Use Of Angiotensin-converting Enzyme Research Articles

Medicines in the rehabilitation of patients after myocardial infarction: angiotensin-converting enzyme inhibitors

The paper analyzes the use of angiotensin-converting enzyme (ACE) inhibitors in patients after prior myocardial infarction. It presents the data of controlled studies, which indicate that it is warranted to use ACE inhibitors to improve prognosis in patients. It is concluded that it is unreasonable for a physician not to prescribe ACE inhibitors to post-myocardial infarction patients with obvious or asymptomatic left ventricular dysfunction and to diabetic patients (if no contraindications).

Conversion to Sirolimus Allows Preservation of Renal Function in Kidney and Kidney–Pancreas Allograft Recipients

The major causes of graft failure are chronic allograft nephropathy (CAN) and patient mortality. Sirolimus (SRL) is a powerful immunosuppressant with a less nephrotoxic profile as well as a lower incidence of cancer. The aim of this study was to evaluate the impact of conversion to SRL from calcineurin inhibitor (CNI)-based therapy in kidney (KT) and kidney–pancreas (SPK) allograft recipients. We analyzed renal function, allograft and patient survival, and SRL-associated adverse effects in 93 adult patients (86 KT and 7 SPK), who were converted to SRL between January 2001 and November 2008. The main reason for conversion was CAN (76; 9%) and 52 (7%) were receiving tacrolimus. Conversion occurred at a median 26.2 months. There was a significant improvement in creatinine clearance (CCr) at 6 months after conversion (CCr baseline 51.4 vs CCr 6m 60.4 mL/min; P < .0001), without changes at 12 and 24 months. However, proteinuria increased significantly at 6 months compared with the baseline: 150 mg/24 hours (0–453) versus 0 mg/24 hours (range, 0–309), respectively ( P < .0001), but did not progress at 12 or 24 months. At the same time we observed more extensive use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 60/5%; 65/3% and 70/2% at 6, 12, and 24 months. There were no changes in blood pressure control. Cholesterol significantly increased at 6 months (218.2 ± 37 vs. 186.6 ± 44 mg/dL; P < .0001). Graft and patient survivals at 4 years were 88% and 95%, respectively. Our experience suggested that conversion to SRL constituted a safe alternative with excellent results in patient and graft survival.

Treatment Strategies to Minimize or Prevent Chronic Allograft Dysfunction in Pediatric Renal Transplant Recipients

Long-term allograft survival poses a major problem in pediatric renal transplantation, with allograft nephropathy being the principal cause of graft failure after the first post-transplant year. The mechanisms of nephron loss resulting in graft dysfunction are multiple, comprising both immunologic factors such as acute and chronic antibody- or T-cell-mediated rejection and non-immunologic components. The latter include peri-transplant injuries and renovascular lesions (renal artery stenosis, thrombosis) as well as cardiovascular risk factors such as arterial hypertension and hyperlipidemia. Another relevant issue leading to progressive nephron loss and declining kidney transplant function is acute and chronic nephrotoxicity induced by the calcineurin inhibitors (CNIs) ciclosporin (cyclosporine microemulsion) and tacrolimus. Furthermore, the presence of an abnormal lower urinary tract as well as bacterial (recurrent pyelonephritis) and viral (cytomegalovirus [CMV], polyomavirus [BK virus; BKV]) infections are crucial factors involved in the incidence of chronic allograft dysfunction and graft failure. Renovascular lesions and lower urinary tract obstruction are typical indicators for surgical intervention. The aim of treatment in pediatric patients with renal failure secondary to a dysfunctional lower urinary tract is to create a sterile, continent, and nonrefluxive reservoir. Surgical techniques such as bladder augmentation and the introduction of intermittent catheterization and anticholinergic therapy have significantly improved graft outcome. Arterial hypertension, another factor responsible for graft function deterioration in pediatric renal transplant recipients, is controlled preferably by the use of angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists, which are known to possess nephroprotective properties in addition to their potent antihypertensive effects. Although treatment of subclinical rejection with augmented immunosuppression has been associated with better graft survival, an increase of the immunosuppressive level to avoid subclinical rejection should be weighed against the risk of infection. The majority of viral infections affecting kidney allografts are caused by CMV and BKV. Antiviral CMV prophylaxis or pre-emptive therapy with ganciclovir has been shown to have beneficial effects in the pediatric renal transplant population. Treatment of BKV-induced nephropathy is based on reduction of the immunosuppressant therapy, although specific antiviral agents such as cidofovir and leflunomide are known to inhibit BKV. However, cidofovir itself is nephrotoxic and should therefore be administered cautiously to pediatric renal transplant patients. Since CNIs are likewise known for their nephrotoxic effects, especially with long-term use, alteration of the immunosuppressant regimen is necessary in case of deteriorating graft function due to CNI-induced histopathologic changes. Complete CNI avoidance seems inappropriate because, in this situation in pediatric renal transplant recipients, other relatively potent immunosuppressant agents such as lymphocyte-depleting antibodies, which are frequently accompanied by a higher incidence of infections, are needed for rejection prophylaxis. CNI withdrawal and switching of the immunosuppressant regimen from CNI therapy to sirolimus may be an option for some pediatric renal transplant patients with less advanced graft function deterioration. Nevertheless, potential adverse events such as aggravation of proteinuria, hyperlipidemia, myelosuppression, and hypergonadotropic hypogonadism have to be considered, and controlled studies are lacking. At present, an immunosuppressant maintenance therapy composed of low-dose tacrolimus or ciclosporin (CNI minimization) and mycophenolate mofetil with low-dose corticosteroids appears to be the most promising strategy to adopt in pediatric renal transplant recipients at low or normal immunologic risk.

