Development of congestive heart failure in type 2 diabetic patients with microalbuminuria or proteinuria: observations from the DIABHYCAR (type 2 DIABetes,Hypertension, CArdiovascular Events and Ramipril) study

OBJECTIVE: The DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) study allowed investigators to analyze factors leading to the development of congestive heart failure (CHF) in type 2 diabetic patients with abnormal urinary albumin concentration. RESEARCH DESIGN AND METHODS: Type 2 diabetic subjects of both sexes aged >or=50 years who had a urinary albumin concentration >or=20 mg/l were randomly allocated to 1.25 mg/day ramipril or placebo in addition to their usual treatment and treated for 3-6 years in a double-blind fashion. Major outcomes including hospitalization for CHF were recorded during the follow-up. RESULTS: Of the 4912 included patients, 187 developed CHF during the study. There was no significant difference in the incidence of CHF between the two treatment groups. Using a multivariate analysis, independent risk factors for the occurrence of CHF were age, history of cardiovascular disease, baseline urinary albumin concentration, baseline HbA(1c), and smoking habits. A total of 68 of the 187 patients (36.4%) died during the 12 +/- 11-month period after the first hospitalization for CHF, whereas the annual mortality rate of the population who did not develop CHF was 3.2%. CONCLUSIONS: Presence of atherosclerotic disease, baseline urinary albumin concentration, and HbA(1c) level were indicators for further development of CHF. Occurrence of CHF is a major prognostic turn in a diabetic patient's life.     

Assessment of patients' and physicians' compliance to an ACE inhibitor treatment based on urinary N-acetyl Ser-Asp-Lys-Pro determination in the Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study

OBJECTIVE: The purpose of this study was to assess patients' and physicians' compliance with ACE inhibitor treatment, by measuring an endogenous biomarker of ACE inhibition, urinary N-acetyl-Ser-Asp-Lys-Pro (AcSDKP), in the Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) trial, which compared ramipril (1.25 mg o.d.) with placebo in 4,912 patients with type 2 diabetes and microalbuminuria/proteinuria. RESEARCH DESIGN AND METHODS: The urine AcSDKP-to-creatinine ratio was measured blind to treatment in all participants who completed follow-up and provided spot urine samples (n = 1,871). RESULTS: The median urinary AcSDKP-to-creatinine ratio was six times higher for ramipril than for placebo. Urinary AcSDKP-to-creatinine ratios displayed a bimodal distribution in both groups, with a very large intergroup overlap. Based on cluster analysis, we defined truly adherent ramipril patients as those with a ratio > or =4 nmol/mmol and truly adherent placebo patients as those with a ratio < 4 nmol/mmol. After excluding patients withdrawing prematurely from the study or known to have used a nonstudy ACE inhibitor, 27.3% of the 597 ramipril patients had ratios <4, indicating poor compliance, and 9.7% of the 621 placebo patients had ratios > or =4, indicating intake of a nonstudy ACE inhibitor. Correcting for compliance by using AcSDKP-guided analysis affected surrogate outcome results (decrease in systolic blood pressure and urinary albumin excretion) only slightly. CONCLUSIONS: The systematic use of spot urinary AcSDKP determination facilitated the detection of defects in compliance with ACE inhibitor treatment in both patients and physicians. Urinary AcSDKP measurement could be a useful biomarker for assessing compliance with ACE inhibition in the routine care of diabetic patients.     

Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy

OBJECTIVES: Experimental and observational studies suggest that vitamin E may reduce the risk of cardiovascular (CV) events and of microvascular complications in people with diabetes. However, data from randomized clinical trials are limited. Therefore, we evaluated the effects of vitamin E supplementation on major CV outcomes and on the development of nephropathy in people with diabetes. RESEARCH DESIGN AND METHODS: The Heart Outcomes Prevention Evaluation (HOPE) trial is a randomized clinical trial with a 2 x 2 factorial design, which evaluated the effects of vitamin E and of ramipril in patients at high risk for CV events. Patients were eligible for the study if they were 55 years or older and if they had CV disease or diabetes with at least one additional coronary risk factor. The study was designed to recruit a large number of people with diabetes, and the analyses of the effects of vitamin E in this group were preplanned. Patients were randomly allocated to daily treatment with 400 IU vitamin E and with 10 mg ramipril or their respective placebos and were followed for an average of 4.5 years. The primary study outcome was the composite of myocardial infarction, stroke, or CV death. Secondary outcomes included total mortality, hospitalizations for heart failure, hospitalizations for unstable angina, revascularizations, and overt nephropathy. RESULTS: There were 3,654 people with diabetes. Vitamin E had a neutral effect on the primary study outcome (relative risk = 1.03, 95% CI 0.88-1.21; P = 0.70), on each component of the composite primary outcome, and on all predefined secondary outcomes. CONCLUSIONS: The daily administration of 400 IU vitamin E for an average of 4.5 years to middle-aged and elderly people with diabetes and CV disease and/or additional coronary risk factor(s) has no effect on CV outcomes or nephropathy.     

