Angiotensin-converting Enzyme Inhibitor Therapy Research Articles

Effect of Combination ACEI (Angiotensin Converting Enzyme Inhibitor) and Diuretics on Potassium Levels of Congestive Heart Failure Patients

ACEI (Angiotensin Converting Enzyme Inhibitors) and diuretics are now the treatment options for heart failure patients. However, the use of ACEI and diuretics can cause potassium balance disorders. This study aimed to evaluate the use of ACEI and diuretics combinations on potassium levels in patients with congestive heart failure. This study used analytical research and sampling, done in total sampling. Samples were divided into 2 groups, group with combination of ACEI, furosemide and spironolactone along with combination group of ACEI and furosemide. Total samples obtained were 38 patients. The results showed that the averaged potassium levels in combinations of ACEI, furosemide and spironolactone before treatment were 3.95mmol/L and after treatment were 3.85 mmol/L (p = 0.061), the averaged potassium levels before receiving therapy were 4.20 mmol/L and after receiving 4.14 mmol/L therapy (p = 0.070) in combinations of ACEI and furosemide. In combinations of ACEI, furosemide and spironolactone, of a total of 25 patients, hypokalemia was found in 6 patients (24%), normal in 19 patients (76%) and 0 patient had hyperkalemia (0%), while combinations of ACEI and furosemide, of a total of 13 patients, all patients have normal potassium levels. So it can be concluded that there were no significant changes between potassium levels before and after receiving therapy of ACEI and diuretics combination.

Renal Impairment in Systemic Sclerosis

Systemic sclerosis (SSc) represents a connective tissue disease, characterized by progressive fibrosis of the skin and internal organs, microvascular abnormalities, and alterations in cellular and humoral immunity. Renal impairment is a relatively common feature in patients with systemic sclerosis. It can take various clinicopathological forms, of which the most specific and severe manifestation is represented by scleroderma renal crisis. This presentation is characterized by acute onset of moderate to malignant hypertension and acute kidney injury. Although some progress has been made in management of scleroderma renal crisis with the introduction of angiotensin-converting enzyme inhibitors therapy, a large population of patients still presents a poor outcome, with up to 50 percent needing renal replacement therapy. Further understanding of disease pathogenesis may lead to improvement in patient’s outcome and survival.

BAG6 Variant rs805303 is Nominally Associated with ACEi-induced Cough among Filipinos

Cough is a common side effect of angiotensin converting enzyme inhibitor (ACEi) therapy. The incidence of ACEi-induced cough has been shown to correlate with genetic variation among different populations. This study aimed to determine the association of candidate genetic polymorphisms with ACEi-induced cough among Filipinos. Two hundred twenty (220) participants on ACEi therapy pressure-lowering in an unmatched case-control study (82 cases with ACEi-induced cough and 138 controls). Genomic DNA samples were extracted and genotyped for selected genetic variants. The association of genetic variants and clinical factors with ACEi-induced cough was determined using regression analyses. Univariate logistic regression showed that the BAG6 variant rs805303 is nominally associated with ACEi-induced cough among Filipinos, at a per-comparison error rate (PCER) of 0.05 (OR 2.10, p = 0.016). The association of the variant with ACEi cough was statistically significant after multiple regression analysis (adjusted OR 2.09, p = 0.022) while adjusting for confounding clinical factors (sex, alcohol intake, and diastolic blood pressure). Further studies are needed to validate these findings.

ACE Inhibitor Therapy Does Not Influence the Survival Outcomes of Patients with Colorectal Liver Metastases Following Liver Resection.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to possibly influence the survival outcomes in certain cancers. The aim of this study was to evaluate the impact of ACE inhibitors on the outcomes of patients undergoing liver resection for colorectal liver metastases (CRLM). The secondary aim was to determine whether ACE inhibitors influenced histopathological changes in CRLM. Patients treated with liver resection for CRLM over a 13-year period were identified from a prospectively maintained database. Data including demographics, primary tumour treatment, surgical data, histopathology analysis and clinical outcome were collated and analysed. A total of 586 patients underwent primary hepatic resections for CRLM during this period including 100 patients on ACE inhibitors. The median follow-up period was 23 (range: 12-96) months, in which 267 patients developed recurrent disease and 131 patients died. Independent predictors of disease-free survival on multivariate analysis included synchronous presentation, neoadjuvant chemotherapy, major liver resection, tumour size and number, extent of hepatic steatosis, R0 resection and presence of perineural invasion. Poorer overall survival was associated with neoadjuvant treatment, major liver resection, presence of multiple metastases, perineural invasion and positive resection margins on multivariate analysis. ACE inhibitors did not influence the survival outcome or histological presentation in CRLM. The use of ACE inhibitors did not affect the survival outcome or tumour biology in patients with CRLM following liver resection.

