Angiotensin Receptor Blocker Therapy Research Articles

Underuse of ACE inhibitors and angiotensin II receptor blockers among patients with diabetic nephropathy in Taiwan

National guidelines recommend angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) therapy for diabetic patients with hypertension and/or proteinuria to hinder renal disease progression. However, little is known about the adequacy of adherence to these guidelines in diabetic patients and about the predictors of such appropriate ACEIs or ARBs use. We sought to define the rates of ACEIs and ARBs use in a large population of patients with diabetic nephropathy (DN). Using linked medical claims from the National Health Insurance Research Database, we studied a cohort of patients with DN. We used multivariate logistic regression to measure the predictors of usage of the agents studied. Of the 7159 DN patients studied, 5564 patients (77.7%) had hypertension. Of these, only 50.6% were administered ACEIs or ARBs during the quarter studied. In multivariate analyses, greater rates for usage of ACEIs or ARBs were found in patients with coronary artery disease or congestive heart failure. Only 50% of the patients with DN received the recommended treatment with ACEIs or ARBs. This shortfall provides an opportunity for quality-improvement interventions that could provide beneficial clinical outcomes for these high-risk patients.

Left Ventricular Dysfunction in Patients Receiving Cardiotoxic Cancer Therapies: Are Clinicians Responding Optimally?

The purpose of this study was to examine treatment practices for cancer therapy-associated decreased left ventricular ejection fraction (LVEF) detected on echocardiography and whether management was consistent with American College of Cardiology/American Heart Association guidelines. Patients treated with anthracyclines or trastuzumab are at risk of cardiotoxicity. Decreased LVEF represents a Class I indication for drug intervention according to American College of Cardiology/American Heart Association guidelines. Patients receiving anthracycline or trastuzumab at Stanford University from October 2005 to October 2007 and who had undergone echocardiography before and after receiving an anthracycline or trastuzumab were identified. Chart review examined chemotherapy regimens, cardiac risk factors, imaging results, concomitant medications, and cardiology consultations. Eighty-eight patients received therapy with an anthracycline or trastuzumab and had a pre-treatment and follow-up echocardiogram. Ninety-two percent were treated with anthracyclines, 17% with trastuzumab after an anthracycline, and 8% with trastuzumab without previous treatment with anthracycline. Mean baseline LVEF was 60%, with 14% having a baseline <55%. Forty percent had decreased LVEF (<55%) after anthracycline and/or trastuzumab treatment. Of these patients, 40% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 51% beta-blocker therapy, and 54% cardiology consultation. Of patients with asymptomatic decreased LVEF, 31% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 35% beta-blocker therapy, and 42% cardiology consultation. Of those with symptomatic decreased LVEF, 67% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 100% beta-blocker therapy, and 89% cardiology consultation. Many cancer survivors are not receiving treatment consistent with heart failure guidelines. There is substantial opportunity for collaboration between oncologists and cardiologists to improve the care of oncology patients receiving cardiotoxic therapy.

Angiotensin receptor blocker/diuretic combination preserves insulin responses in obese hypertensives.

Thiazide diuretics can impair glucose metabolism and increase new-onset diabetes. Adding an angiotensin receptor blocker to diuretics may protect against these metabolic effects; however, the mechanism of this protection is unclear. To explore potential mechanisms, a 16-week multicenter trial was conducted to ascertain the relative glucose metabolism effects of combined hydrochlorothiazide and angiotensin receptor blocker (valsartan) therapy compared with hydrochlorothiazide and calcium channel blocker (amlodipine) treatment in 412 centrally obese hypertensive individuals (BMI = 35 +/- 7 kg/m, seated BP = 159 +/- 8/94 +/- 8 mmHg, and mean age 56 years). Individuals were randomized to valsartan/hydrochlorothiazide, with force-titration to 320/25 mg or hydrochlorothiazide, with titration to hydrochlorothiazide 25 mg and amlodipine 10 mg, respectively. Changes from baseline to week 16 in fasting and 2-h postprandial glucose and insulin levels after an oral glucose load were measured. At week 16, clinic blood pressure reductions were similar (P > 0.05) in both groups. Fasting and 2-h glucose levels increased (P < 0.05) with the amlodipine combination but not with the valsartan combination. In concert with these glucose responses, postprandial insulin increases from baseline were substantially greater with valsartan than with amlodipine plus hydrochlorothiazide group (P = 0.001). The glucose responses were inversely related to insulin responses at the study conclusion. The novel observation of this investigation was that the combination of valsartan and hydrochlorothiazide was associated with greater glucose-stimulated insulin secretory and lesser glycemic excursion responses than the amlodipine combination group. Thus, this data suggests that adding an angiotensin receptor blocker attenuates the negative effects of thiazides on pancreatic beta-cell glucose-induced insulin secretion.

