Angiotensin-converting Enzyme Inhibitor Therapy Research Articles

Effects of combined statin and ACE inhibitor therapy on endothelial function and blood pressure in essential hypertension - a randomised double-blind, placebo controlled crossover study

Background:The aim of this study was to compare the influence of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on endothelial function and blood pressure in patients with essential hypertension on long-term angiotensin-converting enzyme inhibitor therapy.Method:The study was designed as a prospective, double-blind, randomised, placebo controlled, crossover clinical trial. Twenty patients with essential hypertension were treated with an angiotensin-converting enzyme inhibitor; the control group included 10 healthy subjects. Hypertensive patients received in random order 80 mg of fluvastatin daily or placebo for 6 weeks. The following parameters were assessed at baseline and after each treatment period: serum lipids, flow-mediated vasodilation, activity of von Willebrand factor, concentration of vascular endothelial growth factor, C-reactive protein and 24-hour blood pressure profile.Results:Hypertensive patients did not differ from healthy subjects with respect to age, body mass and biochemical parameters, with the exception of C-reactive protein, which was higher in hypertensive patients (P=0.02). After statin therapy, low-density lipoprotein cholesterol (P<0.0001), C-reactive protein (P=0.03), von Willebrand factor (P=0.03) and vascular endothelial growth factor (P<0.01) decreased and flow-mediated vasodilation improved (P<0.001). Statins had no significant effect on blood pressure.Conclusions:Statins added to angiotensin-converting enzyme inhibitors may improve endothelial function and ameliorate inflammation independently of blood pressure.

MON-309 THE NEW ZEALAND PAEDIATRIC EXPERIENCE OF DIFFUSE MESANGIAL SCLEROSIS 1991-2018

Diffuse mesangial sclerosis (DMS) is a rare cause of nephrotic syndrome in the infantile and childhood period. It is generally characterized by rapid progression to end-stage renal disease and can present in isolation or in association with Denys-Drash syndrome. The largest published series to date includes 14 children from a Spanish cohort 1973-2008. We describe the clinical presentation and outcome for our case series of children with DMS. We retrospectively reviewed all cases of DMS diagnosed via renal biopsy in our tertiary paediatric centre between 1991-2018. Starship Children’s hospital is the sole paediatric nephrology referral centre for New Zealand. A total of seven cases were identified consisting of four males and three females. Fiver patients were under 1 year of age at presentation. Two patients in the cohort were siblings. Three children had clinical evidence of Denys-Drash syndrome. The most recent five patients (presenting after year 2000) underwent genetic testing - three displayed WT1 mutations, including one patient who was found to have a novel mutation. This particular patient had a strong family history of focal segmental glomerulosclerosis. Unlike other published series, only four of the seven patients presented in end stage renal disease (ESRD). The remaining cohort displayed variable degrees of proteinuria only. Two patients with proteinuria underwent biopsy due to a significant family history of nephrotic syndrome. All four patients with ESRD on presentation required dialysis, and half of these patients subsequently had bilateral nephrectomies. Two patients proceeded to transplant with no relapse of the disease, though one transplant failed after fourteen years with the patient returning to haemodialysis. One patient died whilst on the deceased donor list due to cardiovascular complications. One patient is currently being worked up for living donor transplant. Two patients with proteinuria are currently being treated with ACE inhibitor therapy with improved proteinuria, normalisation of hypoalbuminaemia and maintainenance of a normal estimated GFR. One patient has moved overseas and is lost to follow up. There is a broad spectrum of DMS presentations ranging from mild proteinuria to ESRD. Karyotyping and genetic testing are important to establish the presence of syndromic associations and in particular WT1 mutations, as these patients require Wilm’s tumour surveillance if nephrectomies are not performed. Early detection of DMS and initiation of anti-proteinuric therapy is hoped to be beneficial to prolong native kidney function. Unfortunately, this may only be possible in patients for whom DMS is already suspected as a potential diagnosis due to a family history.

