Class benefits of AT(1) antagonists in Type 2 diabetes with nephropathy

Diabetes mellitus has reached epidemic proportions in many countries and is the most common cause of end stage renal disease (ESRD). The angiotensin II receptor-1 (AT(1)) antagonists losartan and irbesartan have recently been evaluated as renoprotective agents in large clinical trials of patients with Type 2 diabetes and nephropathy. In the Reduction of End points in Non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist (RENAAL) study, losartan decreased the number of patients reaching the primary end point of a composite of measures of neuropathy. The relative risk reduction was approximately 15% with losartan and this was due to a reduction in both the doubling of creatinine concentration (25%) and of ESRD (28%) but not in death. In the Irbesartan Diabetic Nephropathy Trial (IDNT), the beneficial effect of irbesartan was mainly against the doubling of the baseline creatinine concentration (37% risk reduction) but there was also a 20% reduction in the onset of ESRD. Irbesartan had no effect on mortality. Beneficial effects occurred in addition to blood pressure being controlled by agents other than the AT(1) antagonists. These clinical trials suggest that there may be a class renoprotective action with AT(1) antagonists, although the mechanism is not clear. Patients with Type 2 diabetes and nephropathy should receive either an AT(1) antagonist or the angiotensin converting enzyme inhibitor ramipril to ensure renoprotection.     

Class benefits of AT1 antagonists in Type 2 diabetes with nephropathy

Diabetes mellitus has reached epidemic proportions in many countries and is the most common cause of end stage renal disease (ESRD). The angiotensin II receptor-1 (AT₁) antagonists losartan and irbesartan have recently been evaluated as renoprotective agents in large clinical trials of patients with Type 2 diabetes and nephropathy. In the Reduction of End points in Non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist (RENAAL) study, losartan decreased the number of patients reaching the primary end point of a composite of measures of neuropathy. The relative risk reduction was ~ 15% with losartan and this was due to a reduction in both the doubling of creatinine concentration (25%) and of ESRD (28%) but not in death. In the Irbesartan Diabetic Nephropathy Trial (IDNT), the beneficial effect of irbesartan was mainly against the doubling of the baseline creatinine concentration (37% risk reduction) but there was also a 20% reduction in the onset of ESRD. Irbesartan had no effect on mortality. Beneficial effects occurred in addition to blood pressure being controlled by agents other than the AT₁ antagonists. These clinical trials suggest that there may be a class renoprotective action with AT₁ antagonists, although the mechanism is not clear. Patients with Type 2 diabetes and nephropathy should receive either an AT₁ antagonist or the angiotensin converting enzyme inhibitor ramipril to ensure renoprotection.     

A French cost-consequence analysis of the renoprotective benefits of irbesartan in patients with type 2 diabetes and hypertension

ABSTRACT

Objectives: We performed a cost-consequence analysis in a French setting of the renoprotective benefit of irbesartan in hypertensive type 2 diabetes patients over a 25-year period.

Research design and methods: A previously published Markov model simulated progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, end-stage renal disease and death. Three treatment strategies with analogous blood pressure control were compared: (A) control – conventionally medicated antihypertensive therapy (excluding angiotensin converting enzyme inhibitors, other angiotensin-2-receptor antagonists and dihydropyridine calcium channel blockers) initiated at microalbuminuria; (B) early irbesartan – (300?mg daily added to control, initiated with microalbuminuria) and (C) late irbesartan – (300?mg daily, initiated with overt nephropathy). Probabilities came from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial and other sources. Clinical and economic outcomes were projected over 25 years. Annual discount rates were 3%.

Results: Compared to control, early use of irbesartan added (mean ± standard deviation) 1.51 ± 0.08 undiscounted life years (discounted: 0.94 ± 0.05 years), while late irbesartan added 0.07 ± 0.01 (0.04 ± 0.01) years/patient. Early irbesartan added 1.03 ± 0.06 discounted quality-adjusted life years (QALYs), while late irbesartan added 0.06 ± 0.01 QALYs. Early and late irbesartan treatments were projected to save €22?314 ± 1273 and €6619 ± 820/patient, respectively versus control. Sensitivity analysis showed that even over short time horizons both irbesartan treatments were superior to the control group.

Conclusions: In France, early irbesartan treatment improved quality and length of life and reduced costs in hypertensive patients with type 2 diabetes and microalbuminuria. Late irbesartan therapy is beneficial, but earlier irbesartan leads to better outcomes.     

