Angiotensin-converting Enzyme Inhibitors In Patients Research Articles

The CHARM Program: Study Design Leads to Findings of Clinical and Public Health Importance

In large-scale randomized trials and their meta-analyses, beta-adrenergic blockers and angiotensin-converting enzyme inhibitors provide statistically significant and clinically important additive mortality and morbidity benefits in the treatment of heart failure. The CHARM trials were designed to test whether the angiotensin-receptor blocker candesartan would provide statistically significant and clinically important additive mortality and morbidity benefits to patients with heart failure as an alternative or in addition to angiotensin-converting enzyme inhibitors. CHARM demonstrated that an angiotensin-receptor blocker at a proven dose is an effective and safe therapy as an alternative or in addition to angiotensin-converting enzyme inhibitors in patients with heart failure, 55% of whom were receiving beta-adrenergic blockers. These benefits include reductions in cardiovascular mortality rate as well as in hospitalization for heart failure. Such patients have a 50% mortality rate at 5 years, and heart failure is the leading cause of hospitalization for patients 65 years of age and older.

Blockade of renin–angiotensin system in antifibrotic therapy

Recent studies have shown that the renin-angiotensin system (RAS) plays a pivotal role in liver fibrosis. An intrahepatic RAS is expressed in chronically damaged livers, and angiotensin-II (AT-II) reportedly stimulates contraction and proliferation of the activated hepatic stellate cells (Ac-HSC), and increases the transforming growth factor-beta (TGF-beta) expression through angiotensin type-I receptors (AT1-R). Some studies have demonstrated that the clinically used angiotensin-converting enzyme (ACE) inhibitor (ACE-I), and AT1-R blockers (ARB) significantly attenuated experimental liver fibrosis along with suppression of the Ac-HSC and hepatic TGF-beta expression. Angiotensin-II also stimulates the tissue inhibitor of metalloproteinases-1 (TIMP-1) in a dose- and time-dependent manner via protein kinase-C as an intracellular signaling cascade in the Ac-HSC, and these effects are completely suppressed by ARB. Combination treatment with low-dose interferon (IFN) and ACE-I exerts a stronger inhibitory effect than either single agent on its own. In humans it has been reported that ARB markedly improved the liver fibrosis score and TGF-beta expression in patients with chronic hepatitis C and non-alcoholic steatohepatitis. Serum fibrosis markers also significantly improved by treatment with low-dose IFN and ACE-I in patients with chronic hepatitis C, refractory to IFN monotherapy. Collectively, these data suggest that the interaction between AT-II and AT1-R plays a pivotal role in liver fibrosis development. Because both ACE-I and ARB are widely used in clinical practice without serious side-effects, these drugs in combination with IFN may provide a new strategy for antifibrosis therapy.

Beneficial effects of carvedilol as a concomitant therapy to angiotensin-converting enzyme inhibitor in patients with ischemic left ventricular systolic dysfunction

Studies are scant on the effects of short-term carvedilol treatment as an adjuvant to angiotensin-converting enzyme (ACE) inhibitor in patients with left ventricular (LV) systolic dysfunction. The objective of this study was to find the effects of short-term treatment of carvedilol on patients with ischemic LV systolic dysfunction (defined as LV ejection fraction (LVEF) <or=30% on 2D echocardiography) undergoing coronary artery bypass surgery (CABG). There were 74 patients that received ACE inhibitor without any beta-blocker (control) and 67 patients that received carvedilol in addition to ACE inhibitor following CABG (carvedilol group). After 1 month of drug administration following CABG, the control group was found to have significantly greater percent improvement in LVEF (29.1% +/- 5.39%) as compared with the carvedilol group (15.3% +/- 4.89%). However, after 3 and 6 months, LVEF levels were found to be significantly greater in the carvedilol group as compared with the control group. Further, at 6 months of drug administration, LV end systolic diameter was significantly less in the carvedilol group (39.11 +/- 1.10 mm) as compared with the control group (43.49 +/- 1.39 mm). Thus, carvedilol produces beneficial effect on short-term administration in terms of LV contractility when given along with ACE inhibitor as compared with ACE inhibitor therapy alone.