Hit Two Birds With One Stone Via Thrombolytic Treatment

Early data showed that in the setting of acute myocardial infarction (AMI), left ventricular thrombus (LVT) was present in most frequently in acute apical or anterior AMI. There are several studies on the frequency of LVT formation in patients treated with precurtain coronary intervention (PCI). Solheim et al. reported LVT incidence of 15% in the first 3 months in AMI patients who were treated with primary PCI. In a meta-analysis it was shown that LVT is an important problem especially among patients with anterior AMI and management strategy is a point of interest. The incidence of LVT is in a decline recently. According to the current guidelines, immediate revascularisation of infarct related artery, use of sufficient anticoagulant therapy and agents that improve remodelling of the left ventricle was associated with decrease in incidence of LVT. Although the use of ACE-inhibitors had a favourable effect on left ventricle remodelling, there were no differences in LVT formation between those patients on ACE-inhibitor therapy and those who were not. LVT formation is associated with the infarct region, more frequent in anterior AMI, extent of infarct area and presence of aneurysm. In this case report we present a patient applied to the hospital with neurologic symptoms and diagnosed with acute ischemic stroke possibly due to left ventricle thrombus, possibly developed after the anterior MI 20 days ago. By thrombolytic therapy cardiac thrombus was dissolved and after 7 days the patient had complete neurologic recovery.

An electronic tool to aid community pharmacists in optimizing care for persons with diabetes

ObjectiveTo develop an electronic tool to aid community-based pharmacists in incorporating diabetes-specific clinical services into pharmacy workflow and to determine the utility of the tool. SettingThree independent community pharmacy locations. Practice descriptionRealo Discount Drugs is a group of 18 independent community pharmacies, a specialty pharmacy, and a long-term care pharmacy, all with a common owner, serving eastern North Carolina. Practice innovationAn electronic tool was developed to aid pharmacists in identifying gaps in therapy for patients with diabetes in alignment with the 2018 American Diabetes Association Standards of Medical Care in Diabetes. An RX edit (short code) alerted the pharmacist when a diabetes medication was verified. An electronic tool complemented the RX edit, through which the pharmacist would assess the patient record for the presence of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB), aspirin, or a statin. EvaluationThe pharmacist used an electronic tool to identify gaps in therapy, to document medication therapy problems identified, to make therapeutic recommendations to the patient or provider, and to document interventions using the electronic tool. ResultsPharmacists used the tool 788 times during a 50-day period. Each completion of the tool represented 1 patient profile assessed. Pharmacists identified 99 patients (12.6%) who were not using an ACEI or ARB. Pharmacists recommended ACEI or ARB therapy for 56 patients (56.6%). Pharmacists identified 371 patients (47.1%) who were not using aspirin therapy, and recommended aspirin therapy for 198 patients (53.4%). Pharmacists identified 187 (23.7%) patients who were not given statin therapy and recommended statin therapy for 142 patients (76%). A total of 74 medication therapy problems (18.7%) were resolved. ConclusionAn electronic tool was developed and integrated into the dispensing workflow. The implementation of an electronic tool helped community-based pharmacists to identify gaps in therapy and to make recommendations in alignment with American Diabetes Association guidelines.

Angiotensin receptor blockers as an alternative to angiotensin converting enzyme inhibitors

Cardiovascular disease is the leading cause of mortality in the UK with ischaemic heart disease and heart failure being the main contributors. The renin-angiotensin aldosterone system has an essential role in cardiovascular pathophysiology by increasing preload, afterload and left ventricular workload. Angiotensin converting enzyme inhibitor therapy is a first-line therapy in this patient population except for those who are intolerant of angiotensin converting enzyme inhibitors. Angiotensin receptor blockers are deemed as a safe alternative while achieving the same clinical benefit. Common adverse effects are hypovolaemia, hyperkalemia and renal dysfunction. The nursing role involves cardiovascular assessment, monitoring for adverse effects and patient education.

Efficacy of Pharmacologic and Cardiac Implantable Electronic Device Therapies in Patients With Heart Failure and Reduced Ejection Fraction: A Systematic Review and Network Meta-Analysis.