Chymase: the other ACE?

the therapeutic use of angiotensin-converting enzyme (ACE) inhibitors has been an integral part of the standard of care for hypertension and related diseases for decades. While the beneficial effects of these drugs are universally appreciated, there are a variety of physiological anomalies that

Post‐transplant erythrocytosis: a disappearing phenomenon?

Erythrocytosis is relatively common post-kidney transplantation and may have adverse consequences. This study examined whether the incidence of erythrocytosis has remained stable over time and explored the impact of this condition on patient outcomes. This was a retrospective single center review of an incidence cohort (transplanted between 1993 and 2005). Predictors of erythrocytosis and hemoglobin levels and subsequent patient and allograft survival were examined. Erythrocytosis (hemoglobin >170 g/L for >1 month) was observed in 59 of 511 recipients. Erythrocytosis developed in only 8.1% of those transplanted from 1997 to 2005, compared with 18.7% in those transplanted from 1993 to 1996 (p = 0.0005). Independent predictive factors were use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) (HR 0.176, 95% CI 0.040-0.71, p = 0.016), male gender (HR 3.72, 95% CI 1.54-9.0, p = 0.003), and mycophenolic acid agents (HR 0.49, 95% CI 0.237-0.99, p = 0.049). Patients with erythrocytosis had superior overall survival (HR for death 0.105, 95% CI 0.014-0.760, p = 0.026) but a trend for worse death censored graft loss (univariate HR 2.06, 95% CI 0.91-4.65, p = 0.084). The incidence of erythrocytosis is falling and is likely related to greater ACEi/ARB use and possibly more antiproliferative immunosuppression. Patient survival is excellent in those with erythrocytosis, but long-term graft survival may be compromised.

Therapeutic Management in Patients with Renal Failure who Experience an Acute Coronary Syndrome

Prior reports have suggested that patients with impaired renal function receive less aggressive care after an acute coronary syndrome (ACS). The aim of this study was to determine whether this held true in a contemporary cohort, after thorough adjustment for cotreatments/comorbidities. Patients who were admitted for an ACS in eight participating hospitals were stratified into three groups according to estimated creatinine clearance (CrC): less than 45 ml/min, 45 to 60 ml/min, and reference >60 ml/min. During hospitalization, uses of reperfusion therapy in tertiary care centers [difference between CrC < or =45 ml/min and reference group (Delta): 4%, 95% confidence interval (CI): (-13%, 21%)] and systemic anticoagulation [Delta: 0%, CI (-5%, 5%)] were similar in the three groups. Coronary angiography was performed less often in patients with lower CrC [Delta: -16%, CI: (-31%, -1%)]. At discharge, nearly all patients received either an antiplatelet agent or warfarin regardless of CrC [Delta: -1%, CI: (-3%, 1%)]. Discharge use of angiotensin converting enzyme (ACE) inhibitors or angiotensin-receptor blockers was comparable [Delta: 7%, CI: (-1%, 15%)]. beta-blockers [Delta: -9%, CI: (-17%, -1%)] and lipid-lowering drugs (LLDs) [Delta: -7%, CI: (-13%, -1%)] were used less frequently in patients with lower CrC. In multivariate analyses, decreased CrC predicted lower coronary angiography and LLD use, but not lower beta-blocker use at discharge. These results suggest that in patients with ACS, the extent of undertreatment due to chronic kidney disease is less than reported previously, which is partially explained by more complete adjustment for cotreatments/comorbidities.