Letter by Guazzi and Reina Regarding Article, “Aspirin Use and Outcomes in a Community-Based Cohort of 7352 Patients Discharged After First Hospitalization for Heart Failure”

To the Editor: We read with interest the article by McAlister and colleagues1 that appeared in a recent issue of Circulation . The article deals with the stimulating pharmacotherapeutic dilemma of an unfavorable interaction between aspirin and angiotensin-converting enzyme inhibition in patients with heart …

Evaluation of Medical Treatment for Peripheral Arterial Disease in Chinese High-Risk Patients

Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis and is associated with elevated cardiovascular morbidity and mortality. The aim of the present study was to evaluate the use of antiplatelet agents, statins and angiotensin-converting enzyme inhibitors (ACEI) in Chinese high-risk cardiovascular (CV) patients with PAD, with an emphasis on the need for aggressive medical management of all atherosclerotic manifestations. Medical records from 5,263 Chinese patients at high risk of CV were evaluated for the use of antiplatelet agents, statins and ACEI in patients with and without PAD. PAD was defined as an ankle-brachial index (ABI)<0.9 in either leg. Multivariable logistic regression analyses were performed to compare medication use in the 2 groups. A total of 5,254 patients were analyzed (52.9% male, mean age 67.3 years). The prevalence of PAD in the total patient group was 25.4%; 22.5% of them had PAD only. Overall, 5.7% had PAD only, 19.6% had PAD and coronary heart disease (CHD) or stroke or diabetes, 7.7% had CHD only, 12.6% had stroke only, and 13.6% had diabetes only. The 28.9% subjects having none of PAD, CHD, stroke or diabetes were used as the reference group. Only 65%, 37% and 47% of all patients received antiplatelet agents, statins and ACEI, respectively. Antiplatelets, statins, ACEI and all 3 medications were used less frequently in PAD only patients (58.1%, 35.9, 53.5% and 21.6%) vs CHD only (90.9%, 74.5%, 70.6% and 55.9%, p<0.001). All 3 proven efficacious therapies were prescribed for only 56% of patients with CHD only, 8% with stroke only, 13% with diabetes only and 21% with PAD only. PAD is prevalent in Chinese high-risk CV patients, equivalent to CHD, but these patients receive less intensive treatment than those with CHD. Programs to improve CV risk reduction in these high-risk patients are needed.

β2-Adrenergic receptor polymorphisms and treatment-induced regression of left ventricular hypertrophy in hypertension

Although blood pressure is considered the major determinant of left ventricular hypertrophy in hypertension, genetic variability is increasingly being considered among the factors influencing this complication. beta(2)-Adrenergic receptors (beta(2)ARs) are up-regulated in hypertension and largely polymorphic within the human population. Recently, we have shown that the Glu27 beta(2)AR variant is strongly associated with cardiac hypertrophy in hypertension. The objective of this study is to verify whether this polymorphism also affects hypertrophy regression in response to antihypertensive therapy. In a prospective follow-up study we screened 970 hypertensive patients of Caucasian descent for the Gly16Arg, Gln27Glu, and Thr164Ile beta(2)AR polymorphisms and left ventricular echocardiographic hypertrophy and assigned selected patients to enalapril or atenolol to assess left ventricular hypertrophy regression after 2-year follow-up. Results were stratified according to treatment and the Glu27Gln polymorphism of the beta(2)AR. In cells with stable overexpression of the Glu27 or Gln27 variant of beta(2)AR, we also explored the implications of this polymorphism on hypertrophy-related intracellular signal transduction. Among hypertensive patients, the Gly16 allele was found in 63% of patients and the Glu27 allele was found in 40.6%. Both polymorphisms were in linkage disequilibrium, as expected. Four hundred forty-one hypertrophic hypertensive patients completed the 2-year follow-up. At baseline, patients carrying at least 1 allele of the Glu27 variant presented with a larger cardiac size despite similar blood pressure levels (142.9 +/- 22.5 g/m(2) in Glu27 carriers versus 138.2 +/- 18.4 g/m(2) in Gln27 carriers, P < .02). Blood pressure normalization was achieved by both drugs. At follow-up, compared with the Gln27 patients, the Glu27 patients showed a larger reduction in hypertrophy when treated with enalapril (percent change in left ventricular mass, -6.3% +/- 7.7% in Glu27 carriers versus -2.18% +/- 7.9% in Gln27 carriers; P < .05) but not with atenolol therapy (-2.8% +/- 8.9% in Glu27 carriers versus -2.4% +/- 8.8% in Gln27 carriers, P = not significant). In in vitro studies the activation of p38 and extracellular signal-regulated kinase (ERK-) 1/2 (data not shown) and the activity of the atrial natriuretic factor (ANF) promoter after isoproterenol (INN, isoprenaline) stimulation were larger in Glu27 beta(2)AR overexpressing cells than in Gln27 beta(2)AR overexpressing cells (fold difference compared with unstimulated cells, 9.7 +/- 2.9 for Glu27 beta(2)AR versus 4.2 +/- 0.3 for Gln27 beta(2)AR; P < .05). The Glu27 variant of beta(2)AR enhances hypertension-induced left ventricular hypertrophy. In these patients angiotensin-converting enzyme inhibitors are more efficient than beta-blockers in reducing cardiac size.

