ARB Therapy Research Articles

The President’s Page: Target Response or Target Dose

A pharmacologic issue that has not received adequate attention is the appropriate dosing of cardiovascular drugs. Clinical investigators, biostatisticians and guideline authors have so muddied the water on this problem that they have confused the medical practice community. The International Society of Cardiovascular Pharmacotherapy owes it to our colleagues to deal with this confusion head-on. Drugs such as antihypertensives and lipid-lowering agents have traditionally been dosed to achieve a target effect. In short-term clinical trials aimed at studying their blood pressure and LDL reducing properties, it has been standard practice to titrate the drugs to the desired target level of these so-called risk factors. This has been the advice promulgated in guidelines and advocated to practicing physicians. When these drugs began to be used in other conditions and in long-term outcome trials, however, target responses were not always available. In heart failure, for instance, and in patients who have sustained a recent acute myocardial infarction, the use of these drugs was not to lower an elevated blood pressure or an elevated cholesterol but rather to favorably affect morbidity and mortality. Target dosing became the standard practice, and the dose selected was based on the dosages of the drug employed in the outcome trials. We now had a paradox. Should we be using target doses or target responses? The goal of all cardiovascular therapy is to improve morbidity and mortality. Although popular surrogate markers such as blood pressure and cholesterol may correlate with the risk of morbid events and with their prevention by therapy, it has become increasingly clear in recent years that the magnitude of benefit on the surrogate does not necessarily predict the benefit on outcome. Whether dealing with antihypertensive or lipid-lowering drugs of different classes it is apparent that the measured blood pressure reduction or LDL reduction are not necessarily the sole mechanism for the favorable effect of individual drugs. In an effort to preserve the target response concept, advocates for these measures have fished in their data bases for what might be interpreted as the “optimal level” of these variables. These new levels, such as a blood pressure of 120/80 mmHg or an LDL of 76 mg/dl, have then emerged as the “target response”. Unfortunately, however, these levels did not serve in the trials as the target response but rather were the observed response in the treated patients who benefited. An alternative hypothesis, of course, is that the drug produced the benefit through multiple mechanisms and that the response of the surrogate is in part a reflection of the favorable effect on the disease process or of a particularly responsive, low-risk patient. Advocating target responses to primary care physicians is confusing. The recommended targets differ depending on the patient population, and physicians are notoriously reluctant to titrate drugs based on responses that are difficult to quantitate. Target dosing seems to be an easier recommendation. It has worked quite well in heart failure, for instance, where ACE inhibitor and ARB therapy recommendations have been based on dose. The ISCP should foster a frank discussion of target response vs. target dose. Clarification of the use of these drugs could have a salutary effect on the international practice of medicine. Cardiovasc Drugs Ther (2009) 23:337 DOI 10.1007/s10557-009-6175-6

Impact of adding a pharmacist to primary care teams on blood pressure control in people with type 2 diabetes: a randomized controlled trial (ISRCTN97121854)

| 199 control (p=0.004 for difference). Intervention group subjects were more likely to have BP therapy changes (OR 2.26; 95% CI 1.33-3.84) and more likely to initiate ACEI or ARB therapy (OR 8.21; 95% CI 1.84-36.68) compared to controls. Discussion: Addition of a pharmacist to the primary care team produced a significant reduction in BP and more antihypertensive therapy changes. The magnitude of effect was greatest in those not currently at treatment target. Our results suggest that pharmacists may play a major role in helping to optimize BP control in type 2 diabetes. Models of care delivery No conflict of interest

Cardiovascular Outcomes in High-Risk Patients without Heart Failure Treated with ARBs