Analysis of prescription pattern of antihypertensive medication and adherence to Beers criteria in geriatric department of a tertiary care hospital in Mysuru

Background: The objective of the present study was to evaluate the prescription pattern of anti-hypertensive drugs and adherence to Beers’ criteria in geriatric department of JSS Hospital, Mysuru.Methods: An observational, prospective, cross-sectional study was carried out in geriatric department. The basic demographic information and prescriptions of geriatric patients were studied. Descriptive analysis was used to present the results, prescriptions were analysed and checked for adherence to Beers’ criteria.Results: Out of 485 patients, 82.68% received monotherapy, 15.87% received 2-drug combination therapy and 1.4% received 3-drug combination therapy. Among patients receiving monotherapy, angiotensin receptor blockers (49.06%) was the commonest antihypertensive class of drug prescribed. Telmisartan (38.96%) was the commonest drug prescribed. Among 2-drug combination therapy angiotensin converting enzyme inhibitor and Calcium channel blockers were combined commonly. In 3-drug combination therapy angiotensin converting enzyme inhibitor, beta blockers and diuretics were combined commonly. 99.3% of prescriptions were adhered to 2015 American Geriatrics Society Beers criteria.Conclusions: Almost 82% of the patients were treated with monotherapy. The trends in prescribing of anti-hypertensives were in favor of conventional ones such as Angiotensin receptor blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, diuretics, beta blockers and centrally acting alpha agonists. 99.3% of prescriptions were in accordance with the American Geriatrics Society 2015 Updated Beers criteria.

Renin-Angiotensin-Aldosterone System Triple-A Analysis for the Screening of Primary Aldosteronism.

Primary aldosteronism is recognized as the most frequent cause of secondary hypertension, and its screening is expected to become a routine evaluation in most patients with hypertension. The interference of antihypertensive therapies with the aldosterone-to-renin ratio during screening process is a major confounder. Renin-angiotensin-aldosterone system Triple-A analysis is a novel liquid chromatography/tandem mass spectrometry diagnostic assay that allows simultaneous quantification of aldosterone, equilibrium Ang I (angiotensin I), and Equilibrium Ang II in a single sample of serum. We performed a comparative evaluation of the diagnostic performance of the aldosterone-to-Ang II ratio and 5 renin-based diagnostic ratios, differing in methods to determine aldosterone levels and renin activity in a cohort of 110 patients with hypertension (33 patients with confirmed primary aldosteronism and 77 with essential hypertension). All ratios showed comparable areas under the curves ranging between 0.924 and 0.970 without significant differences between each other. The evaluation of the Ang II-to-Ang I ratio revealed persistent drug intake in some patients as cause for suppressed renin-based diagnostic ratios, while aldosterone-to-Ang II ratio remained unaffected. The Youden index optimal cutoff value for the aldosterone-to-Ang II ratio was 6.6 ([pmol/L]/[pmol/L]) with a sensitivity of 90% and a specificity of 93%, proving noninferiority compared with the aldosterone-to-renin ratio while pointing to the potential for an interference-free application in patients under ACE (angiotensin-converting enzyme) inhibitor therapy. This study shows for the first time the accuracy and reliability of renin-angiotensin-aldosterone system triple-A analysis for the screening of primary aldosteronism that can be applied in clinical routine.

Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: a meta-analysis.