Pharmacology of irbesartan

Despite the introduction of new antihypertensive agents such as angiotensin-converting enzyme inhibitors and calcium channel antagonists, the blood pressure of fewer than 30% of hypertensive patients is controlled with current therapies; compliance and continuation with medication are poor. The renin-angiotensin system is important in the pathophysiology of hypertension, end-organ damage and congestive cardiac failure. Irbesartan is an angiotensin II receptor antagonist that provides dose-dependent, specific, insurmountable blockade of the AT1 receptor both in vivo and in vitro. It is rapidly absorbed after oral administration, has a bioavailability of 60-80% with no food effect, does not require metabolism to a bioactive compound, and is excreted by both biliary and renal routes so that dosage adjustments are unnecessary in patients with renal or hepatic disease. Irbesartan produces dose-dependent blood pressure reductions, with 24 h activity confirmed by ambulatory blood pressure monitoring. Irbesartan is effective in the elderly and non-elderly, men and women and in cases of mild and severe hypertension. The recommended starting dosage is 150 mg once daily (o.d.), which can be increased to 300 mg. Its antihypertensive effect is accentuated by diuretic co-administration. In controlled clinical trials, irbesartan was at least as effective as atenolol, hydrochlorothiazide, amlodipine and enalapril. In a double-blind study, irbesartan 300 mg was more effective than losartan 100 mg, and in a dose-titration study, irbesartan 150-300 mg produced significantly greater blood pressure reductions than losartan 50-100 mg. In pooled data from nine placebo-controlled studies, adverse event and discontinuation rates for irbesartan were similar to those for placebo, and there was no relationship between dose and adverse effects. Preliminary clinical data suggest positive haemodynamic effects in heart failure and renoprotective effects in diabetic nephropathy.     

Irbesartan: a review of its use in hypertension and diabetic nephropathy

Irbesartan (Aprovel, Avapro, Irbetan, Karvea), an angiotensin II receptor type 1 antagonist, is approved in many countries worldwide for the treatment of hypertension. It is also approved in some regions for the treatment of nephropathy in patients with hypertension and type 2 diabetes mellitus. In adults with essential hypertension, irbesartan is effective at reducing blood pressure (BP) over a 24-hour period with once-daily administration. Irbesartan also slows the progression of renal disease in hypertensive patients with type 2 diabetes, with this effect partly independent of its BP-lowering effect. In addition, irbesartan was generally well tolerated in clinical trials. Thus, irbesartan is a useful treatment option for patients with hypertension, including those with type 2 diabetes and nephropathy.     

Pharmacoeconomics of angiotensin II antagonists in type 2 diabetic patients with nephropathy: implications for decision making

Angiotensin II receptor antagonists (angiotensin II receptor blockers; ARBs) are a class of antihypertensive drugs that are generally considered comparable to ACE inhibitors in the prevention of heart and kidney failure. However, these two classes of agents do interfere in different stages of the renin-angiotensin system. In patients with type 2 diabetes mellitus, advantages for ARBs over conventional (non-ACE inhibitor) therapy on progression from micro- to macroalbuminuria and overt nephropathy and end-stage renal disease have been shown in clinical trials. In patients with type 2 diabetes and end-stage renal disease, the need for dialysis and/or transplantation results in the use of major healthcare resources. This paper reviews the available economic evidence on treatment with ARBs in type 2 diabetic patients with advanced renal disease.Within-trial analytic and Markov model economic evaluations of the RENAAL (Reduction of Endpoint in Non-insulin dependent diabetes mellitus with Angiotensin II Antagonist Losartan), IDNT (Irbesartan Diabetic Nephropathy Trial) and IRMA (IRbesartan in type 2 diabetes with MicroAlbuminuria)-2 studies suggest that treatment with ARBs in patients with type 2 diabetes with overt or incipient nephropathy confers health gains and net cost savings compared with conventional (non-ACE inhibitor) therapy. For reimbursement and reference pricing decisions, there is a need for a head-to-head comparison of an ACE inhibitor with ARBs to model all possible costs and effects of ACE inhibitors and ARBs. This will result in a proper pharmacoeconomic outcome, where both types of drugs can be compared for healthcare decisions.     

How different urinary albumin excretion rates can predict progression to nephropathy and the effect of treatment in hypertensive diabetics.

