Clinical evidence of dose-dependent interaction between aspirin and angiotensin-converting enzyme inhibitors

Since coronary artery and cerebrovascular diseases are the most common serious complications of long standing hypertension, there is a great potential for combining treatment with aspirin and angiotensin-converting enzyme inhibitors (ACE-I). However, the data regarding interaction of aspirin and ACE-I in relation to blood pressure control and survival benefits are controversial and inconclusive. We presumed that the appearance of dry cough in some of the patients following initiation of ACE-I treatment could be used as a marker for the presence of their influence, whereas ACE-I cough attenuation after addition of aspirin to treatment could be a sign of aspirin and ACE-I interaction on clinical level. The present study was aimed to use ACE-I induced cough as a clinical marker of ACE-I activity to determine whether dose-dependent aspirin and ACE-I interaction does exist. In a cohort of 750 consecutive ACE-I treated hypertensive and postinfarction outpatients we identified 78 (10.4%) non-smoking ACE-I related coughers. Out of them, 31 (21 men, 10 women; mean age 61 +/- 0.9 years) agreed to take part in the study, which was aimed to compare two regimens of combined ACE-I and aspirin treatment (self-matched control data): intermediate (500 mg daily) vs low-dose aspirin (100 mg daily). On each visit the life quality, cough severity (CS, 0-4) and frequency (CF, 0-10) scores were registered. Low doses of aspirin demonstrated an excellent safety profile and did not influence any life quality score and ACE-I induced cough. In contrast, intermediate doses completely abolished cough in 17 patients and reduced coughing in other 11 patients. Cough severity and cough frequency scores decreased, respectively, from 2.7 +/- 1.1 to 0.7 +/- 1.2 (P < 0.001) and from 7.1 +/- 2.3 to 2.0 +/- 2.2 (P < 0.0001). Overall, the cough frequency score method alone could identify a clear modification of cough in 26 (84%) patients, and cough severity score method alone in 24 (77%). Using the combined frequency/severity score method a modification of cough could be identified in 28 (90%) of the patients receiving intermediate dose of aspirin. Aspirin did not influence heart rate and blood pressure control either in hypertensives or in postinfarction patients. We conclude that using ACE-I induced cough as a clinical marker of ACE-I activity demonstrates that an interaction between ACE-I and aspirin at 500 mg/day does exist. We did not find any evidence supporting the presence of a clinically significant interaction between ACE-I and aspirin at 100 mg/day. Thus, combined treatment by low dose aspirin and ACE-I seems to be both safe and useful.     

Relationship between acute pancreatitis and ACE inhibitors

Most of the acute pancreatitis cases are due to cholelithiasis and alcohol intake.Two percent of the cases are related to medications. Drugs including ACE (angiotensin-converting enzyme) inhibitors and thiazide diuretics may cause acute pancreatitis. Patients with biliary system disorders using certain drugs may develop acute pancreatitis and this may be confusing when considering the aetiology. We report a patient without any known risk factor who developed acute pancreatitis shortly after the intake of lisinopril and hydrochlorothiazide. Common bile duct stone and biliary sludge were diagnosed after physical and radiological evaluation.     

ACE polymorphism and use of ACE inhibitors: effects on memory performance

Memory is an important cognition function, being fundamental to the development and independence of individuals. Our aim was to investigate the influence apolipoprotein E (APOE) and angiotensin I-converting enzyme (ACE) polymorphism and ACE inhibitors use, besides their interaction on memory performance of healthy subjects over 50 years. The sample consisted of 205 subjects assessed for five types of episodic memory, using Wechsler Memory Scale-Revised (WMS-R), who answered a questionnaire about drug use and were assessed for the ACE insertion/deletion polymorphism and APOE polymorphism. We found no influence of the APOE gene. The use of ACE inhibitors beneficially influenced learning ability scores (p = 0.02). Besides, I allele carriers of ACE polymorphism showed higher verbal memory scores compared with homozygous DD. Also, we observed an interaction influencing learning ability between the ACE polymorphism and the use of inhibitors, the beneficial influence of the I allele was present only in individuals who make use of ACE inhibitors. We conclude that the ACE gene has influence on memory performance, and that this influence is modulated by ACE inhibitors use.     