Background The treatment of heart failure with reduced ejection fraction has been the subject of numerous randomized controlled trials involving medications and cardiac implantable electronic device therapies. As newer effective pharmacological therapies suggest significant reductions in all-cause mortality, the role of additional device therapy in heart failure with reduced ejection fraction deserves further scrutiny. Methods A systematic review and network meta-analysis on the effect of medication and device therapies in heart failure with reduced ejection fraction on all-cause mortality was performed. Randomized controlled trials published between January 1980 and July 2017 were identified using Medline, EMBASE, and Cochrane Controlled Register of Trials databases. Pcnetmeta package in R was used to calculate treatment arm-based estimated rates, rate ratios, and probability ranks with 95% credible intervals. Results Combination therapy of ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) with β-blockers (BBs) alone or in addition to implantable cardiac defibrillators or cardiac resynchronization therapy with defibrillators demonstrated a significant reduction of all-cause mortality when compared with placebo. By probability rank, implantable cardiac defibrillator+ACE inhibitor or ARB+BB+mineralocorticoid receptor antagonist, implantable cardiac defibrillator+ACE inhibitor or ARB+BB, and angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist to implantable cardiac defibrillator+optimal pharmacological combination therapy. Conclusions BB and renin-angiotensin system blockers alone or in combination with defibrillator device therapy have robust evidence for a reduction in mortality compared with placebo. The comparative efficacy of pharmacological therapy with angiotensin receptor-neprilysin inhibitors and device therapy deserves further investigation.

180-LB: Impact of a Multidisciplinary Diabetes Care Team in Primary Care Settings on Glycemic Control

Purpose: A multidisciplinary team approach to diabetes management involves various healthcare members to optimize patient outcomes. However, there are limited studies that look at the effect of a multidisciplinary team on diabetes outcomes outside of endocrinology services. This study aimed to evaluate the impact of a primary care multidisciplinary team on glycemic control and additional risk reduction during a 12-week diabetes program. Methods: Retrospective review of medical records for patients who completed the 12-week diabetes program at three primary care clinics from January to August of 2018 occurred. The primary outcome was mean change in hemoglobin A1c (HbA1c). Secondary outcomes included 24-week HbA1c, mean change in blood pressure, weight, Diabetes Distress Scale (DDS) score, and Patient Health Questionnaire (PHQ9) score. Other secondary objectives included the number of patients on statin therapy and ACE inhibitor or angiotensin receptor blocker therapy as indicated. Patients enrolled in the diabetes program were seen by a provider, pharmacist, dietician, and behavioral health specialist at an initial visit and a 12-week follow-up visit. Follow-up occurred either telephonically or face-to-face in the interim for lifestyle counseling and medication adjustments. Results: In total, 85 patients were included in the final analysis. At 3 month follow-up, the mean A1c was significantly decreased (2.1+/-2.3, p &amp;lt; 0.001), 54.1% of patients met their A1c goal (p &amp;lt; 0.001), 80.5% were on statin therapy (p &amp;lt; 0.001), and the mean change in weight (kg) was -1.96+/- 3.9 (p = 0.001) from baseline. Conclusion: This study demonstrates that a multidisciplinary approach to diabetes management can reduce HbA1c and other risk factors. A multidisciplinary model can be replicated in primary care offices to allow for comprehensive care and improvement in health outcomes for a broader patient population who may not have access to specialty services. Disclosure N.E. Handlow: None. B. Nolton: None. S.E. Winter: None. C.M. Wessel: None. J. Pennock: None. Funding R.K. Mellon Foundation

Addition of cyclic angiotensin-(1-7) to angiotensin-converting enzyme inhibitor therapy has a positive add-on effect in experimental diabetic nephropathy