Efficacy and Safety of Zofenopril Versus Ramipril in the Treatment of Myocardial Infarction and Heart Failure: A Review of the Published and Unpublished Data of the Randomized Double-Blind SMILE-4 Study

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.     

Response of plasma neuropeptide Y and noradrenaline to dynamic exercise and ramipril treatment in patients with congestive heart failure

Summary. Forty-two patients with congestive heart failure were studied in order to clarify whether the plasma level of neuropeptide Y-like immunoreactivity (NPY-LI) rises in parallel with plasma noradrenaline (NA) during physical exercise in congestive heart failure (CHF). All patients were studied in a randomized placebo-controlled trial with the ACE-inhibitor ramipril during 12 weeks to determine whether ACE-inhibition alters the response of plasma NPY-LI to exercise. The patients were treated with diuretics and had stable congestive heart failure (NYHA classes II-III). Plasma NPY-LI was 50 5 pmol 1^-1 (mean standard error of the mean) at rest and 60 6 pmol l^-1 at the end of exercise at baseline (P < 0–01). The corresponding values for plasma NA were 2–8 0-2nmoll^-1 and 15-3 l-2nmoll^-1(P < 0–001). Before ACE-inhibition, there was a correlation between high NPY-LI and NA values after exercise. After treatment with ramipril or placebo for 12 weeks, there was no difference in plasma NPY-LI and NA at rest or after exercise between the two treatment groups. The maximal exercise time was unchanged. It is concluded that plasma NPY-LI and NA were elevated at rest in CHF. The additional rise of plasma NPY-LI and NA after exercise was attenuated in CHF compared to healthy individuals. ACE-inhibition with ramipril did not alter plasma NPY-LI or NA at rest or after exercise compared to placebo.     

Survival of myocardial infarction long-term evaluation (SMILE) study: Rationale,design, organization,and outcome definitions

The rationale, design, organization, and outcome definitions of the Survival of Myocardial Infarction Long-term Evaluation (SMILE) study are described in detail. Recruitment of a total of 1500 patients (750 per treatment group) has been planned for this multicenter, double-masked, randomized, placebo-controlled trial investigating the effects of oral treatment with zofenopril calcium (7.5-30 mg twice a day) on the combined short-term total mortality and occurrence of severe refractory congestive heart failure in patients with acute anterior myocardial infarction (AMI). Secondary outcomes of the study include recurrent myocardial infarction, angina, and progression of congestive heart failure, as well as long-term mortality. Patients are initially treated in hospital within 24 hr from the onset of symptoms of AMI and their active follow-up is continued for 6 weeks. In addition, the patients will be passively followed for 12 months from the index AMI to assess vital status and the occurrence of congestive heart failure. The trial data are analyzed on an intention-to-treat basis. An international independent policy and safety monitoring board is acting as the overall supervisory body and is responsible for the ethical conduct of the trial. A scientific committee is responsible for the scientific aspects of the trial and for the regular review of the progress of the study.     

