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ACE Inhibitors (ace + inhibitor)
Terms modified by ACE Inhibitors Selected AbstractsPossible Interaction Between Aspirin and ACE Inhibitors: Update on Unresolved ControversyCONGESTIVE HEART FAILURE, Issue 6 2000Israel M. Barbash BmedSc The widespread use of aspirin and angiotensin converting enzyme (ACE) inhibitors in patients with coronary artery disease contributes significantly to the reduction in morbidity and mortality from this common health problem. These agents are widely and concomitantly used, and they share mechanisms that may interact in negative or positive pathways. Data derived from in vitro preparations, animal studies, human studies, and case-control studies are inconsistent. No study has established firm evidence regarding the safety or adverse effect of aspirin on patients who are on ACE inhibitors. The efficacy and safety of aspirin in combination with ACE inhibitors has been questioned and debated. If a negative interaction does exist, it will affect daily practice in treating patients with coronary artery disease and heart failure. This article reviews the available data regarding the safety of combined aspirin and ACE-inhibitor treatment among patients with ischemic heart disease, to assess the possible interaction between the two drugs and to discuss thesignificance and implications of the data. [source] ACE Inhibitors and ARBs: Are They Better Than Other Agents to Slow Nephropathy Progression?JOURNAL OF CLINICAL HYPERTENSION, Issue 6 2007George L. Bakris MD No abstract is available for this article. [source] ACE Inhibitors and Protection Against Kidney Disease Progression in Patients With Type 2 Diabetes: What's the Evidence?JOURNAL OF CLINICAL HYPERTENSION, Issue 6 2002George L. Bakris MD Although angiotensin-converting enzyme inhibitors are frequently used as antihypertensive agents to lower blood pressure and slow progression of nephropathy in patients with type 2 diabetes, evidence of their efficacy has been drawn primarily from small trials with surrogate end points. No adequately powered, long-term trials have tested their effects to reduce the incidence of hard end points, such as progression to end-stage renal disease or even doubling of serum creatinine in the population of patients with nephropathy from type 2 diabetes. While the results of angiotensin-converting enzyme inhibitor trials from nondiabetic causes and even type 1 diabetes may be extrapolated to the patient with nephropathy associated with type 2 diabetes, the hard evidence is not available. This review critically evaluates the limited evidence in support of angiotensin-converting enzyme inhibitors as renal-protective agents in people with type 2 diabetes. [source] Brain angiotensin-converting enzymes: role of angiotensin-converting enzyme 2 in processing angiotensin II in miceEXPERIMENTAL PHYSIOLOGY, Issue 5 2008Khalid M. Elased Angiotensin (Ang)-converting enzyme 2 (ACE2) metabolizes Ang II to the vasodilatory peptide Ang(1,7), while neprilysin (NEP) generates Ang(1,7) from Ang I. Experiments used novel Surface Enhanced Laser Desorption Ionization-Time of Flight (SELDI-TOF) mass spectroscopic (MS) assays to study Ang processing. Mass spectroscopy was used to measure proteolytic conversion of Ang peptide substrates to their specific peptide products. We compared ACE/ACE2 activity in plasma, brain and kidney from C57BL/6 and NEP,/, mice. Plasma or tissue extracts were incubated with Ang I or Ang II (1296 or 1045, m/z, respectively), and generated peptides were monitored with MS. Angiotensin-converting enzyme 2 activity was detected in kidney and brain, but not in plasma. Brain ACE2 activity was highest in hypothalamus. Angiotensin-converting enzyme 2 activity was inhibited by the specific ACE2 inhibitor, DX600 (10 ,m, 99% inhibition), but not by the ACE inhibitor, captopril (10 ,m). Both MS and colorimetric assays showed high ACE activity in plasma and kidney with low levels in brain. To extend these findings, ACE measurements were made in ACE overexpressing mice. Angiotensin-converting enzyme four-copy mice showed higher ACE activity in kidney and plasma with low levels in hypothalamus. In hypothalamus from NEP,/, mice, generation of Ang(1,7) from Ang I was decreased, suggesting a role for NEP in Ang metabolism. With Ang II as substrate, there was no difference between NEP,/, and wild-type control mice, indicating that other enzymes may contribute to generation of Ang(1,7). The data suggest a predominant role of hypothalamic ACE2 in the processing of Ang II, in contrast to ACE, which is most active in plasma. [source] The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the clinical features of Parkinson's diseaseINTERNAL MEDICINE JOURNAL, Issue 1 2000K. A. Reardon Abstract Background: Animal studies have demonstrated an interaction within the striatum between the angiotensin and dopaminergic systems. In rats, the angiotensin converting enzyme (ACE) inhibitor, perindopril, crosses the blood brain barrier and increases striatal dopamine synthesis and release. In humans, angiotensin type 1 receptors have been found on dopaminergic neurons in the substantia nigra and striatum. In Parkinson's disease, there is a marked reduction of these receptors associated with the nigrostriatal dopaminergic neuron loss. Aims: We performed a double blind placebo controlled crossover pilot study in seven patients to investigate the effect of the ACE inhibitor, perindopril on the clinical features of moderately severe Parkinson's disease. Results: After a four week treatment period with perindopril, patients had a faster onset in their motor response to L-dopa and a reduction in ,on phase' peak dyskinesia, p=0.021 and p=0.014 respectively. Patients also reported more ,on' periods during their waking day in their movement diary, p=0.007. Perindopril was well tolerated without any significant postural hypotension or renal dysfunction. Conclusions: These results suggest that ACE inhibitors such as perindopril may have a place in the management of motor fluctuations and dyskinesia in Parkinson's disease and justify further study. [source] Renal cortex remodeling in nitric oxide deficient rats treated with enalaprilJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2004Noemi Barbuto Abstract The kidney NO synthase is one of the most important renal controlling systems. This paper aims the quantification of renal cortical components involved in blood pressure regulation under NOs blockade. Spontaneous hypertensive rats (SHRs) are submitted to chronic blockade of NOs by L-nitro-arginine-methyl-ester (L-NAME) and an ACE inhibitor (enalapril) in comparison with the normotensive Wistar rats. Twenty SHRs and 5 