Search

Introduction: The association between an ACE-inhibitor and a beta-blocker is recommended in case of complicated arterial hypertension and heart failure with reduced ejection fraction. This retrospective drug-utilization study has described its chronic use from the Italian National Healthcare Service perspective., Methods: From the ReS (Ricerca e Salute) database, collecting Italian healthcare administrative data, patients receiving an ACE-inhibitor or a beta-blocker from 2013 to 2019 were selected. The prevalence of use (patients treated/1000 inhabitants) and of continuous treatment (patients treated for ≥80% period from the supply to the end of the same year - by means of dosage units - per 1000 inhabitants) of each single active substance were assessed. Among patients continuously treated, those supplied with an ACE-inhibitor and a beta-blocker (unfixed and fixed combinations) were analyzed in terms of prevalence of continuous treatment. Subjects treated with the unfixed combination ramipril-bisoprolol in 2019 were characterized by gender and age., Results: The prevalence of ACE-inhibitors' use increased from 49.7/1000 inhab. in 2013 to 50.2 in 2019: ramipril was the most supplied each year (28.9 to 31.6/1000 inhab.). The prevalence of continuous treatment increased from 27.4 to 28.3/1000 inhab.: ramipril the most continuously dispensed (16 to 18/1000 inhab.). The prevalence of beta-blockers' use increased from 61.0 to 90.4/1000 inhab.: bisoprolol the most supplied and with the highest increase (27.1 to 52.2/1000 inhab.). The prevalence of continuous treatment increased from 33.1 to 55.8/1000 inhab.: bisoprolol the most continuously dispensed (18 to 37/1000 inhab.). Among patients with continuous supplies, from 49,843 a 51,496 were treated with associations between an ACE-inhibitor and a beta-blocker on an ongoing basis. Half of them were continuously treated with the unfixed combination ramipril-bisoprolol (4.3 to 4.8/1000 inhab.). In 2019, subjects with continuous supplies of ramipril-bisoprolol were mainly males (63.4%) and elderly (mean age 71±12), and the prevalence of use increased with age., Conclusions: These findings, together with recommendations from the main international guidelines encourage to make available also ramipril and bisoprolol as fixed dose combination, in order to simplify the therapy administration and improve the adherence, especially among elderly and patients with multimorbidity.

The presence of hyperkalemia (HK) in patients with heart failure (HF)or chronic kidney disease (CKD) increases the risk of death. The aims of the present study have been: i) to evaluate if the risk of cardiovascular (CV) events and mortality increases in two cohorts of patients with heart failure (HF) or chronic kidney disease (CKD) affected by hyperkalemia (HK) and treated with renin-angiotensin-aldosterone system inhibitors (RAASi). We have also evaluated the risk of dialysis among CKD patients; ii) to provide an estimate of the increased risk of CV events and mortality caused among HK patients by a non-optimal adherence to RAASi therapy in both HF and CKD cohorts. This is a retrospective study, based on the administrative databases of five Italian Local Health Units. All patients ≥18-year-old discharged from hospital with a diagnosis of HF (ICD-9-CM 428) or CKD (ICD-9-CM585) between January 2010 and December 2017 were enrolled. We defined as index date (ID) the date of first diagnosis during the enrolment period. Only patients that were prescribed RAASi therapy during the first three months after the ID were considered. Serum potassium level was tested in the three months before and after ID. The patients were considered as having HK if they presented a serum potassium level ≥5.5 mmol/l. Results show that patients with HK treated with RAASi were respectively 46% (HF) and 31% (CKD) more at risk of CV events and 88% (HF) and 72% (CKD) more at risk of dying. Moreover, the risk of dialysis in CKD patients increased by 458%. After the onset of HK, non-optimal adherence to RAASi in patients with HK was found to increase notably the risk of CV events (65% HF, 34% CKD) and mortality (127% HF, 122% CKD) in both cohorts., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Angiotensin-converting enzyme (ACE-I) inhibitors and ARBs have shown real efficacy in reducing blood pressure, proteinuria, in slowing the progression of chronic kidney disease (MRC) and in clinical improvement. in patients with heart failure, diabetes mellitus and ischemic heart disease. However, their use is limited by some side effects such as the increase in serum potassium (K), which can be particularly severe in patients with renal insufficiency. In the 23,000 patients followed by the PIRP project of the Emilia-Romagna Region, hyperkalaemia at the first visit (K> 5.5 mEq / L) was present in about 7% of all patients. The prevalence of K values> 5.5 mEq / L increased in relation to the CKD stage, reaching 11% in patients in stage 4 and 5. Among patients with values of K> 5.5 at baseline, 44.8% were in therapy with ACE-I / ARB inhibitors, 3.8% with anti-mineralcortoid and a further 3.9% concurrently taking SRAA-blocking agents and K-sparing diuretics. Counter-measures to avoid the onset of hyperkalemia during treatment with drugs that block the RAAS range from the low-K diet, to diuretics and finally to drugs that promote fecal elimination of K. Among these, polystyrene sulfonates, which have more than 50 years of life, exchange K with sodium or calcium. These drugs, however, in chronic use, can lead to sodium or calcium overload and cause dangerous intestinal necrosis. Recently two new highly promising drugs have been introduced on the market for the treatment of hyperkalemia, the patiromer and sodium zirconium cyclosilicate. The patiromer, which is a potassium-calcium exchanger, acts at the level of the colon where there is a higher concentration of K and where the drug is most ionized. Sodium zirconium cyclosilicate (ZS-9) is a resin with micropores of well-defined dimensions, placed in the crystalline structure of the zirconium silicate. The trapped K is exchanged with other protons and sodium. However, even these drugs will have to demonstrate their long-term efficacy and safety to be considered true partners of RAAS blockers in some categories of patients., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Man, 60 years old, in two weekly haemodialysis from 2009. From 2007 in treatment with once-daily telmisartan 40 mg for hypertension. From 2008 showed recurrent pharingitys. In June 2011 bacterial cystitis showed at the same time. The telmisartan was discontinued and both problems solved.