Evaluation of outcome and cost-effectiveness using an FDG PET-guided approach to management of patients with coronary disease and severe left ventricular dysfunction (PARR-2): rationale, design, and methods

Patients with severe ventricular dysfunction and coronary disease have high morbidity and mortality. They may benefit from revascularization but have significant perioperative morbidity and mortality. Positron emission tomography (PET) imaging with F-18-fluorodeoxyglucose (FDG) can detect viable myocardium that may recover from revascularization in such patients. It is unclear whether use of FDG PET in this population improves outcome or is cost-effective. The principal aim of this study is to determine whether FDG PET-guided therapy improves clinical outcome compared to standard care. Secondary objectives are to determine whether FDG PET-guided therapy improves left ventricular (LV) function, improves quality of life, and provides a cost benefit versus standard care. Included in this multicenter randomized controlled trial are patients with coronary artery disease and severe LV dysfunction who are referred for revascularization, heart failure, or cardiac transplantation or in whom FDG PET is potentially useful. Consenting subjects will be randomized to therapy directed by FDG PET or standard care. The primary outcome is the composite cardiovascular endpoint of cardiac death, myocardial infarction, transplantation, or rehospitalization for unstable angina or heart failure. Secondary outcomes include health-related quality of life, costs, mortality, cardiovascular events, and LV function. Assuming two-sided alpha=0.05, power=80%, a sample size of 206 patients per group is required to detect a 15% absolute difference in the primary outcome between PET-directed therapy compared to standard care. Analyses will be conducted on an intention-to-treat basis. To our knowledge, this is the first large trial to evaluate whether FDG PET-directed therapy is effective and provides a cost benefit in patients with severe LV dysfunction. If so, thousands of such patients can be risk-stratified to select who is likely to benefit from revascularization.     

Ramipril for the prevention and treatment of cardiovascular disease

OBJECTIVE: To evaluate the effectiveness of ramipril in the prevention and treatment of cardiovascular disease and determine its need for inclusion on a formulary. DATA SOURCES: A MEDLINE and PubMed database search was conducted (1987-May 2002). Only journals written in the English language were selected for review. DATA EXTRACTION AND STUDY SELECTION: Articles reporting the use of ramipril in humans were evaluated. Emphasis was placed on randomized, controlled trials assessing efficacy. DATA SYNTHESIS: Ramipril is an angiotensin-converting enzyme (ACE) inhibitor that exerts its effects through inhibition of the renin-angiotensin-aldosterone system. It exhibits a safety profile that is similar to that of other ACE inhibitors and is comparable in cost to the majority of the available agents. Clinical trials have proven the effectiveness of ACE inhibitors in the treatment of hypertension, heart failure, and nephropathy. Ramipril, however, is the only ACE inhibitor currently approved for the prevention of cardiovascular events in high-risk patients without evidence of left-ventricular dysfunction or heart failure, based on the results of the HOPE (Heart Outcomes Prevention Evaluation) trial. Whether this effect is specific to ramipril has yet to be proven. This article emphasizes the major trials involving ramipril including the AIRE (Acute Infarction Ramipril Efficacy), REIN (Ramipril Efficacy in Nephropathy), and HOPE trials. CONCLUSIONS: Although similar to other ACE inhibitors in many aspects, it cannot be assumed that the benefits shown with ramipril in the HOPE trial are a class effect. Ongoing trials should help to clarify this matter. Until this time, current evidence justifies the inclusion of ramipril on a formulary.     

Beta-blockers: a new therapy in congestive heart failure.

BACKGROUND: Until recently, use of beta-blockers was contraindicated in treatment of patients with congestive heart failure. However, empirical evidence suggests that adding beta-blockers to the standard therapy can slow the progression of heart failure and reduce mortality, including sudden cardiac death. PURPOSE: To analyze the results of major, prospective, randomized controlled trials on the effects of beta-blockers in congestive heart failure and to provide recommendations for clinical practice and patients' education. METHODS: MEDLINE (1989-2001) and biomedical databases (1995-2001) were searched for literature on the use of beta-blockers in patients with congestive heart failure. Information on major randomized controlled trials of at least 6 months' duration with mortality as a major end point were reviewed. RESULTS: Both selective and nonselective beta-blockers significantly reduce mortality due to all causes; decrease need for hospitalization due to cardiovascular causes; and improve patients' New York Heart Association functional classification, hemodynamic status, left ventricular ejection fraction, and signs and symptoms of congestive heartfailure. However, clinical use of beta-blockers remains limited. CONCLUSION: Strong empirical evidence supports adding beta-blockers to the standard therapy for congestive heart failure. Future efforts should be directed toward establishing the safety and efficacy of beta-blockers in patients with severe heartfailure.     

Should all patients at high cardiovascular risk receive renin-angiotensin system blockers?