Cardiac biomarkers are a mainstay in diagnosis of cardiovascular disease but their role in cardio-oncology has not yet been systematically evaluated. This meta-analysis aims to determine whether cardiac troponins and (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) predict cancer therapy-related left ventricular (LV) dysfunction. Scientific databases were searched for studies that assessed troponins or BNP/NT-proBNP in adult patients undergoing cancer therapy. Data from 61 trials with 5691 patients were included. Cancer therapy was associated with an increase in troponin levels [odds ratio (OR)14.3, 95% confidence interval (CI) 6.0-34.1; n=3049]. Patients with elevated troponins receiving chemotherapy or human epidermal growth factor receptor 2 inhibitor therapy were at higher risk for LV dysfunction (OR 11.9, 95% CI 4.4-32.1; n=2163). Troponin had a negative predictive value of 93%. Mean BNP/NT-proBNP levels were increased in patients post-treatment (standardized mean difference0.6, 95% CI0.3-0.9; n=912), but the available evidence did not consistently indicate prediction of LV dysfunction (OR1.7, 95% CI 0.7-4.2; n=197). β-blocker and angiotensin-converting enzyme inhibitor therapy to mitigate cardiotoxicity during cancer therapy was associated with a decline in serum troponins (OR4.1, 95% CI 1.7-9.8; n=466). Elevated troponin levels predict LV dysfunction in patients receiving cancer therapy. Assessment of troponin levels may qualify as a screening test to identify patients who require referral to cardio-oncology units and benefit from preventive strategies. Further evidence is required for both biomarkers.

Comparison between angiotensin-converting enzyme inhibitor and angiotensin receptor blocker after percutaneous coronary intervention

BackgroundThe inhibitors for renin-angiotensin-aldosterone system (RAAS) have different mechanisms of action in coronary artery disease (CAD). This study sought to compare the clinical outcomes between angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) therapy in patients with CAD undergoing contemporary percutaneous coronary intervention (PCI). MethodsBased on the National Health Insurance claims data in South Korea, patients aged 18 years or older who had undergone PCI between July 2011 and June 2015 were enrolled. The study participants were classified either as patients with acute myocardial infarction (AMI, n = 21,747) or angina (n = 28,708). And according to the post PCI discharge medications, patients were categorized into ACEI and ARB therapy groups. The primary endpoint was all-cause death, and the two groups were compared using a propensity-score matching analysis. ResultsThe study population had a median follow-up of 2.2 years (interquartile range, 1.2–3.2). In the propensity-score matched AMI group (8341 pairs), the occurrence of all-cause death was significantly lower in the ACEI group than in the ARB group (hazard ratio [HR] of ACEI, 0.823; 95% confidence interval [CI]: 0.715–0.947; p = 0.006). In the propensity-score matched angina group (10,878 pairs), there was no difference in the incidence of the primary endpoint between the ACEI and ARB groups (HR of ACEI, 1.113; 95% CI: 0.986–1.257; p = 0.084). ConclusionsIn this nationwide Korean cohort study, ACEI therapy in patients with AMI and concomitant PCI showed a significant reduction in all-cause mortality rates when compared to that with ARB therapy.

Pregnancy in myositis and scleroderma.

Myositis and scleroderma are both rare autoimmune diseases with female predominance and often occur before and during reproductive years. The rarity of diseases explains the low frequency of concurrent disease and pregnancy. Like other autoimmune diseases, myositis and scleroderma may be more active during pregnancy as well. To date, many patients with myositis and scleroderma can have favorable pregnancy outcomes with careful management. This chapter provides a current overview of pregnancy outcomes in myositis and scleroderma. A major theme that appears to have emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and thus, personalized management is necessary depending on the disease state and comorbidities.

P5011Impact of guideline-recommended medical therapy at discharge on long-term mortality in patients with or without left ventricular dysfunction after primary PCI for STEMI

Abstract Background Clinical practice guidelines provide class I recommendation for the use of angiotensin-converting enzyme inhibitors (ACE-I) and beta-blockers in patients with prior myocardial infarction and left ventricular (LV) dysfunction, whereas their use in patients without LV dysfunction is considered to be a class IIa recommendation. Purpose Our aim was to comparatively assess the impact of ACE-I and/or beta-blockers on 3-year mortality in patients with or without impaired left ventricular (LV) function undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Methods The analysis included 4425 patients admitted for primary PCI during 2009–2015 from a prospective, electronic registry of a high-volume tertiary center, who survived initial hospitalization, and for whom information on LV function and discharge medication were available. Patients were stratified according to LV systolic dysfunction, defined as LVEF <40%. Unadjusted and adjusted Cox regression models were created to investigate the impact of beta-blocker and/or ACE-I therapy on 3-year mortality. Results 22.9% (n=1013) had LV dysfunction, 23.0% (n=1017) received either an ACE-I or a beta-blocker and 72.2% received both medications at discharge (n=3197). The concurrent use of both ACE-I and beta-blockers was not different in LVEF≥40% vs. LVEF<40% (72.4% vs. 71.7%, p=0.43). The use of at least one of the guideline-recommended medications was associated with a significantly lower 3-year mortality in both patients with LVEF≥40% (18.7% if neither was used, 11.2% if either a beta-blocker or an ACE-I were used and 9.4% if both were used, p=0.001), and LVEF<40% (55.4% if neither was used, 32.5% if either a beta-blocker or an ACE-I were used and 22.9% if both were used, p<0.001) (Figure). After adjusting for significant mortality predictors including older age, diabetes, hypertension, renal failure, previous stroke, Killip class ≥2 and non-culprit chronic total occlusion (CTO), the concurrent use of both a beta-blocker and an ACE-I remained independently associated with lower 3-year mortality in both patients with LVEF<40% (HR 0.30, p<0.001) and LVEF≥40% (HR=0.41, p=0.001). The use of a single agent was independently associated with lower mortality in patients with LVEF<40% (HR 0.45, p=0.002), but not in patients with LVEF≥40% (HR 0.61, p=0.07). Conclusions Guideline-recommended use of both a beta-blocker and an ACE-I in post-MI patients was associated with a lower 3-year mortality regardless of the LV function, whereas using only one of the two agents was associated with improved prognosis only in patients with LV dysfunction, but not in patients without LV impairment.