Angiotensin-converting enzyme inhibitors (ACE-i) and angiotensin II receptor blockers (ARBs) are of paramount importance in everyday clinical practice. Developed as antihypertensive drugs, they soon acquired another important indication as a result of their antiproteinuric activity and capacity to delay the progression of chronic kidney disease. ACE-i and ARBs started out being used as single drugs and were subsequently combined to obtain more complete blocking of the renin-angiotensin-aldosterone system (RAAS). The most evident advantages derived from the administration of these drugs - alone or in combination - have been obtained in proteinuric nephropathies, such as chronic glomerulonephritis and diabetic nephropathy, where they have become the treatment choice. Dual RAAS blockade has been recently evaluated in a large trial of high-risk cardiovascular patients, in whom no related benefits were shown. To the contrary, a higher risk of worsening renal function emerged. It is now quite clear that patients with high proteinuria levels are the ones that benefit most from RAAS inhibition, also with combined ACE-i and ARB. It is very important to pay the utmost attention when these drugs are used in patients in whom no benefit is obtained by RAAS inhibition, such as patients with chronic kidney disease and atherosclerosis, elderly patients, and those without any significant proteinuria.

ACE inhibitors and angiotensin receptor blockers confer renal protection in proteinuric nephropaties, but recently worsening of renal outcomes has been reported in non-proteinuric patients treated with a combination of ramipril and telmisartan, compared to ramipril only. In view of these apparently contradictory data, the review wants to shed light on treatment modalities of patients with hypertension and chronic kidney disease.

The aim of the study was to determine incidence, features and outcomes of the adverse drug reactions (ADR) among emergency department (ED) visits of S. Giovanni Battista Hospital in Turin. We evaluated 16.055 patients among ED visits in a period of five months; the mean age was 59.6 +/- 20.2 year (range 17-93 y; 8.054 women and 8.001 men); 426 (2.6%) had ADRs, and 91 (21.4%) were admitted to the hospital. In multivariate analysis only the number of medicines was positive correlated with ADR. The drugs most frequently ADR-related were: anticoagulants (21.8%), antibiotics (17.6%), NSAIDs (9.9%), hypoglycaemic agents (9.6%), ACE-inhibitors (4.7%), antipyretics (4%) and alfa-litics (3.3%); the most common clinic events were: gastrointestinal bleeding (21.1%), rash (19.7%), confusion (23.9%), hypoglycaemia (8.4%), dyspnoea (7.0%), syncope and wheezing (5.6%), gastrointestinal bleeding (2.8%), anaemia (2.8%), haematomas (4.2%), vomiting (4.2%). Factor associated with increased ADR-hospital admission were increasing age (over 65 years old), gastrointestinal diseases, dementia and ADL-dependence. ADR-patients' Emergency Department mortality was higher than noADR-patients' one. The mean duration of hospitalization was higher in ADR-patients. It is necessary to reduce the number of drugs and improve studies and prevention strategies targeted to reduce the impact of ADR, specially in the elderly population.