Balanced prescribing

Balanced prescribing

Dosage adjustment of quinolone antibiotics and angiotensin-converting enzyme inhibitors in patients with renal dysfunction

The aim of this study was to verify an approach for calculating pharmacokinetic parameters suitable for adjusting dosage regimens in patients with renal dysfunction. We carried out a retrospective analysis of the pharmacokinetic profiles of 12 new quinolone antibiotics and 11 angiotensin-converting enzyme inhibitors (ACEIs) in patients with normal and impaired renal function to obtain the renal excretion ratio (R(renal)) of each drug. We demonstrated that the pharmacokinetics of each drug in a patient with renal dysfunction can be adequately estimated using the R(renaI) value of each drug together with the creatinine clearance as an index of the individual's renal function. Using the R(renaI) value obtained, we could successfully simulate pharmacokinetic profiles of the drugs in publications other than that used to obtain the R(renal) values. On the other hand, age-related changes in the pharmacokinetics of new quinolone antibiotics are not always adequately predicted using the R(renal) value compared to using creatinine clearance alone as an index, and the reasons for this are not fully understood. These results demonstrate that dosage regimens of quinolone antibiotics and ACEIs in patients with renal dysfunction can be adequately optimized using the R(renal) value for each drug using the present approach.

Effects of early angiotensin-converting enzyme inhibition in patients with non–ST-elevation acute anterior myocardial infarction

No data are available on the clinical efficacy of the early administration (<24 hours from onset of chest pain) of angiotensin-converting enzyme inhibitors in non-thrombolysed patients with non-ST-elevation myocardial infarction (NSTEMI). We have addressed this issue in a subgroup of NSTEMI patients enrolled in the SMILE trial. Of the overall population of 1556 patients, 526 (33.8%) had an anterior wall NSTEMI, defined as an ST elevation <1 mm or an ST depression in at least two contiguous precordial leads with or without new abnormal Q waves. No patient of the SMILE Study received thrombolytic therapy or was reperfused. Patients were randomized, double-blind, to zofenopril (n = 253) or placebo (n = 273) for 6 weeks. The primary end point was the effect of treatment on the 6-week combined occurrence of death and severe congestive heart failure (CHF). Secondary end points included the evaluation of the 6-week rate of severe CHF as well as the 1-year mortality rate. After 6 weeks of treatment, zofenopril significantly reduced both the incidence of the primary end point (risk reduction 65%, 95% CI 20-80, 2P = .003) and the 6-week incidence of severe CHF (84%, 95% CI 33-97, 2P = .006) in NSTEMI patients. One-year mortality was also significantly reduced by zofenopril treatment (43%, 95% CI 14-57, 2P = .036). Results of this post hoc analysis of the SMILE Study strongly suggest the benefit of the early administration of zofenopril even in patients with an anterior wall NSTEMI.