Wistar rats were divided in 5 groups and observed for 21 days for blood pressure (BP) and serum creatinine: control Wistar (5) (C-W), control SHR (5) (C-SHR), L-SHR (5) - received L-NAME 30 mg/kg/day, L+E-SHR (5) - received L-NAME and Enalapril maleate 15 mg/kg/day, E-SHR (5) - received Enalapril maleate. A quantitative morphometric study (glomerular density, QA[g1], interstitium volume density, Vv[i], tubular surface and length densities, Sv[t] and Lv[t]) were performed at the end. The BP reached 226±15 mmHg in L-SHR group. The BP difference between the L-SHR and the C-SHR groups was significant from the first week while the E-SHR group became significant from the second week. At the end of the experiment the BP of the E-SHR group was similar to the BP in the C-W group. The QA[g1] was similar among C-SHR, L-SHR and L+E-SHR groups and no difference was found between E-SHR and C-W groups. In the L-SHRs serum creatinine was greatly increased, and microscopy showed thickening of arteriolar tunica media with an increase of the wall-to-lumen ratio, perivascular fibrosis, inflammatory infiltrated, tubular atrophy and interstitial fibrosis with focal segmental glomerulosclerosis. The use of enalapril was not completely efficient in reducing BP and morphological injury when the hypertension of SHRs was increased with the NOs blockade suggesting that NO deficiency-induced hypertension is not entirely mediated by the RAAS. [source] Attenuation of changes in Gi -proteins and adenylyl cyclase in heart failure by an ACE inhibitor, imidaprilJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2003R. Sethi Abstract Cardiac dysfunction in animals with congestive heart failure due to myocardial infarction (MI) is known to be associated with a wide variety of defects in receptor and post-receptor mechanisms. Since the heart function have been shown to be improved by treatment with different angiotensin converting enzyme (ACE) inhibitors, we examined the effects of imidapril, an ACE inhibitor, on changes in post-receptor mechanisms involving adenylyl cyclase (AC) and G proteins in the failing heart. Heart failure in rats was induced by occluding the coronary artery and 3 weeks later the animals were treated daily with 1 mg/kg (orally) imidapril for 5 weeks. The animals were assessed for their left ventricular function and crude membranes were isolated from the viable left ventricle and examined for AC activities as well as G-protein activities and expression. Animals with heart failure exhibited depressions in ventricular function and AC activities in the absence or presence of forskolin, NaF and Gpp(NH)p. The AC activity in the presence of pertussis toxin was increased whereas that in the presence of cholera toxin was decreased in the failing heart. Protein contents and mRNA levels for Gi -proteins were increased whereas those for Gs -proteins were unaltered in the infarcted heart. All these changes due to MI were prevented by imidapril treatment. The results indicate that the depressed cardiac function in the failing heart may partly be due to the direct effects of changes in AC and Gi proteins. [source] Evolving Treatment Options for Prevention of Cardiovascular Events in High-Risk Hypertensive PatientsJOURNAL OF CLINICAL HYPERTENSION, Issue 11 2007Prakash Deedwania MD The identification and treatment of high-risk patients for cardiovascular disease reduces the risk of morbidity and mortality. Significant risk factors for cardiovascular events in hypertensive patients over and above dyslipidemia, smoking, and obesity include coronary heart disease, peripheral arterial disease, cerebrovascular/carotid artery disease, and diabetes. Treatment options for the reduction of cardiovascular events in hypertensive patients include diuretics, ,-blockers, ,-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and aldosterone antagonists. All of these agents, in various combinations, have been found to reduce the risk of cardiovascular events, even in high-risk patients. The use of ACE inhibitors or ARBs (usually in combination with a diuretic) has proven especially effective in reducing cardiovascular events in diabetes and, although both classes of drugs target the renin-angiotensin-aldosterone system, each has a different mechanism of action. Some investigators believe that combination therapy with an ACE inhibitor and ARB, usually given with other medications, may be more effective than either agent alone with other drugs. The Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) is evaluating the cardioprotective effect of an ACE inhibitor (ramipril) plus an ARB (telmisartan) in high-risk patients. [source] Type 2 Diabetes: RENAAL and IDNT,The Emergence of New Treatment OptionsJOURNAL OF CLINICAL HYPERTENSION, Issue 1 2002Domenic A. Sica MD The Reduction in End Points in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study and the Irbesartan Diabetic Nephropathy Trial (IDNT) are two recently reported trials with hard end points, conducted in patients in advanced stages of diabetic nephropathy. Two other studies,the Irbesartan Microalbuminuria Study (IRMA)-2 and the Microalbuminuria Reduction with Valsartan study (MARVAL),were trials conducted in patients with type 2 diabetes with microalbuminuria, a cardiovascular risk factor associated with early-stage diabetic nephropathy. These trials all had a common theme,that is, does an angiotensin receptor blocker (ARB) interfere with the natural history of diabetic nephropathy in a blood pressure-independent fashion? Without question, the results of these trials legitimatize the use of the ARB class in forestalling the deterioration in renal function, which is almost inevitable in the patient with untreated diabetic nephropathy. These data can now be added to the vast array of evidence supporting angiotensin-converting enzyme (ACE) inhibitor use in patients with nephropathy associated with type 1 diabetes. It now appears a safe conclusion that the patient with diabetic nephropathy should receive therapy with an agent that interrupts the renin-angiotensin system. These studies have not resolved the question as to whether an ACE inhibitor or an ARB is the preferred agent in people with nephropathy from type 1 diabetes, though the optimal doses of these drugs remain to be determined. Head-to-head studies comparing ACE inhibitors to ARBs in diabetic nephropathy are not likely to occur, so it is unlikely that comparable information will be forthcoming with ACE inhibitors. An evidence-based therapeutic approach derived from these trials would argue for ARBs to be the foundation of therapy in the patient with type 2 diabetes and nephropathy. [source] Undertreatment of congestive heart failure in an Australian settingJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2004P. J. Boyles BPharm (Hons) Summary Aim:, Guidelines for the management of patients with chronic heart failure have undergone change in recent years, with , -blockers and spironolactone shown to reduce mortality when added to angiotensin converting enzyme (ACE) inhibitors, diuretics and digoxin. The aim of this study was to examine the therapeutic management of heart failure in patients admitted to Tasmania's three major public hospitals, with an assessment of the appropriateness of the therapy according to contemporary published guidelines. Methods:, An extensive range of clinical and demographic data was retrospectively extracted from the medical records of consecutive adult patients admitted to the medical wards of the hospitals with heart failure, either as a primary diagnosis or as a comorbidity, during a 6-month period in late 1999,early 2001. Results:, The 450 patients (57% females) had a mean age of 77·8 ± 10·2 years, and were being treated with a median of seven drugs on hospital admission. The percentages of patients being treated with the major drugs of interest were: ACE inhibitors (50%), , -blockers (22%), spironolactone (15%), digoxin (24%), loop diuretics (65%) and angiotensin-II receptor antagonists (8%). Almost 10% were taking a non-steroidal anti-inflammatory agent. Less than one-half the patients who were receiving an ACE inhibitor were taking a target dose for heart failure. There were no significant differences in the pattern of drug use between the three hospitals. Underuse of heart failure medications was most pronounced in women and elderly patients. Conclusions:, The data suggest that current guidelines for the treatment of heart failure are still not being reflected in clinical practice. The relatively low use of drugs shown to improve survival in heart failure is of concern and warrants educational intervention. [source] Angioedema from angiotensin-converting enzyme (ACE) inhibitor treated with complement 1 (C1) inhibitor concentrateACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2006E. W. Nielsen Background:, Up to seven in every 1000 patients experience angioedema from angiotensin-converting enzyme (ACE) inhibitors, even after many years of use. In 2003, every 20th Norwegian used an ACE inhibitor. Case report:, A 61-year-old woman with chronic obstructive pulmonary disease and a past acute myocardial infarction had used 7.5 mg of ramipril daily for the past 7 years. She also used acetylsalicylic acid, simvastatin, theophylline and salmeterol. One night she woke up with edema of the tongue. On hospital arrival, 250 mg of hydrocortisone and 5 mg of dexchlorpheniramine were given intravenously (i.v.) and 0.3 mg of epinephrine was given subcutaneously (s.c.). The edema of the tongue progressed over the next 8 h and made the tongue protrude. Fiberscopy revealed glassy edema of the arytenoids. Inspiratory stridor was heard and the patient could not speak. She became increasingly uneasy and restless. Berinert® complement 1 (C1) inhibitor concentrate (1500 units) was administered i.v. Over the following 20 min, stridor gradually subsided, the patient calmed and she was able to talk. Discussion:, ACE inhibitor-provoked angioedema shares many clinical features with hereditary angioedema (HAE), including a limited effect of steroids, antihistamines and epinephrine. HAE, caused by excess bradykinin formation as a result of C1 inhibitor deficiency, usually has its laryngeal edema effectively reversed by C1 inhibitor in less than 0.5 h. Although patients experiencing ACE inhibitor-provoked angioedema have normal C1 inhibitor values, as in our patient, excess bradykinin is probably important as ACE breaks down bradykinin. It is unknown why ACE inhibitor-provoked angioedema appears in some and sometimes after many years of use. Conclusion:, We believe that C1 inhibitor was effective in reversing the ACE inhibitor-induced angioedema in our patient. [source] How large studies may mislead: the HOPE StudyPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 6 2001Roy Taylor Abstract The HOPE study is widely believed to indicate that anyone over the age of 55 years with a major cardiovascular risk factor should receive prophylactic therapy with ramipril but detailed inspection of the characteristics of the patient groups suggest problems of randomisation. There was a consistent over-representation in the placebo group of patients with each of the most potent risk factors for cardiovascular events: previous history of myocardial infarction, peripheral vascular disease, previous stoke, angina, hypertension and elevated lipids. Moreover, there was an excess of males in the placebo group. The composite end point was of death from cardiovascular cause, myocardial infarction or stoke, and 651 patients in the ramipril group and 827 in the placebo group were affected. This gave an excess of primary endpoints in the placebo group of 176 cases. However, at baseline, there was an excess in the placebo group of individuals with previous ischaemic heart disease (95), peripheral vascular disease (119), previous stroke (13) and hypertension (69). Heart failure surprisingly occurred in similar numbers in the ramipril and placebo groups (81 vs. 79) respectively. The claim that this particular ACE inhibitor protects against cardiovascular disease is unfounded because of baseline imbalance in risk. Copyright © 2001 John Wiley & Sons, Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 21 2007Article first published online: 3 DEC 200 NSAIDs and SSRIs increase GI bleeding Taking an NSAID and an SSRI increases the risk of GI bleeding more than six-fold compared with taking neither drug, a meta-analysis shows (Aliment Pharmacol Ther online: 5 Oct 2007; doi:10.1111/j.1365-2036.20 07.03541.x). The analysis included four observational studies involving a total of 153 000 patients, and 101 cases reported in postmarketing surveillance. Compared with nonuse, the odds ratio for upper GI haemorrhage in patients taking an SSRI alone was 2.36; the number needed to harm (NNH) was 411 for one year's treatment in patients aged over 50 with no risk factors. For those taking an SSRI and an NSAID, it was 6.33 (NNH 106). Of 22 cases where treatment duration was known, the median time to onset of bleeding was 25 weeks and five occurred within one month. The MHRA warns of this interaction in its latest issue of Drug Safety Update, noting: ,corticosteroids, antiplatelet agents, and SSRIs may increase the risk of GI ulceration or bleeding. NSAIDs may enhance the effects of anticoagulants, such as warfarin'. MHRA warning on NSAID safety The MHRA reminds prescribers of new restrictions on prescribing piroxicam