Drugs are commonly considered a rare cause of acute pancreatitis but there are an increasing number of reports of numerous medications that seem to be involved in the pathogenesis of acute pancreatitis with different degrees of causative relationship to the disease (definite--probable--possible). The number of drugs that have been associated to date with acute pancreatitis exceeds 260. The authors report here on their personal series of four cases of drug-induced acute pancreatitis (warfarin, lysinopril/hydrochlorothiazide, lamivudine/stavudine/indinavir, valproic acid), focusing on a number of epidemiological and clinical aspects.

Background: Post kidney transplantation erythrocytosis is a frequent complication in male subjects. In our experience, it occurs in approximately 20% of transplant patients receiving cyclosporine immunosuppression therapy., Methods: Twenty-two patients with post kidney transplantation erythrocytosis were treated using ACE-inhibitors (lisinopril) at a dose of 2-5-5 mg/day for a mean period of 15 months. Owing to the onset of collateral effects, 27% of these patients requested the conversion of ACE into angiotensin II receptor antagonists (AII). Twenty out of 22 patients were male (90%)., Results: Treatment resulted in a 15% reduction of hematocrit values compared to basal levels, which remained stable over time. No collateral effects were recorded, either for the kidneys or in terms of hypotension., Conclusions: ACE-inhibitors (lisinopril) or alternatively the use of angiotensin II receptor antagonists, like Losartan, at low doses, is an effective and safe treatment for patients developing post-transplantation erythrocytosis (PTE).

The discovery of the kinin system is not recent, but its study in clinical field has been done only in the last years. This system is composed by substrates (kininogens) and plasma and tissue kallikreins are the specific activators of these substrates producing two vasoactive peptides called bradykinin and kallidin. The biologic effects of kinins are mediated by specific receptors called B1 and B2. The activation of this system is particularly important in blood pressure regulation and in inflammatory reactions. The kinin system is involved in many clinical situations including respiratory allergic reactions, septic shock, hypertension and its treatment, hypotensive transfusion reactions, heart diseases, pancreatitis, hereditary and acquired angioedema, Alzheimer's disease and liver cirrhosis with ascites. The study of the kinin system in clinical field, which had been limited by methodological difficulties, has now received an important stimulus by the recent availability of specific and sensitive methods of dosage.

Background and Aims: Angiotensin II converting enzyme (ACE) inhibitors represent one of the most important pharmacological instruments for the treatment of arterial hypertension and are currently also used for other cardiovascular indications. The actions of ACE-inhibitors mainly depends on blocking the ACE enzyme in the renin-angiotensin-aldosterone system. However, the ACE enzyme also has a kinase activity. The inhibition of this enzyme may also cause an accumulation of tissue mediators (bradykinin) responsible for a number of adverse reactions., Methods: An intensive hospital monitoring programme of adverse reactions to drugs, known as MIO[symbol: see text]'96, was carried out by the Centre of Pharmacoepidemiology of the Faculty of Medicine and Surgery at the Second University of Naples during the period 25 March-18 April 1996. The main aims of the programme were to highlight the incidence of adverse reactions to the drugs monitored and the definition of the risk/benefit ratio taking account of the main physiological and pathophysiological variations of patients. This paper reports the results of the programme of adverse effects correlated to the use of ACE-inhibitors. A total of 175 records were compiled for 105 patients receiving antihypertensive treatment with a number of ACE-inhibitors (captopril, enalapril, lisinopril); a very high mean incidence of adverse events was documented (22%) without any severe undesirable effects., Results: The following adverse events were documented (the cumulative incidence is given in brackets): dysgeusia (17%), flush (8%), headache (33%), exanthema (17%), diarrhoea (8%), vertigo (8%), xerostomia (8%). Coughing was not reported in any patient., Conclusions: Further periods of intensive monitoring will be required to obtain a greater quantity of data from the Intensive Monitoring of adverse events through the MIO[symbol: see text]'97 programme.