Despite considerable advances in preventative treatment during the last two decades, the increasing burden of cardiovascular (CV) disease constitutes an urgent need for new therapeutic strategies to reduce CV mortality and morbidity in patients at high CV risk. Activation of the renin-angiotensin system (RAS) results in vasoconstrictive, proliferative and pro-inflammatory effects that contribute to the development of atherosclerosis. As a result, the RAS is implicated at all stages of the 'CV continuum' that links risk factors such as hypertension and dyslipidaemia with major CV events, congestive heart failure (CHF) and CV death. The RAS therefore represents a rational and ideal therapeutic target in CV risk reduction strategies. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have been shown to promote beneficial effects on end-organ damage, such as decreases in arterial stiffness and left ventricular hypertrophy (LVH). Several trials have shown that ACE inhibitors and ARBs reduce CV risk in patients with specific risk factors. Furthermore, the HOPE study and, more recently, the ONTARGET? study have shown that ramipril and telmisartan reduce CV risk in patients with a high CV risk profile across the 'CV continuum'. Telmisartan is the first ARB to demonstrate CV prevention in patients at high CV risk, similar to that of the gold-standard ACE inhibitor, ramipril. This extensive clinical trial evidence suggests that ACE inhibitors or ARBs should be part of the standard treatment for patients at risk of CV events. ARBs may represent a preferred option due to their unsurpassed tolerability.     

SGLT2抑制剂对2型糖尿病患者心血管结局影响的网状meta分析

目的 2型糖尿病是一种慢性疾病,而心血管事件是2型糖尿病常见的并发症,已有大型研究表明钠-葡萄糖共转运体抑制剂(SGLT2i)对改善2型糖尿病患者心血管结局具有一定作用。本文通过系统评价,间接比较了5种不同的SGLT2i对2型糖尿病并发不良心血管事件的疗效作用。方法 检索PubMed、Web of science、Cochrane Library、中国知网、万方、维普数据库,收集相关文献,检索时限为建库至2022年7月,由两位研究员独立筛选文献,并提取相应数据,以心力衰竭住院和心血管死亡复合结局为主要结局指标,以心力衰竭住院、心血管死亡和全因死亡为次要结局指标,使用Stata 16.0以及network程序包进行网状meta分析。结果 共检索到340篇文献,最终纳入11篇文献,包括62 904例患者,涉及5种干预手段,分别为:恩格列净、索格列净、达格列净、埃格列净和卡格列净。5种不同的SGLT2i在改变2型糖尿病患者的心力衰竭住院和心血管死亡复合结局、心血管死亡、心力衰竭住院和全因死亡方面差异无统计学意义(P>0.05)。与安慰剂相比,5种不同的SGLT2i均可显著改善2型糖尿病患者心力衰竭住院结局;恩格列净和索格列净在改善心力衰竭住院和心血管死亡复合结局方面差异有统计学意义;而在改善心血管死亡或全因死亡结局方面,安慰剂和5种不同的SGLT2i之间的差异均无统计学意义。结论 在改善2型糖尿病患者心力衰竭住院和心血管死亡复合结局和心力衰竭住院结局方面,恩格列净和索格列净有较显著的获益趋势,而针对心血管死亡或全因死亡结局,5种不同的SGLT2i与安慰剂间的差异无统计学意义,具体机制和原因仍需大型研究进行探索和验证。     

The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not

The Heart Outcomes Prevention Evaluation (HOPE) study found that the ACE inhibitor ramipril can lower the risk of atherosclerotic disease events and death in patients without heart failure but with known atherosclerosis or with diabetes plus at least one cardiovascular risk factor. This benefit was independent of ramipril's effect on blood pressure. Additional benefits were a reduced risk of diabetic nephropathy in diabetic patients, and a lower likelihood of newly diagnosed diabetes. On the other hand, vitamin E in the doses and duration studied (400 IU/day for 4.5 years) did not lower risk significantly.     

