ACE inhibitor-induced angioedema: remarkable new perspectives for intensive care/emergency medicine

1. Early and late onset of angio-oedema. The report reviews angio-oedema as a rare but potential life threatening adverse effect associated with angiotensin converting enzyme (ACE) inhibitors. This class of drugs, widely used in the treatment of hypertension and congestive heart failure, may often induce mild angio-oedema of the skin (face, lips, cheeks) but may rarely involve tongue, subglottis, pharyngeal and laryngeal tissues. Angio-oedema has been previously reported to occur early after start of treatment, mostly within the first 3-4 weeks. However, according to later reports since 1990, first onset may be delayed for months and even until 7 years of treatment. Analysis of patients exhibiting angio-oedema reported to the National Drug Commission in Germany revealed that the number of patients with late onset of angio-oedema is continually increasing over time. The percentage of patients with delayed onset ranging from after six months up to six years was as follows: 1992: 8.9% (of a total of n = 56), 1996: 28% (of a total of n = 79), and 1998: 54% (of a total of n = 46). Eleven cases of patients of the latter group were classified as life-threatening. 2. Recurrence of Angio-oedema. Furthermore, many patients experienced multiple episodes of angio-oedema because even clinicians in emergency departments are not familiar with the association between angio-oedema and ACE inhibitors. In our series from 1992 until early 1998 17% of 125 patients exhibiting angio-oedema had relapses with a maximum of seven events over a period of three years. 3. Widespread Use of ACE Inhibitors, Tactical Approach to Diagnosing Angio-oedema and Prevention of Relapses. Hence, from a practical point of view, it seems very useful to suggest that nowadays every angio-oedema is caused by ACE inhibitor treatment until it is definitely excluded by a thorough review of all medications. Thirteen ACE inhibitors gained more widespread application worldwide. Unfortunately, a large number of drug combinations (> 93) are meanwhile on the market. Therefore, much effort is needed to improve the knowledge and awareness of this insidious adverse effect by well-documented case reports. Moreover, each case of ACE inhibitor-associated angio-oedema should be immediately brought to the attention of the practitioner/cardiologist to emphasise that this class of antihypertensive agents is contraindicated in the affected person to prevent the occurrence of another potentially life-threatening event.     

The significance of converting enzyme inhibitor angiotensin I to angiotensin II in treatment of patients with coronary disease]

Angiotensin-converting enzyme (ACE) inhibitors are now established drugs in the treatment of hypertension and heart failure. The renin-angiotensin-aldosterone system is complex and acts as a circulating hormonal system, a local endogenous tissue system and neuromodular. Current experimental evidence suggests that ACE inhibitors reduce the risk associated with atherosclerotic cardiovascular disease. The antiatherogenic action of ACE inhibitors is related to complex effects mediated by these agent, including an antiproliferative and antimitotic action, beneficial effects on endothelial function, plaque-stabilizing effects and the action of these agents on the sympathetic nervous system. The role of ACE inhibitors in preventing the clinical sequale of atherosclerotic cardiac disease has been evaluated in various patient populations. Several small trial assess the effects of ACE inhibitors in severity of angina pectoris have reported conflicting results, with benefit is some patients and no benefit or even exacerbation of angina in others, indicating that ACE inhibitors do not have consistent antianginal effects in short-term study. ACE inhibitors have the theoretical potential to prevent restenosis after PTCA but they do not prevent restenosis and has no effect on overall clinical outcome. New data suggest that ACE inhibitors may be effective therapy fir patients following acute myocardial infarction. The renin-angiotensin system, is activated during new myocardial infarction and has an impact on the process of remodeling of the left ventricle which causes ist dysfunction and heart failure. In most of the large mortality trials the rationale for early treatment with ACE inhibitors after myocardial infarction was stated. ACE inhibitors have a positive effect in preventing the ventricular dilatation and they reduce the rate of reinfarctions and the mortality rate.     