and the risks associated with ketorolac and ketoprofen in its latest Drug Safety Update (2007;1:Issue 3). Treatment with piroxicam should now only be initiated by a specialist as a second-line drug; patients currently taking it should be reviewed at the next routine appointment. Piroxicam is no longer indicated for any acute indications. These restrictions do not apply to topical piroxicam (Feldene gel). Ketorolac and ketoprofen are associated with a higher risk of adverse GI effects than other NSAIDs. The MHRA advises prescribers to adhere to the licensed indications that limit oral ketorolac therapy to seven days (two days for continuous iv or im use) and the maximum dose of ketoprofen to 100-200mg. Inhaled steroids may increase the risk of pneumonia in patients with COPD. In the TORCH study (N Engl J Med 2007;356:775-89), fluticasone (Flixotide) and fluticasone plus salmeterol (Seretide) were associated with a significantly increased risk compared with salmeterol alone. The MHRA recommends vigilance for signs of pneumonia or bronchitis in patients with COPD who are treated with inhaled steroids; affected patients should have their treatment reconsidered. Other issues reviewed in Drug Safety Update include: a more intense reaction after revaccination with the pneumococcal vaccine, Pneumovax II; exacerbation of osteonecrosis of the jaw by dental surgery in patients taking a bisphosphonate; a lower maximum dose for lorazepam (4mg for severe anxiety, 2mg for severe insomnia) rare reactions with botulinum toxin; and the cardiovascular safety and risk of fractures with the glitazones. Antibiotic resistance GPs who reduce their antibiotic prescribing achieve a significant reduction in bacterial resistance, a study from Wales has shown (Br J Gen Pract 2007;57:785-92). The analysis of 164 225 coliform isolates from urine samples submitted from 240 general practices found a 5.2 per cent decrease in ampicillin resistance in practices with the greatest reductions in total antibiotic prescribing. Overall, ampicillin resistance decreased by 1 per cent for every reduction of 50 amoxicillin prescriptions per 1000 patients. Trimethoprim resistance showed a similar trend. Mortality risk with discontinuing statins Patients who discontinue statin therapy after acute stroke are almost three times more likely to die than those who do not, an Italian study shows (Stroke 2007;38:2652-7). Follow-up of 631 patients discharged after acute stroke revealed that 39 per cent discontinued statin therapy. The hazard ratio for all-cause mortality in the first 12 months was 2.78 compared with those who continued treatment; this compared with a hazard ratio of 1.81 for stopping antiplatelet therapy. The authors argue that patient care should be improved during the transition from hospital to outpatient primary care. ACEI ± ARB = ADRs Combining an ACE inhibitor and an angiotensin-II receptor blocker increases the risk of adverse effects in patients with symptomatic left ventricular dysfunction, according to a US study (Arch Intern Med 2007;167:1930-6). Meta-analysis of four trials involving a total of 17 337 patients followed up for about two years showed that, compared with therapy including an ACE inhibitor, combined treatment increased the risk of stopping treatment due to adverse events by 38 per cent in patients with heart failure and by 17 per cent in patients with MI. The authors estimate that, for every 1,000 patients treated, 25 will discontinue treatment due to adverse effects and 17 will develop renal dysfunction. WOSCOPS: statin protection continues Pravastatin reduces the risk of death years after treatment has stopped, according to a follow-up of the WOSCOPS study (N Engl J Med 2007;357:1477-86). The West of Scotland Coronary Prevention Study originally randomised men with hypercholesterolaemia but no history of myocardial infarction (MI) to treatment with pravastatin or placebo. After five years, the combined incidence of death from CHD or nonfatal MI was reduced from 7.9 to 5.5 per cent in the treatment group. During the 10 years after completion of the trial, the incidence of the combined end-point was 8.6 per cent in those originally assigned to pravastatin and 10.3 per cent in the placebo group. All- cause mortality was also reduced over the entire 15-year period. The proportions of patients still taking a statin in the middle of this period, ie five years after the trial ended, were 39 per cent of the placebo group. Prescribing policies on HRT need reappraisal Health authorities should reconsider their policy on prescribing HRT, the International Menopause Society (IMS) says. In an open letter, the IMS says current safety concerns over HRT use are founded, but have been misinterpreted in observational studies, such as the Women's Health Initiative, that led to changes in guidelines. The IMS says HRT is the most effective treatment for vasomotor and urogenital symptoms and the risk:benefit profile is favourable until age 60. Low-dose oestrogen or the transdermal route of administration may lead to a more favourable risk profile. Flu vaccine does cut morbidity and mortality Following The Lancet's commentary doubting the effectiveness of flu vaccination (Lancet Infectious Diseases 2007;7:658-66), a US cohort study has found that it does reduce morbidity and mortality (N Engl J Med 2007;357:1373-81). The observational study included 713 872 person-seasons in older people living in the community over a 10year period from 1990 to 2000. Vaccination was associated with a 48 per cent reduction in the risk of death and a 27 per cent reduction in admission for pneumonia or flu. These benefits changed little in subgroups or with age. Copyright © 2007 Wiley Interface Ltd [source] Current drug management of chronic heart failurePRESCRIBER, Issue 12 2006Iain Squire MD For most patients with heart failure, treatment will now include a diuretic, an ACE inhibitor or angiotensin-II inhibitor and a beta-blocker. Our Drug review discusses the properties and side-effects of the wide range of drugs available, followed by sources of further information and the Datafile. Copyright © 2006 Wiley Interface Ltd [source] Drug-related pemphigus and angiotensin converting enzyme inhibitorsAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2000Colin S Ong SUMMARY A 105-year-old woman developed pemphigus foliaceus. She had been on fosinopril, an angiotensin-converting enzyme inhibitor (ACE inhibitor) for 4 years. Anti-intercellular cement substance antibodies were positive with titre > 160. She died during admission of an unrelated illness. A 57-year-old man developed pemphigus vulgaris after 11 months treatment with quinapril. At 14 months after developing pemphigus, this man