Trends and Outcomes Associated with Angiotensin-Converting Enzyme Inhibitors

Background Limited recent data are available describing the patterns of use of angiotensin converting enzyme inhibitor (ACEI) therapy in patients with acute myocardial infarction (AMI), particularly from the more generalizable population-based setting. The purpose of this study was to examine trends in the receipt of ACEIs and associated short-term outcomes in patients hospitalized with AMI in a large Northeastern community. Methods We conducted a community-wide study of 7991 patients hospitalized with AMI in all metropolitan Worcester, Massachusetts, medical centers during 8 annual periods between 1990 and 2003. Results Among all patients, 44% received ACEI therapy during their acute hospitalization. There was a marked increase in the use of ACEIs between 1990 (23%) and 2003 (68%), particularly among those who were not on ACEIs before hospitalization. Patients who were previously on ACEIs were more likely to receive this therapy during hospitalization for AMI than were patients who were not previously on this therapy. Patients treated with ACEIs were significantly less likely to die (adjusted odds ratio [OR] 0.33; 95% confidence interval [CI] 0.27-0.41) during hospitalization than were patients who did not receive this therapy, with benefits observed across all subgroups examined. Conclusions The results of this observational study demonstrate marked increases in the use of ACEIs in patients with AMI in the community setting and demonstrate the benefits to be gained from use of this therapy. Despite these encouraging trends, there remains room for more optimal use of this therapy.

Safety of Angiotensin-Converting Enzyme Inhibitors in Patients with Bilateral Renal Artery Stenosis Following Successful Renal Artery Stent Revascularization

Angiotensin-converting enzyme inhibitors (ACEIs) are contraindicated in patients with bilateral renal artery stenosis due to risk of azotemia resulting from preferential efferent arteriolar vasodilation in the renal glomerulus due to inhibition of angiotensin II. Patients with renal artery stenosis who can derive survival benefit from ACE inhibition, therefore, may not receive ACEI therapy. We evaluated the safety of ACEI therapy in patients with bilateral renal artery stenosis following successful revascularization using renal artery stenting. This study is a retrospective analysis of 25 patients who underwent bilateral renal artery stenting for refractory hypertension and had a strong clinical indication for long-term ACEI use (left ventricular dysfunction or diabetes). Eighteen of the 25 patients (72%) have been safely maintained on a target dose of ACEIs, 2 of the 25 have been treated with angiotensin receptor blockers due to cough, and 5 of the 25 are being treated with a hydralazine/nitrate combination due to cough (2 patients) or baseline renal insufficiency (3 patients). We conclude that patients with bilateral renal artery stenoses that have been successfully revascularized using renal stenting may be safely treated with long-term ACEI therapy.

Renal Function and Effectiveness of Angiotensin-Converting Enzyme Inhibitor Therapy in Patients With Chronic Stable Coronary Disease in the Prevention of Events with ACE inhibition (PEACE) Trial

Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function. We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13). Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.

Functional variants of the angiotensinogen gene determine antihypertensive responses to angiotensin-converting enzyme inhibitors in subjects of African origin

