Lisinopril Therapy Research Articles

66-Year-Old Woman With Painless Jaundice

66-year-old woman presented for evaluation of jaundice that had been present for 6 weeks. She first noticed that her urine began to appear darker and then experienced pruritus under her breasts that gradually spread throughout her body. She sought evaluation at an urgent care centerandwasinitiallythoughttohavescabies.Two weeks later, she noted a yellowing of her skin and began having gray-colored stools. Also at this time, she had mild right upper quadrant abdominal discomfort, nausea, and fullness associated with eating fatty food. She modified her diet to mainly carbohydrates and noted resolution of the gastrointestinal symptoms. The patient had no history of hepatitis B or C, alcohol use, fevers, chills, anorexia, vomiting, myalgias, sick contacts, travel outside the United States, or acetaminophen usage. There was no family history of gastrointestinal or autoimmune disease. Her medical history was notable for idiopathic focal sclerosing glomerulonephritis that was diagnosed with renal biopsy when proteinuria was discovered incidentally. Lisinopril therapy was prescribed. At that same time, an antinuclear antibody (ANA) test yielded weakly positive results. She reported having a “liver problem” in the distant past that was associated with an oral antifungal medication and lasted 8 to 9 months, but she could not recall further details. Vital signs were normal on admission. Physical examination revealed an older woman who was not inacutedistressbuthadscleralicterus,skinthatwas diffusely jaundiced, most prominent on the chest and back, and many excoriations on her back, arms, and legs. Her abdomen was soft, nondistended, and mildly tender to palpation of the right upper quadrant with no rebound or guarding. Normoactive bowel sounds and palpable hepatomegaly 4 to 5 cm below the costal margin were noted. There was no splenomegaly.

Lisinopril pharmacokinetics and erythropoietin requirement in haemodialysis patients

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. 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. 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. 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.

Effect of lisinopril on circulating endothelial progenitor cells in patients with essential hypertention

Objective. To assess the effect of lisinopril on the dynamics of circulating endothelial progenitor cells (EPC) as well as the clinical markers of cardiovascular risk in patients with essential hypertension. Design and methods. We have studied the number and functional activity of EPC and clinical markers of cardiovascular risk in carefully selected group of 18 patients with essential hypertension, who have never been treated by angiotensin converting enzyme inhibitors (ACEi), and 19 normotensive control subjects. Hypertensive patients took lisinopril in dose 10-20 mg daily and then were re-examined after 12 weeks of lisinopril therapy. Results. The present study shows that hypertensive patients are characterized by a relative decline in the number of circulating EPC in conditions of endothelial dysfunction. Also the cells with angiogenic potential have a decreased proliferative capacity in hypertensive patients in comparison with healthy controls (1,4 ± 0,9 vs 2,2 ± 1,2 units/mm 2 ; p < 0,01). Changes of the functional activity of EPC are closely associated with pathological vascular remodeling. Conclusions. ACEi lisinopril improves functional properties of the endothelium in hypertensive patients through mobilizing effect on the EPC and stimulates their proliferation activity.

Antioxidant enzymes in erythrocytes from hypertension patients receiving lisinopril monotherapy or combined lisinopril plus simvastatin therapy

Statins and angiotensin-converting enzyme (ACE) inhibitors have beneficial impact on the serum cholesterol and blood pressure. It is supposed that statins and ACE inhibitors may modify the antioxidative status of erythrocytes. The study objective was to compare the effects of two treatments, lisinopril alone vs lisinopril plus simvastatin, on erythrocyte antioxidant enzyme activities. The study involved 32 patients with arterial hypertension, the initial serum total cholesterol, LDL-cholesterol and triglycerides within the normal range. Patients of two groups, each of 16 subjects, were treated with lisinopril (10 mg/day) or with lisinopril (10 mg/day) plus simvastatin (20 mg/day). Before and after 3 and 6 months of follow-up therapy, activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GLR) in purified erythrocytes were determined. In all patients, significantly higher catalase activity (by 79.3-106.5%, p < 0.0001) and significantly lower GPx activity (by 20.7-30.6%, p < 0.001) were observed after therapy as compared to the baselines. Just the same results were obtained in both groups (lisinopril and lisinopril + simvastatin), after both periods (3 and 6 month) of treatments. SOD activity was increased only in the lisinopril group and only after 6 months (p = 0.0345). No changes of GLR reductase activity were seen under all conditions indicated. Thus, the lisinopril monotherapy and combined lisinopril plus simvastatin therapy exhibit specific, pronounced and equipotent effects on antioxidant enzymes in human erythrocytes. Administration of lisinopril or lisinopril plus simvastatin may protect erythrocytes and other tissues from oxidative damage.