Angiotensin Receptor Blockers for Management of Hypertension

The renin-angiotensin-aldosterone system (RAAS) plays a major role in blood pressure regulation and is thus an important therapeutic target in the management of hypertension. Angiotensin receptor blockers (ARBs), which interrupt RAAS overactivity by blocking a specific receptor that mediates the pathogenic activity of angiotensin II, represent a major addition to the clinician's armamentarium for the management of hypertension. A solid body of clinical evidence demonstrates that ARBs are effective in the management of hypertension as monotherapy or in combination with other agents. Although comparable to angiotensin-converting enzyme inhibitors and other major classes of antihypertensive agents in the treatment of hypertension, the favorable tolerability profile of ARBs make them an attractive alternative for many patients. Recent evidence suggests that treatment persistence with ARB therapy during a 12-month period is typically higher than with other antihypertensive classes, a finding perhaps driven by fewer treatment-limiting side effects. The combination of clinical efficacy and tolerability should render ARBs as a major treatment alternative for hypertension.

Keratinocyte cancer prevention with ACE inhibitors, angiotensin receptor blockers or their combination in renal transplant recipients

Skin cancer (SC) is the most frequent malignancy after renal transplantation (RT), especially squamous and basal cell carcinoma. The observation that angiotensin II is a potent angiogenic and growth factor raises the possibility that blocking its effects could reduce the incidence of skin cancer. To evaluate the incidence of keratinocyte cancer in RT recipients, the timing of occurrence of the skin events after RT; to compare the incidence of SC in our RT recipients and in RT patients on angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers therapy (ARBs) and their combination. Risk factors were also evaluated. During follow up, 52 of 565 patients (9.2%), 38 males 14 females, developed SC at a median time of 59 months (range 29 - 74) after RT. 12 of 52 patients (23%) with SC were on ACEi, ARBs therapy or their combination. The incidence was significantly lower in user patients compared to non user (5.6% and 11.4% respectively). BCC was the most frequent type of keratinocyte cancer in non users and in users. No association with incidence of BCC or SCC was observed for other classes of antihypertensive drugs (calcium antagonists, beta-blockers, alpha-blockers). This study confirms that RT patients are at high risk of SC. The use of ACEi or ARBs is associated with an approximately two-fold reduced risk of Keratinocyte cancers compared to non users in RT recipients. We did not observe an association between the incidence of SC and the use of other classes of antihypertensive drugs. Any chemoprotective effect of these agents may reflect inhibition of the growth factor activity of angiotensin II. Use of ACEi or ARBs, when this is possible, should be considered in RT patients with multiple risk factors.

Outpatient Cardiology Practices With Advanced Practice Nurses and Physician Assistants Provide Similar Delivery of Recommended Therapies (Findings from IMPROVE HF)

National guidelines recommend a team model of care to facilitate adherence to evidence-based practices; however, previous studies suggesting benefit may have limited generalizability. The aim of this study was to examine the influence of advanced practice nurse (APN) and physician assistant (PA) staffing on the delivery of guideline-recommended therapies for outpatients with heart failure (HF). The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF), a prospective cohort study, enrolled 167 cardiology practices to characterize outpatient management of 15,381 patients with chronic HF and left ventricular ejection fractions < or =35%. Adherence to guideline-recommended HF therapies was recorded, and the presence of APN and PA staffing was assessed by survey. Multivariate models identified contributions to the delivery of guideline-recommended HF therapies. Of cardiology outpatient practices, 66.0% had APNs and PAs. Practices with 0, >0 to <2, and > or =2.0 APN and PA staffing had similar adherence to the 7 guideline-recommended HF therapies. After adjustment, staffing with > or =2 APNs or PAs was associated with greater conformity with 2 of 7 measures (implantable cardioverter-defibrillator therapy and delivery of HF education, p < or =0.01 for both) and similar conformity to angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, beta-blocker therapy, aldosterone antagonist therapy, anticoagulation for atrial fibrillation, and cardiac resynchronization therapy. In conclusion, staffing with APNs and PAs varied in cardiology outpatient practices. Compared to no APNs or PAs, > or =2.0 APNs or PAs per cardiology practice was associated with the greater use of implantable cardioverter-defibrillator therapy and delivery of HF education and equivalent use of drug and cardiac resynchronization therapies.