Circulating Endothelial Progenitor Cells and Age-Related White Matter Changes

The objective was to evaluate the relationship between circulating endothelial progenitor cells (EPC) and age-related white matter changes (ARWMC). Endothelial dysfunction plays a role in the development of ARWMC. EPC incorporate into sites endothelial damage and are thought to be involved in the repair of vascular risk factor induced endothelial injury. ARWMC can be evaluated using CT or MRI. In 172 individuals, circulating EPC were defined by the surface markers CD31 and von Willebrand factor. ARWMC were rated on CT scan using the ARWMC scale and divided into 3 groups based on ARWMC scale score (ARWMC score 0 [none], score 1-10 [mild-to-moderate], score >10 [severe]). Severity of ARWMC was correlated with levels of EPC and vascular risk factors. On univariate analysis, EPC were found to be significantly lower in patients with severe ARWMC (P=0.01). ARWMC were also associated with hypertension (P<0.001), age (P<0.001), creatinine clearance (P=0.031), C-reactive protein (P<0.001), and use of angiotensin-converting enzyme or angiotensin receptor blocker (P=0.004). Multiple logistic regression analysis identified EPC level, age, hypertension, and hypertriglyceridemia as significant independent predictors of severe ARWMC. Levels of circulating EPC were significantly lower in patients with severe ARWMC. Other variables significantly associated with severe ARWMC were age, hypertension, and hypertriglyceridemia. Further study is required to delineate the pathophysiological relationship between EPC, vascular risk factors, and ARWMC.

Metabolic Syndrome Increases Mortality in Heart Failure

Metabolic syndrome (MetS) is a risk factor for diabetes, cardiovascular disease, and heart failure, but little is known about the impact of MetS in patients who already have heart failure (HF). MetS increases mortality in HF. We performed an analysis in 865 indigent HF patients enrolled in a HF disease management program at the Chabert Medical Center in Louisiana. All subjects were classified as having MetS if they met three or more of the National Cholesterol Education Program criteria. Mortality was defined using the Social Security Death Index. We calculated the relative hazard (RH) of death for those patients with and without MetS. The prevalence of MetS was 40% (95% confidence interval [CI]: 37-43). These subjects had similar ages (54.3+/-13.4 vs 55.7+/-12.8 years), more likely to be female (43% vs 33%), had similar baseline ejection fraction (31.4+/-9.7 vs 30.0+/-11.0), and New York Heart Association (NYHA) classification (2.20+/-0.9 vs 2.15+/-0.9). After 2.6+/-2.2 years of follow-up 24% of the MetS group died compared to 16% in the non-MetS group (p < 0.01). The RH of death for the MetS group was 1.5 (95% CI: 1.1-2.1) when compared to the non-MetS group after adjustment demographics, use of angiotensin-converting enzyme (ACE) inhibitor and beta-blocker, hematocrit, creatinine, educational level, and baseline ejection fraction. The prevalence of MetS is high in indigent HF patients, and it increases the risk of death. Physicians treating patients with HF need to address the current MetS epidemic in HF.

5-Fluorouracil induces arterial vasoconstrictions but does not increase angiotensin II levels