The Renin-Angiotensin System (RAS) possesses a counter-regulatory axis composed of angiotensin converting enzyme (ACE)2, angiotensin-(1-7) [Ang-(1-7)] and the Mas receptor, which opposes many AT1-receptor-mediated effects of ligand angiotensin II. Ang-(1-7), as a ligand of the Mas receptor, has inhibitory effects on renal inflammation and fibrosis in experimental diabetes. However, Ang-(1-7) has a short half-life in plasma, which may render it unsuitable for use in clinics. Here, we investigated the effects of the lanthionine-stabilized Ang-(1-7), cyclic (c)Ang-(1-7), a lanthipeptide that is more peptidase-resistant than the linear peptide, in BTBR ob/ob mice with type 2 diabetic nephropathy. BTBR ob/ob mice received vehicle, cAng-(1-7), or the ACE inhibitor lisinopril. The treatment started at ten weeks of age, when the animals had already developed albuminuria, and ended at 19-20 weeks of age. cAng-(1-7) limited albuminuria progression, and limited podocyte dysfunction similarly to lisinopril. cAng-(1-7), unlike lisinopril, reduced glomerular fibrosis and inflammation, and counteracted glomerular capillary rarefaction. Furthermore, when cAng-(1-7) was combined with lisinopril, a superior antiproteinuric effect than with lisinopril alone was found, in association with better preservation of podocyte proteins and amelioration of capillary density. Thus, adding cAng-(1-7) to ACE-inhibitor therapy could benefit those diabetic patients who do not respond completely to ACE-inhibitor therapy.

The Influence of ACE Inhibition on C1-Inhibitor: A Biomarker for ACE Inhibitor-Induced Angioedema?

Aims: Angioedema is a rare side effect of angiotensin-converting enzyme (ACE) inhibitors. It remains unclear why it is only induced in a few patients taking ACE inhibitors, often after a long period of uneventful treatment. The aim of this study was to analyze the influence of ACE inhibitor treatment on C1-inhibitor (C1-INH) levels. Methods: Captopril (5 mg/25 mg) was added to blood samples of 5 healthy subjects. C1-INH levels were measured before and after incubation for 180 min. The second section of the study was done with 17 patients who received therapy with an ACE inhibitor for the first time. C1-INH levels were measured before ACE inhibitor treatment, 24 h after first drug administration, and 4 weeks later. Results: After incubation of blood samples with 5 mg captopril, there was no detectable change in C1-INH levels. After incubation with 25 mg, C1-INH activity was decreased by an average of 29% and the C1-INH concentration was decreased by an average of 0.06 g/L. In the second study section, inconsistent effects on C1-INH levels were detected. In the majority of patients, 24 h after the first ACE inhibitor administration C1-INH activity was tending to be increased. Conclusions: A dose-dependent effect on C1-INH levels in captopril-incubated blood samples of healthy test persons was shown. In patients with new ACE inhibitor treatment, heterogeneous reactions of C1-INH values were detected. Larger studies are needed over a longer period of time to find correlations between the effect of ACE inhibitor therapy on C1-INH levels and the clinical course/development of side effects.

Utilization and Dose Optimization of Angiotensin-Converting Enzyme Inhibitors among Heart Failure Patients in Southwest Ethiopia.

Background Optimal use of angiotensin-converting enzyme inhibitors (ACEIs) is crucial to improve the treatment outcome in heart failure patients. However, little is known about the optimal use of ACEIs among heart failure patients in our setting. Therefore, our study aimed to investigate the utilization and optimal dosing of ACEIs and associated factors in heart failure patients. Method A cross-sectional study was conducted on randomly selected patients with heart failure between February 2016 and June 2016 at ambulatory care clinic of Jimma University Medical Center, Ethiopia. Data were collected through patient interview and review of medical records. Binary logistic regression analysis was done to identify factors associated with utilization and optimal dosing of ACEIs. Results A total of 308 patients were included in the final analysis of this study. The mean (±standard deviation) age of the patients was 52.3 ±15.5 years. Out of the total, 74.7% of the patients were receiving ACEIs. Among the patients who were receiving ACEIs, only 35.7% were taking optimal dose. New York Heart Association (NYHA) class III (Adjusted odds ratio (AOR):0.12, 95% confidence interval (CI):0.02–0.98), valvular heart disease (AOR: 0.27, 95% CI: 0.13-0.56), hypertension (AOR: 5.82, 95% CI: 2.16-15.71), and diabetes mellitus (AOR: 3.84, 95% CI: 1.07-13.86) were significantly associated with the use of ACEIs, whereas age ≥65 (AOR: 2.61, 95%CI: 1.20-5.64), previous hospitalization for heart failure (AOR: 2.08, 95%CI: 1.11-3.92), diuretic use (AOR: 5.60, 95%CI: 2.75-11.40), and dose of furosemide >40mg (AOR: 9.80, 95%CI: 3.00-31.98) were predictors of suboptimal dosing of ACEIs. Conclusion Although majority of patients were receiving ACEIs, only about one-third were using optimal dosage. Valvular heart disease and NYHA class III were negatively associated with the use of ACEIs while previous hospitalization for heart failure, old age, diuretic use, and diuretic dose were predictors of suboptimal dosing of ACEIs. Therefore, more effort needs to be done to minimize the potentially modifiable risk factors of suboptimal use of ACEIs therapy in heart failure patients.

