Kaposi's sarcoma in a patient with psoriasis vulgaris.

A 54-year-old woman presented with angiomatous lesions located on the upper extremities and right cruris. Histopathological findings were typical of Kaposi's sarcoma (KS). She had had mild to moderate psoriasis since she was 25 years old. She had been using cilazapril (an angiotensin-converting enzyme inhibitor) for the last 9 months. She had had similar lesions in the past while taking the same medication. Because our patient's KS lesions had developed during treatment with cilazapril, the drug was stopped. One month later, spontaneous regression of KS nodules was noted and after 4 months no KS lesions were seen.

Combination of an ACE inhibitor and indapamide improves blood pressure control, but attenuates the beneficial effects of ACE inhibition on plasma adiponectin in patients with essential hypertension.

BACKGROUND: Antihypertensive agents differentially influence the plasma adiponectin concentration and the effects of fixed-dose combination regimens remain unclear. The influence of a combination of an angiotensin-converting enzyme inhibitor (ACEI) and a thiazide-type diuretic or an ACEI alone on plasma adiponectin concentrations in patients with essential hypertension was evaluated in the present study. METHODS AND RESULTS: After a 2-week placebo run-in phase, 30 patients with essential hypertension were randomized to receive preterax (2 mg perindopril/0.625 mg indapamide) or cilazapril (2.5 mg) once daily for 12 weeks. Plasma adiponectin and insulin concentrations were measured before and after treatment. Insulin resistance was measured by homeostasis assessment index (HOMA-IR). Treatment with preterax (P=0.003) and cilazapril (P=0.031) significantly reduced systolic blood pressure (BP), but only preterax reduced diastolic BP (P=0.024). Cilazapril treatment significantly increased the plasma adiponectin concentration (P=0.025) and reduced plasma triglycerides (P=0.041), whereas preterax treatment increased the plasma insulin concentration (P=0.041) and tended to increase HOMA-IR. CONCLUSIONS: The combination of an ACEI and indapamide improved BP control, but attenuated the beneficial effects of ACE inhibition on plasma adiponectin in patients with essential hypertension. Such a combination may be best reserved for improved BP control rather than for metabolic protection in clinical hypertension.

Combination therapy of prednisone and ACE inhibitor versus ACE-inhibitor therapy alone in patients with IgA nephropathy: a randomized controlled trial.

BACKGROUND: Recent studies have shown that both steroids and angiotensin-converting enzyme (ACE) inhibitors improve kidney survival and decrease proteinuria in patients with immunoglobulin A nephropathy. In this study, we aim to investigate whether the addition of steroids to ACE-inhibitor therapy produces a more potent antiproteinuric effect and better protection of kidney function than an ACE inhibitor alone. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: Patients with biopsy-proven immunoglobulin A nephropathy with proteinuria of 1 to 5 g/d of protein. INTERVENTION: 63 patients were randomly assigned to either cilazapril alone (ACE-inhibitor group; n = 30) or steroid plus cilazapril (combination group; n = 33). OUTCOMES & MEASUREMENTS: The primary end point was kidney survival, defined as a 50% increase in baseline serum creatinine level. RESULTS: After follow-up for up to 48 months, 7 patients in the ACE-inhibitor group (24.1%) reached the primary end point compared with 1 patient (3%) in the combination group. Kaplan-Meier kidney survival was significantly better in the combination group than the ACE-inhibitor group after 24 and 36 months (96.6% versus 75.7%, 96.6% versus 66.2%; P = 0.001). Urine protein excretion significantly decreased in patients in the combination group compared with the ACE-inhibitor group (time-average proteinuria, 1.04 +/- 0.54 versus 1.57 +/- 0.86 g/d of protein; P = 0.01). Multivariate analysis showed that combination treatment (hazard ratio, 0.1; 95% confidence interval, 0.014 to 0.946) and time-average proteinuria (hazard ratio, 14.3; 95% confidence interval, 2.86 to 71.92) were independent predictors of kidney survival. LIMITATIONS: Small sample size, a single center, and slight imbalances at baseline. CONCLUSIONS: Our results suggest that the addition of steroid to ACE-inhibitor therapy provided additional benefit compared with an ACE inhibitor alone. However, this was a pilot study with a small number of participants achieving the end points, and thus further validation is necessary.

Efficacy of a very-low-dose combination of perindopril and indapamide--preterax compared with cilazapril monotherapy in patients with inadequate blood pressure control--a randomized, double-blind, add-on study.