Because the mechanisms of 5-Fluorouracil (5-FU) cardiotoxicity have not yet been completely identified, prophylactic options are not available. To our knowledge, there are no published data investigating the use of angiotensin converting enzyme (ACE) inhibitors for 5-Fluorouracil-associated cardiotoxicity. In this study, we aimed to evaluate the influence of 5-FU administration on the diameter of the brachial artery and the levels of angiotensin II. The patients were administered bolus 5-FU/leucovorin in the study group. Angiotensin II and troponin T assays, complete blood cell counts, hepatic and renal function tests were analyzed in five consecutive blood samples in the initiation, just after termination, and on 24, 48, and 72 h after termination of the regimen. Pre- and post-treatment angiotensin II and troponin T assays, complete blood cell counts, hepatic and renal function tests were also analyzed in the control group. Brachial arterial diameters were measured and recorded in all patients before and after the treatment. A total of 59 patients were included in this study. Thirty one out of 59 patients (52.5%) were in the 5-FU study group and the remaining 28 patients (47.5%) were in the control group. Basal and post-treatment brachial artery diameters in the 5-FU study group were 0.436 +/- 0.51 and 0.423 +/- 0.50 cm, respectively (P = 0.001). The corresponding values in the controls were 0.3954 +/- 0.50 and 0.3957 +/- 0.49 cm, basal and post-treatment, respectively (P = 0.979). Angiotensin II levels were not changed significantly at serial measurements (P = 0.496). Moreover, the corresponding measurements were not statistically different in both two groups treated with and without 5-FU (P = 0.372). The pathophysiology of 5-FU-induced cardiac toxicity has not yet been elucidated. In the present study, 5-FU-associated vasoconstriction was not dependent on angiotensin II levels, thus we suggest that the prophylactic administration of ACE inhibitors cannot prevent cardiotoxicity in these patients. The underlying mechanisms of cardiotoxicity related to 5-FU might be multifactorial; nevertheless, further prospective investigation for the toxic effects of fluoropyrimidines on the coronary endothelium and myocardium are needed.

BEHAVIOURAL CHANGES INDUCED BY ANGIOTENSIN‐CONVERTING ENZYME INHIBITION DURING PREGNANCY AND LACTATION IN ADULT OFFSPRING RATS

1. The use of angiotensin-converting enzyme (ACE) inhibitors during pregnancy is contraindicated because of their association with increased risks of fetopathy, including central nervous systems malformations. In addition, some reports have shown that renin-angiotensin system components are expressed differently during embryonic development and adulthood in the rat. 2. Because angiotensin II and its derivative peptides have been implicated in anxiety and modulation of nociception, the aim of the present study was to investigate whether inhibiting ACE during prenatal and neonatal periods would alter behavioural plasticity in adult male offspring rats. 3. Female Wistar rats were treated with captopril (2 mg/mL water; approximately 200 mg/kg per day) during pregnancy and lactation. At adulthood, the offspring were subjected to the open field, elevated plus maze, social interaction, forced swimming and tail flick tests. 4. Perinatal captopril treatment significantly increased ambulation (33%; P < 0.05) and decreased resting time (37.5%; P < 0.05) in the open field test. Perinatal captopril treatment did not alter any of the behavioural parameters of the elevated plus maze; however, captopril treatment did cause a significant increase in social interaction (75.3%; P < 0.05). In the forced swimming test, there was an increased latency period (102.9%; P < 0.001) and a decreased immobility period (38.7, P < 0.05) in rats treated with perinatal captopril. In the tail flick test, perinatal captopril treatment significantly reduced the latency time (26.3%; P < 0.01). 5. The data show that ACE inhibition during prenatal and neonatal periods affects behavioural responses in adult offspring rats, suggesting that ACE is required for the development of neural systems that are associated with adult anxiety and nociceptive behavioural responses.

Squamous Cell Carcinomas in 2 Patients with Diffuse Scleroderma Treated with Mycophenolate Mofetil

Systemic sclerosis (SSc) is a rare multisystem connective tissue disease of unclear etiology in which vascular dysfunction, fibrosis of the skin and internal organs, and autoimmunity occur. Until recently, few treatments have been successful at reducing mortality associated with the disease. The use of angiotensin-converting enzyme (ACE) inhibitors and targeted therapies such as endothelin receptor antagonists, prostacyclins, and PDE5 inhibitors have improved outcomes with respect to renal crisis and pulmonary hypertension, respectively. However, given the natural history of the disease, treatment of severe SSc is problematic. Physicians treating SSc are torn between the principles “do no harm” and “doing good,” largely the latter in many SSc treatments that lack randomized controlled trial data. The mechanism of immune dysregulation is not entirely clear, although it seems to play a pivotal role in disease progression. Activated T2-helper lymphocytes producing fibrogenic interleukin 4 (IL-4) and IL-13 are thought to contribute. In addition, it has been shown that early in the course of disease, activation of B cells causes fibroblasts to adopt a profibrotic phenotype via the production of antibodies. Also, activated macrophages in perivascular infiltrates produce specific chemokines, transforming growth factor-s, and platelet-derived growth factor, all thought to play a role in fibrosis1,2. Given that altered immune function is thought to contribute to disease progression, several immunosuppressive regimens have been explored as possible treatment options. Some investigators have reported on the mechanism of immune regulation with mycophenolate mofetil (MMF). Via its metabolite mycophenolic acid (MPA), MMF interferes with the metabolic pathway of de novo purine synthesis through inhibition of inosine monophosphate dehydrogenase, suppressing both B and T lymphocyte proliferation3. MMF is currently indicated as prophylaxis against allogeneic cardiac, renal, or hepatic transplant rejection. MMF use in transplants gives fewer malignancies than other transplant medications4,5 … Address reprint requests to Dr. Pope; E-mail: janet.pope{at}sjhc.london.on.ca