Erythrocyte antioxidant enzymes in hypertensive patients receiving lisinopril monotherapy or combined lisinopril plus simvastatin therapy

Statins and angiotensin-converting enzyme (ACE) inhibitors have beneficial impact on the serum cholesterol and blood pressure. It is supposed that statins and ACE inhibitors may modify the antioxidative status in erythrocytes. The study objective was to compare the effects of two treatments, lisinopril alone versus lisinopril plus simvastatin, on erythrocyte antioxidant enzyme activities. The study involved 32 patients with arterial hypertension, their initial serum total cholesterol, LDL-cholesterol and triglycerides were within the normal range. Patients of two groups, each of 16 subjects, were treated with lisinopril (10 mg/day) or with lisinopril (10 mg/day) plus simvastatin (20 mg/day). Before and after the ambulatory therapy for 3 and 6 months, activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR) were determined in purified erythrocytes. All treated patients had significantly higher catalase activity (by 79.3–106.5%, p < 0.0001) and significantly lower GPx activity (by 20.7–30.6%, p < 0.001) as compared to the baselines. The same results were obtained in both groups (lisinopril and lisinopril + simvastatin), after both periods (3 and 6 month) of treatments. SOD activity increased only in the lisinopril group and only after 6 months (p = 0.0345). No changes of GR activity were observed under all conditions studied. Thus, the lisinopril monotherapy and combined lisinopril plus simvastatin therapy exhibit specific, pronounced and equipotent effects on antioxidant enzymes in human erythrocytes. Peroral administration of lisinopril or lisinopril plus simvastatin may protect erythrocytes and other tissues against oxidative damage.

Hypotension and bradycardia associated with concomitant tizanidine and lisinopril therapy

A case of severe bradycardia and hypotension associated with concomitant tizanidine and lisinopril therapy is reported. An 85-year-old man with a chief complaint of profound weakness was admitted to the hospital with a blood pressure reading of 60/32 mm Hg and a heart rate of 37 beats/min. His medical history included type 2 diabetes mellitus, congestive heart failure, gastroesophageal reflux disease, chronic obstructive pulmonary disease, osteoarthritis, restless leg syndrome, benign prostatic hyperplasia, generalized anxiety disorder with depression, and severe chronic back pain for which he was receiving treatment at a pain clinic. Two days before hospital admission, he had been seen at the pain clinic and started on ti-zanidine. Additional medications included acetaminophen, chlorpromazine, citalopram, finasteride, lidocaine patch, lisinopril, metformin, pramipexole, omeprazole, simvastatin, theophylline, diclofenac topical gel, hydrocodone-acetaminophen, and ondansetron. After taking three doses of the newly prescribed tizanidine, he developed severe hypotension and bradycardia. Notable laboratory test values included a serum creatinine concentration of 1.90 mg/dL, a blood urea nitrogen concentration of 21 mg/dL, a serum potassium concentration of 5.5 meq/L, and a serum sodium concentration of 128 meq/L. Upon admission, tizanidine, lisinopril, theophylline, omeprazole, and simvastatin were withheld, and i.v. fluids were administered. The patient's vital signs began to gradually improve. Within 24 hours, the patient's blood pressure and heart rate had improved, as had the previously abnormal laboratory test values. Tizanidine was discontinued, and all of his other preadmission medications were restarted at discharge. The addition of tizanidine in a patient receiving long-term treatment with lisinopril was associated with severe hypotension and bradycardia.

Unique case of presumed lisinopril-induced hepatotoxicity

A case of presumed lisinopril-induced hepatotoxicity is reported. 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. 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.

Lisinopril‐Induced Nightmares

Drug‐induced nightmares have been reported in the literature and are a known adverse effect of certain antihypertensive agents such as α‐agonists and β‐blockers. Data are limited, however, on the association of this adverse effect with angiotensin‐converting enzyme (ACE) inhibitors. We describe a 63–year‐old, obese woman, with no history of illicit drug abuse, alcohol abuse, or psychiatric illness, who developed nightmares after starting lisinopril 10 mg/day for blood pressure control. The drug was discontinued, triamterene‐hydrochlorothiazide was started, and her nightmares ceased. One year later, the patient continued to have no complaints of nightmares. At that time, however, her blood pressure was slightly elevated. Triamterene was discontinued, and lisinopril was restarted at a lower dose of 5 mg/day in addition to hydrochlorothiazide 25 mg/day. Her nightmares returned; however, the patient decided to continue taking the lisinopril and tolerate the nightmares. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patient's development of nightmares and lisinopril therapy. The exact mechanism by which ACE inhibitors cause this drug reaction is not known. Clinicians should be aware of this potential adverse effect when monitoring patients receiving ACE inhibitors.