HYPOTHESIS: The efficacy of a treatment in a clinical trial depends in part on where the cut-off point is placed for the test result used to select patients for the trial, and this applies to irbesartan in the Irbesartan Microalbuminuria II (IRMA II) trial for preventing nephropathy. PATIENTS AND METHODS: Patients in the IRMA II trial were stratified into different pre-treatment albumin excretion rate (AER) ranges to compare the proportion of patients starting in these different ranges (i) that progressed to develop nephropathy within 24 months and (ii) whose AER was over 40 microg/minute at three months. RESULTS: The proportion of patients with pre-treatment AER values between 20 and 40 microg/minute progressing to develop nephropathy was 1.25% in the placebo group and 0.78% in the irbesartan group, while for pre-treatment AER values between 41 and 200 microg/minute, 24.4% and 11.2% develop nephropathy respectively in the placebo and irbesartan groups. In patients with a pre-treatment AER of 20 to 30 microg/minute, 32.5% and 13.6% respectively in the placebo and irbesartan groups had a value exceeding 40 microg/minute at three months. CONCLUSIONS: The data demonstrate that irbesartan is effective in reducing the onset of nephropathy within two years when the pre-treatment AER is above 40 microg/minute, but if the AER is below this level it progresses unusually to nephropathy within two years. Irbesartan also slows progression of AER to over 40 microg/minute for patients with pre-treatment AER values at or above 20 microg/minute and these patients should be treated.     

厄贝沙坦联合氨氯地平治疗老年高血压伴2型糖尿病的疗效

目的探讨厄贝沙坦联合氨氯地平治疗老年高血压伴2型糖尿病的疗效和安全性。方法 90例高血压伴2型糖尿病的老年患者随机分成3组,每组30例：对照组A单纯口服厄贝沙坦,对照组B单纯口服氨氯地平,观察组服用厄贝沙坦联合氨氯地平,以12周为1个疗程,对比三组的总有效率以及胆固醇、甘油三酯、低密度脂蛋白的变化,同时监测心率、血常规、尿常规、肝肾功能以及服药后的不良反应。结果治疗1个疗程后,对照组A和对照组B的总有效率比较,差异无统计学意义（P〉0.05）。观察组的总有效率高于对照组A和对照组B（P〈0.05）,三组不良反应的发生率差异无统计学意义（P〉0.05）。结论厄贝沙坦联合氨氯地平对老年高血压伴2型糖尿病疗效良好,且不良反应少。     

Clinical and experimental aspects of olmesartan medoxomil, a new angiotensin II receptor antagonist

Olmesartan medoxomil is a new orally active angiotensin II (Ang II) type 1 receptor antagonist. It is a prodrug and is rapidly de-esterified during absorption to form olmesartan, the active metabolite. Olmesartan is a potent, competitive and selective Ang II type 1 receptor antagonist. Olmesartan is not metabolized by the cytochrome P-450 and has a dual route of elimination, by kidneys and liver. In patients with essential hypertension olmesartan medoxomil administered once daily at doses of 10-80 mg dose-dependently reduced diastolic blood pressure (DBP). Troughto-peak ratios for both DBP and systolic blood pressure (SBP) were above 50%. At the recommended once-daily starting doses, olmesartan medoxomil (20 mg) was more effective than losartan (50 mg), valsartan (80 mg) or irbesartan (150 mg) in reducing cuff DBP in patients with essential hypertension. The results of cuff SBP and mean 24-h DBP and SBP were similar to those of cuff DBP measurement. In mild-to-moderate hypertensive patients the recommended starting dose of olmesartan medoxomil was as effective as that of amlodipine besylate (5 mg/day) in reducing both cuff and 24-h blood pressure. In lowering DBP olmesartan medoxomil, at 10-20 mg/day, was as effective as atenolol at 50-100 mg/day. In mild-to-moderate hypertensive patients, olmesartan medoxomil, at 5-20 mg once daily, was more effective than captopril at 12.5-50 mg twice daily. At 20-40 mg once daily olmesartan medoxomil was as effective as felodipine, at 5-10 mg once daily. Olmesartan medoxomil has minimal adverse effects with no clinically important drug interactions. Animal studies have shown that olmesartan medoxomil provides a wide range of organ protection. Olmesartan medoxomil ameliorated atherosclerosis in hyperlipidemic animals and ameliorated cardiac remodeling and improved survival in rats with myocardial infarction. Olmesartan medoxomil has renoprotective effects in a remnant kidney model and type 2 diabetes models. Future investigation should reveal whether these beneficial effects of olmesartan medoxomil are applicable to human diseases.     