Therapeutic advantage of angiotensin-converting enzyme inhibitors in patients with proteinuric chronic kidney disease

Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) is recommended for the treatment of hypertension in patients with chronic kidney disease (CKD). The relation of ACEI to renal prognosis was investigated in CKD patients in a retrospective cohort study. The objectives were patients with nondiabetic CKD of stage 4 or below receiving monotherapy with calcium channel blocker (CCB), ACEI, or ARB, and combination therapy. For the endpoint of progression to CKD stage 5, Cox's proportional hazards analysis was conducted with explanatory variables of age, sex, baseline estimated GFR (eGFR), and proteinuria (UP) at the start of the observation period, and final blood pressure (BP) and UP at completion of the observation period. Analyzed patients comprised 131 males and 117 females, with mean age of 47.8 years. Patients were observed for 44.2 months, and the parameters of final SBP, DBP, eGFR, and UP were 127.6 +/- 6.9 mmHg, 77.8 +/- 5.8 mmHg, 38.1 +/- 10.6 ml/min/1.73 m(2), and 1.08 +/- 0.57 g/gCr, respectively, where 42 patients progressed to CKD stage 5. Drugs of CCB, ACEI, and ARB types were administered to 93, 85, and 127 patients, respectively. In the multivariate analysis, extracted common prognostic factors included the baseline eGFR and final UP, the odds ratio of which was 0.876 (every increase by 1 ml/min of eGFR) and 2.229 (every increase by 1 g of UP), respectively. Among drugs in use, ACEI was an independent prognostic factor, whose odds ratio was 0.147. The present study suggests that ACEI is a prognostic factor independent of hypotensive action and UP in CKD patients.

Systolic Heart Failure

To the Editor: In the Clinical Practice article on systolic heart failure, McMurray (Jan. 21 issue)1 proposes that in patients with persistent symptoms, angiotensin-receptor blockers (ARBs) should be added to the optimal dose of an angiotensinconverting–enzyme (ACE) inhibitor and a betablocker. Two meta-analyses2,3 of patients with left ventricular dysfunction showed that this combination was associated with marked increases in adverse events (including symptomatic hypotension with or without syncope, worsening renal function, and severe or life-threatening hyperkalemia), leading to higher rates of discontinuation of combination therapy, as compared with ACE-inhibitor therapy alone. Despite a decrease in the rate of hospitalization and a reduction in symptoms of heart failure, the combined ACEinhibitor–ARB therapy has no positive effects on overall mortality, and the unacceptable adverse events associated with it limit the application of this strategy.

Application of Direct Renin Inhibition to Chronic Kidney Disease

PurposeChronic kidney disease has serious implications with a high risk for progressive loss of renal function, increased cardiovascular events as well as a substantial financial burden. The renin-angiotensin-aldosterone system (RAAS) is activated in chronic kidney disease, especially in diabetes and hypertension, which are the leading causes of chronic kidney disease. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease the rate of progression of diabetic and non-diabetic nephropathy and are recommended therapy for chronic kidney disease.MethodsKey clinical trials supporting the use of ACE inhibitors and ARBs in chronic kidney disease are discussed. Recent developments in our understanding of RAAS biology and the use of direct renin inhibition are reviewed in the context of their potential impact on the prevention and management of chronic kidney disease.ResultsDespite the clinical success of ACE inhibitors and ARBs the rates of mortality and progression to renal failure remain high in these patient populations. ACE inhibitor or ARB monotherapy, in doses commonly used in clinical practice does not result in complete suppression of the RAAS. Aliskiren, a direct renin inhibitor, offers a novel approach to inhibit the RAAS in chronic kidney disease.ConclusionsHigh dose ARB therapy or combination therapies with ACE inhibitors and ARBs have shown beneficial effects on surrogate markers of chronic kidney disease. Early data based on urinary protein excretion rates as a surrogate marker for renal function suggest a possibly novel role for aliskiren alone or in combination with ARBs in chronic kidney disease.