N-terminal proBNP: a novel biomarker for the diagnosis, risk stratification and management of congestive heart failure

Congestive heart failure is a leading cause of morbidity and mortality throughout the world and is now the leading cause of hospitalizations in adults over 65 years of age with an estimated annual expenditure in excess of USD 20 billion. In addition, it is the only cardiovascular disorder that continues to increase in both incidence and prevalence, and as the population continues to age, it is expected that the prevalence of this disease will continue to rise. Ironically, the armamentarium of medications that decrease mortality due to congestive heart failure also continues to grow; however, the relative number of eligible patients with congestive heart failure (or at risk for congestive heart failure) that receive these important therapies remains low. Thus, better tools to aid the early diagnosis and management of this disease are needed. Testing for natriuretic peptide markers, such as B-type natriuretic peptide or its amino-terminal fragment, has emerged as an important tool to assist in the optimal diagnosis and risk stratification of patients with congestive heart failure and may also play a valuable role in guiding therapy.     

Cardiovascular death in patients with atrial fibrillation is better predicted by left atrial thrombus and spontaneous echocardiographic contrast as compared with clinical parameters.

We hypothesized that altered intra-atrial thrombogenicity, as reflected by the presence of left atrial (LA) thrombus or spontaneous echocardiographic contrast (SEC), would predict cardiovascular death in patients with atrial fibrillation (AF). In 175 patients with AF and no more than mild mitral regurgitation as detected by transesophageal echocardiography (TEE), 13 cardiovascular deaths occurred during a mean follow-up of 31 +/- 20 months. Multivariate logistic regression analysis using clinical variables identified the presence of congestive heart failure (relative risk [RR] = 4.22; P = .02) as the only positive predictor of cardiovascular death. However, when the TEE variables were added to the model, LA thrombus (RR = 5.52; P = .024) and LA SEC (RR = 7.96; P = .013) emerged as the only positive predictors of cardiovascular death. Kaplan-Meier analysis demonstrated a lower event-free survival from cardiovascular death in patients with LA thrombus and/or SEC ( P = .0013). These findings support AF as a contributing cause of cardiovascular death independent of clinically associated risk factors, such as hypertension, diabetes mellitus, smoking, congestive heart failure, and prior myocardial infarction.     

N-terminal proBNP: a novel biomarker for the diagnosis,risk stratification and management of congestive heart failure

Congestive heart failure is a leading cause of morbidity and mortality throughout the world and is now the leading cause of hospitalizations in adults over 65 years of age with an estimated annual expenditure in excess of US$20 billion . In addition, it is the only cardiovascular disorder that continues to increase in both incidence and prevalence , and as the population continues to age, it is expected that the prevalence of this disease will continue to rise. Ironically, the armamentarium of medications that decrease mortality due to congestive heart failure also continues to grow [3–5]; however, the relative number of eligible patients with congestive heart failure (or at risk for congestive heart failure) that receive these important therapies remains low. Thus, better tools to aid the early diagnosis and management of this disease are needed. Testing for natriuretic peptide markers, such as B-type natriuretic peptide or its amino-terminal fragment, has emerged as an important tool to assist in the optimal diagnosis and risk stratification of patients with congestive heart failure and may also play a valuable role in guiding therapy.     

卡维地洛在充血性心力衰竭治疗中的应用

目的研究新型β-受体阻滞剂国产卡维地洛(Carvedilol)对充血性心力衰竭患者心功能及神经内分泌激素的影响。方法40例住院慢性充血性心力衰竭患者,双盲随机分为安慰剂组及治疗组。治疗组在常规治疗基础上加服卡维地洛,安慰剂组在常规治疗基础上加服用等量安慰剂片。观察心率、血压、6 min步行距离、心功能级别、超声心动图测量左室射血分数(LVEF)、左室内径(LVDd),血浆去甲肾上腺素(NE)、肾素(PRA)、血管紧张素Ⅱ(AngⅡ)及血生化指标,并分别于治疗后1个月,3个月复查。结果心力衰竭患者血浆中NE、PRA、AngⅡ水平均较正常安慰剂组明显升高(P<0.01),且心衰越重,升高越明显。治疗组经治疗后血浆NE、PRA、AngⅡ水平均较治疗前明显下降(P<0.01),且心衰恶化发生率亦明显低于安慰剂组,严重心脏事件发生率亦较安慰剂组降低了76%(P=0.028),6 min步行距离、心功能级别均有明显改善,LVEF明显提高,LVDd缩小。结论卡维地洛能降低心衰患者血循环去甲肾上腺素、肾素及血管紧张素水平,改善慢性充血性心力衰竭患者的生活质量,改善心功能。     