Angiotensin II type 1 receptor antagonists (ARBs) are widely used as a substitute for angiotensin-converting enzyme inhibitors (ACEIs) to treat patients without heart failure, but their effect on cardiovascular morbidity and mortality has not been clearly determined. A systematic review and meta-analysis was undertaken to determine the impact of ARBs on cardiovascular outcomes in high-risk patients without heart failure. A computerized literature search was carried out using PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, and EMBASE, from January 1990 to April 2008. The following search terms were used: 'hypertension', 'clinical trial', 'sartan', 'ARB', 'angiotensin receptor antagonist', 'losartan', 'candesartan', 'valsartan', 'irbesartan', 'eprosartan', 'telmisartan', 'olmesartan', 'coronary disease', 'coronary heart disease', 'myocardial infarction', 'cardiovascular disease', 'cerebrovascular disease', and 'stroke'. Criteria for inclusion of clinical trials in our meta-analysis were the use of a randomized control group not receiving an ARB and the availability of outcome data for any one of four endpoints: myocardial infarction (MI), stroke, cardiovascular death, and all-cause death (these were not always pre-specified endpoints in all trials). Out of 45 potentially relevant studies, 37 trials met the inclusion criteria. We tabulated all occurrences of these four adverse outcomes. Homogenous subgroups were combined by means of a fixed-effects model, while heterogenous subgroups were not combined. In the subgroup without heart failure, ARBs, when compared with the control group, had an odds ratio of 1.09 (95% CI 1.00, 1.18; p = 0.05) for MI. Other endpoints, namely, cardiovascular death and all-cause death, did not reach statistical significance. There was a clear trend for fewer strokes in the ARB group, but these studies were clearly heterogenous, and therefore a pooled risk estimate was not computed. After pooling more than 89 000 patients, there is no evidence to suggest that ARBs confer cardiovascular protection akin to ACEIs, and the results that emerged are not in favor of ARB therapy in terms of its use as a substitute for ACEIs in non-heart failure patients. ARBs may have a small benefit in terms of stroke risk, but the studies are heterogenous, making it very difficult to quantify this effect. Given that ACEIs protect against both stroke and MI, caution is advised in the use of ARBs as a substitute for ACEIs in patients without a heart failure indication, who are tolerant of an ACEI.

Use of ACE inhibitors or angiotensin receptor blockers and survival in patients on peritoneal dialysis

Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve outcome in patients with renal failure not on dialysis therapy and patients on haemodialysis (HD). However, their effect on survival has not been studied in peritoneal dialysis (PD) patients. The present study examined the association between therapy with ACE inhibitor/ARB and mortality in patients undergoing chronic PD. All patients who commenced PD between 1 January 2000 and 31 December 2005 at the University Health Network were included. Patients were grouped according to whether they had been treated with ACE inhibitor/ARB. They were followed up from the date of PD initiation until death, cessation of PD, transfer to other centres or to the end of the study (31 December 2006). A total of 306 patients were included in the study. One hundred and sixty-five were treated with ACE inhibitors/ARB (treated group) and 141 were not (untreated group). The treated group patients were younger (56.9 +/- 16.6 versus 62.3 +/- 17.8 years, P < 0.01) and more likely to have a history of hypertension than the untreated group. At the initiation of PD, systolic and diastolic blood pressures were higher in the treated than the untreated group (138.8 +/- 21.8 versus 128.6 +/- 22.4 mmHg, P < 0.001; 79.8 +/- 14.1 versus 74.5 +/- 12.5 mmHg, P = 0.001) and remained significantly higher during the follow-up (133.5 +/- 16.4 versus 125.1 +/- 16.7 mmHg; 77.3 +/- 9.8 versus 73.2 +/- 9.7 mmHg, both P < 0.001). The treated group had a significantly longer survival compared to the untreated group (log rank 19.191, P < 0.001). After adjusting for age, blood pressure and other demographic and clinical parameters, multivariable Cox proportional hazards modelling showed that the use of ACE inhibitor/ARB was associated with 62% reduced risk for death (HR 0.382, 95% CI 0.232-0.631, P < 0.001). In this retrospective analysis, ACE inhibitor/ ARB therapy was associated with a dramatically reduced mortality in patients on peritoneal dialysis independent of blood pressure and other clinical and demographic variables.

Expression of human endothelin-converting enzyme isoforms: role of angiotensin IIThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