Cardiovascular Effects of Angiotensin Converting Enzyme Inhibition or Angiotensin Receptor Blockade in Hemodialysis

Cardiovascular (CV) disease causes significant morbidity and mortality among the hemodialysis (HD) population. This meta-analysis was performed to determine whether angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) reduce fatal and nonfatal CV events and left ventricular (LV) mass in patients receiving HD. Studies were identified by searching electronic databases, bibliographies, and conference proceedings. Two reviewers independently selected randomized controlled trials using ACEIs or ARBs compared with control among patients receiving HD. Studies were independently assessed for inclusion, quality, and data extraction. Random-effects models were used to estimate the pooled relative risk (RR) for CV outcomes and the weighted mean difference (WMD) for pooled change-from-baseline comparisons for LV mass for ACEI or ARB treated patients compared with control. Compared with control, the RR of CV events associated with ACEI or ARB use was 0.66 [95% confidence interval (CI) 0.35 to 1.25; P = 0.20]. ACEI or ARB use resulted in a statistically significant reduction in LV mass, with a WMD of 15.4 g/m(2) (95% CI 7.4 to 23.3; P < 0.001). Treatment with an ACEI or ARB reduced LV mass in patients receiving HD. However, their use was not associated with a statistically significant reduction in the risk of fatal and nonfatal CV events. Larger, high-quality trials in the HD population are required to determine if the effects of ACEI or ARB therapy on LV mass translate into decreased CV morbidity and mortality.

Cough in Pediatric Patients Receiving Angiotensin-Converting Enzyme Inhibitor Therapy or Angiotensin Receptor Blocker Therapy in Randomized Controlled Trials

The incidence of cough in children receiving antihypertension therapy with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) is unknown. We analyzed patient-level data from eight randomized trials for the treatment of pediatric hypertension, six of them involving ACEis and two involving ARBs. The incidence of cough in children receiving ACEis (reported cough, 3.2%) was similar to that in children receiving ARBs (reported cough, 1.8%) (P = 0.34). Reports of cough were lower in children than in adults.

Relationship of blood pressure to retinal vessel diameter in type 1 diabetes mellitus.

To examine the relationship of blood pressure (BP) and use of angiotensin-receptor blocker or angiotensin-converting enzyme inhibitor to retinal vessel diameter in normotensive, normoalbuminuric persons with type 1 diabetes mellitus. In a randomized, controlled clinical trial, clinic and 24-hour ambulatory BPs were measured in persons with type 1 diabetes mellitus and gradable fundus photographs both at baseline (n = 147) and at 5-year follow-up (n = 124). Retinal arteriole and venule diameters were measured by a computer-assisted technique. Individual arteriole and venule measurements were combined into summary indexes that reflect the average retinal arteriole (central retinal arteriole equivalent [CRAE]) and venule (central retinal venule equivalent [CRVE]) diameter of an eye, respectively. While controlling for age, study site, glycosylated hemoglobin level, and ambulatory pulse rate, the daytime ambulatory systolic (-0.29-microm effect per 1 mm Hg; P = .02), daytime ambulatory diastolic (-0.44-microm effect per 1 mm Hg; P = .04), nighttime ambulatory systolic (-0.27-microm effect per 1 mm Hg; P = .03), and 24-hour ambulatory systolic (-0.31-microm effect per 1 mm Hg; P = .03) BPs were cross-sectionally associated with a smaller CRAE. While controlling for age, study site, glycosylated hemoglobin level, ambulatory pulse rate, and baseline CRAE, no BP measure was associated with a change in CRAE or CRVE during 5 years of follow-up. Treatment with losartan potassium or enalapril maleate was not associated with a statistically significant change in CRAE or CRVE. Angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker therapy does not affect retinal arteriole or venule diameter in normotensive persons with type 1 diabetes mellitus. Trial Registration clinicaltrials.gov Identifier: NCT00143949.

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers for the Prevention of Migraines