2110 A Case of IgA Vasculitis in Crohn’s Disease and Recurrent Clostridioides difficile Infection

INTRODUCTION: IgA vasculitis (IgAV) is an immune-mediated systemic vasculitis characterized by palpable purpura, arthralgias, abdominal pain, and renal disease. Approximately 90% of cases occur in children; however, adults are at increased risk for more severe disease. The pathogenesis of IgAV is associated with inflammatory, infectious, autoimmune, and medication triggers, including tumor necrosis factor (TNF) alpha inhibitors. We describe a case of a man with Crohn’s disease (CD) who developed IgAV in the setting of a perirectal abscess, recurrent Clostridioides difficile infection (CDI), and anti-TNF therapy. CASE DESCRIPTION/METHODS: A 20 year old man with ileocolonic Crohn’s disease and perianal involvement, inflammatory arthropathy, and recurrent CDI presented to an outside ED with increased abdominal pain and rash on the extremities, trunk, and soft palate. Medications included etanercept, vedolizumab, and prednisolone. In the ED, the patient was hypotensive and tachycardic. CT abdomen/pelvis noted multifocal active inflammatory disease and a 3.2 cm abscess in the left ischiorectal fossa. He was initiated on broad spectrum antibiotics for septic shock and underwent emergent perirectal drain placement; post-operatively, his shock resolved. He was transferred to our institution for further management. Upon arrival, the patient was hemodynamically stable and remained on broad spectrum antibiotics and high dose prednisolone. Review of systems was notable for worsening abdominal pain and hematuria. Biopsy of the rash demonstrated IgA vasculitis. C. difficile toxin PCR was positive. Repeat urinalysis demonstrated nephrotic range proteinuria and hematuria, consistent with IgA nephropathy. ACE-inhibitor therapy was initiated, and skin lesions gradually improved with topical triamcinolone. DISCUSSION: We report a case of a patient with ileocolonic and perianal Crohn’s disease on TNF-alpha inhibitor therapy who developed IgA vasculitis in the setting of septic shock secondary to perirectal abscess and recurrent CDI. This case highlights anti-TNF therapy, infection and inflammatory bowel diseases as potential causes of systemic vasculitis. A high clinical suspicion is needed in order to obtain an early histopathologic diagnosis for IgAV and prompt evaluation of other organ system involvement.

P1568Cardiac biomarkers for the prediction of cardiotoxicity in cancer patients: a meta-analysis