Recent Advances in Cardiovascular Risk Reduction: Implications of ONTARGET

Renin-angiotensin-aldosterone system (RAAS) overactivity is associated with increased cardiovascular risk, a finding that may be explained by the key role of the RAAS in stimulating vascular and cardiac remodeling. Inhibition of RAAS activity with the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) has been shown to reduce cardiovascular mortality in patients with heart failure. ACE inhibitors have also been shown to reduce the incidence of stroke, myocardial infarction (MI), and heart failure in high-risk patients without heart failure. These findings led to the evaluation of the ARB telmisartan versus the ACE inhibitor ramipril in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), a cardioprotection trial conducted in high-risk patients without left ventricular dysfunction or heart failure. The results of this trial showed that the ACE inhibitor ramipril and the ARB telmisartan are equally effective in reducing the incidence of cardiovascular death, MI, stroke, and hospitalization for heart failure in patients without heart failure or left ventricular dysfunction but at high risk for cardiovascular disease (CVD). These results confirm that RAAS inhibition, using ACE inhibitors or ARBs, is an effective approach to reducing cardiovascular mortality and morbidity in patients without heart failure who are at high risk for CVD.

Renal transplantation in the modern immunosuppressive era in Spain: four-year results from a multicenter database focus on post-transplant cardiovascular disease: New strategies to prevent cardiovascular risk in chronic kidney disease

To evaluate cardiovascular disease (CVD) after renal transplantation we established a CVD database (no-intervention) including all patients transplanted among 2000-2002 in 14 hospitals from Spain (Renal Forum Group) (n=2600). They were prospective followed annually thereafter and we present herein the most important results concerning survival figures and CVD at four years. Mean recipient age was 49.7+/-13.7 years: 16% retransplanted and 12.5% hyperimmunized. Tacrolimus, mycophenolate mofetil, and steroids was used in 63%. Acute rejection (AR) rate at 1 year was 14.8%. Graft and patient survival at 48 months were 85.6% (death censored) and 91.7% respectively. The first cause of graft loss was vascular in the first year, death with function during the 2-3 years, and chronic allograft nephropathy at the 4th year. Donor age, time on dialysis, acute tubular necrosis (ATN), AR, SCr at 6 months, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in the first year, and systolic blood pressure at 24 months were independent risk factors for graft loss at 4th year. The first cause of death was CVD (predominantly ischemic heart disease (IHD) in the first year). Recipient age, ATN, and SCr at 6 months were independent predictors of mortality. Despite worsening of donor age, comorbidity, and advanced age of recipients, survival figures at four years are considered good in our Spanish non-selected population. Cardiovascular mortality is the most important cause of death and graft loss particularly, IHD in the first year. Therefore, to decrease post-transplant mortality a careful cardiovascular evaluation and treatment in the waiting list and a close follow-up of patients after transplantation is mandatory.

Angioedema After Local Trauma in a Patient on Angiotensin-Converting Enzyme Inhibitor Therapy

Angioedema is a side effect that is often associated with the use of angiotensin-converting enzyme (ACE) inhibitor medications. These medications result in increased levels of circulating bradykinins. This case illustrates the result of a local traumatic event to the upper lip, presumably causing marked bradykinin release in a patient who was taking an ACE inhibitor. The local release of bradykinin from trauma, in addition to decreased bradykinin catabolism secondary to ACE inhibitor therapy, resulted in angioedema predominantly in the upper lip. The angioedema resolved with discontinuation of the ACE inhibitor.