BACKGROUND: Combined regimen may be superior to monotherapy in blood pressure (BP) control. Since BP control is critically related to cardiovascular mortality and morbidity in hypertensive patients, this study aimed to evaluate the efficacy and safety of a low-dose combined regimen of preterax compared with cilazapril monotherapy for better BP control in treated hypertensive patients. METHODS: Stable hypertensive patients were evaluated if their systolic BP (SBP) was > 130 mmHg and/or diastolic BP (DBP) was > 85 mmHg even with up to 2 antihypertensive drugs. Patients were excluded if they were on angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers or a diuretic. They were then randomized to receive either preterax (perindopril 2 mg and indapamide 0.625 mg) or cilazapril 2.5 mg once daily in a double-blind fashion for a period of 12 weeks after a 2-week placebo run-in phase. Sitting BP was recorded and the safety and efficacy were evaluated at each visit every 4 weeks. Response was defined as positive if SBP was < or = 140 mmHg and DBP was < or = 90 mmHg at the last visit or there was > 20 mmHg reduction in SBP and/or > 10 mmHg reduction in DBP using either treatment. Plasma biochemical analysis was performed both before and after the treatment. RESULTS: Among the 47 patients initially enrolled, 41 completed the study (21 in the preterax group, 20 in the cilazapril group). There was no difference in the number of adverse events between the 2 groups. SBP was significantly reduced by preterax (13.43 +/- 12.48mmHg, p < 0.0001) and cilazapril (9.00 +/- 13.75 mmHg, p < 0.05). However, DBP was significantly reduced only by preterax (7.67 +/- 9.40 mmHg, p = 0.0009) but not by cilazapril (3.60 +/- 8.37 mmHg, p > 0.05). The response rate was significantly higher to preterax (100%) than to cilazapril (70%) (p = 0.0086). CONCLUSION: Though similar in safety, combined regimen preterax was more effective than cilazapril to facilitate adequate BP control in already-treated hypertensives. It can be added on to other antihypertensives for better BP control in clinical hypertension.

Dual blockade of the renin-angiotensin-aldosterone system with high-dose angiotensin-converting enzyme inhibitor for nephroprotection: an open, controlled, randomized study.

OBJECTIVE: Despite the proven effectiveness of combination therapy with an angiotensin I-converting enzyme inhibitor (ACEI) and angiotensin II-receptor blockers (ARBs) for the prevention and treatment of kidney disease, it has not proved possible to inhibit the progress of chronic nephropathies completely. To improve renal outcome one may consider using increased dosages of ACEI above those usually recommended for hypertension. MATERIAL AND METHODS: A randomized, open, controlled study was conducted to evaluate the influence of two combination therapies on proteinuria, markers of tubular injury and renal fibrosis. A total of 18 patients with a creatinine level of 109+/-36 micromol/l and proteinuria of 0.97+/-0.76 g/24 h were enrolled in the study. In the 8-week run-in period, an ACEI (cilazapril 5 mg once-daily) and an ARB (telmisartan 80 mg once-daily) were administered to achieve the target blood pressure of < or = 130/80 mmHg. Next, the patients were randomly assigned to either an increased dose of cilazapril (10 mg) or the previous dose (5 mg) in two active-treatment periods, each lasting 8 weeks. RESULTS: A significant increase in renin activity was observed after administration of cilazapril 10 mg (6.46+/-1.12 vs 4.67+/-0.7 ng/ml/h; p=0.028). Proteinuria, urine excretion of N-acetyl-beta-D-glucosaminidase, and alpha1-microglobulin and amino-terminal propeptide of type III procollagen were unchanged. CONCLUSION: An increased dosage of cilazapril (twice the maximum recommended dose) in addition to combination therapy with telmisartan was associated with increased blockade of the renin-angiotensin-aldosterone system, with no additional effect on proteinuria, markers of tubular injury or renal fibrosis.

Not all ACE inhibitor related angioedema is always evident: a case which is misdiagnosed as panic attack and speech disorder.

Angiotensin-converting enzyme (ACE) inhibitors are the most common medications responsible for angioedema. Angioedema is a potentially life threatening conditions especially in geriatric age patients that they have take a several medications include ACE inhibitors and non steroidal anti inflammatory drugs. We present a case an ACE inhibitor induced angioedema that confused many clinical events.

Dechallenge and rechallenge method showed different incidences of cough among four ACE-Is.