Acute pancreatitis associated with the use of lisinopril

OBJECTIVE: To report a case of acute pancreatitis associated with lisinopril use. CASE SUMMARY: A 67-year-old man with no past history of pancreatitis or its associated risk factors developed acute pancreatitis after taking lisinopril for two years. To date, the use of angiotensin-converting enzyme (ACE) inhibitors and development of pancreatitis has been described in the literature with captopril, enalapril maleate, and one case temporally related to lisinopril use. CONCLUSIONS: The use of ACE inhibitors as first-line agents in controlling hypertension and congestive heart failure has increased. In addition to monitoring for efficacy and commonly reported adverse effects, clinicians need to be aware that acute pancreatitis may occur with all ACE inhibitors.     

ACE inhibitor use is associated with hospitalization for severe hypoglycemia in patients with diabetes. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside, Scotland. Medicines Monitoring Unit

OBJECTIVE: To evaluate the association between the use of ACE inhibitors and hospital admission for severe hypoglycemia and to explore the effects of potential confounding variables on this relationship. RESEARCH DESIGN AND METHODS: The association between the use of ACE inhibitors and the incidence of hypoglycemia is controversial. A recent study reported that 14% of all hospital admissions for hypoglycemia might be attributable to ACE inhibitors. We performed a nested case-control study, using a cohort of 6,649 diabetic patients taking insulin or oral antidiabetic drugs, on the Diabetes Audit and Research in Tayside, Scotland (DARTS) database. From 1 January 1993 to 30 April 1994, we identified 64 patients who had been admitted to Tayside hospitals with hypoglycemia and selected 440 control patients from the same cohort. RESULTS: Hypoglycemia was associated with the use of ACE inhibitors (odds ratio [OR] 3.2, 95% CI 1.2-8.3, P = 0.023), whereas use of beta-blockers and calcium antagonists was not associated with an increased risk of hospitalization for hypoglycemia with ORs of 0.9 (95% CI 0.3-3.3) and 1.7 (95% CI 0.2-2.1), respectively. There were significant differences between case and control patients in type of diabetes treatment, diabetes duration, place of routine diabetes care, and congestive cardiac failure. These differences did not confound the relationship between ACE inhibitors and hypoglycemia (adjusted OR 4.3, 95% CI 1.2-16.0). CONCLUSIONS: The results show that the association between ACE inhibitor therapy and hospital admission for severe hypoglycemia is not explained by these confounding factors. Although ACE inhibitors have distinct advantages over other antihypertensive drugs in diabetes, the risk of hypoglycemia should be considered.     

Use of baclofen to suppress cough induced by angiotensin-converting enzyme inhibitors

OBJECTIVE: To determine whether baclofen can suppress the cough induced by angiotensin-converting enzyme (ACE) inhibitors. DESIGN: Prospective, open-label, clinical trial of a 4-week course of low-dose oral baclofen (5 mg tid days 1-7, 10 mg tid days 8-28). SUBJECTS: Seven patients with severe, persistent ACE inhibitor-induced cough. SETTING: University-affiliated teaching hospital. MAIN OUTCOME MEASURES: Study participants kept daily diaries monitoring the frequency of cough during and after completion of baclofen therapy. RESULTS: All subjects demonstrated diminution of cough after initiation of baclofen. Initial improvement was noted by a mean of 4.0 days (range 3-6), and maximal improvement during treatment was achieved by a mean of 10.7 days (range 5-15). In addition, all subjects demonstrated persistent suppression of cough (range 25-74 d) after discontinuation of the study drug. CONCLUSIONS: Low-dose oral baclofen therapy caused a prolonged antitussive effect in all subjects without inducing any adverse reactions. Baclofen may offer an alternative to the discontinuation of ACE inhibitor therapy in patients for whom these drugs are required.     

Hypotensive reactions to white cell-reduced plasma in a patient undergoing angiotensin-converting enzyme inhibitor therapy

