Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in clinical practice

This survey was performed to determine the clinical characteristics of patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors in clinical practice. A total of 386 investigators were asked to consecutively include outpatients under treatment with RAAS inhibitors (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers [ARBs] or both) for at least 6 months. In total, 2895 patients were included. The most frequent reason for prescribing RAAS inhibitors (particularly ARBs) was hypertension (p < 0.0001). When compared with ARBs, angiotensin-converting enzyme inhibitors were more frequently prescribed in patients with ischemic heart disease or heart failure, but lesser prescribed in those with left ventricular hypertrophy, diabetic nephropathy or microalbuminuria. Patients with left ventricular hypertrophy, diabetic nephropathy or microalbuminuria were more commonly treated with the combination of treatments.     

Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension

BACKGROUNDRecent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers (ACEIs/ARBs) had no harmful effects on coronavirus disease 2019 (COVID-19) patients complicated with hypertension.AIMTo investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs.METHODSAll COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study. Some patients switched from ACEIs/ARBs to calcium channel blocker (CCBs) after admission, while others continued using non-ACEIs/ARBs. We compared characteristics and clinical outcomes between these two groups of patients. RESULTSA total of 53 patients were enrolled, 27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs. After controlling potential confounding factors using the Cox proportional hazards model, hospital stay was longer in patients who discontinued ACEIs/ARBs, with a hazard ratio of 0.424 (95% confidence interval: 0.187-0.962; P = 0.040), upon discharge than patients using other anti-hypertensive drugs. A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases [hazard ratio = 0.224 (95% confidence interval: 0.005-0.998; P = 0.0497)]. CONCLUSIONPatients in the discontinued ACEIs/ARBs group had longer hospital stays. Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.     

Early application of angiotensin converting enzyme inhibitors in acute myocardial infarction]

Inhibitors of angiotensin converting enzyme (ACE) were tried in patients early after myocardial infarction (MI) irrespective of the severity of circulation insufficiency. Monopril was used in 23 patients in the dose 7.6 mg/day. Ednit was given to 21 patients in the dose 5.3 mg/day. Control groups included 19 and 21 patients, respectively. All the patients underwent treadmill test and echocardiography on MI day 1 and 13-14. ACE inhibitors provide better exercise tolerance and favourable course of MI even in the absence of marked manifestations of cardiac failure though left ventricular ejection changed insignificantly. They may also prevent myocardial ischemia. The difference between monopril and ednit effects was insignificant.     

The role of angiotensin receptor blockers and/or angiotensin converting enzyme inhibitors in the prevention of atrial fibrillation in patients with cardiovascular diseases: meta-analysis of randomized controlled clinical trials

The inhibition of the renin-angiotensin system has demonstrated both experimental and clinical effects in preventing atrial fibrillation. However, there is still uncertainty about the role of these drugs in clinical practice. The objective of this review has been to assess the effects of angiotensin II type-1 receptor blockers (ARBs) and/or angiotensin converting enzyme inhibitors (ACEIs) for preventing atrial fibrillation. We searched the Cochrane controlled Trials Register (Cochrane Library Issue 4, 2002), MEDLINE (January 1980 to November 2003), EMBASE (January 1980 to November 2003) and reference list of articles. We also contacted manufacturers and researchers in the field. Selection criteria: We conducted a meta-analysis of all randomized controlled clinical trials that compared ARBs and/or ACEIs with either placebo or conventional therapy in patients with either hypertension, heart failure, ischemic heart disease, or diabetes mellitus. The pooled outcome was the development of new onset atrial fibrillation. Two reviewers independently assessed trial quality and extracted data. In some cases, the study authors were contacted for additional information. Seven trials involving a total of 24,849 patients were included (11,328 randomized to active therapy and 13,521 to control). There was a significant statistical difference in the pooled development of atrial fibrillation between the treatment and control group. (OR, 0.57; 95% CI, 0.39 to 0.82); test for overall effect z = 2.98 P = 0.003). Treatment with ACEIs/ARBs markedly reduces the risk of development or recurrence of atrial fibrillation.     

