The effect of diminazene, an angiotensin-converting enzyme 2 activator, on adenine-induced chronic kidney disease in rats.

The present study investigated the effect of diminazene, lisinopril, or valsartan on adenine-induced chronic kidney disease (CKD) in rats. The animals were divided into five groups (n = 6). The first and second groups received normal diet and adenine in the feed at a dose of 0.25% w/w for 35 days, respectively. The third, fourth, and fifth groups were treated as the second group but also received diminazene (15 mg/kg/day), lisinopril (10 mg/kg/day), and valsartan (30 mg/kg/day), respectively, for 35 days. Adenine significantly increased plasma urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), calcium, phosphorus, and uric acid. In addition, adenine increased urinary albumin/creatinine ratio and N-Acetyl-ß-D-glucosaminidase (NAG)/creatinine ratio and reduced creatinine clearance. Adenine also significantly increased the plasma concentrations of inflammatory cytokines (plasma tumor necrosis factor-alpha [TNF-α] and interleukin-1beta [IL-1ß]) and significantly reduced antioxidant indices (catalase, glutathione reductase [GR], and superoxide dismutase [SOD]). Histopathologically, renal tissue from adenine-treated rats showed necrosis of renal tubules, tubular casts, shrunken glomeruli, and increased renal fibrosis. All drugs ameliorated adenine-induced biochemical and histopathological changes. The protective effect of the three drugs used is, at least partially, due to their anti-inflammatory and antioxidant effects. Our results show that administration of diminazene, lisinopril, or valsartan had a comparable effect on the reversal of the biochemical and histopathological indices of adenine-induced CKD in rats.

67-year-old man • upper extremity pain & edema • recent diagnosis of heart failure • Dx?

► Upper extremity pain ► Upper extremity edema ► Recent diagnosis of heart failure.

Randomized Trial of Lisinopril Versus Carvedilol to Prevent Trastuzumab Cardiotoxicity in Patients With Breast Cancer.

BACKGROUND: Trastuzumab is highly effective for human epidermal growth factor receptor type 2 (HER2)-positive breast cancer but is associated with a decline in left ventricular ejection fraction. OBJECTIVES: The purpose of this study was to determine whether angiotensin-converting enzyme inhibitors or beta-blockers reduce the rate of trastuzumab-induced cardiotoxicity (left ventricular ejection fraction decrease >10%, or >5% if below 50%) and limit treatment interruptions. METHODS: In this double-blind, multicenter, placebo-controlled trial, cardiotoxicity and treatment interruptions in patients with HER2-positive breast cancer treated with trastuzumab for 12 months were evaluated over a 2-year period. Patients were stratified by anthracycline use and then randomized to receive lisinopril, carvedilol, or placebo. RESULTS: The study included 468 women, age 51 ± 10.7 years. For the entire cohort, cardiotoxicity was comparable in the 3 arms and occurred in 32% of patients on placebo, 29% on carvedilol, and 30% on lisinopril. For patients receiving anthracyclines, the event rates were higher in the placebo group (47%) than in the lisinopril (37%) and the carvedilol (31%) groups. Cardiotoxicity-free survival was longer on both carvedilol (hazard ratio: 0.49; 95% confidence interval: 0.27 to 0.89; p = 0.009) and lisinopril (hazard ratio: 0.53; 95% confidence interval: 0.30 to 0.94; p = 0.015) than on placebo. In the whole cohort, as well as in the anthracycline arm, patients on active therapy with either angiotensin-converting enzyme inhibitor or beta-blockers experienced fewer interruptions in trastuzumab than those on placebo. CONCLUSIONS: In patients with HER2-positive breast cancer treated with trastuzumab, both lisinopril and carvedilol prevented cardiotoxicity in patients receiving anthracyclines. For such patients, lisinopril or carvedilol should be considered to minimize interruptions of trastuzumab. (Lisinopril or Coreg CR in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab; NCT01009918).

Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study).