BACKGROUND: Hypotensive reactions to platelet transfusions performed with white cell (WBC)-reduction filters with negatively charged surfaces have been reported recently in patients taking angiotensin-converting enzyme (ACE) inhibitors. Experimental studies have shown that the filter material can activate bradykinin, which may cause symptoms in patients with reduced bradykinin catabolism. Symptomatic adverse reactions after the administration of fresh-frozen plasma (FFP) through a WBC-reduction filter have not been reported in a patient on ACE Inhibitor medication. CASE REPORT: A 58-year-old man with congenital coagulation factor V deficiency and hypertension treated with an ACE inhibitor was admitted for rehabilitation after orthopedic surgery. On 3 consecutive days, he received FFP through a WBC-reduction filter; within minutes of the beginning of each infusion, he experienced a drop in blood pressure, facial erythema, abdominal pain, and anxiety. When the infusions were stopped, symptoms quickly abated without treatment. Multiple prior transfusions of unfiltered FFP and FFP filtered through a WBC-reduction filter made by a different manufacturer, as well as subsequent transfusions of unfiltered FFP, had not produced such reactions. CONCLUSION: Facial flushing, hypotension, and abdominal pain after FFP administration in a patient on ACE inhibitor medication appeared to be associated with a specific type of WBC-reduction filter. This association and other reported studies suggest that special caution is warranted when patients who are treated with ACE inhibitors receive blood components administered through WBC-reduction filters capable of generating bradykinin.     

Renal protection and angiotensin converting enzyme inhibition in microalbuminuric type I and type II diabetic patients

BACKGROUND: Many studies have emphasized the role of antihypertensive drugs and in particular angiotension converting enzyme (ACE) inhibitors in the retardation of diabetic nephropathy. Although these studies have focused predominantly on patients with overt proteinuria, more recently a number of investigators have explored the role of ACE inhibitors in both type I and type II diabetic patients with an earlier phase of diabetic renal disease known as microalbuminuria. These agents are now being considered as renoprotective agents not only in hypertensive patients but also in those with 'normal' blood pressure. Initially, studies in type I diabetic patients showed that ACE inhibition was effective in retarding the increase in albuminuria which was observed in placebo treated groups. More recently, several multi-centre placebo controlled studies have been performed suggesting that prolonged treatment not only reduced albuminuria but also preserved renal function. The role of ACE inhibition in microalbuminuric type II diabetic patients is less well characterised although several studies have recently described beneficial effects of ACE inhibition on albuminuria and possibly on renal function. REVIEW: Although ACE inhibitors have been clearly shown to reduce urinary albumin excretion in diabetic patients, the issue as to whether they confer a specific benefit over other classes of antihypertensive agents remains controversial. Several meta-analyses have suggested that ACE inhibitors are more potent at decreasing albuminuria or proteinuria than other antihypertensive agents, for a given reduction in blood pressure. The Melbourne Diabetic Nephropathy Study Group has instituted a study which is placebo-controlled and is confined to normotensive type I and type II diabetic patients. The ACE inhibitor perindopril has been compared not only with placebo but also with the dihydropyridine calcium channel blocker, nifedipine. Preliminary analysis reveals that after 12 and 24 months of treatment, perindopril is more effective in reducing albuminuria than placebo or nifedipine. CONCLUSION: ACE inhibitors are a promising class of antihypertensive agents in diabetic patients with microalbuminuria. These drugs should be considered as first line agents in such patients, even in the absence of systemic hypertension.     

Temporal patterns in the medical treatment of congestive heart failure with angiotensin-converting enzyme inhibitors in older adults, 1989 through 1995

BACKGROUND: Evidence from clinical trials in the past decade has consistently shown that angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with congestive heart failure (CHF). The extent to which clinical practice has adopted ACE inhibitor therapy is unknown. METHODS: The Cardiovascular Health Study is a prospective observational study of 5201 community-dwelling adults aged 65 years and older. Prevalent CHF cases were identified on study entry (from June 10, 1989, through May 31, 1990) and incident CHF cases were identified throughout 5 years of follow-up. Medication data were collected from annual medication inventories. The percentage of patients with CHF using ACE inhibitors was calculated at each annual examination. Temporal trends in CHF treatment with ACE inhibitors between June 10, 1989, through May 31, 1990, and June 1, 1994, through May 31, 1995, were analyzed. RESULTS: Use of ACE inhibitors to treat CHF increased slightly over time among prevalent cases at each annual examination: 26% of prevalent CHF cases were treated in 1989-1990 compared with 36% of prevalent cases in 1994-1995. This 10% increase was statistically significant (P<.01). Participants with low ejection fractions were 2 times more likely to be treated with ACE inhibitors than were those with normal ejection fraction and this tendency did not change over time. Among cases newly diagnosed in the year before the 1990-1991 examination, 42% were using ACE inhibitors; among those newly diagnosed in the year before 1994-1995, 40% were using ACE inhibitors. This 2% decrease was not statistically significant (P=.68). CONCLUSION: These findings suggest that, while the medical management of CHF with ACE inhibitors has increased modestly over time in prevalent cases, these drugs may still be underused, especially among incident cases.     