The therapeutical approach to arterial hypertension in the general population is now relatively well classified, whereas it remains a controversial problem in dialytic patients. The aim of this study was to evaluate the antihypertensive drugs used in dialytic patients in Piedmont and to identify correlations with other personal and clinical data. The authors analysed the data in the Piedmont Dialysis and Transplant Register concerning new patients admitted to dialysis during the period 1990-1995 (2,664 patients at 31/12/1995) and 1,373 patients who began dialysis during the period 1990-1993. A study of the antihypertensive drugs using in single and combined therapy over the five-year period shows major variations in the 45-65 year-old age bracket (increased ACE-inhibitors in single therapy, 15.5-25.6%, increased vasodilators in combined therapy, 15.3-21%). In patients aged > or = 65 years old a slight increase was found in the use of beta-blockers in monotherapy. Antihypertensive drugs at the 1st control (1990-1995 entries) appeared to be stable over the five-year period. From the 1,373 patients who started dialysis in the period 1990-1993, with at least three subsequent controls, the authors selected those hypertensive or normotensive patients receiving ACE-inhibitor therapy (best survival in general population) and compared their survival with that of patients receiving alternative antihypertensive treatment. No significant differences were found. The stability of the antihypertensive drugs taken by these patients over the past 5 years backs the hypothesis of a greater attention paid by nephrologists to the introduction of new drugs, both because of the frequent onset of collateral effects and owing to the special pharmacokinetics present in dialytic patients.

ACE-inhibitors antagonize both angiotensin production and bradykinin breakdown, resulting in enhancement of vasodilating prostaglandin release. This provides an explanation for the experimental observation that cycloxygenase blockers (such as aspirin or indomethacin) may counteract the antihypertensive efficacy of the ACE-inhibitors; it may be also possible that hypertensive patients taking aspirin as an antiplatelet agent may fail to benefit from ACE-inhibition. This study was aimed at: evaluating the magnitude and incidence of the inhibitory phenomenon; defining the minimal aspirin dosage that produces an antagonistic effect, as well as the possible reasons for a different individual susceptibility. We have studied untreated patients with mild (10 cases, Group 1), moderate (16 cases, Group 2) or severe (26 cases, Group 3) hypertension. The ACE-inhibitor enalapril was used at doses of 10 mg bid (groups 1 and 2) or 20 mg bid (Group 3). Active drug treatment periods had a 5-day duration. A daily dose of aspirin of 100 mg had no effect on the antihypertensive efficacy of enalapril. On the contrary, when a dose of 300 mg was used, 60, 57 and 50% of patients in Group 1, 2 and 3, respectively, showed a > 20% restraint of the mean arterial pressure fall with enalapril (20% was the lower arbitrary limit for defining antagonism). Inhibition was independent of the sequence of drug administration. In these patients counteraction averaged 60, 70 and 90%, respectively. In them, and not in the remaining patients in each group, aspirin substantially attenuated the renin rise elicited by ACE-inhibition. These data suggest that: a dosage of 100 mg aspirin is devoid of any inhibitory effect; more that 50% of ACE inhibited patients are, at least in the short term, susceptible to the action of 300 mg aspirin, regardless of the severity of hypertension; counteraction is seemingly mediated through a prostaglandin inhibition and depends on the individual predominance of prostaglandin activation (also as a renin secretory stimulus) or angiotensin inhibition by the ACE-inhibitor.

The above study was performed as a single blind trial in 70 elderly patients (average age 66 years) who were randomized into two groups of 36 and 34 subjects respectively. After clinical and laboratory evaluation without treatment for at least two weeks, the two groups were treated with enalapril 5-10 or 20 mg daily plus doxazosin at the dosage of 1-2-4- or 8 mg daily; they were observed for 24 weeks. During the trial, pressure values, both systolic and diastolic, were seen to diminish significantly in both groups. This effect was accompanied by minor, usually transient side effects. At echocardiography at the end of the treatment period, doxazosin was found to reduce some volumetric cardiac parameters, thus showing to be apt to counteract left ventricular hypertrophy. These findings go to counteract left ventricular hypertrophy. These findings go to show that alpha-1 inhibitors are a valid alternative in the "first step" of antihypertensive therapy, especially in patients at risk for cardiovascular complications.

In this review, the Authors analyzes the more recent data in the Literature about the major cardiovascular risks in diabetic patients affected by systemic arterial hypertension. The more effective pharmacological and not pharmacological treatment is suggested. Particularly the advantages and more important side-effects of antihypertensive drugs are emphasized.

The Authors describe a clinical case of a patient affected by arterial hypertension of severe degree (IV grade OMS) that during therapy with ACE inhibitors and diuretics developed acute renal failure that reversed after stopping treatment. The clinical course was quite similar to acute renal failure induced by ACE inhibitors and diuretics in patient with bilateral renal artery stenosis. In interpreting the pathogenesis, the Authors suppose, beside a reductions of effective plasma flow, the coexistence of hyalinosis of renal arterioles. They underline the necessity of monitoring renal function at least in the first weeks of therapy when a treatment with ACE inhibitors and diuretics is started especially in patients with hypertension of high degree and/or reduced renal function.