厄贝沙坦联合氨氯地平治疗2型糖尿病合并高血压的临床效果分析

目的探讨厄贝沙坦联合氨氯地平片治疗2型糖尿病合并高血压患者的临床疗效。方法选取本院2013年1月—2014年1月收治的2型糖尿病合并高血压患者65例,随机分为观察组和对照组,两组患者均常规降糖治疗,对照组在此基础上采用氨氯地平治疗,观察组在此基础上采用氨氯地平联合用厄贝沙坦治疗,观察两组患者治疗后舒张压（DBP）、收缩压（SBP）及降压效果。结果治疗后两组患者的SBP、DBP均降低,且观察组的SBP、DBP低于对照组,差异有统计学意义（P〈0.05）。观察组治疗总有效率为91.5%（32/35）,高于对照组的76.7%（23/30）,差异有统计学意义（P〈0.05）。两组患者治疗期间均未出现明显不良反应。结论厄贝沙坦联合氨氯地平治疗2型糖尿病合并高血压患者可取得更好的降压效果,且安全性高。     

厄贝沙坦治疗中国高血压性2型糖尿病伴有微蛋白尿症患者的成本-效果分析

目的 :预测不同治疗方案对高血压性2型糖尿病伴有微蛋白尿症患者终末期肾病累计发病率的影响 ,以供决策者参考。方法 :用一个同行评议的Markov模型来模拟从微蛋白尿症到肾病 ,双倍血清肌酐 ,终末期肾病及包含所有死因的伴有微蛋白尿的高血压性糖尿病患者的死亡率。对3种治疗方案进行比较 :(1)早期服用厄贝沙坦 (患者伴有微蛋白尿症时即治疗 ) ;(2)晚期服用厄贝沙坦 (患者已有肾病 ) ;(3)标准的高血压治疗。在1个千例患者的假设队列中预测终末期肾病成本、期望寿命和累计发病率。特异治疗的进展和死亡几率从已发表的试验报道中引证 ,包括IRMA -2(微蛋白尿症临床试验 )和IDNT(显性肾病临床试验 )。成本从国内已发表的文献中获得。计算时间跨度为25年。未来的成本和期望寿命计算时用3 %的年贴现率。结果 :与标准高血压治疗对照组比较 ,早期服用厄贝沙坦可降低终末期肾病累计发病率8 %～22 % ,节省费用30348元 (RMB)或相当于3667美元 ,每个治疗患者可延长0. 638寿命年。晚期服用厄贝沙坦次于早期服用但优于对照。盈亏平衡点发生在服用厄贝沙坦13年后。结论 :早期治疗伴有微蛋白尿症的高血压性2型糖尿病患者预测可降低终末期肾病发病率 ,减少成本 ,延长寿命。晚期治疗仍有一定的效果。     

Olmesartan medoxomil/amlodipine/hydrochlorothiazide: fixed-dose combination in hypertension

The antihypertensive agents olmesartan medoxomil, amlodipine and hydrochlorothiazide (HCTZ) are now available as a fixed-dose combination tablet (olmesartan medoxomil/amlodipine/HCTZ). In a 12-week, randomized, double-blind, multicentre trial (TRINITY) in adults with moderate to severe hypertension, olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy produced significantly greater least squares mean reductions from baseline in seated diastolic blood pressure (BP) [primary endpoint] and seated systolic BP than olmesartan medoxomil/amlodipine, olmesartan medoxomil/HCTZ or amlodipine?+?HCTZ. Furthermore, significantly more patients achieved BP goals and targets with the triple combination regimen than with any of the dual combination regimens at week 12, with olmesartan medoxomil?+?amlodipine?+?HCTZ also demonstrating benefit over the dual regimens in terms of ambulatory BP control. According to subgroup analyses of the TRINITY trial, olmesartan medoxomil?+?amlodipine?+?HCTZ was more effective in reducing BP and achieving BP goals than each of the dual therapies, irrespective of hypertension severity, age, sex, race or diabetes mellitus status. Data from a number of smaller clinical studies indicated that olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy provides antihypertensive efficacy in patients whose BP is not adequately controlled with olmesartan medoxomil?+?amlodipine. Olmesartan medoxomil?+?amlodipine?+?HCTZ was generally well tolerated in the TRINITY study, with adverse events usually being mild or moderate in severity.     