Effects of Atorvastatin and Lisinopril on Endothelial Dysfunction in Patients with Behçet's Disease

Behçet's disease is a chronic inflammatory vasculitis. Vascular involvement is one of the major complications of Behçet's disease, during the course of the disease. Previous studies showed that ACE inhibitors and statins may improve endothelial functions in endothelial dysfunction. The aim of our study is to compare the effects of atorvastatin and lisinopril to placebo on endothelial dysfunction in patients with Behçet's disease. We prospectively studied 92 (48 female) Behçet's patients who were diagnosed according to the International Study Group criteria. Endothelial dysfunction was evaluated by brachial artery flow-mediated dilatation (FMD) method using high-resolution vascular ultrasound device at baseline and after for 3-month therapy. Patients were consecutively randomized into three groups as (atorvastatin (n = 31), lisinopril (n = 31), and placebo groups (n = 30). Patients in atorvastatin group received 20 mg atorvastatin, lisinopril group received 10 mg lisinopril per day, and placebo group received placebo per day for 3 months. The baseline characteristics of patients were similar among three groups; however, high-sensitive C-reactive protein (hs-CRP) levels were lower in atorvastatin group than placebo group. A significant improvement in FMD was observed in both atorvastatin (5.0 ± 1.4 vs. 12.8 ± 3.6%, P < 0.001) and lisinopril groups (5.0 ± 1.2 vs. 11.4 ± 5.0%, P < 0.001). Partial significant enhancement was observed in placebo group (4.9 ± 1.1% vs. 5.7 ± 1.0, P = 0.002). However, it was lower than the cutoff value for endothelial dysfunction. These findings suggest that atorvastatin and lisinopril improve endothelial functions in Behçet's disease patients. However, large studies are needed to determine the long-term effects of atorvastatin and lisinopril therapy.

Randomized Controlled Trial: Lisinopril Reduces Proteinuria, Ammonia, and Renal Polypeptide Tubular Catabolism in Patients With Chronic Allograft Nephropathy

Angiotensin-converting enzyme inhibitors in native nephropathies reduce proteinuria and delay progression to renal failure. Data in renal transplantation remain limited. A negative effect on glomerular filtration rate was concluded in a recent systematic review. In this novel randomized controlled trial, 47 patients with chronic allograft nephropathy, severe renal impairment, and more than or equal to 1 g/24 hr proteinuria were randomized to lisinopril (group A) or other hypotensives (group B) for 1 year. Sodium bicarbonate was given to all patients to treat metabolic acidosis prophylactically (acidosis increases significantly with lisinopril). The annual rate of decline of graft function was measured isotopically (primary outcome) and 24 hr proteinuria, genotyping, radiolabeled polypeptide aprotinin proximal tubular catabolic studies (in group A only) as secondary outcome measurements were undertaken. At baseline, groups were comparable except for greater proteinuria in group A. After 1 year, the rate of decline of graft function and graft survival were comparable in both groups. Proteinuria decreased significantly in group A patients only. Lisinopril also significantly reduced radiolabeled aprotinin uptake and metabolism, plasma aldosterone, and ammonia excretion. Plasma potassium, bicarbonate, and mean arterial pressures were comparable in both groups. Patients with more than or equal to 30% reduction in proteinuria had a significant association with rs699 polymorphism in the angiotensinogen gene. The rate of decline of renal graft function in patients with chronic allograft nephropathy was not adversely affected by lisinopril therapy given for 1 year. Lisinopril significantly reduced proteinuria, renal proximal tubular polypeptide catabolism, plasma aldosterone, and ammonia excretion suggesting relative preservation of graft function. Treating metabolic acidosis allowed safe and prolonged use of angiotensinogen-converting enzyme inhibitors.