The efficacy and safety of the treatment of arterial hypertension with the ACE-inhibitor quinapril, were evaluated in a multicentre study conducted in Italy. The study, lasting 14 weeks, after a preliminary wash-out period, allowed response-based titration of quinapril dose from 10 mg to 40 mg once a day, with provision to combine additional hydrochlorothiazide (12.5 to 25 mg), in case of persistently high diastolic pressure levels. The efficacy sample included 1267 patients: at therapy week 14, 78.6% of patients were treated with quinapril alone. Global response rate (intent-to-treat) was 83.3%, with a mean reduction of diastolic pressure of 15.8 mmHg (95% confidence interval from 15.5 to 16.2 mmHg). 91 patients reported 126 associated adverse events (7.0%); the most frequently reported event was cough (2.7%). First-dose hypotension was rarely reported (1.3%), even in elderly and diabetic patients.

The occurrence of a dry, nonproductive cough during ACE inhibitors therapy has been described in several reports. However, the mechanism of this effect is still unknown. In order to clarify whether ACE inhibitor-induced cough is a symptom of an asthmatic disturbance, six patients (age 54-68) with cough related to captopril or enalapril were rechallenged with ACE inhibitors after an adequate washout period. Baseline airway function and bronchial reactivity to metacholine were measured at the end of the washout period and on the fourth day of rechallenge which was accompanied by the reappearance of cough without wheezing. Rechallenge did not cause changes in dynamic lung function; a low and not significant (p less than 0.1) increase in metacholine dose causing a 15% and a 20% reduction in baseline FEV 1 was observed. It is concluded that cough and bronchoconstriction are likely to be mediated through different nervous pathways and that ACE inhibitor-induced cough is not a variant of asthmatic cough.

ACE-inhibitors have been shown to have considerable therapeutic effectiveness in the treatment of heart failure and to be able to significantly prolong the survival of treated patients. The benefits of these drugs when used in the treatment of heart failure are due to their vasodilator action on both arterial and venous vessels. An even more relevant mechanism might be the modulation of some neuro-endocrine responses induced by heart failure, such as angiotensin-aldosterone production, which are sometimes excessive or harmful. The molecules presently available in Italy are four (captopril, enalapril, lisinopril, quinapril), endowed with considerably different pharmacological characteristics, but substantially similar as far as effectiveness and tolerability are concerned. Although general guidelines cannot be suggested on the basis of the pharmacological profile alone, the choice of the drug to be used in every single patient with heart failure should be made taking into account the adequacy of the pharmacological properties for the specific situation.

In the present paper the authors review the results of more than ten years' experience with ACE-inhibitors in the therapy of hypertension and congestive heart failure. The importance of tissue rather than serum ACE level for the long-term response to these agents has been mainly stressed. Clinical studies have shown the importance of these agents for the general practitioner in view of both their efficacy and the low incidence of untoward effects. If further studies succeed in showing the extent to which individual mechanisms of action of ACE inhibitors contribute to the overall therapeutic effect it can be expected that it will become possible to synthetize new molecules with more selective action. Considering the hypothesis according to which these agents are also effective for the prevention and management of myocardial infarction and in the management of chronic renal failure, these studies would appear to be particularly urgent.

One-hundred patients suffering from slight-moderate hypertension (53 m, 47 f, aged between 18 and 78, average 49.08) have been studied in order to assess the effectiveness and tolerance of lisinopril ("Zestril", ICI-Pharma), a new ACE inhibitor in a single daily administration at doses of between 10 and 80 mg in relation to pressure values. Monotherapy with Lisinopril proved effective in 84 patients (88.4%), in 74 of whom (7.9%) pressure values were returned to normal. 11 patients (11.6%) did not respond to treatment. In most cases, the result was obtained with a dose of 20 mg in a single administration (32.6%). The incidence of side-effects was limited and in no case required the withdrawal of the drug.

An examination of the literature provides the basis for a definition of first dose iatrogenic hypotension or "first dose syndrome", its nature, degree and frequency. The drugs that often cause this phenomenon are listed with details of the mechanisms involved as are the physiological, pathological and iatrogenic conditions that may trigger and/or exacerbate the gravity and duration of the syndrome. In a series of patients with essential arterial hypertension treated with ACE inhibitors, 6 developed first dose syndrome, two of them after captopril and 4 after enalapril maleate, two of whom were also receiving theophylline and nitro derivates. Though wide personal experience suggests that first dose syndrome caused by ACE inhibitors is a rare event and those drugs are undeniably effective and well tolerated, treatment should always start with minimum doses administered before bed time especially in patients receiving other medication and/or presenting the physiological or pathological conditions in which first dose syndrome has already been observed and described.