Abstract Background Cancer therapy-related heart failure is the most concerning cardiac adverse event in patients undergoing cancer therapy. Valid diagnostic measures are fundamental for a timely diagnosis but systematic data on the use of diagnostic parameters in this collective is sparse. Cardiac biomarkers may be beneficial for diagnosis and screening of cancer therapy-related heart failure. Purpose Systematic data for cardiac biomarkers in cancer therapy-related cardiotoxicity is urgently needed to establish guideline recommendations. We therefore conducted the present systematic review and meta-analysis to assess cardiac troponin and (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) in the prediction of left ventricular (LV) systolic dysfunction in cancer patients. Methods Cochrane, PubMed, Web of Science, and Wiley Library were screened for studies investigating cardiac troponin or BNP/NT-proBNP in cancer patients receiving cytotoxic chemotherapy with and without anthracyclines, human epidermal growth factor receptor 2 (HER2) inhibitor therapy and radiotherapy. Reduced LV ejection fraction (LVEF) was defined as primary endpoint. Results A total of 5772 patients from 58 studies were included. Chemotherapy and HER2 inhibitor therapy was associated with an elevation of troponin levels above the 99th percentile (odds ratio (OR) = 14.3; 95% confidence interval (CI): 6.9–29.5). Patients treated with anthracyclines and high-dose chemotherapy had the highest rates of troponin elevation (OR = 17.5; 95% CI: 10.1–30.2 for anthracyclines; OR = 75.1; 95% CI: 4.4–1296.9 for high-dose chemotherapy, respectively). The risk for LVEF impairment was increased in troponin positive patients compared to troponin negative patients under high-dose regimens (OR = 97.9; 95% CI: 52.1–183.8) and anthracyclines with and without concomitant HER2 inhibitors (OR = 7.0; 95% CI: 1.4–34.1 and OR = 10.5; 95% CI: 2.0–54.3). Cardiac troponin below the 99th percentile had a negative predictive value of 94% for the prediction of cardiotoxicity. Absolute plasma BNP/NT-proBNP was increased in patients with LV dysfunction (standardized mean difference = 0.6; 95% CI = 0.0–1.2) but pathologically increased BNP/NT-proBNP did not predict decreased LVEF (OR = 2.0; 95% CI: 0.9–7.2). Preventive β-blocker therapy and angiotensin converting enzyme (ACE) inhibitor therapy was associated with decreased troponin elevation compared to control (OR = 2.9; 95% CI: 1.1–7.3; Figure 4). The effect was more pronounced in ACE inhibitor-treated patients compared to β-blocker-treated patients (Chi2 = 4.4; p=0.04; I2 = 77.4%). Conclusion Elevated troponin levels predict left ventricular dysfunction in cancer patients and a decrease in troponin may indicate response to cardioprotective therapy in cancer therapy-related cardiotoxicity. Cardiac troponin qualifies as a screening test to identify patients at high risk for manifest cardiotoxicity who require referral to cardio-oncology units. Acknowledgement/Funding IFORES research grant of the Medical Faculty, University Duisburg-Essen, Essen, Germany

P3120Prevention of heart failure in treatments with trastuzumab and anthracyclines: a meta-analysis

Abstract Background Trastuzumab and anthracyclines are conventional chemotherapies used in breast cancer. Unfortunately, they are associated with a decrease in left ventricular function potentially leading to heart failure (HF). In order to prevent this, randomised controlled trials (RCTs) assess the preventive effect of concomitant beta-blocker (BB), angiotensin receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) therapy during chemotherapy. Purpose To assess the preventive effect of BB, ARB or ACEIs on left ventricular ejection fraction (LVEF) during trastuzumab and anthracycline treatment in patients without HF. Methods Our primary outcomes were the effect of BBs or ARB/ACEIs during 1) trastuzumab and 2) anthracycline treatment. Secondary outcomes were the distinct effects of 1) BBs and 2) ARB/ACEIs in either trastuzumab or anthracycline treatments. Through the search term “(RCTs), prevention, cancer chemotherapy and cardiotoxicity” in PubMed, studies were selected, excluding those without randomising to a BB, ARB/ACEI and a placebo control group during chemotherapy. Means of the LVEF and the standard deviation (SD) post-chemotherapy were applied. Meta-analyses estimated the standardised mean difference (SMD) in the LVEF. Heterogeneity was calculated as the I2. Results A total of 7 studies (Table 1) were included in the analysis. Between 93 and 100% were woman. Age varied from 41 to 51 years. Treatment time varied from 12 to 52 weeks. Concomitant BB or ARB/ACEI therapy during trastuzumab treatment was not associated with the LVEF, significantly (Fig. 1A; p=0.07). Oppositely, in the anthracycline regime the LVEF remained significant higher in the concomitant BB and ARB/ACEI groups as compared to controls (Fig. 1B). BB and ARB/ACEI separation in the analysis showed both to influence the LVEF positively independent of chemotherapy (P=0.03 & p=0.005). Table 1 Study reference Year Chemotherapies Preventive drugs Pituskin et al., “Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research (MANTICORE 101-Breast): A Randomized Trial for the Prevention of Trastuzumab-Associated Cardiotoxicity.” 2017 Trastuzumab Perindopril. bisoprolol Gulati et al., “Prevention of Cardiac Dysfunction during Adjuvant Breast Cancer Therapy (PRADA).” 2016 Trastuzumab Candesartan, metoprolol Boekhout et al., “Angiotensin II-Receptor Inhibition With Candesartan to Prevent Trastuzumab-Related Cardiotoxic Effects in Patients With Early Breast Cancer: A Randomized Clinical Trial.” 2016 Trastuzumab Candesartan Janbabai et al., “Effect of Enalapril on Preventing Anthracycline-Induced Cardiomyopathy.” 2017 Anthracycline Enalapril Nabati et al., “Cardioprotective Effects of Carvedilol in Inhibiting Doxorubicin-Induced Cardiotoxicity.” 2017 Anthracycline Carvedilol Tashakori Beheshti et al., “Carvedilol Administration Can Prevent Doxorubicin-Induced Cardiotoxicity: A Double-Blind Randomized Trial.” 2016 Anthracycline Carvedilol Kaya et al., “Protective Effects of Nebivolol against Anthracycline-Induced Cardiomyopathy: A Randomized Control Study.” 2013 Anthracycline Nebivolol Figure 1 Conclusions Concomitant BB and ARB/ACEI therapy both favoured maintenance of the LVEF during trastuzumab and anthracyclines regimens as compared to controls.