To determine whether the response to angiotensin-converting enzyme inhibitor (ACEI) monotherapy in subjects of African origin is determined by genetic variants within the angiotensinogen (AGT) gene. A total of 194 hypertensive patients of African ancestry were recruited from district clinics in Johannesburg, South Africa. Eighty patients received open-label ACEI (enalapril or lisinopril) monotherapy, and 114 open-label calcium antagonist (nifedipine) as a drug class comparator. Twenty-four hour ambulatory blood pressure (ABP) monitoring was performed at baseline (off medication) and after 2 months of therapy. DNA was analysed for functional variants (-217G-->A and -20A-->C) of the AGT gene. The impact of genotype on ABP responses to ACEI monotherapy or calcium antagonists; and on plasma aldosterone and renin levels after ACEI monotherapy was assessed. Adjusting for baseline ABP and type of ACEI in the ACEI-treated group, the -217G-->A variant predicted ABP responses to ACEI (n = 77; P < 0.01), but not to nifedipine (n = 108). ACEI in patients with the AA genotype of the -217G-->A variant failed to elicit an antihypertensive response [change in ABP, mmHg: systolic blood pressure (SBP) +0.84 +/- 2.89, P = 0.78; diastolic blood pressure (DBP) -0.47 +/- 1.74, P = 0.79]. In contrast, those patients with at least one copy of the -217G allele developed a 7.23 +/- 1.55 and 5.38 +/- 1.12 mmHg decrease (P < 0.0001) in SBP and DBP, respectively, after ACEI administration. Similarly, the -20A-->C variant predicted ABP responses to ACEI monotherapy (P < 0.01) but not to nifedipine. Moreover, patients who were AA genotype for both variants failed to develop an antihypertensive response to ACEI (change in ABP, mmHg: SBP +1.06 +/- 3.05, P = 0.73; DBP -0.39 +/- 1.83, P = 0.83); whereas patients with at least one copy of both the -217G and the -20C allele developed substantial decreases in ABP (change in ABP, mmHg: SBP -14.08 +/- 3.72, P < 0.0001; DBP -9.62 +/- 2.74, P < 0.0001). Patients with at least one copy of the -217G allele demonstrated a significant reduction in the aldosterone-to-renin ratio (-0.098 +/- 0.035, P < 0.01), whereas in those patients who were -217AA genotype the ratio was unchanged (-0.03 +/- 0.16, P = 0.85). Functional variants of the AGT gene contribute to the variability of antihypertensive responses to ACEI monotherapy in individuals of African ancestry, with genotype determining whether or not responses occur.

Immediate postoperative treatment with angiotensin-converting enzyme inhibitors in patients with preoperative reduced left-ventricle systolic function

Villacorta, J.1; Kerbaul, F.1; Collart, F.2; Bonnet, M.1; Nguyen, K.1; Gouin, F.1; Guidon, C.1 Author Information

Angiotensin-converting enzyme inhibition in patients with coronary artery disease and preserved left ventricular function: Ischemia Management with Accupril post–bypass graft via inhibition of angiotensin-converting enzyme (IMAGINE) compared with the other major trials in coronary artery disease

It has been hypothesized that angiotensin-converting enzyme (ACE) inhibition, independent from its effect on ventricular function and blood pressure, could affect the atherosclerotic process and reduce the incidence of ischemic events and its complications. Several large clinical outcome trials were designed to test this hypothesis: QUIET, HOPE, EUROPA, PEACE, and IMAGINE. The results of the PEACE study were recently reported, leaving the IMAGINE study as the last chapter in our efforts to evaluate the role of ACE inhibition in coronary artery disease with preserved left ventricular function. In this report, we compare these studies with respect to their methodology and patient population and analyze the unique nature of the last ongoing study, IMAGINE. The reported studies show that patients with coronary artery disease who are at low-to-moderate or high risk should receive an ACE inhibitor if tolerated. However, when the absolute risk of a patient decreases, and intensive contemporary management is given, with good control of risk factors, the absolute and perhaps relative benefits of an ACE inhibitor decrease and their routine use in these patients may not be warranted. The role of ACE inhibition started early post–coronary artery bypass graft in patients with preserved left ventricular function, and intensive contemporary management remains to be determined and should get answered by the IMAGINE study. Moreover, the IMAGINE population is not only a lower risk population than those enrolled in HOPE or EUROPA, but also the risk for this population is bimodal in nature (early post-revascularization inflammation and thrombosis vs long-term atherosclerosis progression) and may provide further insight into underlying mechanisms.

Angiotensin-Converting Enzyme Inhibitors in Patients With Coronary Artery Disease and Absence of Heart Failure or Left Ventricular Systolic Dysfunction

Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction. We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced. Angiotensin-converting enzyme inhibitors reduce total mortality and major cardiovascular end points in patients who have CAD and no left ventricular systolic dysfunction or heart failure.