To evaluate the literature examining the efficacy of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for migraine prophylaxis. MEDLINE (1966-October 2009) and International Pharmaceutical Abstracts were searched using the terms migraine, headache, renin-angiotensin system, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, aldosterone antagonist, and the individual agents in these classes. English-language human clinical trials, case reports, and systematic reviews were evaluated for efficacy and safety data. The references of reviewed articles were examined to identify additional sources. Preventative trials evaluating ACE inhibitors consist of a case series, 2 open-label trials, and a placebo-controlled trial. Lisinopril reduced headache hours 20%, headache days 17%, and migraine days 21% versus placebo in the controlled trial (p < 0.05). Clinically significant (>50%) reductions in migraine measures were more common (52-66%) in open-label ACE inhibitor trials than in the controlled (32-36%) trial. Preventive trials evaluating ARBs consist of a meta-analysis, an open-label trial, and 2 placebo-controlled trials. Candesartan reduced headache hours 31%, headache days 26%, and migraine days 28% versus placebo in the first controlled trial (p < or = 0.001). Telmisartan did not reduce any prespecified primary or secondary outcome measures in the second controlled trial. Clinically significant reductions (>50%) in migraine measures were more common (54-88%) in open-label ARB trials than in the controlled (26-38%) trials. A prescription database review found that ACE inhibitor or ARB therapy halved the use of abortive migraine agents compared to diuretic therapy. ACE inhibitors and ARBs have migraine prophylaxis activity similar to that of some currently utilized agents. Low-dose lisinopril or candesartan may be reasonable second- or third-line agents, particularly in patients with other indications for ACE inhibitor or ARB therapy. Further controlled clinical trials are needed to delineate the role of these agents in migraine prevention.

Pleiotropic Effects of Inhibitors of the RAAS in the Diabetic Population: Above and Beyond Blood Pressure Lowering

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are indispensable therapeutic agents for treating hypertension and proteinuria in patients with diabetes mellitus. Studies have shown that the renin-angiotensin-aldosterone system (RAAS) has effects on various organ systems, including the central nervous system, heart, and kidneys. Angiotensin II has major deleterious effects on vascular compliance, vascular relaxation, and plasma markers of inflammation, which are surrogate markers of cardiovascular disease. Evidence is established from major trials that ACE inhibitors and ARB therapy improve these surrogate markers and reduce cardiovascular disease, renal disease, and stroke. Accumulating evidence also supports the newer class of medication, the direct renin inhibitor aliskiren, as beneficial in hypertensive persons with diabetes mellitus. In this article, we review the mechanisms through which inhibitors of the RAAS benefit persons with hypertension and decrease the development of cardiovascular and renal disease above and beyond blood pressure lowering.

メタアナリシス論文における評価基準の作成と分析 ～糖尿病とレニン・アンジオテンシン系阻害薬の関連～

In recent years, evidence-based medicine is practiced in medical care, and meta-analysis is positioned as the highest quality research paper. However, there are no unified criteria to evaluate meta-analysis. Thus, we developed and evaluated objective criteria of meta-analysis paper. Meta-analysis was evaluated from the standpoint of format and quality. Format score was developed based on QUOROM statement. Quality scores were evaluated in each step of meta-analysis. We evaluated meta-analysis for advantageous or adverse effect in the relationship between Renin-angiotensin system (RAS) inhibitor and diabetes mellitus. Research articles either in English or Japanese were searched in PubMed and the Cochrane Library in July 2009. Fifty-five studies were evaluated for format and quality score. Format score was 64.5+/-25.3% (Mean+/-S.D.), and quality score was 57.1+/-21.6%. After plotting each score along the X-Y coordinate, format score was correlated with quality score (R2=0.702, p<0.001). In studies with quality score of 70% or higher, RAS inhibitor prevented new-onset diabetes mellitus. Angiotensin converting enzyme (ACE) inhibitor reduced risk of myocardial infarction, however, angiotensin receptor blockers (ARB) increased the incidence in odds ratio 1.21 (95%CI: 1.04-1.40). We evaluated meta-analysis by format and quality score, and these factors showed correlation. Therefore, assessment of quality score leads to prompt and reliable evaluation of meta-analysis. According to articles evaluated by quality score, RAS inhibitor showed effectiveness on diabetes mellitus. However, careful attention must be given in ARB therapy on patients with myocardial infarction risk.

A case of losartan induced angioedema

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) target the renin-angiotensin system and are used in the management of hypertension. Both classes of drugs have similar side effects. ARBs are considered to be much better tolerated than ACE inhibitors with lesser incidence of side effects. Angioedema is a very rare side effect associated with ACE inhibitors (ACEI) and even rarer so with ARBs. The cause for angioedema in ACE inhibitors is said to be the rise in bradykinin levels. It has been postulated that angiotensin II receptor activates the bradykinin-prostaglandin-nitric oxide cascade, resulting in bradykinin-mediated side effects of ARBs such as angioedema, but the true mechanism remains largely unknown. We present here a rare case of late onset angioedema associated with losartan (an ARB) in a female patient. She had been started on an ARB as a first line treatment for uncomplicated mild to moderate hypertension. She had no prior exposure to ACE inhibitors and did not have any other significant medical history. Though rare angioedema is a serious recognized side effect of ARB therapy and the patients started on them should be warned to look for the early signs so as to take corrective action.