BACKGROUND: Persistent proteinuria seems to be a risk factor for progression of renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot study showed that 2-year lisinopril therapy is effective and safe for children with mild IgA nephropathy. When combined with ACEI and ARB, reported results are of greater decrease in proteinuria than monotherapy in chronic glomerulonephritis, including IgA nephropathy. To date, however, there have been no randomized controlled trials in children. METHODS: This is an open-label, multicenter, prospective, and randomized phase II controlled trial of 63 children with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and safety between patients undergoing lisinopril monotherapy and patients undergoing combination therapy of lisinopril and losartan to determine better treatment for childhood proteinuric mild IgA nephropathy. RESULTS: There was no difference in proteinuria disappearance rate (primary endpoint) between the two groups (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89% [combination vs monotherapy]). Moreover, there were no significant differences in side effects between the two groups. CONCLUSIONS: We propose lisinopril monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there are no advantages of combination therapy. CLINICAL TRIAL REGISTRATION: Clinical trial registry, UMIN ID C000000006, https://www.umin.ac.jp .

Lisinopril-associated bullous pemphigoid in an elderly woman: a case report of a rare adverse drug reaction.

An 87-year-old woman with a long-standing history of hypertension, hypothyroidism and diabetes presented to us with scaly and pruritic vesicles of an erythematous base and crusted surface of 2-month duration. They first appeared on her abdomen and gradually spread to her lower back, thighs, before spreading to her upper and lower limbs. Her lesions were non-painful, aggravated by sun exposure only, and sparing mucous membranes. Nikolsky sign was positive with no discernible fluid-filled bullae. History was remarkable only for a doubling of her Lisinopril dosage 2 months prior to the appearance of her lesions, with no other potential environmental and/or drug triggers recognizable on history taking. In light of the appearance of her lesions after her Lisinopril dose escalation, in the absence of any other discernible triggers, an adverse drug reaction (ADR) was entertained, yielding a corresponding Naranjo ADR probability score of 7. Particularly, drug-induced pemphigus foliaceus was initially suspected given her clinical presentation and the morphology and distribution of her lesions. However, her skin biopsy altered our diagnosis to drug-induced bullous pemphigoid (BP) instead, making this the second case reported to date on Lisinopril-induced BP, and the first to report a dose-response variant of this adverse reaction.

Recognizing a Rare Phenomenon of Angiotensin-Converting Enzyme Inhibitors: Visceral Angioedema Presenting with Chronic Diarrhea-A Case Report.

INTRODUCTION: Peripheral angioedema of the face and upper airways is a well-known phenomenon of angiotensin-converting enzyme inhibitors occurring in only 0.1% to 0.7% of patients. We describe a case of the even less-common manifestation of visceral angioedema, which causes symptoms of chronic and intractable diarrhea. CASE PRESENTATION: A 68-year-old white woman presented with large-volume diarrhea, caused by visceral angioedema secondary to lisinopril therapy. Initial imaging studies were significant for distended small bowel loops, with subsequent unremarkable findings on colonoscopy and biopsy studies. After an exhaustive laboratory work-up, her diarrhea resolved only after the discontinuation of lisinopril. DISCUSSION: Use of angiotensin-converting enzyme inhibitors is increasing, making the recognition of visceral angioedema important in preventing significant morbidity and avoiding invasive and costly studies.

Impact of switching from different treatment regimens to a fixed-dose combination pill (polypill) in patients with cardiovascular disease or similarly high risk.

Aims Cardiovascular fixed-dose combination pills, or polypills, may help address the widespread lack of access and adherence to proven medicines. Initiation of polypill-based care typically entails switching from current separately taken medications. Given the heterogeneity in usual care, there is interest in the impact of polypill treatment across different patterns of prior medication regimen. Methods A total of 2004 participants with established cardiovascular disease or estimated 5-year cardiovascular risk of over 15% were randomised to polypill-based treatment (aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg) or usual care. Baseline medications were classified by potency relative to polypill components. Estimated cardiovascular risk reduction was calculated by combining risk factor changes with results seen in meta-analyses of previous randomised trials. Results For cholesterol reduction conferred by polypills, there was a dose response across baseline statin groups, with mean low-density lipoprotein (LDL)-cholesterol differences of 0.37, 0.22, 0.14 and 0.07 mmol/L among patients taking no statin, less potent, equipotent and more potent statin at baseline, respectively. Similarly there were differences in mean systolic BP of 5.4, 6.2, 3.3 and 1.8 mmHg among patients taking 0, 1, 2 or 3 BP-lowering agents. Among patients taking more potent statins at baseline, there was no significant difference in LDL-cholesterol but there were benefits for BP and aspirin adherence. Similar results were seen among patients taking 3 BP-lowering agents at baseline. Switching to a polypill-based strategy resulted in estimated cardiovascular relative risk reductions across a wide range of usual care patterns of antiplatelet, statin and BP-lowering therapy prescribing. Conclusion Adherence benefits from switching to a polypill resulted in risk factor changes that were at least as good as usual care across a wide variety of treatment patterns, including equally potent or more potent regimens. The benefits of switching to polypill-based care were greatest among those stepped up from partial treatment or less potent treatment.