continues on prednisone and azathioprine. We speculate that these are cases of ACE-inhibitor-related pemphigus and we review ACE-inhibitor-related pemphigus. [source] Different angiotensin-converting enzyme inhibitors have similar clinical efficacy after myocardial infarctionBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2008Morten L. Hansen What is already known about this subject ,,Treatment with an angiotensin-converting enzyme (ACE) inhibitor benefits many patients with cardiovascular disease. ,,ACE inhibitors are generally assumed to be equally effective, but this has never been fully verified in clinical trials. What this study adds ,,Studying the association among ACE inhibitors after myocardial infarction demonstrated similarity in clinical outcome and supports a dosage,response relationship. ,,Therefore, for long-term benefits for patients who need treatment with an ACE inhibitor, a focus of treatment at the recommended dosage is most important and not which ACE inhibitor is used. Aim Therapy with angiotensin-converting enzyme (ACE) inhibitors is common after myocardial infarction (MI). Given the lack of randomized trials comparing different ACE inhibitors, the association among ACE inhibitors after MI in risk for mortality and reinfarction was studied. Methods Patients hospitalized with first-time MI (n = 16 068) between 1995 and 2002, who survived at least 30 days after discharge and claimed at least one prescription of ACE inhibitor, were identified using nationwide administrative registries in Denmark. Results Adjusted Cox regression analysis demonstrated no differences in risk for all-cause mortality, but patients using captopril had higher risk of reinfarction (hazard ratio 1.18, 95% confidence interval 1.05, 1.34). However, following adjustment for differences in used dosages, all ACE inhibitors had similar clinical efficacy. Risk of all-cause mortality: trandolapril (reference) 1.00, ramipril 0.97 (0.89, 1.05), enalapril 1.04 (0.95, 1.150), captopril 0.95 (0.83, 1.08), perindopril 0.98 (0.84, 1.15) and other ACE inhibitors or angiotensin II receptor blockers (ARB) 1.06 (0.94, 1.19). Reinfarction: trandolapril (reference) 1.00, ramipril 0.98 (0.89, 1.08), enalapril 1.04 (0.92, 1.17), captopril 1.05 (0.89, 1.25), perindopril 0.96 (0.81, 1.14) and other ACE inhibitors or ARB 0.99 (0.86, 1.14). Furthermore, the association between ARBs and clinical events was similar to ACE inhibitors (trandolapril reference): all-cause mortality 0.99 (0.84, 1.16) and recurrent MI 0.99 (0.83, 1.19). Conclusions Our results suggest a class effect among ACE inhibitors when used in comparable dosages. Focus on treatment at the recommended dosage is therefore most important, and not which ACE inhibitor is used. [source] The vascular biology of hypertension and atherosclerosis and intervention with calcium antagonists and angiotensin-converting enzyme inhibitorsCLINICAL CARDIOLOGY, Issue S5 2001Carl J. Pepine M.D. Recent advances in the understanding of vascular disease genesis suggest that atherosclerosis and hypertension, primary targets of therapy in the INternational VErapamil SR/trandolapril STudy (INVEST), are closely related. A unified model for the development of cardiovascular disease (CVD) is emerging from recent advances related to atherosclerosis and hypertension. The process of vascular disease appears to begin early in life, when signs of endothelial dysfunction first appear. A primary cause of CVD progression is increased oxidative stress in the endothelium caused by multiple risk factor conditions, including heredity, dyslipidemia, smoking, diabetes, and elevated systolic blood pressure (SBP > 110 mmHg). The renin-angiotensin and kallikrein-kinin systems are important regulators of blood pressure and atherosclerosis. In the reninangiotensin system, angiotensin-converting enzyme (ACE) mediates generation of angiotensin II (ang II) at local vascular sites and in the plasma and also degrades bradykinin. Information derived from INVEST will help to identify treatment strategies, such as those containing a calcium antagonist and an ACE inhibitor, that are targeted directly at the vascular disorder responsible for hypertension and atherosclerosis. [source] Heart Failure Drug Utilization Patterns for Medicaid Patients Before and After a Heart Failure-Related HospitalizationCONGESTIVE HEART FAILURE, Issue 3 2005Patricia A. Howard PharmD The authors examined heart failure (HF) drug utilization patterns in Medicaid patients before and after a HF-related hospitalization. This was a retrospective claims analysis of Kansas Medicaid beneficiaries hospitalized for HF between July 1, 2000, and March 31, 2001. HF drugs were tracked 6 months prior and 6 months following the admission. Angiotensin-converting enzyme (ACE) inhibitor doses were compared with target ranges. The cohort of 135 patients had a mean age of 53.6 years and was predominantly female (66.7%) and Caucasian (70.4%) with a high prevalence of cardiovascular comorbidities. Before hospitalization, less than one third of patients were receiving ACE inhibitors, angiotensin receptor blockers, , blockers, digoxin, or vasodilators. Following hospitalization, increased utilization was observed for , blockers, digoxin, and angiotensin receptor blockers, but overall usage remained low. ACE inhibitors and vasodilator use remained constant. ACE-inhibitor doses were below target ranges before and after hospitalization. In this Medicaid cohort, HF-related hospitalizations did not lead to improved HF therapy. [source] Possible Interaction Between Aspirin and ACE Inhibitors: Update on Unresolved ControversyCONGESTIVE HEART FAILURE, Issue 6 2000Israel M. Barbash BmedSc The widespread use of aspirin and angiotensin converting enzyme (ACE) inhibitors in patients with coronary artery disease contributes significantly to the reduction in morbidity and mortality from this common health problem. These agents are widely and concomitantly used, and they share mechanisms that may interact in negative or positive pathways. Data derived from in vitro preparations, animal studies, human studies, and case-control studies are inconsistent. No study has established firm evidence regarding the safety or adverse effect of aspirin on patients who are on ACE inhibitors. The efficacy and safety of aspirin in combination with ACE inhibitors has been questioned and debated. If a negative interaction does exist, it will affect daily practice in treating patients with coronary artery disease and heart failure. This article reviews the available data regarding the safety of combined aspirin and ACE-inhibitor treatment among patients with ischemic heart disease, to assess the possible interaction between the two drugs