老年心力衰竭患者甲状腺激素和血浆N末端原脑钠肽的变化及其与预后的关系

目的探讨老年慢性心力衰竭患者心功能与血清甲状腺激素、血浆N末端原脑利钠肽(NT-proBNP)的变化及对预后的影响。方法选择60例老年慢性心力衰竭患者,根据NYHA心功能Ⅱ、Ⅲ、Ⅳ级分为2组,分别测定血NT-proBNP、血清三碘甲状腺原氨酸(T3),甲状腺素(T4),游离三碘甲状腺原氨酸(FT3),游离甲状腺素(FT4)及促甲状腺素(TSH)水平。比较2组间甲状腺激素变化及NT-proBNP变化。根据住院期间是否发生心血管事件(恶性心律失常、心衰反复或加重、心肌梗死、死亡)分为事件组和非事件组。结果心功能Ⅳ级患者与心功能Ⅱ级、Ⅲ级患者比较,T3和FT3明显降低,(P<0.05),NT-proBNP随着心功能不全加重而升高(P<0.05)。而T4、FT4、TSH均无明显变化(P>0.05)。心脏事件组与非事件组比较:NT-proBNP明显升高,T3和FT3明显降低,(P<0.05)。结论甲状腺激素、NT-proBNP与老年慢性心力衰竭患者的心功能严重程度有关,影响预后。     

Pharmacotherapy of congestive heart failure in elderly patients

With longer life expectancy, as well as better survival rates after myocardial infarction, the population of elderly patients with congestive heart failure steadily increases. Large, randomized, placebo-controlled studies have shown significant beneficial effects for several classes of drugs (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, aldosterone antagonists) in patients with congestive heart failure. In most of these studies, however, elderly patients were either excluded or represented only a minority of the study population. Therefore, the treatment benefit for the large population of patients aged 65 and older is still not very well documented. In this paper, we critically review the current literature with regard to outcome of heart failure therapy in this particular subpopulation.     

Cardiovascular risk,hypertension, and NSAIDs

During the past 2 years, a great deal of evaluation has been conducted on the cardiovascular (CV) effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase (COX)-2 inhibitors. This review focuses on the effects of the NSAIDs and COX-2 inhibitors on blood pressure and CV events. Clinical trial databases for NSAIDs and COX-2 inhibitors have shown varying levels of destabilization of blood pressure control in treated hypertensive patients as well as variable incident rates of the development of arrhythmias, congestive heart failure, myocardial infarction, and stroke. Nonselective and COX-2 selective NSAIDs can be used carefully in arthritis patients with hypertension and stable CV disorders (excluding congestive heart failure and moderate to severe kidney dysfunction) when the individual clinical benefit of anti-inflammatory therapy outweighs the CV and gastrointestinal risk.     

Serum cholesterol levels on admission and survival in patients with acute myocardial infarction treated with zofenopril: a post hoc analysis of the Survival of Myocardial Infarction Long-term Evaluation trial

To evaluate the clinical efficacy of early angiotensin-converting enzyme (ACE) inhibition by zofenopril in patients with anterior myocardial infarction and normal or high plasma low density lipoprotein-cholesterolaemia. Post hoc analysis of the Survival of Myocardial Infarction Long-Term Evaluation study, a double-blind, clinical trial including 1400 patients with anterior myocardial infarction, randomized to zofenopril ( n  = 699, 66% hypercholesterolemics) or placebo ( n  = 701, 64% hypercholesterolemics) for 6 weeks. The rate of the primary end-point (6-week combined occurrence of death and severe congestive heart failure) was 8.1% in hypercholesterolemic and 6.4% in normocholesterolemic patients ( P  < 0.03). The favourable effect of treatment with zofenopril was enhanced in hypercholesterolemics patients when compared with normocholesterolemics (RRR = 43%, P  = 0.034 vs. 25%, P  = 0.19). One-year mortality was 10% in hypercholesterolemic patients vs. 7.5% in normocholesterolemic patients ( P  = 0.037), equally reduced in both hypercholesterolemic and normocholesterolemics patients by zofenopril. The presence of hypercholesterolaemia in patients with anterior myocardial infarction could be associated with more favourable effects of early ACE-inhibition.