THE IMPACT OF A COMPREHENSIVE HEART FAILURE MANAGEMENT PROGRAM INCLUDING PHARMACOLOGICAL OPTIMIZATION WITH VALSARTAN/SACUBITRIL ON CARDIAC FUNCTION AND FUNCTIONAL CAPACITY IN REDUCED EJECTION FRACTION HEART FAILURE

Heart Failure with reduced ejection fraction (HFrEF) carries a high risk of mortality and hospitalization. The landmark PARADIGM-HF study demonstrated that Angiotensin II Receptor Blocker Neprilysin Inhibitor (ARNI) therapy with Valsartan/sacubitril to be more effective than ACE-inhibitor therapy reducing mortality, and hospitalization rates. However, PARADIGM-HF did not establish a mechanism for the improvements in clinical outcomes with ARNI therapy. Improvements in LV systolic function as measured by ejection fraction (EF) has been demonstrated to reduce mortality and hospitalization rates significantly.

A comparison between statin with ACE inhibitor or ARB therapy in STEMI patients who underwent successful PCI with drug-eluting stents

Background and aimsStudies of the comparative clinical outcomes between statin with angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in ST-segment elevation myocardial infarction (STEMI) patients are limited. We compared 2-year clinical outcomes between statin with ACEI or ARB therapy in STEMI patients after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES). MethodsA total of 11,706 STEMI patients were enrolled and separated into two groups: the ACEI group (statin + ACEI, n = 8705) and the ARB group (statin + ARB, n = 3001). The primary endpoint was major adverse cardiac events (MACE) defined as all-cause death, recurrent MI (re-MI), and any coronary revascularization. Secondary endpoints were the individual components of MACE and target vessel failure (TVF). ResultsAfter propensity score-matched (PSM) analysis, two PSM groups (2729 pairs, n = 5458, C-statistic = 0.675) were generated. The cumulative incidences of MACE, re-MI, and any coronary revascularization were similar between the two groups. However, the cumulative incidences of all-cause death (hazard ratio [HR], 1.548; 95% confidence interval [CI], 1.091–2.197; p = 0.014) and cardiac death (HR, 1.850; 95% CI, 1.218–2.811; p = 0.004) were significantly higher in the ARB group compared with the ACEI group after PSM analysis. ConclusionsThe combination of statin with ACEI may be the preferred treatment strategy to reduce mortality rates in STEMI patients after successful PCI with DES rather than statin with ARB in this study during a 2-year follow-up period.

Impact of a Complement Factor H Gene Variant on Renal Dysfunction, Cardiovascular Events, and Response to ACE Inhibitor Therapy in Type 2 Diabetes.