[Eosinophilic pleuritic: An unusual complication of treatment with an angiotensin converting enzyme inhibitor]. / Pleurésie à éosinophiles: une complication rare d'un traitement par inhibiteur de l'enzyme de conversion de l'angiotensine.

BACKGROUND: Eosinophilic pleural effusions are defined by an eosinophil count ≥10% in pleural fluid and represent approximately 10% of exudative pleural effusions. OBSERVATION: We report the first case of eosinophilic pleural effusion occurring due to lisinopril treatment. Improvement after drug discontinuation and recurrence after reintroduction indicated that lisinopril was responsible for the effusion. CONCLUSION: The main causes of eosinophilic pleural effusions are infections including tuberculosis, and malignancies. Drug-induced eosinophilic pleural effusions have only rarely been described, mainly caused by cardiovascular or neuropsychiatric medicines.

[Results of the Russian EKSPERT program: post-marketing supervision over efficacy and influence of the preparation Ekvator on quality of life at out-patients with arterial hypertension].

Results of an open multicenter prospective postmarketing observational program EKSPERT (post-marketing surveillance of the effectiveness and impact of the EKVATOR treatment on quality of life in patients with arterial hypertension in ambulatory practice). Observation of 10 000 patients conducted in 300 medical center in various regions of the Russian Federation in 1005 doctors. Selected for the final analysis 4954 registration cards. It is shown that in patients with initially insufficient effective antihypertensive treatment has a large number of risk factors: men older than 55 years--56.5%, women older than 65 years--27.8%, unfavorable family history of arterial hypertension (AH)--87.9%, diabetes mellitus (DM)--13.4%, smoking--of patients 18.6%, obesity--35%, angina--35.59%, heart failure--41.3% with a history of myocardial infarction--10.9%, stroke--4.5%, renal disease--11.8%, hypercholesterolemia > 5.0 mmol/l--76.7%. Initially drug antihypertensive treatment was performed in 76.6% of patients, while 43.9% were treated regularly. Prior studies angiotensin converting enzyme inhibitors (ACE) afforded 60.56%, sartans--11% of patients, beta-blockers--41.9%, duretics--41.46%, calcium antagonists used in 21.42% of the patients. After the cancellation of previously used other ACE inhibitors, calcium antagonists and sartans patients were switched to therapy with the EKVATOR (amlodipine and lisinopril). Intensity reduction in systolic and diastolic blood pressure (SBP and DBP) did not depend on sex of the patients, the presence of angina, diabetes. Greater reduction in blood pressure in hypertensive duration more than 5 years, in the presence of congestive heart failure due to more frequent initiation of therapy with full-dose combination (amlodipine 10 mg and lisinopril 20 mg). After 1 months of starting therapy changes uorvney target blood pressure (< 140 and 90 mmHg) reached 51.5% of patients. Target SBP reached 59.7% of patients, the target level of DBP--69.4%. It is important that the majority of patients crossed over lowti graduation SBP and DBP and significantly improved their quality of life assessment. Incidence of adverse events was low--1.5% of them are the most common were swelling in the legs, headache, dizziness, and dry cough. Replacing the previous therapy different ACE inhibitors, sartans and calcium antagonists to the fixed combination amlodipine and lisinopril) (drug EKVATOR), leads to a rapid, pronounced, and safe reduction of BP and improve health in the majority of patients with previously uncorrected BP.

Iatrogenic angioedema associated with ACEi, sitagliptin, and deficiency of 3 enzymes catabolizing bradykinin.