Differential antiplatelet effects of angiotensin converting enzyme inhibitors

BACKGROUND: Increasing evidence suggests that angiotensin converting enzyme (ACE) inhibitors exert antithrombotic effects. Based on the assumption of differential effects of various ACE inhibitors on coagulation, the aim of the present study was to evaluate the coagulative activities of cardiovascular (CV) patients treated with either ramipril, captopril, and enalapril, and to compare these with patients treated with established antithrombotics such as aspirin (ASA) and clopidogrel or none of these medication. METHODS: Blood samples of 320 CV patients with coronary artery disease and/or arterial hypertension were analyzed by wholeblood aggregometry. Platelet aggregation was determined by measuring the increase in impedance across paired electrodes in response to the aggregatory agents collagen and adenosine diphosphate (ADP), respectively. These data were correlated with medical treatment. RESULTS: Platelet aggregation was attenuated ex vivo by ramipril and captopril as well as by ASA and clopidogrel. While collagen-induced platelet aggregation was significantly reduced by ramipril (35%; P <0.01) and captopril (27%; P = 0.01), no change was seen with enalapril. After induction with ADP, platelet aggregation was reduced in the presence of captopril therapy by 46% (P <0.05). There was a trend of inhibition with ramipril (32%, P = n.s.), whereas no antithrombotic effect was seen with enalapril. CONCLUSION: Our findings demonstrate that ACE inhibitors decrease platelet aggregation ex vivo. The differential antiaggregatory profile may explain at least in part different effects of ACE inhibitors on cardiovascular endpoints as observed in large clinical trials.     

Use of angiotensin receptor blockers (ARBs) in the metabolic syndrome

The metabolic syndrome is a syndrome characterized by visceral obesity, and is associated with lipid abnormalities, hypertension, and hyperglycemia. The prevalence of this syndrome is increasing in Japan, mainly because of widespread lifestyle changes. Studies from our and other laboratories have shown that early intervention with an ARB can attenuate the development of hypertension in animal models, with a similar trend found in the recent TROPHY clinical study. ARBs also cause inhibition of new-onset diabetes, and may have beneficial effects on insulin resistance and lipid metabolism. The results of multiple laboratory studies and clinical trials suggest that early intervention with ARBs will play an increasing role in preventing progression of the metabolic syndrome and its complications.     

甲状腺功能亢进性心肌病兔血管紧张素转换酶及血管紧张素Ⅱ型受体的表达

目的 探讨甲状腺功能亢进性心肌病(甲亢性心肌病)的发病机制.方法 将40只健康成年新西兰大白兔随机均分为空白对照组、L-甲状腺素(L-Thy)组、咪哒普利组和缬沙坦组4组.用L-Thy 45 μg· kg-1·d-1连续腹腔注射28 d建立甲亢性心肌病动物模型.测定各组动物左右心室肥厚指数和心肌细胞直径;用Masson染色法测定胶原容积分数;用放射免疫法检测血浆及组织血管紧张素Ⅱ(AngⅡ)浓度;用逆转录-聚合酶链反应(RT-PCR)半定量法检测血管紧张素转换酶(ACE)、Ⅰ型血管紧张素Ⅱ受体(AT1R)、Ⅱ型血管紧张素Ⅱ受体(AT2R)的mRNA表达;用蛋白质免疫印迹法(Western blotting)检测ACE、AT1R、AT2R的蛋白表达.结果 L-Thy可诱导心肌肥厚及心肌纤维化,使血浆与局部组织AngⅡ浓度升高,并可使ACE、AT1R、AT2R的mRNA及蛋白表达均上调(P均＜0.01).咪哒普利和缬沙坦均可显著抑制L-Thy诱导的心肌肥厚和纤维化(P均＜0.05);咪哒普利还可降低血浆与局部心肌组织AngⅡ水平(P均＜0.01),对AT1R、AT2R和ACE的mRNA和蛋白表达均无影响(P均＞0.05);缬沙坦能显著升高血浆AngⅡ浓度(P＜0.01),但不升高组织AngⅡ浓度(P＞0.05),并能显著上调AT1R、AT2R的mRNA及蛋白表达(P均＜0.01),对ACE的mRNA和蛋白表达无影响(P均＞0.05).结论 肾素-血管紧张素系统可能参与甲亢性心肌病的发病机制.咪哒普利和缬沙坦可以改善L-Thy诱导的心室重构.     

Serum angiotensin converting enzyme activity in patients with psoriasis

Serum angiotensin converting enzyme activity is frequently increased in patients with active sarcoidosis. In spite of a reported association between sarcoidosis and psoriasis, serum angiotensin converting enzyme activities have not been reported for patients with psoriasis. We found the mean (SD) angiotensin-converting enzyme activity for 51 healthy subjects was 18.6 (5.8) kU/l, but for 52 patients with psoriasis without coexisting sarcoidosis, it was 28.3 (6.7) kU/l. There is a significant difference between these means (p less than 0.01). Forty-two percent (22/52) of the psoriasis patients had an increased serum angiotensin converting activity. Other diseases sometimes associated with an increased serum angiotensin converting enzyme activity were excluded as possible causes of a elevated activity in our patients with psoriasis. We conclude that almost half of the patients with psoriasis will have an elevated serum angiotensin converting enzyme activity, even when coexisting sarcoidosis is absent.     