ACE inhibitor suppresses cardiac remodeling after myocardial infarction by regulating dendritic cells and AT2 receptor-mediated mechanism in mice

Dendritic cells (DCs) play a complex role in the progression of myocardial infarction (MI). The impact of angiotensin-converting enzyme (ACE) inhibitor therapy, partly via affecting DCs maturation and recruitment, was tested on a MI mouse model. Furthermore, the cardioprotective effects of ACEI were enhanced through attenuating migration of DCs from the spleen into peripheral circulation, thereby inhibiting DCs maturation and tissue inflammation. ACEI repress DCs immune inflammatory response through down-regulating DCs maturation surface markers and regulating inflammatory cytokines, which led to a higher survival rate, improved function and remodeling through decreased inflammatory response after MI. However, inhibition of AT2R activation, resulted in a reduction of ACEI effects on DCs. The potent anti-inflammatory effect of ACEI can partially be attributed to its impact on DCs through activation of AT2R, which may provide a new target mechanism for ACEI therapy after MI.

Efficacy of Long-term Selenium Supplementation in the Treatment of Chronic Keshan Disease with Congestive Heart Failure

Few effective treatments for chronic Keshan disease have been available till now. The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive. This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up. A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years. Of the 302 chronic Keshan disease patients, 170 (56.3%) were given selenium supplementation until the end point of follow-up. Cox proportional hazards regression models were used to identify the independent predictors of cardiac events. Our results showed that during the follow-up, there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group (101/170, 59.4%) and 98 in non-selenium supplementation group (98/132, 74.2%). Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death (HR 0.39, 95% CI 0.28-0.53) after adjustment for baseline age, sex, cigarette smoking, family history of Keshan disease, body mass index (BMI), heart rate, electrocardiogram (ECG) abnormalities, blood pressure, initial cardiothoracic ratio, left ventricular ejection fractions (LVEF) and whole-blood selenium concentration. Our ten-year follow-up analysis indicated that selenium supplementation, specifically combined with the use of angiotensin-converting enzyme inhibitor and beta blocker therapy, improved the survival of patients with chronic Keshan disease with congestive heart failure. BMI, selenium deficiency, male, combined ECG abnormalities, LVEF, and fast heart rate increased the risk of cardiac events.

Nephroprotective therapy with angiotensin converting enzyme inhibitors effect evaluation on the course of chronic kidney disease in children with urinary system congenital malformations

The aim : to evaluate the effect of angiotensin-converting enzyme inhibitor (ACEI) therapy on the course of chronic kidney disease (CKD) in children with urinary system congenital malformations. Patients and methods . 119 patients with urinary system congenital malformations aged 3 to 18 years were examined. A control group of 10 clinically healthy children. There were 3 groups: I - 55 children with congenital vesicoureteral reflex, II - 34 children with congenital hydronephrosis, III - 30 children with other forms of urinary systems dysembryogenesis. ACEI therapy Enap (KRKA, Slovenia), held for 6 months (children up to 14 years at a dose of 0.2 mg/kg/24 h in 1 reception, adolescents 5-10 mg/24 h in 1 reception). Results . were evaluated according to clinical data, according to the daily monitoring of blood pressure (BP), renal function, renin concentration, plasma aldosterone. Renin and aldosterone production was determined in blood plasma (lying down) by enzyme immunoassay. Results . During ACEI treatment in all children there was stabilization of BP, renal function improvement. Patients with hypertension showed a significant decrease in the concentration of renin. ACEI therapy leads to normalization of aldosterone concentration in patients with hypertension and without hypertension. Conclusion. The analysis of the course of CKD in patients with US CM on the background of ACEI therapy demonstrates the main aspects of the anti-fibrotic action of the pharmacological blockade of the renin-aldosterone ACEI system.