The effect of exenatide on lisinopril pharmacodynamics and pharmacokinetics in patients with hypertension

This study evaluated the potential effect of exenatide on the pharmacokinetics and pharmacodynamics of lisinopril in patients with mild-to-moderate hypertension. 22 patients with mild-to-moderate primary hypertension participated in a double-blind, randomized, placebo-controlled, 2-period, 2-sequence crossover study. Patients on stable lisinopril therapy were randomly assigned to receive subcutaneous exenatide (10 microg b.i.d.) and placebo b.i.d. separated by at least 2 days washout period. The primary pharmacodynamic parameters were baseline-adjusted 24-hour mean systolic and diastolic blood pressure. Steady state plasma lisinopril concentration-time profiles were also assessed. Mean blood pressure changes were not significantly different between exenatide and placebo coadministered with lisinopril. The least squares mean differences (95% CI) between treatments were +1.38 mmHg (-1.41, 4.17) for diastolic and +1.38 mmHg (-1.95, 4.71) for systolic blood pressure. Exenatide delayed the time to attain maximum lisinopril concentration (tmax,ss) by 2 hours but did not significantly alter maximum lisinopril concentration (Cmax,ss) or area under the concentration-time profile (AUCtau,ss) over the 24-hour steady-state dosing interval. This study demonstrated that concurrent administration of exenatide did not produce clinically relevant changes in blood pressure and did not significantly alter lisinopril pharmacokinetics in patients with mild-to-moderate hypertension.

Efficacy and safety of lisinopril for mild childhood IgA nephropathy: a pilot study

Even in children with mild immunoglobulin (Ig)A nephropathy (IgA-N) showing minimal/focal mesangial proliferation, persistent proteinuria seems to be a risk factor for progression of the disease, indicating the need for an effective and safe treatment even in such cases. Studies carried out to date have indicated that angiotensin-converting enzyme inhibitors (ACEIs) reduce urinary protein excretion and preserve renal function in adult IgA-N. However, no prospective study of ACEI only for childhood IgA-N has yet been carried out. In this prospective single-arm pilot trial, we administered lisinopril (0.4 mg/kg per day) as therapeutic treatment to 40 children with mild IgA-N with proteinuria [morning urinary protein/creatinine ratio (uP/Cr) >or= 0.2 g/g]. Thirty-three patients reached the primary endpoint (uP/Cr < 0.2) during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by the Kaplan-Meier method was 80.9%. Mean uP excretion was reduced from 0.40 to 0.18 g/m(2)/day (p < 0.0001). Of the 40 patients treated, five (12.5%) showed dizziness, and four of these five needed the lisinopril dose reduced. However, lisinopril therapy was continued in all patients during the 2-year treatment period. No other side effect, such as cough, was observed. We conclude that the efficacy and safety of lisinopril is seemingly acceptable for the treatment of children with mild IgA-N.

Reduction of proteinuria with angiotensin receptor blockers

Renal pathophysiology is elicited by activation of angiotensin II type 1 (AT(1)) receptors at all stages of renovascular disease. Angiotensin receptor blockers (ARBs) that specifically block the AT(1) receptor offer the potential to prevent or delay progression to end-stage renal disease independently of reductions in blood pressure. Proteinuria--an early and sensitive marker for progressive renal dysfunction--is reduced by ARB use in patients with type 2 diabetic nephropathy and microalbuminuria or macroalbuminuria. Retrospective analysis of data available from early trials has confirmed this finding and has shown that albuminuria reduction is associated with lessening of cardiovascular risk. The ARB telmisartan is equivalent to enalapril in preventing glomerular filtration rate decline, and equivalent to valsartan in reducing proteinuria. Telmisartan is more effective than conventional therapy in lowering the risk of transition to overt nephropathy in hypertensive and normotensive patients. An additive effect has been seen in smaller studies when telmisartan has been added to lisinopril therapy, and high-dose telmisartan reduces albuminuria better than low-dose telmisartan. Similar data were obtained with other ARBs such as candesartan, losartan, valsartan, or irbesartan. These data support the proposition that blockade of the renin-angiotensin system beyond that required for maximum blood pressure reduction provides optimum renal protection.