Complement activation has been increasingly implicated in the pathogenesis of type 2 diabetes and its chronic complications. It is unknown whether complement factor H (CFH) genetic variants, which have been previously associated with complement-mediated organ damage likely due to inefficient complement modulation, influence the risk of renal and cardiovascular events and response to therapy with angiotensin-converting enzyme inhibitors (ACEi) in type 2 diabetic patients. Here, we have analyzed the c.2808G>T, (p.Glu936Asp) CFH polymorphism, which tags the H3 CFH haplotype associated to low plasma factor H levels and predisposing to atypical hemolytic uremic syndrome, in 1,158 type 2 diabetics prospectively followed in the Bergamo nephrologic complications of type 2 diabetes randomized, controlled clinical trial (BENEDICT) that evaluated the effect of the ACEi trandolapril on new onset microalbuminuria. At multivariable Cox analysis, the p.Glu936Asp polymorphism (Asp/Asp homozygotes, recessive model) was associated with increased risk of microalbuminuria [adjusted hazard ratio (HR) 3.25 (95% CI 1.46–7.24), P = 0.0038] and cardiovascular events [adjusted HR 2.68 (95% CI 1.23–5.87), P = 0.013]. The p.Glu936Asp genotype significantly interacted with ACEi therapy in predicting microalbuminuria. ACEi therapy was not nephroprotective in Asp/Asp homozygotes [adjusted HR 1.54 (0.18–13.07), P = 0.691 vs. non-ACEi-treated Asp/Asp patients], whereas it significantly reduced microalbuminuria events in Glu/Asp or Glu/Glu patients [adjusted HR 0.38 (0.24–0.60), P < 0.0001 vs. non-ACEi-treated Glu/Asp or Glu/Glu patients]. Among ACEi-treated patients, the risk of developing cardiovascular events was higher in Asp/Asp homozygotes than in Glu/Asp or Glu/Glu patients [adjusted HR 3.26 (1.29–8.28), P = 0.013]. Our results indicate that type 2 diabetic patients Asp/Asp homozygotes in the p.Glu936Asp CFH polymorphism are at increased risk of microalbuminuria and cardiovascular complications and may be less likely to benefit from ACEi therapy. Further studies are required to confirm our findings.

National Trends in Statin Medication Prescribing in Patients With a History of Stroke or Transient Ischemic Attack

Background: Guidelines support statin therapy post-stroke or transient ischemic attack (TIA); however, previously reported utilization rates are suboptimal. Objective: This study investigates the incidence of statin usage in patients with a documented stroke or TIA while identifying predictors of statin use. Methods: A retrospective, cross-sectional study utilizing data from the National Ambulatory Medical Care Survey. Results: A total of 2963 unweighted visits were included in the analysis, representing a total of 52 645 000 office visits when weighted. Statin therapy was initiated or continued in 35.7% (95% confidence interval [CI]: 32.4-39.0%) of office visits. Upon multivariate analysis, positive predictors of statin therapy included a diagnosis of hyperlipidemia (odds ratio [OR]: 3.60; 95% CI: 2.40-5.41), angiotensin-converting enzyme inhibitor (ACE-I) therapy (OR: 2.52; 95% CI: 1.69-3.76), aspirin therapy (OR: 2.02; 95% CI: 1.40-2.93), and clopidogrel therapy (OR: 2.60; 95% CI: 1.69-4.02). Negative predictors of statin therapy included office visits with neurologists when compared to visits with primary care practitioners (OR: 0.55; 95% CI: 0.33-0.90) and office visits in rural areas when compared to office visits in urban areas (OR: 0.64; 95% CI: 0.41-0.99). Conclusion: Various factors impact statin therapy use with overall utilization being suboptimal, highlighting an opportunity for medication optimization.

Trends in Kidney Function Outcomes Following RAAS Inhibition in Patients With Heart Failure With Reduced Ejection Fraction