A key step in endothelin-1 (ET-1) synthesis is the proteolytic cleavage of big ET-1 by the endothelin-converting enzyme-1 (ECE-1). Four alternatively spliced isoforms, ECE-1a to ECE-1d, have been discovered; however, regulation of the expression of specific ECE-1 isoforms is not well understood. Therefore, we stimulated primary human umbilical vein endothelial cells (HUVECs) with angiotensin II (Ang II). Furthermore, expression of ECE-1 isoforms was determined in internal mammary arteries of patients undergoing coronary artery bypass grafting surgery. Patients had received one of 4 therapies: angiotensin-converting enzyme inhibitors (ACE-I), Ang II type 1 receptor blockers (ARB), HMG-CoA reductase inhibitors (statins), and a control group that had received neither ACE-I, ARB (that is, treatment not interfering in the renin-angiotensin system), nor statins. Under control conditions, ECE-1a is the dominant isoform in HUVECs (4.5+/-2.8 amol/microg RNA), followed by ECE-1c (2.7+/-1.0 amol/microg), ECE-1d (0.49+/-0.17 amol/microg), and ECE-1b (0.17+/-0.04 amol/microg). Stimulation with Ang II did not change the ECE-1 expression pattern or the ET-1 release. We found that ECE-1 mRNA expression was higher in patients treated with statins than in patients treated with ARB therapy (5.8+/-0.76 RU versus 3.0+/-0.4 RU), mainly attributed to ECE-1a. In addition, ECE-1a mRNA expression was higher in patients receiving ACE-I therapy than in patients receiving ARB therapy (1.68+/-0.27 RU versus 0.83+/-0.07 RU). We conclude that ECE-1a is the major ECE-1 isoform in primary human endothelial cells. Its expression in internal mammary arteries can be regulated by statin therapy and differs between patients with ACE-I and ARB therapy.

Pioglitazone Enhances the Antihypertensive and Renoprotective Effects of Candesartan in Zucker Obese Rats Fed a High-Protein Diet

The metabolic syndrome is a risk factor for the development of chronic kidney disease. Angiotensin II type 1 receptor blockers (ARBs) and thiazolidinediones (TZDs) provide renovascular protection, probably in the metabolic syndrome. However, the effect of both agents administered together in patients with metabolic syndrome remains to be determined. The aim of this study was to assess the effects of ARB plus TZD combination therapy in Zucker obese rats fed a high-protein diet, an animal model of metabolic syndrome and renal injury. Zucker obese rats were fed a high-protein diet (OHP; n=6), a high-protein diet containing candesartan, an ARB (OHP+C; n=6), or a high-protein diet containing both candesartan and pioglitazone (OHP+CP; n=6) for 12 weeks. Systolic blood pressure and urinary protein excretion were measured throughout the study, and renal histology and immunohistochemistry were assessed at 12 weeks. OHP rats developed hypertension (157+/-4 mmHg) and proteinuria (178+/-44 mg/d), and these conditions were significantly ameliorated by candesartan (to 143+/-3 mmHg and 84+/-25 mg/d, respectively). Pioglitazone enhanced the antihypertensive and anti-proteinuric effects of candesartan (121+/-3 mmHg, 16+/-8 mg/d, respectively). Histologically, candesartan ameliorated glomerulosclerosis, podocyte injury, interstitial fibrosis and monocyte/macrophage infiltration into the tubulointerstitium in the kidneys of OHP rats. Pioglitazone abrogated residual interstitial fibrosis in the kidneys of OHP+C rats. Our results suggested that pioglitazone augmented the antihypertensive, anti-proteinuric and possibly renal anti-fibrotic actions of candesartan in Zucker obese rats fed a high-protein diet. The combination therapy of ARB and TZD may protect against renal injury in patients with metabolic syndrome.

Comparison of practice patterns of hospitalists and community physicians in the care of patients with congestive heart failure

The objective of the present study was to compare the practice patterns of hospitalists and community physicians in the care of patients with congestive heart failure. The study was a retrospective chart review of 342 patients treated for congestive heart failure at a community-based teaching hospital. Use of established therapeutic modalities for congestive heart failure and utilization of resources by hospitalists and nonhospitalists were compared. Outcome measures were adjusted length of stay (LOS), costs per case, in-hospital mortality, acute renal failure rate, and readmission rate. The patients of hospitalist were more likely to receive ACE-I or ARB therapy within 24 hours of admission (86% vs. 72%; P = .003), intravenous diuretics (90% vs. 73%; P < .001), and social work consultation (48% vs. 29%; P < .001). They were less likely to have had serial chest radiographs (4% vs. 13%; P = .01) and multiple consultants (8% vs. 16%; P = .03). Hospitalists' patients with an illness whose severity was categorized as minor had a 40% reduction in LOS, those with a moderately severe illness had a 20% reduction, and those with an extremely severe illness had a 13% reduction (P = .002). Costs per case were reduced by $1000-$3100 across all severity categories (P < .001). Rates of acute renal failure and readmission were similar between the groups. Early use of ACE-I/ARB, aggressive approach to diuresis, greater involvement of social work services and decreased use of chest radiographs and medical consultants were identified as distinct practices of hospitalists in this medical center. These practices may have led to a shorter LOS and lower costs while preserving quality of care and possibly improving clinical outcomes.