Penile angioedema associated with the use of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers

Two cases of penile angioedema associated with the use of angiotensin-converting-enzyme inhibitors and angio-tensin II receptor blockers are reported. The first case of penile angioe-dema involved a 68-year-old man who arrived at the emergency department (ED) with a 2-12-hour history of penile swelling occurring three days after initiation of irbesartan in addition to longstanding lisinopril therapy. All parts of the physical examination were normal, except for the genital examination. The patient's penis was edematous at midshaft only and was nontender with normal skin coloring. The edema was nonpitting and limited to the skin. The patient was instructed to stop taking both lisinopril and irbesartan, and symptoms resolved within 48 hours with supportive care alone. In the second case, a 48-year-old man arrived at the ED complaining of penile swelling over the previous two days. Enalapril had been initiated one month before his arrival at the ED. The patient's penis was nontender and edematous at midshaft. The edema was nonpitting and limited to the skin. The patient was instructed to stop taking enalapril, given oral prednisone 60 mg, and asked to continue his prednisone for five days after discharge. The swelling resolved within two days of stopping enalapril, and he had no further episodes of penile swelling. Neither patient was rechallenged with the offending medications. Penile angioedema was reported in two patients. The first case involved a patient receiving both lisinopril and irbesartan. The second patient was receiving enalapril only.

MICROALBUMINURIA AS A FORECAST FACTOR FOR CARDIO-VASCULAR COMPLICATIONS AND A MARKER OF THERAPY EFFICACY IN PATIENTS WITH ARTERIAL HYPERTENSION

Aim. To assess the microalbuminuria (MAU) and vascular wall elasticity in patients with essential hypertension (HT) and evaluate the possibilities to reduce in fatal cardiovascular risk due to lisinopril (Listril, Dr Reddy’s) therapy. Material and methods. 42 patients (60,3±0,83 y.o.) with HT were involved in the study. Pulse wave velocity was estimated by volume sphygmography. MAU levels were detected with micral-test (Roche Diagnostics, Germany). Patients received lisinopril as a first-step antihypertensive drug, if necessary the dose of lisinopril was increased or amlodipine was added. The treatment lasted for 12 weeks. Results. MAU was revealed more often in patients with increased body mass index as compared with whole population of hypertensive patients. MAU was associated with increased vascular wall stiffness. Lisinopril therapy during 4 weeks allowed to reach target level of blood pressure (BP) in 42,9% of patients and decreased in MAU level by 54,5%. Therapy continuation during 12 weeks allowed to reach target level of BP in 90,4% of patients and reduce in fatal cardiovascular risk by 36,6%. Conclusion. Lisinopril therapy resulted in significant reduction in BP, MAU and fatal cardiovascular risk in patients with HT.

A Case of Fatal Necrotizing Pancreatitis: Complication of Hydrochlorothiazide and Lisinopril Therapy

We report a case of fatal necrotizing pancreatitis associated with hydrochlorothiazide and lisinopril therapy. A 49-year-old man who presented with 2 days of abdominal pain and vomiting was found to have severe pancreatitis. The patient denied any alcohol use. In addition, abdominal ultrasound examinations showed no evidence of cholelithiasis or bile duct dilations. Review of his medication history with the family revealed that he was being treated with hydrochlorothiazide and lisinopril for hypertension. An exploratory laparotomy was performed and revealed no common bile duct stones. Unfortunately, the patient's hospital course was complicated with multiple organ failure, which resulted in death. To the best of our knowledge, there are only 3 other reported cases of hydrochlorothiazide-induced necrotizing pancreatitis reported in the literature.

Acute Renal Failure During Lisinopril and Losartan Therapy for Proteinuria

The use of combined therapy with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) for treatment of proteinuria has been gaining support. Limited data are available regarding this treatment in the pediatric population. This report describes a case of acute compromise of renal function associated with hypotension in a 7-year-old boy treated with the ACE inhibitor lisinopril and the ARB losartan. It emphasizes the need for close surveillance of renal function and blood pressure during such therapy even in patients with relative preservation of renal function. Further investigation into the utility and safety of dual therapy with an ACE inhibitor plus an ARB in pediatric patients is warranted. Key Words: renal failure, proteinuria, angiotensin-converting enzyme inhibitor, ACEI, angiotensin II receptor blocker, ARB.

Impact of chronic lisinopril therapy on left atrial volume versus dimension in chronic organic mitral regurgitation