Angiotensin-Converting Enzyme Inhibitors in Coronary Artery Disease and Preserved Left Ventricular Systolic Function: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

This study sought to assess the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in patients with coronary heart disease and preserved left ventricular (LV) function. The ACEIs have been shown to improve outcomes in patients with heart failure and myocardial infarction (MI). However, there is conflicting evidence concerning the benefits of ACEIs in patients with coronary artery disease (CAD) and preserved LV systolic function. An extensive search was performed to identify randomized, placebo-controlled trials of ACEI use in patients with CAD and preserved LV systolic function. Of 61 potentially relevant articles screened, 6 trials met the inclusion criteria. They were reviewed to determine cardiovascular mortality, nonfatal MI, all-cause mortality, and revascularization rates. We performed random-effect model meta-analyses and quantified between-studies heterogeneity with I(2). There were 16,772 patients randomized to ACEI and 16,728 patients randomized to placebo. Use of ACEIs was associated with a decrease in cardiovascular mortality (relative risk [RR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01), nonfatal MI (RR 0.84, 95% CI 0.75 to 0.94, p = 0.003), all-cause mortality (RR 0.87, 95% CI 0.81 to 0.94, p = 0.0003), and revascularization rates (RR 0.93, 95% CI 0.87 to 1.00, p = 0.04). There was no significant between-studies heterogeneity. Treatment of 100 patients for an average duration of 4.4 years prevents either of the adverse outcomes (one death, or one nonfatal myocardial infarction, or one cardiovascular death or one coronary revascularization procedure). The cumulative evidence provided by this meta-analysis shows a modest favorable effect of ACEIs on the outcome of patients with CAD and preserved LV systolic function.

Section 7: Heart Failure in Patients With Left Ventricular Systolic Dysfunction

Section 7: Heart Failure in Patients With Left Ventricular Systolic Dysfunction

Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C

To evaluate the effect of combination treatment with the interferon (IFN) and angiotensin-converting enzyme inhibitor (ACE-I) on several fibrotic indices in patients with refractory chronic hepatitis C (CHC). Perindopril (an ACE-I; 4 mg/d) and/or natural IFN (3 MU/L; 3 times a week) were administered for 12 mo to refractory CHC patients, and several indices of serum fibrosis markers were analyzed. ACE-I decreased the serum fibrosis markers, whereas single treatment with IFN did not exert these inhibitory effects. However, IFN significantly augmented the effects of ACE-I, and the combination treatment exerted the most potent inhibitory effects. The serum levels of alanine transaminase and HCV-RNA were not significantly different between the groups, whereas the plasma level of transforming growth factor-beta was significantly attenuated almost in parallel with suppression of the serum fibrosis markers. The combination therapy of an ACE-I and IFN may have a diverse effect on disease progression in patients with CHC refractory to IFN therapy through its anti-fibrotic effect.

Blockade of the renin–angiotensin–aldosterone system: a key therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes

Diabetes (particularly type 2 diabetes) represents a global health problem of epidemic proportions. Individuals with diabetes are not only more likely to develop hypertension, dyslipidemia, and obesity, but are also at a significantly higher risk for coronary heart disease, peripheral vascular disease, and stroke. Angiotensin II plays a key pathophysiological role in the progression of diabetic renal disease, and blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II antagonists has therefore become an important therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. Several studies have demonstrated the effects of angiotensin II antagonists on the reduction of albuminuria and the progression of renal disease from microalbuminuria to macroalbuminuria. More importantly, several endpoint trials have shown that the antiproteinuric effects of losartan and irbesartan translate into cardiovascular and renoprotective benefits beyond blood pressure lowering, thereby delaying the need for dialysis or kidney transplantation by several years. These and other studies indicate that angiotensin II antagonists not only improve survival and quality of life of patients with diabetic nephropathy, but also have the potential to reduce the substantial healthcare burden associated with managing these patients. ACEi also appear to exert similar beneficial effects in diabetic patients, but whether clinically significant differences in renoprotection or mortality exist between angiotensin II antagonists and ACEi in patients with type 2 diabetes remains to be fully investigated in appropriate head-to-head studies.