Angiotensin-converting enzyme (ACE) inhibitors are beneficial in heart failure with reduced ejection fraction (HFrEF). We sought to describe longitudinal trends in estimated glomerular filtration rate (eGFR) in HFrEF and how ACE-inhibitor therapy influences these changes. Post hoc analysis of trial data. Symptomatic (Treatment Trial, n=2,423) and asymptomatic (Prevention Trial, n=4,094) patients from the Studies of Left Ventricular Dysfunction (SOLVD). Enalapril versus placebo. Early and long-term eGFR slope (ie, within and after the first 6 weeks) and 4 kidney end points: (1) serum creatinine level increase by≥0.3mg/dL, (2)>30% eGFR decline, (3)>40% eGFR decline, and (4) incident eGFR<30mL/min/1.73m2. Shared parameter models, multivariable Cox regression models. Baseline mean eGFR was lower in the Treatment Trial than in the Prevention Trial, 69.5±19.8 (SD) versus 76.2±18.6mL/min/1.73m2. Following randomization, an early eGFR decline occurred in the enalapril group; however, slopes during the median 3-year follow-up were not statistically different by randomization arm in either the Treatment Trial (-0.84 in enalapril vs-1.36mL/min/1.73m2 per year in placebo; P=0.08) or Prevention Trial (-1.27 in enalapril vs-1.36mL/min/1.73m2 per year in placebo; P=0.7). Random assignment to enalapril treatment increased the risk for all 4 outcomes in the Treatment Trial in the first 6-week period (HRs were 1.48 [95% CI, 1.10-1.99] for creatinine increase by≥0.3mg/dL; 1.38 [95% CI, 0.98-1.94] for eGFR decline> 30%; 2.60 [95% CI, 1.30-5.21] for eGFR decline> 40%; and 4.71 [95% CI, 1.78-12.50] for eGFR<30mL/min/1.73m2), but after the first year was not significantly associated with increased risk. A similar albeit less pronounced pattern was observed in the Prevention Trial, with risks present only in the early period. Creatinine results were not blinded, making it possible that ACE-inhibitor/placebo dosing was influenced by creatinine level. Kidney function decline is slow in HFrEF. Although random assignment to enalapril treatment results in a statistically increased risk for kidney surrogates, the risk is limited to the early phase and late eGFR slopes and risks are not different by randomly assigned group.

Intrarenal Renin-Angiotensin-System Dysregulation after Kidney Transplantation

Angiotensin-converting enzyme inhibitors (ACEis) are beneficial in patients with chronic kidney disease (CKD). Yet, their clinical effects after kidney transplantation (KTx) remain ambiguous and local renin-angiotensin system (RAS) regulation including the ‘classical’ and ‘alternative’ RAS has not been studied so far. Here, we investigated both systemic and kidney allograft-specific intrarenal RAS using tandem mass-spectrometry in KTx recipients with or without established ACEi therapy (n = 48). Transplant patients were grouped into early (<2 years), intermediate (2–12 years) or late periods after KTx (>12 years). Patients on ACEi displayed lower angiotensin (Ang) II plasma levels (P < 0.01) and higher levels of Ang I (P < 0.05) and Ang-(1–7) (P < 0.05) compared to those without ACEi independent of graft vintage. Substantial intrarenal Ang II synthesis was observed regardless of ACEi therapy. Further, we detected maximal allograft Ang II synthesis in the late transplant vintage group (P < 0.005) likely as a consequence of increased allograft chymase activity (P < 0.005). Finally, we could identify neprilysin (NEP) as the central enzyme of ‘alternative RAS’ metabolism in kidney allografts. In summary, a progressive increase of chymase-dependent Ang II synthesis reveals a transplant-specific distortion of RAS regulation after KTx with considerable pathogenic and therapeutic implications.

Orolingual Angioedema After Tissue Plasminogen Activator Administration in Patients Taking Angiotensin-Converting Enzyme Inhibitors

Orolingual angioedema is a rare adverse effect (1%-5%) of tissue plasminogen activator (tPA) that can lead to significant morbidity in patients with acute ischemic stroke. It is thought that increased levels of bradykinin and histamine resulting from tPA administration can result in angioedema. Angiotensin-converting enzyme (ACE) inhibitors can also lead to increased levels of bradykinin and appear to be a risk factor for tPA-associated angioedema. A literature review was conducted to examine previous cases of orolingual angioedema associated with tPA administration in patients also taking ACE inhibitors to better understand the relationship between ACE inhibitors and tPA-induced angioedema. Over a 20-year period, 27 patients who experienced angioedema with tPA while on ACE inhibitor therapy were identified. In this patient population, the onset of angioedema symptoms appeared as soon as 15 min after the tPA bolus and as late as 2 hr after the tPA infusion. Most patients required a combination of supportive medications such as corticosteroids (81.5%), antihistamines (74%), and epinephrine (18.5%) for the management of angioedema. Severe presentations of orolingual angioedema resulted in intubation for airway protection (26%). Symptom resolution ranged from shortly after the administration of supportive medications to 72 hr after symptom onset. Orolingual angioedema after tPA administration has the potential to cause significant morbidity, indicating patients should be monitored closely for a few hours after administration for the development of airway compromise. ACE inhibitors should not be the preferred antihypertensive agents for patients who require blood pressure lowering prior to tPA administration.