and to discuss thesignificance and implications of the data. [source] Association between Endothelial Function and Chronotropic Incompetence in Subjects with Chronic Heart Failure Receiving Optimal Medical TherapyECHOCARDIOGRAPHY, Issue 3 2010M.D., Timothy J. Vittorio M.S. Objective: Impairment of flow-mediated, endothelium-dependent vasodilatation (FMD) of the brachial artery identifies peripheral endothelial dysfunction in subjects with chronic congestive heart failure (CHF) and is associated with increased morbidity and mortality. To further elucidate the interaction of peripheral and central mechanisms in the syndrome of CHF, we examined the association between endothelial function and chronotropic incompetence, an emerging prognostic marker in CHF. Methods: Thirty subjects with stable New York Heart Association (NYHA) functional class II,III CHF were studied. A vascular ultrasound study was performed to measure brachial artery FMD. The percentage of age-adjusted maximal predicted heart rate (MPHR) reached during cardiopulmonary exercise tolerance testing (CPETT) was used to assess the degree of chronotropic competence. All patients received ACE inhibitors and ,-adrenoceptor blockers. Results: Brachial artery FMD averaged 1.3 ± 2.4% and age-adjusted % MPHR 74.1 ± 11.7%. FMD correlated with % MPHR among all patients (r = 0.60, P = 0.01). FMD and resting heart rate (RHR) did not significantly correlate (r = 0.13, P = 0.55). Conclusions: FMD, a measure of peripheral endothelial dysfunction, and % MPHR, a central determinant of cardiac output, are moderately correlated in heart failure patients receiving optimal medical therapy. Whether a cause-effect relationship underlies this association remains to be investigated. (Echocardiography 2010;27:294-299) [source] Angiotensin-converting enzyme polymorphisms and risk of spontaneous deep intracranial hemorrhage in TaiwanEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2008C.-M. Chen Background and purpose:, This study examines whether angiotensin-converting enzyme (ACE) gene polymorphisms are associated with the risk of spontaneous deep intracerebral hemorrhage (SDICH) in Taiwan using a case,control study. Methods:, Totally, 217 SDICH patients and 283 controls were recruited. Associations of ACE A-240T and ACE I/D polymorphisms with SDICH were examined under the additive model and adjusted for gender, age, body mass index, total cholesterol level, smoking history, alcohol use, hypertension, and use of ACE inhibitors. Results:, Hypertension, diabetes mellitus, family history of spontaneous intracerebral hemorrhage (SICH), and low cholesterol level increase risk of female SDICH, whereas hypertension, alcohol use, smoking history, family history of SICH, and low cholesterol level are an important risk factor for male SDICH. After adjusting for covariates, only haplotype ACE T-D (OR = 2.7, 95% CI, 1.1,6.5, P = 0.02) was associated with female SDICH. Conclusions:, This study demonstrates that environmental risk factors play a major role and ACE polymorphisms play a minor role in contributing risk of SDICH in Taiwan. [source] Combined use of selective inhibitors and fluorogenic substrates to study the specificity of somatic wild-type angiotensin-converting enzymeFEBS JOURNAL, Issue 8 2006Nicolas D. Jullien Somatic angiotensin-converting enzyme (ACE) contains two homologous domains, each bearing a functional active site. Studies on the selectivity of these ACE domains towards either substrates or inhibitors have mostly relied on the use of mutants or isolated domains of ACE. To determine directly the selectivity properties of each ACE domain, working with wild-type enzyme, we developed an approach based on the combined use of N-domain-selective and C-domain-selective ACE inhibitors and fluorogenic substrates. With this approach, marked differences in substrate selectivity were revealed between rat, mouse and human somatic ACE. In particular, the fluorogenic substrate Mca-Ala-Ser-Asp-Lys-DpaOH was shown to be a strict N-domain-selective substrate of mouse ACE, whereas with rat ACE it displayed marked C-domain selectivity. Similar differences in selectivity between these ACE species were also observed with a new fluorogenic substrate of ACE, Mca-Arg-Pro-Pro-Gly-Phe-Ser-Pro-DpaOH. In support of these results, changes in amino-acid composition in the binding site of these three ACE species were pinpointed. Together these data demonstrate that the substrate selectivity of the N-domain and C-domain depends on the ACE species. These results raise concerns about the interpretation of functional studies performed in animals using N-domain and C-domain substrate selectivity data derived only from human ACE. [source] The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the clinical features of Parkinson's diseaseINTERNAL MEDICINE JOURNAL, Issue 1 2000K. A. Reardon Abstract Background: Animal studies have demonstrated an interaction within the striatum between the angiotensin and dopaminergic systems. In rats, the angiotensin converting enzyme (ACE) inhibitor, perindopril, crosses the blood brain barrier and increases striatal dopamine synthesis and release. In humans, angiotensin type 1 receptors have been found on dopaminergic neurons in the substantia nigra and striatum. In Parkinson's disease, there is a marked reduction of these receptors associated with the nigrostriatal dopaminergic neuron loss. Aims: We performed a double blind placebo controlled crossover pilot study in seven patients to investigate the effect of the ACE inhibitor, perindopril on the clinical features of moderately severe Parkinson's disease. Results: After a four week treatment period with perindopril, patients had a faster onset in their motor response to L-dopa and a reduction in ,on phase' peak dyskinesia, p=0.021 and p=0.014 respectively. Patients also reported more ,on' periods during their waking day in their movement diary, p=0.007. Perindopril was well tolerated without any significant postural hypotension or renal dysfunction. Conclusions: These results suggest that ACE inhibitors such as perindopril may have a place in the management of motor fluctuations and dyskinesia in Parkinson's disease and justify further study. [source] Maximising antihypertensive effects of angiotensin II receptor blockers with thiazide diuretic combination therapy: focus on irbesartan/hydrochlorothiazideINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 12 2007J. M. Flack Summary Background:, Evidence-based guidelines for the management of hypertension are now well established. Studies have shown that more than 60% of patients with hypertension will require two or more drugs to achieve current treatment targets. Discussion:, Combination