椎基底动脉供血不足患者与血管紧张素转换酶基因和AT1R基因多态性的相关性研究

目的　探讨椎基底动脉供血不足 (VBI)与血管紧张素转换酶 (ACE)基因插入 /缺失(insertion/deletion ,I/D)和血管紧张素Ⅱ的 1型受体 (AT1R)基因A116 6 C多态性的关系。方法　采用聚合酶链反应 限制性内切酶片段长度多态性技术 (PCR RFLP)分别检测 12 0例VBI患者和 14 6名正常人对照的ACEI/D基因及AT1RA116 6 C突变位点基因型。结果　VBI患者中ACEI/D基因的基因型频率、等位基因频率与正常对照组比较 ,差异具有显著意义 (P <0 0 5) ;VBI患者中AT1R基因型频率、等位基因频率与正常对照组比较 ,差异具有显著意义 (P <0 0 5)。两组ACE和AT1R联合基因分析 :Ⅱ AA基因型频率VBI组与正常对照组比较 ,差异具有非常显著意义 (P <0 0 1) ,DD AA基因型频率VBI组与正常对照组比较 ,差异具有显著意义 (P <0 0 5) ,其余联合基因型分析均P >0 0 5,尚不能认为差异具有统计学意义。结论　ACE基因中D等位基因及AT1R基因A116 6 点突变基因型C可能对VBI的发生有重要意义 ;在VBI的发生中 ,ACE基因及AT1R基因多态性Ⅱ AA联合基因型对VBI的发生可能存在负协同作用 ,而DD AA则可能对VBI的发生存在正协同作用     

Acute effects of the angiotensin converting enzyme inhibitor ramipril in patients with coronary heart disease

We investigated the acute effect of the new long-acting ACE-inhibitor ramipril on angina-limited exercise tolerance and exercise-induced ST-depression in 18 normotensive patients with angiographically confirmed coronary artery disease in a double-blind, placebo-controlled study. Patients underwent a repeat exercise ECG 24 hours following either 5 mg ramipril p.o. or placebo. Plasma-ACE activity (nmol/min x ml) in the ramipril-group (n = 8) was significantly reduced 24 hours after 5 mg ramipril compared to placebo (n = 10): 14.0 +/- 2.0 vs 87.2 +/- 13.5, p less than 0.001. Exercise-induced ST-segment depression was not different before and after ramipril or placebo. Heart rate at rest and during angina-limited exercise was not different between the first exercise-ECG and that after ramipril or placebo, nor between the groups. Systolic arterial pressure (mmHg) was slightly, but insignificantly, lower after than before ramipril at rest (113.8 +/- 5 vs 125 +/- 6.8) and at maximal exercise, 1.5 watt/kg (150 +/- 9.4 vs 158.3 +/- 13.3). In the placebo group, blood pressure at rest and during exercise was not different before and after placebo: 126 +/- 4.7 vs 125.5 +/- 7.5 and 157.5 +/- 3.8 vs 158 +/- 3.6. Rate-pressure-product (mmHg/min x 1000) at rest prior to (8.42 +/- 0.83 and 8.95 +/- 0.51) and after ramipril or placebo (8.00 +/- 0.94 and 8.93 +/- 0.71) showed no significant difference. Similarly, rate-pressure-product at maximal exercise was equal among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: what we know and current controversies

A little more than a decade ago, management of heart failure was changed forever when a number of randomized clinical trials confirmed that a class of drugs, angiotensin-converting enzyme (ACE) inhibitors, could improve survival in patients with heart failure. The recognition that blockade of one of the neurohumoral systems activated in heart failure could improve outcomes prompted widespread testing of other neurohumoral blockers, such as beta-adrenergic blocking agents, aldosterone antagonists, and most recently, angiotensin II type 1 receptor blockers (ARBs) for the treatment of heart failure. This article describes what is known about the use of ACE inhibitors and ARBs in the management of heart failure and presents the current controversies surrounding the use of these agents.     

血管紧张素转换酶抑制剂降低高血压患者心房颤动发生危险

目的　研究血管紧张素转换酶抑制剂 (ACEI)对高血压患者发生心房颤动 (房颤 )危险的影响。方法　将高血压患者分为房颤组 (n =1 5 6 )和非房颤组 (n =1 5 6 ) ,对其服药情况进行回顾性调查。结果　房颤组服用ACEI者有 4 0例 (2 5 .6 % ) ,非房颤组服用ACEI者有 6 5例 (4 1 .7% ) ,两组相比差异具有统计学意义 (P<0 .0 1 ) ,服用ACEI的患者发生房颤的危险降低 (OR =0 .4 8)。结论　ACEI能够降低高血压患者房颤发生危险