Factor Deficiency in the Anemia of Renal Transplant Patients With Grade III–IV Chronic Kidney Disease: Baseline Results of the ARES Study

ARES is a multicenter, prospective study of the prevalence, management, and repercussions on the quality of life of anemia in renal transplant patients with a reduced renal function (creatinine clearance according to Cockcroft-Gault: ≤60 and >15 mL/min). The frequency of factor deficiency and its relationship with anemia were analyzed at the baseline time of the study. Of the 500 patients included in the main study, valid data were available for iron metabolism in n = 419 μg/dL; folic acid, n = 205 ng/mL; and vitamin B12, n = 210 pg/mL. Anemia was defined as hemoglobin ≤13 g/dL (men) or ≤12 g/dL (women) and/or use of erythropoietin (EPO). Anemic patients (59.4%) had less sideremia (73.4 vs 81.2 μg/dL; P = .008), but no significant differences were observed for transferrin saturation index (25.9% vs 25.5%), ferritin (167 vs 171 ng/mL), iron insufficiency (26.5% vs 36.2%), pronounced ferropenia (20.4% vs 20.1%), folic acid (7.5 vs 6.6 ng/mL), or vitamin B12 (486 vs 530 pg/mL). Treatment with oral or intravenous iron was much more frequent in anemic patients (31.6% vs 9.9%; P < .001). The logistic regression analysis of factors associated with anemia revealed that renal function and the use of angiotensin-converting enzyme (ACE) inhibitors were significant but not the degree of iron deficiency. In conclusion, iron deficiency in renal transplant patients with chronic nephropathy is frequent and insufficiently treated. Although it may be an aggravating factor, it was not shown to be a determining factor for the presence or absence of anemia in the patients as a group.

Renal manifestations of systemic sclerosis--clinical features and outcome assessment

Renal manifestations occur frequently in scleroderma (SSc). Commonest is a reduction in renal function due to chronic disease but most clinically important is the scleroderma renal crisis (SRC). This life-threatening complication occurs in up to 15% of the cases of dcSSc. Mortality is reduced by use of angiotensin converting enzyme (ACE) inhibitors. Renal outcome can be assessed by quantifying renal function, measuring proteinuria, exploring the frequency of renal crisis episodes and through assessment of renal outcome following SRC-such as frequency and duration of dialysis, or recovery of renal function.

Association of ACE Inhibitors and Angiotensin Receptor Blockers with Keratinocyte Cancer Prevention in the Randomized VATTC Trial

The observation that angiotensin II is a potent angiogenic and growth factor raises the possibility that blocking its effects could reduce the incidence of cancer. We evaluated associations between use of angiotensin-converting enzyme (ACE) inhibitors and of angiotensin receptor blockers (ARBs) and keratinocyte cancer incidence in a population at high risk of the disease. A cohort study design was conducted using data on 1051 participants in the randomized Department of Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) Trial, all of whom were at increased risk of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). We followed participants from enrollment (November 1998 through January 2003) until first BCC or SCC. Study participants were examined every 6 months by a study dermatologist; biopsies were taken on all suspicious lesions and centrally reviewed. Use of ACE inhibitors and ARBs was ascertained from VA pharmacy records. Cox proportional hazards models were used to estimate adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of BCC and SCC with use of ACE inhibitors or ARBs. During a median follow-up of 3.4 years, 472 incident BCCs, 309 SCCs, and 200 deaths from any cause were observed. Compared with nonusers, users of ACE inhibitors or ARBs had statistically significantly reduced risks of BCC (IRR(BCC) = 0.61, 95% CI = 0.50 to 0.76) and SCC (IRR(SCC) = 0.67, 95% CI = 0.52 to 0.87). The combined absolute incidence rates of BCC and SCC were 237 per 1000 person-years among users of ACE inhibitors or ARBs and 374 per 1000 person-years among nonusers. The greatest reduction in keratinocyte cancer was seen among people who initiated use of ACE inhibitors or ARBs during the study period (IRR(BCC) = 0.45 [95% CI = 0.34 to 0.59]; IRR(SCC) = 0.48 [95% CI = 0.35 to 0.67]). Among a high-risk group of veterans, users of ACE inhibitors or ARBs had a lower incidence of keratinocyte cancers than nonusers. The more pronounced reduction among those who initiated use during the study may indicate an immediate effect.