Perceptions of Canadian Vascular Surgeons Toward Pharmacologic Risk Reduction in Patients with Peripheral Artery Disease: 2018 Update

Vascular surgeons have a central role in managing peripheral artery disease (PAD). This study assessed their knowledge, attitudes, and behaviors regarding pharmacologic risk reduction in PAD and results were compared to a similar 2004 survey conducted by our group. An online questionnaire was administered to 161 active members of the Canadian Society for Vascular Surgery. Forty-eight participants (30%) completed the survey. Recommended targets for low-density lipoprotein cholesterol, blood pressure, and glucose were known by 52%, 38%, and 50% of vascular surgeons, respectively. Almost all participants recognized antiplatelet dosages and statin indications, but less than half could identify indications (29%) and precautions (44%) for angiotensin converting enzyme (ACE) inhibitor therapy. A majority (58%) routinely evaluate risk factors in <50% of their patients. Most vascular surgeons regularly provide risk reduction counseling, but less than 10% initiate or modify antihypertensive or ACE inhibitor therapy. Compared to 2004, knowledge of targets and indications/precautions for common cardiovascular medications and frequency of risk factor assessment have not changed. Rates of counseling for diabetes control and statin prescription have improved, but remain suboptimal. Regarding newer medications with cardiovascular benefit, less than 10% would prescribe proprotein convertase subtilisin/kexin type 9 and sodium-glucose cotransporter 2 inhibitors if they were available. The majority of vascular surgeons rate their PAD risk reduction knowledge as average and support an up-to-date Canadian PAD guideline. Most participants believe that risk reduction therapy is best provided by family physicians and internists, but also acknowledge that vascular surgeons should be well-versed in assessing and managing risk factors in PAD. Significant knowledge and action gaps exist among Canadian vascular surgeons with regards to pharmacologic cardiovascular risk reduction in PAD. Although there is recognition that vascular surgeons are central to the medical management of patients with PAD, few routinely evaluate risk factors and prescribe medications. There is little evidence of sufficient improvement since 2004. New educational and clinical strategies are needed to improve PAD risk reduction pharmacotherapy among Canadian vascular surgeons.

Angiotensin-converting enzyme inhibitors modulate the activation of the tissue factor pathway within aortic valves in patients with aortic stenosis: Links between blood coagulation and inflammation

Background: Similarities between the pathobiology of aortic stenosis (AS) and atherosclerosis have led to the concept that pharmacological strategies effective in atherosclerosis might attenuate valvular inflammation. Objective: The objective of this study was to assess how angiotensin-converting enzyme inhibitors (ACEIs) might affect valvular expression of coagulation and inflammatory proteins in AS. Material/Methods: We studied 111 advanced AS patients (62 males, aged 63.3±11.2 years) undergoing valve replacement. Plasma levels, valvular expression and mRNA transcripts of tissue factor (TF), TF pathway inhibitor (TFPI), prothrombin, along with C-reactive protein (CRP) and interleukin-6 (IL-6) were evaluated. Results: TF-, TFPI-, CRP and prothrombin valvular expression was not related to demographics, concomitant diseases or plasma TF, free-TFPI or IL-6. ACEIs-treated patients (n=37), mainly due to hypertension (n=24, 65%), showed decreased areas for valvular TF (13.64±6.43 vs. 18.05±6.81%, p=0.03), TFPI (32.6±7.8 vs. 49.15±9.5%, p&lt;0.001), prothrombin (23.47±1.93 vs. 26.61±1.4%, p&lt;0.001), CRP (0.75 [0-9] vs. 1.4 [0-8]%, p=0.009), and IL-6 (3.2±0.65 vs. 6.4±1.83%, p&lt;0.001) compared with non-ACEIs patients. Similarly, patients treated with ACEIs showed lower mRNA expression of TF (1.22±0.47 vs. 2.27±1.42, p=0.041), prothrombin (0.13±0.07 vs. 0.81±0.37, p&lt;0.001), CRP (0.73±0.29 vs. 1.25±0.69, p=0.04), and IL-6 (7.6±5.16 vs. 13.67±7.3, p=0.046). Conclusions: In patients with severe AS, ACEIs use is associated with lower expression of valvular proteins involved in coagulation and inflammation, thus ACEIs therapy could be important in altering atherosclerosis-like processes within stenotic aortic valves.