therapy is recommended as first-line treatment by the JNC-7 guidelines for patients with a blood pressure > 20 mmHg above the systolic goal or 10 mmHg above the diastolic goal, while the International Society of Hypertension in Blacks recommends combination therapy when BP exceeds targets by > 15/10 mmHg. Current European Society of Hypertension-European Society of Cardiology guidelines also recommend the use of low-dose combination therapy in the first-line setting. Furthermore, JNC-7 recommends that a thiazide-type diuretic should be part of initial first-line combination therapy. Thiazide/diuretic combinations are available for a variety of classes of antihypertensive, including ACE inhibitors, angiotensin receptor blockers (ARBs), beta blockers and centrally acting agents. This article focuses on clinical data investigating the combination of an ARB, irbesartan, with the diuretic, hydrochlorothiazide. Conclusions:, These data indicate that the ARB/HCTZ combination has greater potency and a similar side effect profile to ARB monotherapy and represents a highly effective approach for attaining goal BP levels using a therapeutic strategy that very effectively lowers BP, is well tolerated and minimises diuretic-induced metabolic effects. [source] Plasma renin and the antihypertensive effect of the orally active renin inhibitor aliskiren in clinical hypertensionINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2007J. Nussberger Summary Background:, Aliskiren is the first in a new class of orally effective renin inhibitors for the treatment of hypertension. Methods:, In 569 patients with mild-to-moderate hypertension, blood pressure (BP), plasma renin activity (PRA) and plasma renin concentration (PRC) were measured before and after 8 weeks of double-blind treatment with once-daily oral doses of aliskiren (150, 300 or 600 mg), irbesartan 150 mg or placebo. Results:, Aliskiren 150, 300 and 600 mg and irbesartan 150 mg significantly reduced mean cuff sitting systolic BP (SBP) from baseline (p < 0.001 vs. placebo). Aliskiren 150, 300 and 600 mg significantly reduced geometric mean PRA by 69%, 71% and 75% from baseline respectively (p < 0.05 vs. placebo). Irbesartan 150 mg significantly increased PRA by 109% (p < 0.05 vs. placebo). Aliskiren dose-dependently increased PRC from baseline by 157%, 246% and 497%, at 150, 300 and 600 mg respectively, compared with a 9% decrease with placebo (p < 0.05). PRC increased significantly more with aliskiren 300 and 600 mg compared with irbesartan 150 mg (105%; p < 0.05). Regression analysis showed no significant correlations between baseline PRA and changes in SBP in any of the treatment groups, but interestingly, the slopes of the regression lines between changes in SBP and log-transformed baseline PRA were +2.0 for placebo and ,1.5, ,1.8 and ,2.3 for aliskiren 150, 300 and 600 mg respectively. The slope for irbesartan 150 mg (,1.4) was similar to that for aliskiren 150 mg. Conclusions:, Aliskiren reduces SBP and PRA and increases PRC dose-dependently. In contrast, irbesartan reduces SBP but increases both PRC and PRA. As PRA is a measurement of angiotensin I-generating capacity, PRA can be used for measuring the ability of an antihypertensive agent to prevent the generation or action of Ang II, either directly (renin inhibitors, beta-blockers, central ,2 -agonists) or indirectly (AT1 -receptor blockers, ACE inhibitors). [source] The Effect of Dementia on Outcomes and Process of Care for Medicare Beneficiaries Admitted with Acute Myocardial InfarctionJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2004Frank A. Sloan PhD Objectives: To determine differences in mortality after admission for acute myocardial infarction (AMI) and in use of noninvasive and invasive treatments for AMI between patients with and without dementia. Design: Retrospective chart review. Setting: Cooperative Cardiovascular Project. Patients: Medicare patients admitted for AMI (N=129,092) in 1994 and 1995. Measurements: Dementia noted on medical chart as history of dementia, Alzheimer's disease, chronic confusion, or senility. Outcome measures included mortality at 30 days and 1-year postadmission; use of aspirin, beta-blocker, angiotensin-converting enzyme (ACE) inhibitor, thrombolytic therapy, cardiac catheterization, coronary angioplasty, and cardiac bypass surgery compared by dementia status. Results: Dementia was associated with higher mortality at 30 days (relative risk (RR)=1.16, 95% confidence interval (CI)=1.09,1.22) and at 1-year postadmission (RR=1.18, 95% CI=1.13,1.23). There were few to no differences in the use of aspirin and beta-blockers between patients with and without a history of dementia. Patients with a history of dementia were less likely to receive ACE inhibitors during the stay (RR=0.89, 95% CI=0.86,0.93) or at discharge (RR=0.90, 95% CI=0.86,0.95), thrombolytic therapy (RR=0.82, 95% CI=0.74,0.90), catheterization (RR=0.51, 95% CI=0.47,0.55), coronary angioplasty (RR=0.58, 95% CI=0.51,0.66), and cardiac bypass surgery (RR=0.41, 95% CI=0.33,0.50) than patients without a history of dementia. Conclusion: The results imply that the presence of dementia had a major effect on mortality and care patterns for this condition. [source] Quality of Care of Nursing Home Residents Hospitalized With Heart FailureJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2002Ali Ahmed MD, FACP OBJECTIVES: To determine whether the quality of heart failure (HF) care of hospitalized nursing home (NH) residents is different from that of patients admitted from other locations. DESIGN: Retrospective chart review. SETTING: Nursing home residents discharged from hospitals. PARTICIPANTS: Medicare beneficiaries aged 65 and older. MEASUREMENTS: Subjects were discharged with a primary discharge diagnosis of HF in Alabama in 1994. They were categorized as having been admitted from a NH or other locations. Bivariate logistic regression analysis was used to estimate crude odds ratios (ORs) and 95% confidence intervals (CIs) for left ventricular function (LVF) evaluation and angiotensin-converting enzyme (ACE) inhibitor use for NH residents relative to nonresidents. Multivariate generalized linear models were developed to determine independence of associations. RESULTS: Subjects (N = 1,067 years) had a mean age ± standard deviation of 79 ± 7.4, 60% were female, and 18% were African Americans. Fewer NH residents (n = 95) received LVF evaluation (39% vs 60%, P < .001) and ACE inhibitors (50% vs 72%, P = .111). NH residents had lower odds for LVF evaluation (OR = 0.42, 95% CI = 0.27,0.64). The odds for ACE inhibitor use, although of similar magnitude, did not reach statistical significance (OR = 0.40, 95% CI = 0.12,1.28). After adjustment