New concepts of idiopathic and iatrogenic angioedema underline the role of bradykinin, and the importance of catabolizing enzymes. A case is described of Angiotensin converting enzyme inhibitor (ACEi) and sitagliptin induced angioedema, where AO attacks decreased after the withdrawal of lisinopril but resolved only after the withdrawal of sitagliptin, an inhibitor of dipeptylpeptidase IV. ACE, aminopeptidase P and carboxypeptidase N were decreased down to 17%, 42%, 64% of median references values, and remained low one year after the interruption of these drugs: 56%, 28% and 50%, respectively. The combined deficiency of APP and CPN might enhance the inhibiting effect of the DPP IV inhibitor. The fact that this triple deficiency remained latent before and after the treatment indicates that searching for latent enzyme deficiencies should be carried out when there is intention to treat with a combination of drugs interfering with the bradykinin metabolism.

Intraoperative cardiac arrest: was it the ACE inhibitor?

Continuing renin-angiotensin-aldosterone system antagonist therapy on the day of surgery is controversial, and appears to contribute to intraoperative hypotension. A patient presenting for cerebral aneurysm clipping continued her angiotensin-converting enzyme inhibitor on the morning of surgery, and subsequently experienced significant postinduction hypotension that culminated in cardiac arrest. Following successful resuscitation, she returned 6 weeks later to have her aneurysm clipped using identical anesthetic management; her blood pressure medications were held on the day of surgery.

ACE inhibitor-induced angioedema.

Angiotensin-converting enzyme inhibitors (ACEI) are commonly prescribed for blood pressure control and renal protection. ACEI angioedema is a common problem in patients who are taking ACEI, although, in most cases, the disorder is self-limited, and spontaneous episodes of apparently unprovoked angioedema stop with the discontinuation of the medication. In a subset of patients, hospitalization and even intubation are required for airway protection. The diagnosis is made clinically. There are no laboratory studies that establish the diagnosis. However, such investigations help exclude alternative diagnoses as the cause for the patient's presentation. Conventional treatment with regimens used to control allergic angioedema is ineffective in this condition. The mechanism of ACEI-induced angioedema is thought to be related to its effect on the kallikrein-kinin system. Kallikrein is a protease that converts high-molecular-weight kininogens into kinins, primarily bradykinin. Medications recently developed, primarily icatibant and ecallantide, to control hereditary angioedema, a disorder also associated with kallikrein-kinin activation, have been used to treat ACEI angioedema with some success. The efficacy of these agents and their optimal use remains to be established by randomized and placebo controlled trials.

Unnecessary surgery for acute abdomen secondary to angiotensin-converting enzyme inhibitor use.

Acute abdominal pain is the reason for 5% to 10% of all emergency department visits. In 1 in every 9 patients, operated on for an acute abdomen, laparotomy is negative. In a minority of patients, the acute abdomen is caused by side effects of medication. We present a case of unnecessary abdominal surgery in a patient with acute abdominal pain caused by intestinal angioedema (AE), which was eventually due to angiotensin-converting enzyme inhibitor (ACE-i) use. We hope that this case report increases awareness of this underdiagnosed side effect. Emergency department physicians, surgeons, internists, and family physicians should always consider ACE-i in the differential diagnosis of unexplained abdominal pain. Since early withdrawal of the medication causing intestinal AE can prevent further complications and, in some cases, needless surgery, we propose an altered version of the known diagnostic algorithm, in which ACE-i and nonsteroidal anti-inflammatory drugs-induced AE is excluded at an early stage.

High flow and high dose neosynephrine are effective to maintain perfusion pressure for the patient with preoperative angiotensin converting enzyme inhibitor during cardiopulmonary bypass.