ACE inhibitors and chronotherapy

Chronotherapy can improve the effectiveness and reduce the adverse reactions of drugs and actually is used for several conditions including cardiovascular diseases. Although angiotensin converting enzyme (ACE) inhibitors are available for the therapy of patients with hypertension and/or heart failure, these agents have some characteristic adverse effects such as angioedema and dry cough. It has been reported that the dosing of ACE inhibitor at an inactive period has a better protective effect against cardiac hypertrophy in hypertensive rats, and changing dosing time from morning to evening reduces the severity and frequency of the drug-induced dry cough of hypertensive patients treated in the morning. Thus, the dosing of ACE inhibitors in the inactive span is more effective and safe. Dosing in the evening may be an alternative for hypertensives with dry cough with a morning dose of ACE inhibitors, if one ascertains that no circadian hyperamplitude tension is induced by the evening dose of this or any other antihypertensive drug.     

Effects of aspirin and clopidogrel on plasma brain natriuretic peptide in patients with heart failure receiving ACE inhibitors

BACKGROUND: By inhibiting prostaglandins, aspirin may be deleterious in heart failure (HF) and/or may counteract angiotensin-converting enzyme (ACE) inhibitor efficacy. Conversely, clopidogrel has no effect on prostaglandin metabolism. AIM: To investigate the effect of aspirin and clopidogrel on brain natriuretic peptide (BNP) levels in HF patients treated with ACE inhibitors. METHODS: 36 patients with stable HF (65+/-13 years, 24 males/12 females, NYHA class II to IV, ejection fraction <40%, 13 with coronary disease, all treated with ACE inhibitors) were enrolled in this prospective, double-blind study and randomised to aspirin 325 mg/day or clopidogrel 75 mg/day for 14 days. BNP was determined at day 0 and day 14. RESULTS: 19 patients were randomised to aspirin and 17 to clopidogrel. Baseline characteristics were similar in both groups. BNP levels increased in the aspirin group from day 0 to day 14 (107+/-103 to 144+/-149 pg/ml, p=0.04) whereas clopidogrel had no effect (104+/-107 and 97+/-99 pg/ml respectively, p=0.61). CONCLUSION: This study demonstrates an adverse effect of aspirin 325 mg/day on BNP plasma levels in HF patients treated with ACE inhibitors. In contrast clopidogrel 75 mg/day had no effect.     

Sudden death: ACE inhibitors and beta-blockers

Sudden death is extremely common in patients suffering from cardiovascular diseases. At least one third of those with hypertension and probably about half of those who survive a myocardial infarction or suffer from cardiac failure who die in a clinical trial, die suddenly. Beta-blockers reduce the risk of sudden death in patients with cardiovascular disease, particularly in those who have had a myocardial infarction or heart failure. ACE inhibitors are perhaps less effective. Other cardiovascular drugs have not been shown to reduce the risk of sudden death.     

从机制谈ACE/ACE2、RAS抑制剂与COVID-19的关系

2019冠状病毒病(COVID-19)的发现与蔓延引起社会各界广泛关注,医学界关于血管紧张素转换酶(ACE)/ACE2、肾素-血管紧张素系统(RAS)抑制剂与COVID-19之间的关系众说纷纭。ACE和ACE2结构相似但作用相反,体内正向ACE-AngⅡ-AT1R轴和负向ACE2-Ang(1-7)-Mas轴相互制衡,维持血压及内环境的稳定。多项基础研究显示,不同RAS抑制剂对ACE2的影响不一致,尚不能明确ACE2与COVID-19的因果关系,也未发现使用RAS抑制剂有加重COVID-19的临床证据。ACE2影响COVID-19病情的考量,基本来自于RAS理论推导和SARS基础研究的结果推论。合并COVID-19的心血管疾病患者使用RAS抑制剂应结合临床实践情况并权衡利弊,不能在当前模棱两可形势下就随意停用循证医学证据充分的RAS抑制剂。     

Cough and ACE inhibitors.

To assess the prevalence of cough as a side effect of angiotensin-converting enzyme inhibitor antihypertensive therapy, we reviewed 300 consecutive patient charts from a private practice and 200 consecutive patient charts from a university-based referral center for hypertension. Incidence of definite angiotensin-converting enzyme inhibitor-induced cough in the private practice was 25% and in the university practice, 7%, with an additional 6% of university-practice patients reporting a possible angiotensin-converting enzyme-inhibitor induced cough. This incidence is considerably greater than listed in the Physicians' Desk Reference. Reasons for the variability in incidence as reported in the literature are explored. Clinicians must be aware of this potentially disturbing side effect of angiotensin-converting enzyme inhibitors to avoid expensive and unnecessary diagnostic evaluations.