The role of ACE inhibitors in cardiovascular disease

Cardiovascular disease is the leading cause of death in the UK, with heart failure and ischaemic heart disease the commonest forms of the condition. The renin–angiotensin–aldosterone system is recognised as having an integral pathophysiological role by increasing afterload, promoting sodium and water retention and contributing to ventricular remodelling. Evidence from randomised controlled trials has demonstrated that angiotensin-converting enzyme (ACE) inhibitors reduce mortality, slow disease progression and reduce left ventricular workload. This is achieved by inhibiting the conversion of angiotensin I to angiotensin II. Preload and afterload are reduced, which preserves left ventricular function. Common adverse effects include cough, hypotension, hyperkalaemia and a decline in renal function. The nurses' role in caring for patients receiving ACE inhibitor therapy includes clinical assessment, monitoring and detecting adverse effects as well as patient education.

Randomised placebo-controlled trial of combination ACE inhibitor and beta-blocker therapy to prevent cardiomyopathy in children with Duchenne muscular dystrophy? (DMD Heart Protection Study): a protocol study

IntroductionAlthough cardiologists were ‘late-comers’ to the multidisciplinary team—contributing to the complex care of patients with Duchenne muscular dystrophy (DMD), they now recognise the importance of systematic cardiac surveillance and timely...

Abstract 17278: Concomitant Use of Ivabradine in the Setting of Cardiogenic Shock: A Case Series

Background: Ivabradine, a selective sinus node inhibitor, is indicated for patients with chronic heart failure with reduced ejection fraction (HFrEF). Use in cardiogenic shock is currently contraindicated. However, studies have suggested increasing heart rate may be deleterious for patients with HFrEF due to an inverted Bowditch-Treppe response. Limited case series have suggested use of Ivabradine in decompensated HFrEF may be beneficial. We present a case series of patients who presented with severely decompensated HFrEF and received inotropic support and concomitant ivabradine. Methods: We selected four patients with HFrEF presenting with elevated sinus heart rate and cardiogenic shock (cardiac index &lt;2.0L/min*m2with pulmonary artery wedge pressure &gt; 20 mmHg by invasive hemodynamic monitoring) while on inotropic therapy and were intolerant of beta blockade due to hypotension. Ivabradine 2.5 mg 12 h was initiated and subsequently titrated with continued monitoring with baseline, 24 h and latest obtained parameters recorded. Other treatments occurred at the discretion of the attending physician. Results: Four male patients (mean age 44 years) with non-ischemic cardiomyopathy (mean EF 17%, mean NT-pro-BNP 5104 pg/ml) were included. Ivabradine was tolerated in all cases, with a mean dose of 6 mg q12h. Mean heart rate and pulmonary wedge pressure fell 20% and 32% respectively from baseline to last measurement, while stroke volume increased with an overall improvement in cardiac index. (Table 1) There were no changes noted in mean arterial blood pressure. All patients underwent successful wean of inotropic support within 48 hours and were discharged alive on beta blocker and ACE inhibitor therapy. No adverse events attributed to use of Ivabradine were observed. Conclusion: In our small series of patients with cardiogenic shock, beta blocker intolerance and elevated sinus heart rate, Ivabradine was added without any deleterious hemodynamic effect and associated with early clinical improvement. Further studies are needed to better assess its potential use in this population.

ACE-inhibitors: a preventive measure for bone flap resorption after autologous cranioplasty?