Pathological Regression by Angiotensin II Type 1 Receptor Blockade in Patients with Mesangial Proliferative Glomerulonephritis

Although angiotensin II type 1 receptor blocker (ARB) therapy reduces proteinuria and retards the progression of renal injury in patients with glomerulonephritis, whether these drugs actually ameliorate pathological damages in human glomerulonephritis has not been determined. Fifteen patients with biopsy-proven mild-to-moderate mesangial proliferative glomerulonephritis (10 with immunoglobulin A [IgA] nephropathy and 5 with non-IgA mesangial proliferative glomerulonephritis) received ARB monotherapy. In these patients, repeated renal biopsy was performed after a mean of 28.1 months, and pathological changes (including the mesangial matrix expansion ratio and interstitial fibrosis expansion ratio) were quantitatively examined using an image analyzer. Clinical markers were also evaluated, including the serum creatinine, serum IgA, creatinine clearance (Ccr), 24-h urinary protein excretion, urinary N-acetyl-beta-D-glucosaminidase (NAG), and blood pressure. ARB therapy significantly reduced urinary protein excretion (0.68+/-0.63 to 0.20+/-0.32 g/day, p=0.016) and the blood pressure (systolic: 133.3+/-18.2 to 123.4+/-10.5 mmHg, p=0.041; diastolic: 79.4+/-11.9 to 72.0+/-8.2 mmHg, p=0.038). Although the global glomerular sclerosis ratio was unchanged (6.3+/-8.5% to 10.7+/-16.1%, p=0.33), the mesangial matrix expansion ratio (33.1+/-10.8% to 22.7+/-7.8%, p=0.001) and the interstitial fibrosis ratio (19.9+/-5.8% to 13.8+/-4.4%, p=0.034) were significantly reduced by ARB treatment. The levels of pathological improvement were similar between patients with IgA nephropathy and those with non-IgA mesangial proliferative glomerulonephritis. The results of the present study strongly suggest that ARB monotherapy can significantly reverse pathological changes, including mesangial matrix expansion and interstitial fibrosis, in human glomerulonephritis.

Nongenomic Renal Effects of Aldosterone

There is increasing evidence for a dependency on aldosterone in the development of hypertension.1 How aldosterone influences the physiology that determines blood pressure or for that matter promotes the pathophysiology of high blood pressure turns out to be less than straightforward. There is the genomic pathway that begins with the binding of aldosterone to the classical mineralocorticoid receptor (MR) and ends with sodium reabsorption at the distal nephron. But aldosterone can convey nongenomic influences as well, actions that have received less attention, possibly in part because they seem counterintuitive to our genomic view of biology. Adding to the complexity of aldosterone’s actions is the fact that there are also nonepithelial (nondistal nephron) targets of aldosterone, such as the heart, the vasculature, the kidney, and other sites. In this issue of Hypertension , Schmidt et al2 describe a rapid (thus nongenomic) effect of administered aldosterone to increase resistance in renal vasculature (a nonepithelial target) in healthy human subjects. The findings follow on the heels of a rather large body of work on the genomic actions of aldosterone. Aldosterone’s nongenomic effects were first recognized more than a decade before an aldosterone-inducible gene was identified in the late 1990s.3 A nongenomic action characteristically occurs almost immediately, usually within several minutes,4 before sufficient time has elapsed for gene …

Should we employ combination ACEI and ARB therapy in primary hypertension?

Should we employ combination ACEI and ARB therapy in primary hypertension?

Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Type 1 Receptor Antagonist Therapy Is Associated with Prolonged Patient and Graft Survival after Renal Transplantation

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) reduce cardiovascular death in the general population, but data for renal transplant recipients remain elusive. Similarly, ACEI/ARB have been shown to reduce proteinuria, but data on graft survival are lacking. Therefore a retrospective open cohort study was conducted of 2031 patients who received their first renal allograft at the Medical University of Vienna between 1990 and 2003 and survived at least 3 mo. Patient and graft survival was compared between patients with versus without ACEI and/or ARB therapy. Data were analyzed with and without propensity score models for ACEI/ARB therapy. Medication and comorbidities were analyzed as time-dependent variables in the Cox regression analyses. Ten-year survival rates were 74% in the ACEI/ARB group but only 53% in the noACEI/ARB group (P<0.001). The hazard ratio (HR) of ACEI/ARB use for mortality was 0.57 (95% confidence interval [CI] 0.40 to 0.81) compared with nonuse. Ten-year actual graft survival rate was 59% in ACEI/ARB patients but only 41% in nonusers (P=0.002). The HR of actual graft failure for ACEI/ARB recipients was 0.55 (95% CI 0.43 to 0.70) compared with nonusers; the HR of functional graft survival was 0.56 (95% CI 0.40 to 0.78). Ten-year unadjusted functional graft survival rates were 76% among ACEI/ARB patients and 71% in noACEI/ARB recipients (P=0.57). In summary, the use of ACEI/ARB therapy was associated with longer patient and graft survival after renal transplantation. More frequent use of these medications may reduce the high incidence of death and renal allograft failure in these patients.