Angiotensin converting enzyme inhibitors for hypertension

The review paper presents modern opinions upon angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension. It describes their hypotensive properties and therapeutic efficacy. The review discusses also using of ACE inhibitors for disorders often coexisting with hypertension, likewise it presents ACE inhibitors in combination with other hypotensive drugs. The paper discusses also side effects of ACE inhibitors as well as diseases, in which ACE inhibitors are contraindicated.     

Inhibitory effects of angiotensin-converting enzyme inhibitor on cefroxadine uptake by rabbit small intestinal brush border membrane vesicles

Effects of angiotensin-converting enzyme (ACE) inhibitors, captopril, enalapril maleate and quinapril, on the uptake of aminocephalosporin antibiotic, cefroxadine, by rabbit small intestinal brush border membrane vesicles were examined. These ACE inhibitors significantly inhibited the uptake of cefroxadine, which is transported by H+/dipeptide transporter in the membrane, in the order of captopril < enalapril < quinapril in the presence of an inward H+ gradient. Inhibitory effect of quinapril was more marked than that of aminocephalosporin cephradine, while in the absence of an inward H+ gradient inhibition by these ACE inhibitors was much less. Dixon plot analysis showed that the inhibition by enalapril and quinapril in the presence of an inward H+ gradient occurred in a competitive manner and estimated inhibition constants of these two drugs to be 5.3 mM and 0.46 mM, respectively. These results suggested the strong affinity of these ACE inhibitors, especially quinapril, on the H+/dipeptide transporter.     

Effects of a prosthetic dental device used to treat obstructive sleep apnea syndrome, and compliance of patients using the device

OBJECTIVE: To determine whether older persons with hypertension who use specific calcium antagonists and ACE inhibitors have a different risk of mortality than those using beta-blockers. DESIGN: A prospective cohort study continuing from 1988 through 1992. SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: Hypertensive participants aged > or = 71 years (n = 906) who had no evidence of congestive heart failure and who were using either beta-blockers (n = 515), verapamil (n = 77), diltiazem (n = 92), nifedipine (n = 74), or ACE inhibitors (n = 148). Nifedipine was of the short acting variety. MEASUREMENTS: The main outcome measure was all-cause mortality. Age, gender, smoking, HDL-cholesterol, blood pressure, intake of digoxin and diuretics, physical disability, self-perceived health, and comorbid conditions were examined as confounders. RESULTS: During 3538 person-years of follow-up, 188 participants died (53 deaths per 1000 person-years). Compared with beta-blockers, after adjusting for age, gender, comorbid conditions and other health-related factors, the relative risks (95% confidence interval) for mortality associated with use of verapamil, diltiazem, nifedipine, and ACE inhibitors were 0.8 (0.4-1.4), 1.3 (0.8-2.1), 1.7 (1.1-2.7), and 0.9 (0.6-1.4), respectively. The results were unchanged after excluding participants with other potential contraindications to beta-blockers and after stratifying on coronary heart disease and use of diuretics. Higher doses of nifedipine were associated with higher mortality. CONCLUSION: Compared with beta-blockers, use of short acting nifedipine was associated with decreased survival in older hypertensive persons. However, selective factors influencing the use of specific drugs in higher risk patients could not be completely discounted, and final conclusions will depend on clinical trials.     