Chronic mitral regurgitation imparts a volume load on the left atrium (LA). Because this chamber may dilate asymmetrically, changes in left atrial size may be underestimated using standard two-dimensional or M-mode techniques. The effect of lisinopril therapy in the setting of chronic organic mitral regurgitation on LA dimension was studied using standard M-mode techniques and LA volumes using the biplane Simpson's method. Mitral regurgitant fraction was reduced at one year in the lisinopril group versus the placebo group (-6.7%+/-3.5% versus 3.5%+/-3.2%, respectively; P<0.05). Significant reductions in both maximum and minimum LA volumes were seen in the lisinopril group (88+/-33 mL to 75+/-23 mL and 46+/-20 mL to 38+/-16 mL, respectively; P<0.01). This change in LA size was not appreciated when measurements were performed using standard M-mode techniques (from 44.3+/-6.9 mm to 44.1+/-7.4 mm; P=not significant). There was no significant relationship between change in LA volume and change in regurgitant fraction or systolic blood pressure. Change in LA volume was moderately correlated with change in left ventricular mass. Angiotensin-converting enzyme inhibitor therapy reduces LA volume in the setting of chronic mitral regurgitation. This change in LA size is not apparent when standard M-mode techniques are used. Therefore, a volumetric assessment of atrial size in the setting of chronic mitral regurgitation proved to be superior to standard two-dimensional techniques.

Quantitative measurement of retinal thickness in patients with diabetic macular edema is useful for evaluation of therapeutic agents

The effect of lisinopril (an angiotensin-converting enzyme inhibitor) on diabetic macular edema (DME) was investigated by quantitative measurement of macular thickness. In a nonrandomized clinical trial, 19 normotensive type 2 diabetic patients with DME prospectively received oral lisinopril therapy for 2 months. Another 10 normotensive type 2 diabetic patients with similar DME were prospectively followed for two months without treatment. Central macular thickness was measured with a retinal thickness analyzer (RTA). In the lisinopril group, visual acuity improved by two lines or more in two out of 19 eyes (11%), was unchanged in 15 eyes (78%), and deteriorated by two lines or more in two eyes (11%). The mean central macular thickness was significantly reduced after 2 months of treatment (381.3 ± 121.1 μm) compared with that before administration (475.2 ± 171.0 μm, P = 0.0093). In the control group, central macular thickness was not significantly decreased after 2 months (458.5 ± 113.7 μm, P = 0.2178) compared with the baseline value (464.7 ± 152.2). Fluorescein angiography showed that macular leakage was decreased in 10 patients from the lisinopril group (53%) and was unchanged in nine patients (47%). There was a significant difference of central macular thickness between the patients with and without improvement of macular leakage ( P = 0.0040). Lisinopril therapy may reduce macular thickness in patients with DME, as shown by this quantitative study. In addition, quantitative measurement of retinal thickness is useful when evaluating therapeutic agents for DME.

Clinical pharmacy specialist implementation of lisinopril therapy in patients with coronary artery disease and diabetes mellitus.

As the results of the Heart Outcomes Prevention Evaluation trial suggested that patients with both coronary artery disease (CAD) and diabetes mellitus would benefit from angiotensin-converting enzyme (ACE) inhibitor therapy, our objective was to increase the percentage of patients with both of these conditions receiving the goal dosage (20 mg/day) or highest tolerated dosage of the ACE inhibitor lisinopril through intervention of a clinical pharmacy service. Prospective study with historic comparison (control group). Clinical Pharmacy Cardiac Risk Service. Hospitalized patients with CAD and type 2 diabetes mellitus. At hospital discharge, lisinopril 5 mg/day was started in eligible patients; the drug was titrated to a goal dosage of 20 mg/day or the highest tolerated dosage. Potassium level, serum creatinine level, and blood pressure were monitored at baseline, at each dosage titration, and 2 weeks after the goal or highest tolerated dosage was reached. The group receiving usual care (control group) consisted of 95 patients; the treatment group had 101 patients. At baseline, 19 patients (20%) in the control group were receiving the goal dosage of lisinopril, 34 (36%) were taking a suboptimal dosage, 16 (17%) were excluded from treatment, and 26 (27%) were eligible but were not receiving lisinopril therapy. After 9 months, ACE inhibitor dosages had changed minimally in the control group. In the treatment group, at baseline, 37 patients (36%) were at their goal dosage and therefore titration was not necessary; 15 (15%) were receiving a suboptimal dosage, 35 (35%) were excluded from treatment, and 14 (14%) were eligible but not receiving therapy. After the titration period, 55 (54%) treatment group patients were at the goal dosage, 11 (11%) were taking a suboptimal dosage, and 35 (35%) were not candidates for ACE inhibitor therapy. The most common reasons for exclusion were renal insufficiency, cough, and baseline hypotension. Changes in potassium level, serum creatinine level, and blood pressure were not significant during the study. The clinical pharmacy service more than doubled the number of patients with CAD and diabetes who achieved the goal dosage of an ACE inhibitor, a drug class that has been shown to decrease morbidity and mortality in this patient population.