Long-term safety of high dose ARB therapy: Effects on renal function

In conclusion, high dose ARB therapy in patients with hypertension and renal disease is not associated with any long term negative effects on serum creatinine or potassium and is thus a safe therapeutic approach to further reduce proteinuria.

Nifedipine Enhances the Cardioprotective Effect of an Angiotensin-II Receptor Blocker in an Experimental Animal Model of Heart Failure

This study was designed to examine the hypothesis that a calcium channel blocker nifedipine (CCB) could enhance the cardioprotective effect of an angiotensin-ll receptor blocker candesartan (ARB) in the treatment for heart failure. Isoproterenol (ISP) was injected into male rats at 300 mg/kg to produce progressive heart failure. Three months later, the rats were divided into 4 groups and treated for 4 weeks with 1) vehicle (n = 20), 2) ARB at 0.2 mg/kg/day (n = 6), 3) CCB at 10 mg/kg/day (n = 6), or 4) both drugs (n = 8). Rats injected with saline served as controls (n = 13). ISP caused severe myocardial degeneration and decreased the capillary density (D(cap)) of the left ventricular (LV) myocardium (mean +/- SD: 2,197 +/- 627 vs. 2,847 +/- 298 N/mm2 for normal controls), while increasing plasma thiobarbituric acid-reactive substances (TBARS; 3.6 +/- 1.1 vs. 1.9 +/- 0.5 nmol/ml). Although ARB therapy preserved cardiac morphology, it had little effect on D(cap) or oxidative stress. On the other hand, CCB decreased plasma TBARS and 4-hydroxy-2-nonenal protein expression in LV myocardium. Furthermore, the combination of CCB and ARB increased D(cap) and preserved the ultrastructure of LV myocardium, so this combination may be a useful option for the treatment of heart failure.

Examining chronic kidney disease management in a single center

The management of patients with chronic kidney disease in outpatient clinics was assessed for the ability to achieve targets of care advocated in clinical practice guidelines. 272 records of outpatients with increased serum creatinine (> or = 1.5 mg/dl for women, > or = 2.0 mg/dl for men) were reviewed for details of their assessment and management. Prevailing data on blood pressure, anemia, bone disease and lipid status as well as therapeutic changes were evaluated. The subjects were aged 64 +/- 18 years, serum creatinine 2.6 +/- 1.1 mg/dl, and calculated GFR (MDRD formula) 19.2 +/- 9.9 ml/min. Median UproV was 1.0 (0.024 - 12.4) g/day. Causes of CKD were diabetes (33.5%), HTN (8.8%), GN (19.5%), and adult PKD (3.3%). Treatment targets were BP < 130/85 mmHg, Hct > or = 36%, serum Ca++ > or = 8.5 mg/dl, serum Po4 < 4.5 mg/dl and cholesterol < 200 mg/dl. Of the patients with abnormal findings, mean values for SBP were 153 +/- 17 mmHg, DBP 93 +/- 6 mmHg, Hct 31.7 +/- 2.9%, Ca++ 8.0 +/- 0.7 mg/dl, PO4 5.6 +/- 1.0 mg/dl, and cholesterol 236 +/- 37 mg/dl. Only a minority of patients with abnormal values had their treatment altered. Furthermore, only 54% of patients with hypertension were treated with either ACEi or ARB therapy. Finally, only 6% of patients with hypercholesterolemia had fasting lipid levels measured. This data suggests that treatment of patients with CKD has improved, but that many opportunities exist to optimize their care.

A newly developed angiotensin II type 1 receptor antagonist, CS866, promotes regression of cardiac hypertrophy by reducing integrin beta1 expression.