Decompressive craniectomy (DC) is an established treatment for refractory intracranial hypertension. It is usually followed by autologous cranioplasty (AC), the reinsertion of a patient's explanted bone flap. A frequent long-term complication of AC is bone flap resorption (BFR), which results in disfigurement as well as loss of the protective covering of the brain. This study investigates risk factors for BFR after AC, including medical conditions and antihypertensive drug therapies, with a focus on angiotensin-converting enzyme inhibitors (ACEIs), which have been associated with a beneficial effect on bone healing and bone preservation in orthopedic, osteoporosis, and endocrinology research. In this single-center, retrospective study 183 consecutive cases were evaluated for bone flap resorption after AC. Information on patient demographics, medical conditions, antihypertensive therapy, and BFR-defined as an indication for revision surgery established by a neurosurgeon based on clinical or radiographic assessments-was collected. A Kaplan-Meier analysis of time from AC to diagnosis of BFR was performed, and factors associated with BFR were investigated using the log-rank test and Cox regression. A total of 158 patients were considered eligible for inclusion in the data analysis. The median follow-up time for this group was 2.2 years (95% CI 1.9-2.5 years). BFR occurred in 47 patients (29.7%), with a median time to event of 3.7 years (95% CI 3.3-4.1 years). An ACEI prescription was recorded in 57 cases (36.1%). Univariate Kaplan-Meier analysis and the log-rank test revealed that ACEI therapy (2-year event free probability [EFP] 83.8% ± 6.1% standard error vs 63.9% ± 5.6%, p = 0.02) and ventriculoperitoneal (VP) shunt treatment (2-year EFP 86.9% ± 7.1% vs 66% ± 5.0%, p = 0.024) were associated with a lower probability of BFR. Multiple Cox regression analysis showed ACEI therapy (HR 0.29, p = 0.012), VP shunt treatment (HR 0.278, p = 0.009), and male sex (HR 0.500, p = 0.040) to be associated with a lower risk for BFR, whereas bone fragmentation (HR 1.92, p = 0.031) was associated with a higher risk for BFR. Hypertensive patients treated with ACEIs demonstrate a lower rate of BFR than patients treated with other hypertensive medications and nonhypertensive patients. Our results are in line with previous reports on the positive influence of ACEIs on bone healing and preservation. Further analysis of the association between ACEI treatment and BFR development is needed and will be evaluated in a multicenter prospective trial.

Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With Outcomes After Acute Kidney Injury

Patients with acute kidney injury (AKI) are at an increased long-term risk of death. Effective strategies that improve long-term outcomes in patients with AKI are unknown. To evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) after hospital discharge is associated with better outcomes in patients with AKI. This retrospective cohort study used data from the Alberta Kidney Disease Network population database to evaluate 46 253 adults 18 years or older with an episode of AKI during a hospitalization between July 1, 2008, and March 31, 2015, in Alberta, Canada. All patients who survived to hospital discharge were followed up for a minimum of 2 years. Use of an ACEI or ARB within 6 months after hospital discharge. The primary outcome was mortality; secondary outcomes included hospitalization for a renal cause, end-stage renal disease (ESRD), and a composite outcome of ESRD or sustained doubling of serum creatinine concentration. An AKI was defined as a 50% increase between prehospital and peak in-hospital serum creatinine concentrations. Propensity scores were used to construct a matched-pairs cohort of patients who did and did not have a prescription for an ACEI or ARB within 6 months after hospital discharge. The study evaluated 46 253 adults (mean [SD] age, 68.6 [16.4] years; 24 436 [52.8%] male). Within 6 months of discharge, 22 193 (48.0%) of the participants were prescribed an ACEI or ARB. After adjustment for comorbidities, ACEI or ARB use before admission, demographics, baseline kidney function, other factors related to index hospitalization, and prior health care services, ACEI or ARB use was associated with lower mortality in patients with AKI after 2 years (adjusted hazard ratio, 0.85; 95% CI, 0.81-0.89). However, patients who received an ACEI or ARB had a higher risk of hospitalization for a renal cause (adjusted hazard ratio, 1.28; 95% CI, 1.12-1.46). No association was found between ACEI or ARB use and progression to ESRD. Among patients with AKI, ACEI or ARB therapy appeared to be associated with lower mortality but a higher risk of hospitalization for a renal cause. These results suggest a potential benefit of ACEI or ARB use after AKI, but cautious monitoring for renal-specific complications may be warranted.