Effect of angiotensin-converting enzyme inhibitors on the power spectrum of heart rate variability in post-myocardial infarction patients

BACKGROUND: Heart rate variability (HRV) time and frequency domain indices are strong predictors of malignant arrhythmias and sudden cardiac death. The effect of various angiotensin-converting enzyme (ACE) inhibitors on HRV in patients with acute myocardial infarction (AMI) has not been studied. METHODS: Ninety patients with uncomplicated AMI (age range 39-75 years, median 61 years) were assigned randomly to six groups of 15 patients each. They were treated with placebo or one of the following ACE inhibitors for 30 days: captopril, cilazapril, enalapril, lisinopril or quinapril. HRV was assessed 3 days after the onset of AMI (baseline), and 30 days after treatment. Fifteen patients with stable coronary artery disease and 15 healthy volunteers, age- and sex-matched with AMI patients, served as controls. RESULTS: At baseline, time and frequency domain HRV indices in the AMI groups were equally less than those in patients with stable coronary artery disease and normal volunteers. Compared with placebo, quinapril, lisinopril and captopril changed frequency domain HRV indices 30 days after initiation of treatment, indicating an increase in vagal tone, whereas enalapril and cilazapril had no significant effect on these indices. Most of the time domain HRV indices 30 days after initiation of treatment increased significantly in all patients treated with ACE inhibitors, but remained unchanged in the placebo group. Frequency domain and time domain HRV indices 30 days after treatment in the quinapril group did not differ statistically from those in patients with stable coronary artery disease, but were less than those in normal volunteers. CONCLUSIONS: Quinapril, lisinopril and captopril improved frequency domain HRV indices related to vagal tone, whereas cilazapril and enalapril had no effect on these indices. This influence of some ACE inhibitors on HRV may be beneficial in reducing the risk for sudden death in post-myocardial infarction patients.     

The therapy of arterial hypertension: a comparison between ACE inhibitors and angiotensin-II-receptor antagonists

The efficaciousness of ACE inhibitors in arterial blood hypertension is well known. These drugs decreased the incidence of hypertension and myocardial infarction in population. However, they increase tissue levels of some kinines, that may be responsible of some adverse reactions (cough, etc.). Angiotensin-receptor antagonists can minimize the adverse reactions due to kinine accumulation and may increase the safety of the antihypertensive drug-treatment. Pharmacological and clinical aspects of angiotensin-receptor antagonists are discussed.     

Do angiotensin-converting enzyme inhibitors prolong life in patients with heart failure treated in clinical practice?

Angiotensin converting enzyme (ACE) inhibitors have emerged as a significant advance in the treatment of heart failure; yet only a minority (i.e., 30% to 40%) of eligible patients are being treated with these drugs, and even among treated patients, the doses used in clinical practice are substantially lower than those used in the clinical trials that established the efficacy and safety of these agents. The preference for low doses is based on the belief that low and high doses exert similar benefits but that high doses produce more side effects. Yet, most studies indicate that large doses of ACE inhibitors produce greater hemodynamic and clinical effects than small doses, with no additional toxicity. However, it is uncertain whether the survival effects of these drugs are also related to dose. To address this question, a large multinational, double-blind clinical trial (Assessment of Treatment With Lisinopril and Survival [ATLAS]) was launched to compare the effects of low and high doses of the ACE inhibitor lisinopril on the survival of patients with heart failure. If the study demonstrates that large doses are needed to produce optimal effects on mortality, then the low dose strategies that are now widely used in clinical practice may be inadvertently nullifying the enormous potential benefits that ACE inhibitors might otherwise have on public health.     

Cough induced by quinapril with resolution after changing to fosinopril

OBJECTIVE: To report a case of chronic, nonproductive cough secondary to the angiotensin-converting enzyme (ACE) inhibitor quinapril, with complete resolution after switching to another ACE inhibitor, fosinopril. DATA SOURCES: All relevant articles from January 1985 through February 1993 were identified, primarily through MEDLINE search and review of pertinent articles' bibliographies. CASE SUMMARY: A 68-year-old woman developed a dry, irritating cough within one month of starting quinapril therapy for the treatment of essential hypertension. The patient was a nonsmoker with no respiratory illnesses. The cough continued for the duration of therapy with quinapril. One month after changing to fosinopril therapy, the patient reported complete resolution of the cough. She remains cough-free to date. DISCUSSION: Cough induced by ACE inhibitors is a frequently documented adverse effect. It is severe enough to require discontinuation of therapy in 1-10 percent of patients. The cough is considered to be a class-related adverse effect with cross-reactions between ACE inhibitors routinely reported. At this time, changing to another ACE inhibitor or additive therapy with nonsteroidal antiinflammatory drugs is not recommended. Discontinuation of the ACE inhibitor results in rapid alleviation of the cough, although this is not always necessary, as most patients may experience a cessation or decrease in cough. We report a case of cough following the administration of quinapril, with complete resolution after changing to the alternative ACE inhibitor fosinopril in a patient with essential hypertension. CONCLUSIONS: Cough has been encountered commonly after the administration of ACE inhibitors. Frequency of cough is variable and although this complication has been described as a class effect, patients with a persistent, severe ACE inhibitor-induced cough may benefit from a trial of fosinopril therapy. This may be particularly useful in patients unable to tolerate an alternative class of antihypertensive agents.     