Previous studies have demonstrated that integrins link the extracellular matrix to the hypertrophic response pathway of cardiac myocytes in vitro. To examine the direct relation between integrin beta1 and cardiac hypertrophy in vivo, we studied the effects of a newly developed angiotensin II type 1 (AT1) blocker, CS866 (ARB; 10 mg/kg/day), an angiotensin-converting enzyme inhibitor, temocapril (ACEI, 10 mg/kg/day), or both on modulation of integrin beta1 in the hypertrophied hearts of stroke-prone spontaneously hypertensive rats (SHRSP) 6 to 12 weeks of age. Treatments with ARB, ACEI, and combination therapy significantly reduced systolic blood pressure. However, the reduction in cardiac hypertrophy was greater in SHRSP treated with ARB or combination therapy than in those treated with ACEI. Multiplex reverse transcription-polymerase chain reaction revealed significantly higher mRNA expression of atrial natriuretic factor, AT1 receptor, and integrin beta1 in untreated SHRSP than in normotensive Wistar-Kyoto rats (WKY). The mRNA levels of ANP, AT1 receptor, and integrin B1 in SHRSP were significantly decreased by treatment with ARB, ACEI, or combination therapy. Decreased mRNA expression of ANP, AT1 receptor, and integrin beta1 in the treated SHRSP was associated with reductions in blood pressure; ARB and combination therapy produced greater decreases in expression than did ACEI. These observations suggest that CS866 has a beneficial effect on myocyte hypertrophy and that down-regulation of AT1 receptor and suppression of integrin beta1 participate in the regression of pressure-induced cardiac hypertrophy in vivo. The correlation between the expression of integrin beta1 and AT1 receptor was significant. Our results also suggest that integrin expression by myocytes might be modulated by angiotensin II via AT1 receptor.

Effects of imidapril and TA-606 on rat dilated cardiomyopathy after myocarditis.

For the management of chronic heart failure, both angiotensin converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) are useful, however, the differences between the two groups of agents are unclear. We compared the effects of long-term treatment with an ACEI (imidapril) and an ARB (TA-606) in rats that had recovered from experimental autoimmune myocarditis (EAM). Forty-two Lewis rats were immunized with porcine cardiac myosin on day 0 and divided into 6 groups, group C (distilled water), group IL (imidapril 0.5 mg/kg/day), group IH (imidapril 2 mg/kg/day), group TL (TA-606 2 mg/kg/day), group TH (TA-606 6 mg/kg/day), and group IT (imidapril 0.5 mg/kg/day + TA-606 2 mg/kg/day). Drugs were administered from day 28. Hemodynamic parameters, heart weight/body weight ratio (HW/BW), and area of fibrosis were measured on days 70-74. Only the high dose of imidapril significantly decreased central venous pressure and significantly increased maximum dP/dt and the absolute value of minimum dP/dt. HW/BW was suppressed in groups IH, TH, and IT. Thus, in treatment of chronic heart failure in rats, a sufficient dose of ACEI was needed to improve hemodynamics and to prevent ventricular hypertrophy. The hemodynamic effects of ARB and combination therapy of both drugs at low doses were not significant.

Combination ACEI and ARB therapy

Purpose of reviewThe fact that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers antagonize the renin-angiotensin system at different levels suggests that these agents, already each of confirmed clinical benefit in retarding the progression of chronic renal disease, may have

Combination ACEI and ARB therapy: additional benefit in renoprotection?

The fact that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers antagonize the renin-angiotensin system at different levels suggests that these agents, already each of confirmed clinical benefit in retarding the progression of chronic renal disease, may have additive effects that result in even greater renoprotection when used in combination. In the light of the persisting need for treatments that afford more effective renoprotection, this Special Commentary examines available experimental and clinical evidence in support of this hypothesis. Experimental studies to date have failed to distinguish clearly between the additive antihypertensive effects of combination therapy and additive intrinsic renoprotective effects. Clinical studies, albeit with relatively small patient numbers and short follow-up periods, have shown that combination therapy results in greater antihypertensive and antiproteinuric effects than monotherapy in diabetic nephropathy and non-diabetic forms of chronic renal disease. At present we recommend the addition of angiotensin receptor blocker therapy in patients with continued hypertension or proteinuria despite angiotensin-converting enzyme inhibition. Further long-term studies are required to evaluate more fully the renoprotective potential of this combination.

Analysis of Recent Papers in Hypertension

Analysis of Recent Papers in Hypertension

Analysis of Recent Papers in Hypertension

Analysis of Recent Papers in Hypertension