OBJECTIVE: To determine the incidence of cough secondary to (1) Cilazapril, (2) Enalapril, (3) Imidapril, and (4) Perindopril and their efficacy in the control of hypertension. STUDY DESIGN AND SETTING: Randomized double-blind study conducted in selected medical centers in the Philippines from the first quarter of 1999 to March, 2001. RESULTS: A total of 301 patients, aged 28-86 years with stage I or II hypertension were included. Patients were randomized to Cilazapril 2.5-5.0 mg/day (n=70), Enalapril 10-20 mg/day (n=82), Perindoril 4-8 mg/day (n=73), or Imidapril 10-20 mg/day (n=76). Hydrochlorothiazide 12.5 mg/day was added if needed. Using a dechallenge and rechallenge method, a strict criteria to attribute cough to angiotensin converting enzyme inhibitors (ACE-Is) not yet used in previous reports, the cough incidence were as follows: (1) Cilazapril--22.86% (16/70), (2) Enalapril--21.95% (18/82), (3) Perindopril--10.96% (6/73), and (4) Imidapril--13.16% (10/76) (P=0.041). Control of hypertension was significantly better with Enalapril during the first follow-up period. CONCLUSION: Statistically significant differences in the incidence of cough among the studied ACE-Is were noted. Control of hypertension was observed to be better in those with a higher incidence of cough; however, the mean change of both systolic and diastolic blood pressure levels were not significantly different.

Pemphigus vulgaris triggered by glibenclamide and cilazapril.

A case of pemphigus triggered by glibenclamide and cilazapril is described. The suspicion of drug induction was confirmed in a laboratory study in which a pemphigus-like effect was induced by glibenclamide in cultured human skin explants. Withdrawal of the drugs and their replacement by hydrochlorothiazide and metformin resulted in subsidence of the lesions and no appearance of new lesions. The laboratory study carried out to verify the suspicion of drug induced pemphigus and to confirm the diagnosis proved useful in the differential diagnosis in this case.

[A prospective study on the cough mechanism induced by angiotensin-converting enzyme inhibitors in patients with hypertension].

OBJECTIVE: To explore the possible mechanisms underlying cough induced by angiotensin-converting enzyme inhibitors (ACEI) in patients with hypertension. METHODS: 127 patients with hypertension were enrolled to receive ACEI (97 cases prescribed cilazapril and 30 cases prescribed benazepril hydrochloride) for 8 weeks. Patients who had coughed in the period were assigned to the cough group (48 cases) and patients who hadn't coughed were assigned to the non-cough group (79 cases). The serum ACE activity before and after administration of the drugs and the polymorphism of ACE gene (including homozygous-alleles II, DD, and heterozygous ID) were analyzed. Binary logistic regression was used as a statistical method to determine the factors associated with cough. RESULTS: The frequencies of the I alleles and II genotype of ACE gene in the cough group (0.70% and 56.3%) were significantly higher than those in the non-cough group (0.42% and 23.3%, P < 0.05). The mean serum ACE activity before and after administration of the ACEI in the cough group [(26 +/- 6) U/L, (4 +/- 4) U/L] was significantly lower than that in the non-cough group [(33 +/- 8) U/L, (8 +/- 8) U/L, all P < 0.01]. The difference in the range of decrease of serum ACE activity after ACEI between the cough group [(22 +/- 7) U/L] and the non-cough group [(25 +/- 9) U/L] was not significant (P = 0.077). Serum ACE activity before ACEI was highest in the homozygous-alleles DD group [(36 +/- 8) U/L], secondly in the heterozygous ID group [(29 +/- 6) U/L] and the lowest in homozygous-alleles II group [(26 +/- 7) U/L], differences being significant among three groups (P < 0.01). ACEI-related cough showed no relationship with sex, smoking habit and the ACEI used. CONCLUSIONS: The serum ACE activity was associated with polymorphism of ACE gene. Cough induced by ACEI was related to I allele and II genotype. There was a relationship between the serum ACE activity before administration of ACEI and cough induced by ACEI.

Angiotensin converting enzyme inhibitor induced cough: experience in Siriraj Hospital.

With the increasing use of angiotensin converting enzyme inhibitors (ACEI) in the treatment of hypertension, particularly in diabetic patients, and heart failure, an annoying cough has frequently been observed. According to the post marketing surveillance studies, the prevalence of cough associated with ACEI was only 0.1-4 per cent. However, many recent studies have observed a very much higher frequency. To examine the incidence and pattern of cough associated with the usage of ACEI (C-ACEI) in a Thai population, mixed retrospective and prospective studies were performed in hypertensive patients who attended the out-patient department, Siriraj Hospital between December 1999 and August 2000. A thousand cases who had used or have been using ACEI were studied. C-ACEI was present in 179 cases of 760 retrospective studied cases (23.6%) and 75 cases of 240 prospective studied cases (31.3%). Cough was typically described as irritative (93.8% retrospectively and 98.7% prospectively, p = 0.05) and nocturnal in onset (74.9% retrospectively and 80% prospectively, p = 0.12), and usually appeared within the first 4 weeks of treatment (41.3% retrospectively and 46.7% prospectively, p = 0.43). Patients who received a full dosage of ACEI did not have to posses an increasing risk of C-ACEI. There was no difference in the prevalence of C-ACEI among types of ACEI, except cilazapril and quinapril which were found to be higher than enalapril in the retrospective study (p < 0.0001 and p = 0.002, respectively). Types of study were shown to influence the prevalence of C-ACEI. Prospective studies yielded a higher rate of C-ACEI than retrospective ones.

