Lisinopril dose‐response relationship in essential hypertension.

Gómez, Héctor W.; Cirillo, VJ; Sromovsky, J. A.; Otterbein, E S; Shaw, W. R.; Rush, JE; Chrysant, SG; Ah, Gradman; Leon, AS; MacCarthy, E. Paul

doi:10.1111/j.1365-2125.1989.tb03521.x

Cited by 28 publications

(20 citation statements)

References 15 publications

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“…Previous dose titration studies with lisinopril have been conducted in (1) non-diabetic patients with essential hypertension, using BP reductions as the main outcome [2,3]; and (2) patients with non-diabetic nephropathies [9,10]. Lisinopril 40 mg was shown to lower albuminuria and BP more effectively than lisinopril 20 mg. Higher doses have only been tested in essential hypertension studies.…”

Section: Discussionmentioning

confidence: 99%

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Optimal dose of lisinopril for renoprotection in type 1 diabetic patients with diabetic nephropathy: a randomised crossover trial

et al. 2008

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Aims/hypothesis The purpose of this study was to evaluate the optimal renoprotective effect of ultrahigh doses of lisinopril, as reflected by short-term changes in urinary albumin excretion rate (UAER), in type 1 diabetic patients with diabetic nephropathy. Methods At the Steno Diabetes Center, 49 type 1 diabetic patients with diabetic nephropathy completed this doublemasked randomised crossover trial consisting of an initial washout period followed by three treatment periods each lasting 2 months, where all patients received lisinopril 20, 40 and 60 mg once daily in randomised order in addition to slow-release furosemide. Allocation was concealed by sequentially numbered opaque sealed envelopes. UAER, 24 h ambulatory blood pressure (ABP) and estimated GFR were determined at baseline and after each treatment period. Reductions in UAER from baseline were 63%, 71% and 70%, respectively, with the increasing doses of lisinopril (p<0.001). Compared with lisinopril 20 mg there was a further reduction in UAER of 23% with lisinopril 40 mg and 19% with 60 mg, p<0.05. ABP was reduced from baseline by 10/5, 13/7 and 12/7 mmHg (p<0.001 vs baseline, p<0.05 for diastolic ABP 20 vs 40 mg, otherwise NS between doses). The difference in UAER between 20 and 40 mg lisinopril was significant after adjustment for changes in ABP (p<0.01). Two patients were excluded from the study because of an increase in plasma creatinine and one because of high BP; otherwise the study medication was well tolerated with few, mild, dose-independent adverse effects. Conclusions/interpretation Lisinopril 40 mg once daily is generally safe and offers additional reductions in BP and UAER in comparison with the currently recommended dose of 20 mg. Lisinopril 60 mg offers no further beneficial effect.Trial registration: ClinicalTrials.gov NCT00118976 Funding: This study was financed out of local funds and was not supported by the medical industry.

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Section: Discussionmentioning

confidence: 99%

“…Dose titration studies of ACEIs are traditionally conducted according to BP levels in essential hypertension [2,3]. The optimal BP-lowering dose is not, however, necessarily the same as the optimal dose for renoprotection.…”

Section: Introductionmentioning

confidence: 99%

Optimal dose of lisinopril for renoprotection in type 1 diabetic patients with diabetic nephropathy: a randomised crossover trial

et al. 2008

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“…No further reduction of urinary albumin excretion rate and BP have been reported when comparing 80 and 160 mg in a 1-yr study of 62 type II patients with microalbuminuria (32). From studies in patients with moderate-tosevere essential hypertension, no evidence of an additional antihypertensive effect of doses of captopril up to 600 mg or enalapril/benazepril up to 80 mg (33)(34)(35)(36) exists. Increasing the dose of valsartan from 80 to 160 mg resulted in an additional drop in systolic and diastolic BP of Ͻ 1 mmHg in mild-to-moderate hypertension (37).…”

Section: Discussionmentioning

confidence: 99%

Additive Effect of ACE Inhibition and Angiotensin II Receptor Blockade in Type I Diabetic Patients with Diabetic Nephropathy