Effects of Angiotensin II Receptor Blockers on the Relationships Between Ambulatory Blood Pressure and Anti-Hypertensive Effects, Autonomic Function, and Health-Related Quality of Life

The aim of the present study was to examine the relationships between the anti-hypertensive effects, autonomic function, and health-related quality of life (HRQOL) following treatment of hypertensive subjects with angiotensin receptor blockers (ARBs) in hypertensives. Nineteen patients with hypertension were assigned randomly to daily treatment with ARBs. After 16 weeks of treatment, blood pressure (BP) and 24 h the ratio of low frequency to high frequency component (LF/HF), an index of sympathovagal balance were decreased by ARBs. The HRQOL scores improved during the study. In this study, ARB therapy was associated with an improvement in BP, autonomic function, and HRQOL.

Reduction of amiodarone pulmonary toxicity in patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers

Amiodarone (AM) is a widely used anti-arrhythmic medication. Its utility is, however, limited by adverse side effects. The mechanism of amiodarone-induced toxicity (APT) in the lungs is attributed primarily to stimulation of the angiotensin enzyme system leading to lung cell apoptosis and cell death. This mechanism has been demonstrated by in vitro and in vivo experimental animal studies. To date, however, no in vivo human studies have confirmed this mechanism for APT. This study was undertaken to determine whether angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) offer a protective effect against APT in humans. Demonstration of a protective effect of an ACE-I or ARB would suggest that stimulation of the angiotensin enzyme system may be a key process in APT. An 8-year retrospective analysis of all patients on AM therapy at the James H. Quillen Veterans Affairs Medical Center was undertaken. A total of 1000 patients on AM were identified. One-hundred-and-seventeen were excluded from the study. Five-hundred-and-twenty-four patients were simultaneously on an ACE-I or ARB. The remaining 359 patients were not. Pulmonary toxicity attributed to AM was identified in five and 14 patients with and without concomitant ACE-I or ARB therapy, respectively. The APT rate for the entire patient sample was 2.2%. APT occurred in 1% of patients on an ACE-I or ARB and in 3.9% of patients not taking an ACE-I or ARB. This observed difference in percentage of APT was statistically significant. The concomitant use of ACE-I or ARB in patients taking AM appears to offer a protective effect against APT. This observation suggests that the stimulation of the angiotensin enzyme system may play an important role in APT in humans.

Dual renin-angiotensin system blockade in the ONTARGET study: Clinically relevant risk for the kidney?

Inhibition of the renin-angiotensin system contributes to reductions in proteinuria and in progression of chronic kidney disease. Indeed, monotherapy with either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) has been shown to decrease proteinuria and slow the decline of chronic kidney disease, but incompletely. Therefore, there is increasing interest in whether combination strategies will provide more complete blockade of the renin-angiotensin system, which may translate into superior renoprotective and cardioprotective effects compared with either agent alone. There have been several reports on combination strategies. However, the recent report of the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) has received much of the attention. The renal outcomes in ONTARGET suggest that combined ACE inhibitor and ARB therapy contributes to a higher rate of adverse renal outcomes than monotherapy. Therefore, this review explores data from ONTARGET in relation to other available evidence on the use of combination therapies.

Effects of Angiotensin‐Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Therapy After Hospital Discharge on Subsequent Rehospitalization for Acute Myocardial Infarction and Heart Failure

American College of Cardiology/American Heart Association guidelines recommend angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy following acute myocardial infarction (MI) or development of heart failure (HF). This study estimated the effects of initiating these therapies after hospitalization for MI or HF on subsequent 1-year rehospitalization rates for MI or HF. A retrospective multivariate analysis of medical claims for 14,327 patients receiving and 7905 not receiving an ACEI or ARB after discharge for MI or HF was conducted. Rehospitalization for MI or HF was lower for treated vs untreated patients (MI: odds ratio [OR]=0.53, P<.001; HF: OR=0.52, P<.001). Rehospitalization was lower in treated patients with high medication compliance (medication possession ratio [MPR]>80%) and medium compliance (MPR 40%-79%) vs patients with low compliance (ORs for MI: high=0.54, medium=0.69; P<.001); ORs for HF: high=0.38, medium=0.62; P<.001). In conclusion, ACEI or ARB therapy initiated after hospitalization for MI or HF reduced risk of rehospitalization, and greater risk reduction was achieved with higher medication compliance.