantly reduced by zofenopril treatment (43%, 95% CI 14-57, 2P = .036). CONCLUSIONS: Results of this post hoc analysis of the SMILE Study strongly suggest the benefit of the early administration of zofenopril even in patients with an anterior wall NSTEMI.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Idoso , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Captopril/análogos & derivados , Captopril/farmacologia , Captopril/uso terapêutico , Método Duplo-Cego , Eletrocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Fatores de TempoRESUMO
BACKGROUND: The aim of the SMOOTH (San Marino Observational Outlooking Trial on Hypertension) study was to explore hypertension awareness, treatment and control and the associated metabolic abnormalities and risk factors in the population of San Marino, a small state in the Mediterranean area, for which limited evidence is available. METHODS: Nine general practitioners enrolled 4590 consecutive subjects (44% of the San Marino population age 40-75 years), seen in their office by collecting history, physical and laboratory data and office blood pressure (BP) measurements. RESULTS: Of these subjects, 2446 were normotensive and 2144 hypertensive; 62.3% of hypertensive patients were aware of their condition, 58.6% were treated (monotherapy 31.5%, combination therapy 27.1%), and 21.7% were controlled. Hypertension awareness and treatment were more frequent above age 50 and in females; BP control was similarly low in both genders. As compared to normotensives, hypertensive subjects were less frequently smokers (20.1 versus 27.8%), had greater body mass index (28.1 +/- 4.5 versus 25.8 +/- 3.7 g/m), and a higher prevalence of diabetes mellitus (15.8 versus 6.3%), lower high-density lipoprotein (HDL) cholesterol and higher prevalence of increased blood total cholesterol (66.1 versus 51.3%), triglycerides and serum uric acid. Values of subjects with 'high-normal' blood pressure were closer to those of hypertensive subjects. The prevalence of metabolic syndrome was higher in hypertensive than in normotensive subjects, and in treated than in untreated hypertensives. CONCLUSIONS: Even in a small Mediterranean country with high health-care standards, hypertension awareness, treatment and control are inadequate and hypertension clusters with metabolic abnormalities and risk factors as in non-Mediterranean areas.