Comparison of monotherapy with irbesartan 150 mg or amlodipine 5 mg for treatment of mild-to-moderate hypertension.

OBJECTIVE. The primary objective of this study was to compare the antihypertensive efficacy of the angiotensin II receptor blocker irbesartan 150 mg and the calcium channel blocker amlodipine 5 mg in the treatment of patients with seated diastolic blood pressure (DBP) 95-110 mmHg. DESIGN. Multicentre, randomised, double-blind, comparative pilot study. METHODS. Subjects were 18-65 years of age, with DBP 95-110 mmHg, and of non-African American origin. Following a three week, single-blind, placebo lead-in period, 181 subjects were randomised in a 1:1 ratio to receive once-daily irbesartan 150 mg (n=89) or amlodipine 5 mg (n=92) for four weeks. Trough (24+/-3 hours post-dosing) BP measurements were obtained at baseline and at Weeks 2 and 4 under standardised, controlled conditions. Response was defined as DBP <90 mmHg or a reduction from baseline of 10 mmHg. RESULTS. After four weeks of treatment, the mean (+/-SE) decrease from baseline in DBP was 9.4+/-0.6 mmHg in the irbesartan group vs. 9.6+/-0.6 mmHg in the amlodipine group (p=0.806). The mean decrease from baseline in seated systolic BP was 12.2+/-1.0 mmHg in the irbesartan group vs. 12.0+/-1.0 mmHg in the amlodipine group (p=0.885). Overall, 62% of subjects in the irbesartan group and 63% in the amlodipine group had a response (p=0.609), and 54% and 56% of patients (p=0.596), respectively, had their DBP normalised (<90 mmHg). Adverse events were reported by 21.3% of patients receiving irbesartan and 20.7% receiving amlodipine. Conclusions. Irbesartan 150 mg demonstrated comparable efficacy to amlodipine 5 mg, thereby confirming its value as an antihypertensive treatment option in non-African American patients with DBP 95-110 mmHg.     

Irbesartan: an updated review of its use in cardiovascular disorders

Irbesartan interrupts the renin-angiotensin system via selective blockade of the angiotensin II subtype 1 receptor; the latter being responsible for the pressor related effects of angiotensin II. As treatment for mild to moderate hypertension, irbesartan 150 mg/day controlled diastolic BP in 56% of patients according to pooled data from several phase III studies and 77% of patients in a large phase IV study. in comparative trials, irbesartan was significantly more effective than losartan and valsartan as treatment for mild to moderate essential hypertension and as effective as enalapril or atenolol. Results from many studies show an additive antihypertensive effect when hydrochlorothiazide is added to irbesartan monotherapy. The drug also induces statistically significant regression of left ventricular mass in patients with hypertension and left ventricular hypertrophy, and preliminary evidence suggests it has beneficial haemodynamic effects in patients with heart failure. Irbesartan is very well tolerated, exhibiting an adverse event profile similar to that seen with placebo in comparative trials. In conclusion, although the role of irbesartan as a treatment for heart failure is little clearer than it was 2 years ago, the place of the drug in the management of hypertension is now better established. There is evidence to suggest the drug may have a role as initial therapy for hypertension, although formal recommendation in management guidelines will almost certainly not occur until long term morbidity and mortality benefits are established.     

Manidipine: a review of its use in hypertension.