Jacobsen¹,

Andersen²,

Jensen³

et al. 2003

Journal of the American Society of Nephrology

194

146

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Abstract. Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients. This study tested whether dual blockade of the renin-angiotensin system (RAS) with both an angiotensin-converting enzyme (ACE) inhibitor (ACE-I) and an Angiotensin-II receptor blocker (ARB) is superior to either drug alone in type I diabetic patients with diabetic nephropathy (DN). A randomized double-blind crossover trial was performed with 8-wk treatment with placebo, 20 mg of benazepril once daily, 80 mg of valsartan once daily, and the combination of 20 mg of benazepril and 80 mg of valsartan. Twenty type I diabetic patients with DN were included. At the end of each treatment period, albuminuria, 24-h BP, and GFR were measured. Eighteen patients completed the study. Placebo values were: albuminuria [mean (95% CI)], 701 (490 to 1002) mg/24 h; BP [mean (SEM)], 144 (4)/79 (2) mmHg, and GFR [mean (SEM)], 82 (7) ml/min per 1.73 m 2 . Treatment with benazepril, valsartan, or dual blockade significantly reduced albuminuria and BP compared with placebo. Benazepril and valsartan were equally effective. Dual blockade induced an additional reduction in albuminuria of 43 % (29 to 54 %) compared with any type of monotherapy, and a reduction in systolic BP of 6 (0 to 13) mmHg and 7 (1 to 14) mmHg (versus benazepril and valsartan, respectively) and a reduction of 7 (4 to 10) mmHg diastolic compared with both monotherapies. GFR was reversibly reduced on dual blockade compared with monotherapy and placebo. All treatments were safe and well tolerated. In conclusion, dual blockade of the RAS may offer additional renal and cardiovascular protection in type I diabetic patients with DN.Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes (1,2). Antihypertensive treatment, especially ACE-I, has been shown to reduce albuminuria, to diminish loss of kidney function, and to improve survival in type I patients with DN (1-3). Studies of diabetic and nondiabetic kidney disease suggest the initial degree of reduction in albuminuria after blockade of the reninangiotensin system (RAS) predicts an attenuated rate of decline in GFR, as reviewed by Rossing (1). As a consequence, albuminuria may serve as a surrogate end point for monitoring treatment efficacy and prognosis in DN (4).A superior effect on BP and a tendency toward a more pronounced drop in urinary albumin excretion of dual blockade of the RAS compared with single blockade has been reported in type II patients with microalbuminuria (5). We have recently shown additional drop in albuminuria and diastolic BP when adding an angiotensin receptor blocker (ARB) to angiotensinconverting enzyme inhibitor (ACE-I) treatment in type l patients with albuminuria Ͼ1 g/24 h and BP Ͼ135/85 mmHg, despite conventional antihypertensive therapy including three different agents (6). However, this subgroup is highly selected; therefore, it may differ from the patients in general with DN, especially with regard to RAS activity and ...

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“…6 Cohen has indicated that this degree in half-tablet weight variability is acceptable since therapeutic outcomes would likely be unchanged. 5 Given the wide therapeutic index of lovastatin 12,13 and lisinopril, 14 it would appear that splitting these 2 products is acceptable. Gee at al.…”

Section: Lovstatin and Lisinopril: Clinical Considerationsmentioning

confidence: 99%

Weight Uniformity of Split Tablets Required by a Veterans Affairs Policy

Polli

Kim²,

Martin³

2003

JMCP

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OBJECTIVE: To split several tablet products relevant to the Veterans Affairs (VA) Maryland Healthcare System and assess whether the resulting half tablets provide equal doses.METHODS: From a VA list of products that are required to be split, 7 products were evaluated, along with 5 other commonly split tablet products. A trained pharmacy student split tablets using a tablet splitter provided by the VA. Half tablets were assessed for weight uniformity.RESULTS: Of the 12 products subjected to splitting, 8 products (atorvastatin, citalopram, furosemide, glipizide, metoprolol, paroxetine, sertraline, and warfarin) yielded half tablets that passed the weight-uniformity test. The 4 failing products were lisinopril, lovastatin, rofecoxib, and simvastatin. Unusual tablet shape and high tablet hardness predisposed products to failing the weight-uniformity test. The 4 failing products resulted in half tablets that were generally within 20% of their target weight range, suggesting that splitting these specific products would not result in adverse therapeutic effects due to dose variation created by tablet-splitting.CONCLUSION: Split-tablet results were relatively favorable and generally support a VA practice to split specific tablets. Public quality standards for half tablets, including their content uniformity, are needed to better delineate the policies for acceptable tablet splitting.

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Lisinopril dose‐response relationship in essential hypertension.

Cited by 28 publications

References 15 publications

Optimal dose of lisinopril for renoprotection in type 1 diabetic patients with diabetic nephropathy: a randomised crossover trial

Optimal dose of lisinopril for renoprotection in type 1 diabetic patients with diabetic nephropathy: a randomised crossover trial

Additive Effect of ACE Inhibition and Angiotensin II Receptor Blockade in Type I Diabetic Patients with Diabetic Nephropathy

Weight Uniformity of Split Tablets Required by a Veterans Affairs Policy

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