[The relationship between polymorphism of angiotensin converting enzyme gene and cough caused by angiotensin converting enzyme inhibitors].

OBJECTIVE: To investigate the relationship between the polymorphism of angiotensin converting enzyme (ACE) gene and ACE inhibitor (ACEI)-induced cough in Chinese elderly with essential hypertension. METHODS: ACE I/D polymorphism was performed on DNA samples from patients using the polymerase chain reaction (PCR) followed by agarose gel electrophoresis. Serum ACE levels were measured using a colorimetric assay. RESULTS: The frequencies of ACE II genotype were 40% in patients with cough and 20% in those without cough, respectively (P < 0.05). The frequencies of I allele were 60% in patients with cough and 41% in those without cough (P < 0.01); The serum ACE level was highest in the DD genotype, followed by the ID genotype and the II genotype. The ACE level in patients with cough was significantly lower than that in patients without cough (P < 0.001). The sensitivity and specificity were 81% and 78% respectively when the serum ACE levels were used to predict ACEI-induced cough. CONCLUSION: ACEI-induced cough was related to the serum ACE level and ACE gene polymorphism in Chinese elderly with essential hypertension.

[Refractory hypotension sustained during general anesthesia due to chronic treatment with angiotensin-converting enzyme inhibitors]. / Hipotensión refractaria y sostenida durante una anestesia general asociada al tratamiento crónico con inhibidores de la enzima conversiva de la angiotensina.

Perioperative management of angiotensin-converting enzyme inhibitors (ACEI) is controversial because of associated hypertensive episodes during induction and maintenance of anesthesia. A 71-year-old woman with a non-functioning thyroid node was scheduled for thyroid lobectomy. Her medical history included high blood pressure and she was being chronically treated with ACEI, which were taken until the morning of surgery. After induction of anesthesia, arterial hypotension refractory to crystalloid therapy developed and worsened in spite of administration of a gelatin-type colloid (Gelafundina). The patient did not respond to ephedrine or dopamine and required stabilization with adrenalin in continuous perfusion for 12 hours. Later evolution was satisfactory and recovery took place without sequelae. We discuss the anesthetic implications of chronic ACEI treatment and possible hemodynamic repercussions of associated administration with gelatin-type solutions or human albumin.

The ACE gene polymorphism and cough threshold for capsaicin after cilazapril usage.

Persistent dry cough is an occasional but clinically important adverse reaction to angiotensin I-converting enzyme (ACE) inhibitors (ACEI). Its reported incidence is variable, and why cough occurs in only certain individuals has been unclear. An insertion/deletion (I/D) polymorphism of the ACE gene is associated with serum ACE activity. We have previously shown that susceptibility to cough induced by ACEI is associated with this polymorphism such that patients with genotype II are more susceptible to cough than patients with other genotypes. In order to confirm and extend our previous observation, we conducted a randomized, placebo-controlled, double-blind, cross-over study in 10 healthy volunteers with genotype II and 10 with genotype DD. The cough threshold was determined by the concentration of inhaled capsaicin causing two or more coughs. After the usage of an ACEI, cilazapril, for 4 weeks, changes in the cough threshold in subjects with genotype II [before: 6.6+/-3.7 nM (mean+/-SD); after: 5.0+/-4.6 nM] significantly differed from those in subjects with genotype DD (before: 9.0+/-9.4 nM; after: 9.3+/-9.1 nM). Skin responses to intradermal bradykinin, which is a substrate of ACE and tussigenic, were significantly increased in subjects with genotype II (before: 1.6+/-0.6 vs. after: 2.6+/-0.5 cm2, P<0.05) but not in subjects with genotype DD (before: 1.4+/-0.5 vs. after: 1.6+/-0.6 cm2, n.s.) after usage of cilazapril. By contrast, skin responses to intradermal substance P did not change in subjects with either genotype. These findings provide further evidence of a link between ACEI-induced cough and I/D polymorphism of the ACE gene and suggest that ACEIs induce cough by modulating the tissue level of bradykinin.