Angiotensin converting enzyme inhibitors (ACEIs) are widely used in the treatment of hypertension, myocardial infarction, and congestive heart failure. They have a known adverse effect of unresponsiveness to vasoconstrictors resulting in hypotension for the patients undergoing cardiac surgery. We report a case of a 43-year-old female patient with preoperative lisinopril (2.5 mg per day for a week prior to cardiac surgery), who was diagnosed with severe mitral and tricuspid valve regurgitation. She underwent both a mitral and tricuspid valve replacement operation using cardiopulmonary bypass (CPB). To address her ACEI-associated hypotension on cardiopulmonary bypass, bypass flows were as high as cardiac index of greater than 3 (3.1 +/- .2) L/min/m2 to provide sufficient perfusion indicated by cerebral oxymetry monitoring and adequate urine on pump. In addition, due to unresponsiveness to regular concentration of neosynephrine (neo), boluses of higher concentrations up to 320 microg/mL of neo were administered to maintain the perfusion pressure on pump. The patient was weaned from CPB uneventfully and was discharged home on postoperative day 7. Additional therapeutic treatment to ACEI-associated hypotension and unresponsiveness to neo for the patients undergoing cardiac surgery using CPB is reviewed as well in this paper.

Lisinopril pharmacokinetics and erythropoietin requirement in haemodialysis patients.

BACKGROUND: There is ongoing controversy whether angiotensin-converting enzyme inhibitors (ACE-I) contribute to anaemia by causing hyporesponsiveness to erythropoiesis-stimulating agents (ESA). However, it is unknown whether or not plasma levels or area under the curve (AUC) of ACE-I are associated with responsiveness to ESA therapy. MATERIALS AND METHODS: We examined the association between lisinopril AUC, lisinopril plasma levels and ESA requirements that was assessed using an ESA index [(ESA IU/week/body weight kg)/(haemoglobin g/dL)]. After screening 184 haemodialysis patients, 14 fulfilled the inclusion criteria, mainly long-term use of oral lisinopril in the upper end of dosage range for this population with stable haemoglobin levels and intravenous ESA therapy. Lisinopril plasma levels were measured at eight different time points (predialysis, immediate post-dialysis and hourly for 6h thereafter; AUC1), and the seven post-dialysis lisinopril plasma levels were used for calculation of AUC2. RESULTS: The mean ESA index of all patients was 27·90±25·84 (IU/week/kg)/(g/dL). Average lisinopril AUC1 was 1212·48±1209·75 [mg*h/L], whereas AUC2 averaged 947·67±977·07 [mg*h/L]. Two patients (14%) had no detectable lisinopril plasma levels, indicating their noncompliance. There was no association between ESA index and AUC or plasma levels of lisinopril at any time point for all 14 or for the 12 compliant patients. CONCLUSIONS: Our study shows that long-term, high-dose lisinopril therapy has no effect on ESA responsiveness. Thus, avoidance or a dose reduction of ACE-I in dialysis patients will not necessarily lead to reduced ESA requirements and costs.

Terapia com inibidor da ECA com dosagens relativamente altas e risco de agravamento renal na insuficiência cardíaca crônica / ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure

FUNDAMENTO: O efeito renoprotetor dos inibidores da ECA vem sendo questionado no caso de diminuição do volume circulante efetivo, como na insuficiência cardíaca crônica direita ou biventricular. Objetivo: Detectar os preditores clínicos de agravamento renal na população de pacientes com ICC, caracterizado por dois tipos de regime de dosagem de inibidores da ECA. MÉTODOS: De acordo com um desenho de coorte retrospectiva, seguimos dois grupos de pacientes com ICC - tanto direita quanto biventricular -, todos na classe III da NYHA, tratados com inibidores da ECA (enalapril ou lisinopril), e com fração de ejeção do ventrículo esquerdo (FEVE) < 50 por cento, por meio de distinção em sua dosagem de inibidor da ECA: média-baixa (< 10 mg por dia) ou dosagem "alta" (> 10 mg por dia) de enalapril ou lisinopril. A disfunção renal agravada (ARD) foi definida pelo aumento de Cr > 30 por cento com relação ao segmento basal. O modelo de risco proporcional de Cox foi utilizado para identificar os preditores da ARD entre as seguintes variáveis: os inibidores da ECA com "alta" dosagem, idade, FEVE basal, histórico de repetidas terapias intensivas com diuréticos de alça por via intravenosa (diurético intravenoso), diabete, Cr basal, histórico de hipertensão, pressão arterial sistólica < 100 mmHg. RESULTADOS: Cinquenta e sete pacientes foram recrutados, dos quais 15 foram tratados com inibidor da ECA com dosagem "alta". Durante um seguimento médio de 718 dias, a ARD ocorreu em 17 pacientes (29,8 por cento). Apenas o inibidor da ECA com "alta" dosagem (RR: 12,4681 IC: 2,1614 - 71,9239 p = 0,0050) e Cr basal (RR:1,2344 IC: 1,0414 - 1,4632 p = 0,0157) foi demonstrado ser preditor da ARD. Além disso, demonstrou-se que o inibidor da ECA com dosagens "altas" não previu ARD em ICC sem diurético intravenoso e ICC com diabete. CONCLUSÃO: Na ICC de classe III da NYHA, o inibidor da ECA com "altas" dosagens e um maior Cr basal foi preditor da ARD. A nefrotoxicidade relacionada com inibidores da ECA em "altas" dosagens foi aumentada com o diurético intravenoso, ao passo que, em pacientes com ICC com diabete, aquela não foi detectada.

BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50 percent, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30 percent from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8 percent) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

Meta-analysis of randomized controlled trials on effect of angiotensin-converting enzyme inhibitors on cancer risk.

The renin-angiotensin system is an important mediator of tumor progression and metastasis. A recent meta-analysis of randomized controlled trials reported an increased risk of cancer with angiotensin receptor blockers. It is unknown whether angiotensin-converting enzyme (ACE) inhibitors may have a similar effect. Our primary objective was to determine the effect of ACE inhibitors on cancer occurrence and cancer death. Our secondary objective was to determine the effect of ACE inhibitors on occurrence of gastrointestinal (GI) cancers given previous concerns of increased risk. Systematic searches of SCOPUS (covering MEDLINE, EMBASE, and other databases) and the Food and Drug Administration official web site were conducted for all randomized controlled trials of ACE inhibitors. Trials with ≥1 year of follow-up and enrolling a minimum of 100 patients were included. Fourteen trials reported cancer data in 61,774 patients. This included 10 trials of 59,004 patients providing information on cancer occurrence, 7 trials of 37,515 patients for cancer death, and 5 trials including 23,291 patients for GI cancer. ACE inhibitor therapy did not have an effect on occurrence of cancer (I(2) 0%, risk ratio [RR] 1.01, 95% confidence interval [CI] 0.95 to 1.07, p = 0.78), cancer death (I(2) 0%, RR 1.00, 95% CI 0.88 to 1.13, p = 0.95), or GI cancer (RR 1.09, 95% CI 0.88 to 1.35, p = 0.43). In conclusion, ACE inhibitors did not significantly increase or decrease occurrence of cancer or cancer death. There was also no significant difference in risk of GI cancer.

Unique case of presumed lisinopril-induced hepatotoxicity.

PURPOSE: A case of presumed lisinopril-induced hepatotoxicity is reported. SUMMARY: A 30-year-old woman had complained of fatigue and yellow eyes for two days. Her medical history included hypertension and nephrotic syndrome. Her medications included furosemide 20 mg daily (for almost 6.5 years) and lisinopril 10 mg daily (for eight months). She had been treated with quinapril, enalapril, and lisinopril in the past by different primary care physicians without any adverse effects. She did not abuse alcohol and denied any liver-related problems in the past. Her physical examination revealed icterus and right-upper-quadrant abdominal tenderness. Initial laboratory tests revealed elevated liver enzyme values. Ultrasonography and computed tomography (CT) scans of the patient's abdomen suggested hepatocellular disease with mild hepatomegaly and a normal biliary tract. Due to worsening bilirubin and liver enzyme values, lisinopril was stopped. In the absence of a probable cause of the patient's hepatotoxicity, a CT-guided liver biopsy was performed. Histological examination of the liver tissue showed moderate chronic inflammatory cell infiltrates in the portal area, predominantly composed of lymphocytes with mild-to-moderate interface hepatitis. No centrolobular necrosis or steatosis was seen. After lisinopril was discontinued, there was a rapid improvement in the patient's clinical and biochemical pictures. On her follow-up clinic visit approximately two months later, all of her liver enzyme values had normalized. CONCLUSION: A woman who had received quinapril, enalapril, and lisinopril in the past without apparent adverse effects developed hepatocellular disease that became evident eight months after lisinopril therapy was reinstituted. The presumed hepatotoxicity resolved after discontinuation of lisinopril.