Manidipine is a dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. The resulting reduction in blood pressure (BP) in patients with hypertension is maintained over 24 hours. Manidipine 10 to 40 mg once daily for 4 weeks significantly lowered office BP from baseline and compared with placebo, and significantly reduced 24-hour BP compared with placebo in patients with essential hypertension in a well controlled trial. The decline in BP was maintained over 24 hours (trough to peak BP ratios were >50%) without disturbing the circadian BP pattern. BP reductions with therapeutic dosages of manidipine were maintained for up to 1 year in noncomparative trials. The BP-lowering capacity of manidipine 5 to 20 mg/day appears to be similar to that of other calcium antagonists with which it has been compared in randomised double-blind and nonblind trial. In a well controlled short term trial, manidipine 10 mg daily significantly decreased trough sitting BP compared with placebo in elderly patients with mild to moderate essential hypertension. Decreases in BP were maintained for up to 3 years of treatment. The drug (10 or 20 mglday) also significantly lowered sitting BP from baseline in patients with hypertension and type 2 diabetes mellitus in randomised, long term comparative trials. In general, the observed reduction in BP with manidipine was similar to that observed with amlodipine, enalapril or delapril. The effects of manidipine on urinary albumin excretion (UAE) have not been clearly demonstrated in clinical trials in this patient group. BP was also reduced with manidipine in patients with impaired glucose tolerance. Manidipine was well tolerated in clinical trials, with most adverse effects related to vasodilation. Commonly reported events included ankle oedema, headache. palpitation. flushing, dizziness, rash and fatigue. Manidipine appears to have less potential for pedal oedema than amlodipine. CONCLUSIONS: Manidipine has shown antihypertensive efficacy and appears to be well tolerated in adult and elderly patients with mild or moderate essential hypertension. The BP-lowering effects of the drug in patients with hypertension and type 2 diabetes mellitus or impaired glucose tolerance were not associated with any adverse metabolic effects. The effects of manidipine on UAE in this patient group remain unclear. Manidipine provides an additional treatment option for patients for whom dihydropyridine calcium antagonists are appropriate. Manidipine is a dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. The resulting reduction in blood pressure (BP) in patients with hypertension is maintained over 24 hours. Manidipine 10 to 40mg once daily for 4 weeks significantly lowered office BP from baseline and compared with placebo, and significantly reduced 24-hour BP compared with placebo in patients with essential hypertension in a well controlled trial. The decline in BP was maintained over 24 hours (trough to peak BP ratios were >50%) without disturbing the circadian BP pattern. BP reductions with therapeutic dosages of manidipine were maintained for up to 1 year in non-comparative trials. The BP-lowering capacity of manidipine 5 to 20 mg/day appears to be similar to that of other calcium antagonists with which it has been compared in randomised double-blind and nonblind trial. In a well controlled short term trial, manidipine 10 mg daily significantly decreased trough sitting BP compared with placebo in elderly patients with mild to moderate essential hypertension. Decreases in BP were maintained for up to 3 years of treatment. The drug (10 or 20 mg/day) also significantly lowered sitting BP from baseline in patients with hypertension and type 2 diabetes mellitus in randomised, long term comparative trials. In general, the observed reduction in BP with manidipine was similar to that observed with amlodipine, enalapril or delapril. The effects of manidipine on urinary albumin excretion (UAE) have not been clearly demonstrated in clinical trials in this patient group. BP was also reduced with manidipine in patients with impaired glucose tolerance. Manidipine was well tolerated in clinical trials, with most adverse effects related to vasodilation. Commonly reported events included ankle oedema, headache. palpitation. flushing, dizziness, rash and fatigue. Manidipine appears to have less potential for pedal oedema than amlodipine. CONCLUSIONS: Manidipine has shown antihypertensive efficacy and appears to be well tolerated in adult and elderly patients with mild or mo     

伊贝沙坦和依那普利治疗原发性高血压疗效比较

目的 :比较伊贝沙坦与依那普利对轻中度原发性高血压的降压疗效和安全性。方法 :75例轻中度原发性高血压患者随机接受伊贝沙坦和依那普利治疗 6周。结果 :伊贝沙坦和依那普利的降压总有效率分别是 90 .0 %和 88.6 % (P >0 .0 5 )。结论 :伊贝沙坦对轻中度原发性高血压疗效较好而且安全。     

厄贝沙坦联合氨氯地平治疗高血压肾病的疗效观察

目的:观察厄贝沙坦联合氨氯地平治疗高血压肾病的临床疗效。方法:将我院诊断为高血压肾病的患者300例,随机B1:组1:。1分3组为均3治组疗:A4组周口,观服察厄治贝疗沙前坦后1530组m患g,者qd收;B缩组压口、服舒氨张氯压地、尿平素5氮mg、,血qd肌;C酐组、2采4h用尿厄蛋贝白沙定坦量联治合疗氨效氯果地。平结治果疗:,治用疗法后用3量组同患A者、收缩压、舒张压和24h尿蛋白定量均明显降低(P<0.05);与A、B组比较,C组降低更为显著(P<0.01)。3组均未见严重不良反应发生。结论:厄贝沙坦联合氨氯地平治疗高血压肾病疗效及安全性较好,可有效控制血压及降低24h尿蛋白。     

Effects of valsartan versus olmesartan addition to amlodipine/hydrochlorothiazide combination in treating stage 2 hypertensive patients

Objective: The objective of this study was to assess the effects of valsartan or olmesartan addition to dual therapy with amlodipine + hydrochlorothiazide (HCTZ) in the treatment of stage 2 hypertension.