Hospital intensive monitoring of adverse reactions of ACE inhibitors

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.     

Renal effects of angiotensin converting enzyme inhibitors in heart failure: a clinician's guide to minimizing azotemia and diuretic-induced electrolyte imbalances

Angiotensin converting enzyme (ACE) inhibitors have proved to be valuable, life-saving medications in the management of heart failure. While reducing myocardial oxygen consumption, they increase cardiac output and thus renal plasma flow. Despite reports in the literature of adverse effects of these drugs on renal function, the risks of functional deterioration are predictable in patient populations and remediable. Patients at greatest risk of declining renal function during therapy with ACE inhibitors are those in whom maintenance of renal function is dependent on angiotensin II. Reducing the dose of the concomitant diuretic, liberalizing the dietary intake of sodium, and increasing the dose of the ACE inhibitor usually restores renal function to baseline. In patients with severe renal insufficiency, reducing the dose of the ACE inhibitor might be necessary to preserve the glomerular filtration rate.     

The antiproteinuric action of angiotensin-converting enzyme inhibitors in chronic glomerulonephritis and diabetic nephropathy

Antiproteinuria effects of angiotensin-converting enzyme (ACE) inhibitors was studied in 23 patients with chronic nephritis (CN) and 32 patients with diabetic nephropathy (DN). CN patients received Capoten, DN patients were given enalapril. The drugs were also examined for the action on systemic arterial pressure, renal function and intrarenal hemodynamics. Significantly decreased urinary excretion of protein occurred in DN patients on the treatment month 1, in CN subjects on month 3. In both groups ACE inhibitors produced marked hypotensive effect, did not affect renal function, noticeably improved intraglomerular hemodynamics. Hypotensive and antiproteinuria activity of the drugs were unrelated. The mechanism of antiproteinuria action of ACE inhibitors works via normalization of intrarenal hemodynamics. Systemic arterial hypertension seems to be an additional factor aggravating disturbances of intrarenal circulation and provoking proteinuria.     

Angiotensin receptor antagonists and ACE inhibitors

BACKGROUND: ACE inhibitors are valuable and effective drugs in the treatment of hypertension, heart failure, myocardial infarction and nephropathy. Angiotensin receptor antagonists, which have recently been introduced into clinical practice, have the potential to replace ACE inhibitor therapy in many patients. OBJECTIVE: To review the mechanisms of action, indications and side effects of ACE inhibitors and angiotensin receptor antagonists and to highlight similarities and differences between the two drug classes. DISCUSSION: Angiotensin receptor antagonists have the theoretical advantage of being more effective in blocking the effects of angiotensin II at angiotensin type I receptors. The potential disadvantage of not potentiating bradykinin may be compensated by the unopposed action of angiotensin II on vascular angiotensin type II receptors, which appear to mediate similar beneficial cardiovascular effects to bradykinin. Angiotensin II receptor antagonists have a lower incidence of adverse effects than ACE inhibitors as they do not produce cough and appear much less likely to produce angioedema. Although ACE inhibitors are the most commonly prescribed antihypertensive drug class in Australia, they are underused for the treatment of heart failure and left ventricular dysfunction following myocardial infarction. Angiotensin receptor antagonists may become alternative therapies to ACE inhibitors in these disorders. However, at present they are only indicated for the treatment of hypertension.