The role of the renin angiotensin system blocking in the management of atrial fibrillation

Objective — The objective of the study was to review the current available clinical evidence for the role of renin-agiotensin system (RAS) blockade in the treatment of atrial fibrillation (AF).Method — We conducted a pubmed and medline literature search (January 1980 through-05-2007) to identify all clinical trials published in English involving the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) for preventing the occurrence or recurrence of AF. Discussing pathophysiology and experimental evidence in detail is beyond the scope of this article.Conclusion — There is no solid evidence to support using ACE inhibitors or ARBs as antiarrhythmic therapy in patients with AF. However, in view of the possible benefits and the low incidence of side effects with ACE inhibitors and ARBs, they might be given in patients with recurrent AF, particularly if there are other indications for their use such as hypertension, HF, or diabetes mellitus. Possible benefits from pre-treatment argue in favour of using ACE inhibitors and ARB as firstline therapy in patients with hypertension.

Preoperative Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Is Associated with Increased Risk for Acute Kidney Injury after Cardiovascular Surgery

Acute kidney injury (AKI) occurs commonly after cardiac surgery. Most patients who undergo cardiac surgery receive long-term treatment with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). The aim of this study was to determine whether long-term use of ACEI/ARB is associated with an increased incidence of AKI after cardiac surgery. This was a retrospective cohort study of 1358 adult patients who underwent cardiac surgery between January 1, 2001, and December 31, 2005, in two tertiary care hospitals in Buffalo, NY. The incidence of AKI was determined after cardiac surgery. Clinical data were collected using a standardized form that included comorbid condition, use of ACEI/ARB, and intraoperative and postoperative complications. Overall, 40.2% of patients developed AKI. Preoperative variables that were significantly associated with development of AKI included increasing age; nonwhite race; combined valve surgery and coronary artery bypass grafting compared with coronary artery bypass grafting alone; American Society of Anesthesiologists (ASA) Risk Score category 4/5 compared with 2 to 3; presence of diabetes, congestive heart failure, or neurologic disease at baseline; use of ACEI/ARB; and emergency surgery. Intra- and postoperative factors that were associated with postoperative AKI were hypotension during surgery, use of vasopressors, and postoperative hypotension. Multiple regression logistic model confirmed an independent and significant association of AKI and preoperative use of ACEI/ARB. This was confirmed using a bivariate-probit and propensity score model that adjusts for confounding by indication of use and selection bias. Preoperative use of ACEI/ARB is associated with a 27.6% higher risk for AKI postoperatively. Stopping ACEI or ARB before cardiac surgery may reduce the incidence of AKI.

Heart Failure Care in the Outpatient Cardiology Practice Setting

Background— Few data exist regarding contemporary care patterns for heart failure (HF) in the outpatient setting. IMPROVE HF is a prospective cohort study designed to characterize current management of patients with chronic HF and ejection fraction ≤35% in a national registry of 167 US outpatient cardiology practices. Methods and Results— Baseline patient characteristics and data on care of 15381 patients with diagnosed HF or prior myocardial infarction and left ventricular dysfunction were collected by chart abstraction. To quantify use of therapies, 7 individual metrics (use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, β-blocker, aldosterone antagonist, anticoagulation, implantable cardioverter defibrillator, cardiac resynchronization therapy, and HF education) and composite metrics were assessed. Care metrics include only patients documented to be eligible and without contraindications or intolerance. Among practices, 69% were nonteaching. Patients were 71% male, with a median age of 70 years, and a median ejection fraction of 25%. Use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (80%) and β-blocker (86%) was relatively high in eligible patients in the outpatient cardiology setting; other metrics, such as aldosterone antagonist (36%), device therapy (implantable cardioverter defibrillator/cardiac resynchronization therapy with defibrillator, 51%; cardiac resynchronization therapy, 39%), and education (61%), showed lower rates of use. A median 27% of patients received all HF therapies for which they were potentially eligible on the basis of chart documentation. Use of guideline-recommended therapies by practices varied widely. Conclusions— These data are among the first to assess treatment in the outpatient setting since the release of the latest national HF guidelines and to demonstrate substantial variation among cardiology practices in the documented therapies provided to HF patients.