Research design and methods: 180 patients with diastolic blood pressure (DBP) ≥ 99 and < 110 mm Hg were treated with amlodipine 5 mg + HCTZ 12.5 mg combination. After 4 weeks, 149 patients whose blood pressure (BP) was not controlled, were randomized to the combination of valsartan 160 mg + amlodipine 5 mg + HCTZ 12.5 mg or olmesartan 20 mg + amlodipine 5 mg + HCTZ 12.5 mg for 4 weeks.

Main outcome measures: At the end of each period, clinical and ambulatory BP measurements were recorded.

Results: Both triple combinations produced greater ambulatory and clinical SBP/DBP reduction than dual therapy. However, mean reduction from baseline in the valsartan + amlodipine + HCTZ-treated patients was significantly greater than in the olmesartan + amlodipine + HCTZ-treated patients. Compared with dual therapy, the add-on effect of valsartan was significantly greater than that of olmesartan, the difference being more evident for nighttime SBP/DBP values (-3.3 (95% CI 0.44 – 3.51)/3.0 (95% CI 0.59 – 3.34) mm Hg, p < 0.01).

Conclusions: The addition of valsartan to amlodipine + HCTZ produced greater BP reduction than the addition of olmesartan.     

Angiotensin II receptor blockers for the treatment of hypertension

The rising incidence of stroke, congestive heart failure (CHF) and end stage renal disease (ESRD) has signalled a need to increase awareness, treatment and control of hypertension. There continues to be a need for effective antihypertensive medications since hypertension is a major precursor to various forms of cardiovascular disease. The renin-angiotensin (AT) aldosterone system (RAAS) is a key component to the development of hypertension and can be one target of drug therapy. Angotensin II (ATII) receptor blockers (ARBs) are the most recent class of agents available to treat hypertension, which work by by inhibiting ATII at the receptor level. Currently, national consensus guidelines recommend that ARBs should be reserved for hypertensive patients who cannot tolerate angiotensin converting enzyme (ACE) inhibitors (ACEIs). ARBs, however, are moving to the forefront of therapy with a promising role in the area of renoprotection and CHF. Recent trials such as the The Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes Trial (IDNT), the Effect of Irbesartan on the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes (IRMA2), and The Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy (RENAAL) study have demonstrated the renoprotective effects of ARBs in patients with Type 2 diabetes. The Valsartan Heart Failure Trial (Val-HeFT) adds to the growing body of evidence that ARBs may improve morbidity and mortality in CHF patients. As a class, ARBs are well tolerated and have a lower incidence of cough and angioedema compared to ACEIs. This article reviews the differences among the ARBs, existing efficacy data in hypertension, and explores the role of ARBs in CHF and renal disease.     

Angiotensin II receptor blockers for the treatment of hypertension

The rising incidence of stroke, congestive heart failure (CHF) and end stage renal disease (ESRD) has signalled a need to increase awareness, treatment and control of hypertension. There continues to be a need for effective antihypertensive medications since hypertension is a major precursor to various forms of cardiovascular disease. The renin-angiotensin (AT) aldosterone system (RAAS) is a key component to the development of hypertension and can be one target of drug therapy. Angotensin II (ATII) receptor blockers (ARBs) are the most recent class of agents available to treat hypertension, which work by by inhibiting ATII at the receptor level. Currently, national consensus guidelines recommend that ARBs should be reserved for hypertensive patients who cannot tolerate angiotensin converting enzyme (ACE) inhibitors (ACEIs). ARBs, however, are moving to the forefront of therapy with a promising role in the area of renoprotection and CHF. Recent trials such as the The Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes Trial (IDNT), the Effect of Irbesartan on the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes (IRMA2), and The Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy (RENAAL) study have demonstrated the renoprotective effects of ARBs in patients with Type 2 diabetes. The Valsartan Heart Failure Trial (Val-HeFT) adds to the growing body of evidence that ARBs may improve morbidity and mortality in CHF patients. As a class, ARBs are well tolerated and have a lower incidence of cough and angioedema compared to ACEIs. This article reviews the differences among the ARBs, existing efficacy data in hypertension, and explores the role of ARBs in CHF and renal disease.