of patient and care characteristics, admission from a NH was significantly associated with lower LVF evaluation (adjusted OR = 0.64, 95% CI = 0.49,0.82) but not with ACE inhibitor use (adjusted OR = 0.59, 95% CI = 0.16,2.14). CONCLUSIONS: Quality of HF care received by hospitalized NH residents was lower than that received by others. Further studies are needed to determine reasons for the lack of appropriate evaluation and treatment of NH patients with HF who are admitted to hospitals. [source] Prescription Duration After Drug Copay Changes in Older People: Methodological AspectsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2002Sebastian Schneeweiss MD OBJECTIVES: Impact assessment of drug benefits policies is a growing field of research that is increasingly relevant to healthcare planning for older people. Some cost-containment policies are thought to increase noncompliance. This paper examines mechanisms that can produce spurious reductions in drug utilization measures after drug policy changes when relying on pharmacy dispensing data. Reference pricing, a copayment for expensive medications above a fixed limit, for angiotensin-converting enzyme (ACE) inhibitors in older British Columbia residents, is used as a case example. DESIGN: Time series of 36 months of individual claims data. Longitudinal data analysis, adjusting for autoregressive data. SETTING: Pharmacare, the drug benefits program covering all patients aged 65 and older in the province of British Columbia, Canada. PARTICIPANTS: All noninstitutionalized Pharmacare beneficiaries aged 65 and older who used ACE inhibitors between 1995 and 1997 (N = 119,074). INTERVENTION: The introduction of reference drug pricing for ACE inhibitors for patients aged 65 and older. MEASUREMENTS: Timing and quantity of drug use from a claims database. RESULTS: We observed a transitional sharp decline of 11%± a standard error of 3% (P = .02) in the overall utilization rate of all ACE inhibitors after the policy implementation; five months later, utilization rates had increased, but remained under the predicted prepolicy trend. Coinciding with the sharp decrease, we observed a reduction in prescription duration by 31% in patients switching to no-cost drugs. This reduction may be attributed to increased monitoring for intolerance or treatment failure in switchers, which in turn led to a spurious reduction in total drug utilization. We ruled out the extension of medication use over the prescribed duration through reduced daily doses (prescription stretching) by a quantity-adjusted analysis of prescription duration. CONCLUSION: The analysis of prescription duration after drug policy interventions may provide alternative explanations to apparent short-term reductions in drug utilization and adds important insights to time trend analyses of drug utilization data in the evaluation of drug benefit policy changes. J Am Geriatr Soc 50:521,525, 2002. [source] Implantable Cardioverter Defibrillators: Do Women Fare Worse Than Men?JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2009Gender Comparison in the INTRINSIC RV Trial Introduction: Due to limited enrollment of women in previous trials, there is a paucity of data comparing outcome and arrhythmic events in men versus women with implantable cardioverter defibrillators (ICDs). Methods and Results: We analyzed outcome of patients in the INTRINSIC RV (Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs) trial based on gender. Women comprised 19% (293/1530) of the INTRINSIC RV population. Compared with men, women were less likely to have coronary disease, ischemic cardiomyopathy, and hyperlipidemia, and were more likely to have congestive heart failure and diabetes. Women were less likely to receive beta blockers and ACE inhibitors, and more likely to receive diuretics. Over 10.8 ± 3.5 months of follow-up, unadjusted mortality was higher in women than men (6.8% vs 4.1%, P = 0.04). Heart failure hospitalizations occurred in 7.9% of women versus 5.7% of men (P = 0.13). After adjustment for baseline differences and drug therapy, there was no significant difference in mortality between men and women. Adverse events were observed more often in women. There were no gender differences in the percentage of patients receiving appropriate or inappropriate ICD shocks. Conclusions: In INTRINSIC RV, women receiving ICDs differed from men regarding baseline characteristics and drug therapy. After adjusting for baseline differences and medical therapy, there were no differences in heart failure hospitalization, survival, or ICD shock therapy during follow-up. Apparent undertreatment of heart failure and greater frequency of adverse advents in women receiving ICDs warrant further investigation. [source] Heart failure: a hemodynamic disorder complicated by maladaptive proliferative responsesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2003A. M. Katz Abstract Heart failure has traditionally been viewed as a hemodynamic syndrome characterized by fluid retention, high venous pressure, and low cardiac output. Over the past decade, however, it has become clear that because of deterioration and progressive dilatation (remodeling) of the diseased heart, this is also a rapidly fatal syndrome. The importance of prognosis came to be appreciated when clinical trials showed that therapy which initially improves such functional abnormalities, as high venous pressure and low cardiac output, often fail to improve survival, and that some drugs which improve hemodynamics worsen long-term prognosis. The latter is true for most vasodilators which, in spite of alleviating the adverse short-term consequences of high afterload, shorten survival. Notable exceptions are ACE inhibitors, whose vasodilator effects do not explain their ability to prolong survival; instead, these drugs slow both deterioration and remodeling of the failing heart. Inotropic agents, while providing immediate relief of symptoms, generally shorten long-term survival, whereas ,-blockers slow deterioration and remodeling, and reduce mortality. Aldosterone antagonists exert beneficial effects on prognosis that are not easily explained by their diuretic effects, but instead can be explained by their ability to inhibit signaling pathways that stimulate maladaptive hypertrophy, remodeling, apoptosis and other deleterious responses that cause deterioration of the failing heart. These and other findings demonstrate that heart failure is more than a hemodynamic disorder; these patients suffer from maladaptive proliferative responses that cause cardiac cell death and progressive dilatation that play a key role in determining the poor progressive in this syndrome. [source] | ||||||||||||||||||||||||||||||||||