Blood Pressure-Lowering Efficacy of Amiloride versus Enalapril as Add-On Drugs in Patients with Uncontrolled Blood Pressure Receiving Hydrochlorothiazide

Guerrero, P. Pérez; Fuchs, Flávio Danni; Moreira, Leila M; Martins, Vítor Magnus; Bertoluci, Carolina; Fuchs, Sandra Cristina Pereira Costa; Gus, Miguel

doi:10.1080/10641960802441906

Cited by 25 publications

(18 citation statements)

References 31 publications

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“…Our findings confirm that this association is independent of blood pressure levels. We had previously shown, in a secondary analysis of a randomized clinical trial [29], that the time-rate index was independent even from blood pressures changes induced by drug treatment [30]. …”

Section: Discussionmentioning

confidence: 99%

Association between different measurements of blood pressure variability by ABP monitoring and ankle-brachial index

Wittke

Fuchs

et al. 2010

BMC Cardiovasc Disord

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BackgroundBlood pressure (BP) variability has been associated with cardiovascular outcomes, but there is no consensus about the more effective method to measure it by ambulatory blood pressure monitoring (ABPM). We evaluated the association between three different methods to estimate BP variability by ABPM and the ankle brachial index (ABI).Methods and ResultsIn a cross-sectional study of patients with hypertension, BP variability was estimated by the time rate index (the first derivative of SBP over time), standard deviation (SD) of 24-hour SBP; and coefficient of variability of 24-hour SBP. ABI was measured with a doppler probe. The sample included 425 patients with a mean age of 57 ± 12 years, being 69.2% women, 26.1% current smokers and 22.1% diabetics. Abnormal ABI (≤ 0.90 or ≥ 1.40) was present in 58 patients. The time rate index was 0.516 ± 0.146 mmHg/min in patients with abnormal ABI versus 0.476 ± 0.124 mmHg/min in patients with normal ABI (P = 0.007). In a logistic regression model the time rate index was associated with ABI, regardless of age (OR = 6.9, 95% CI = 1.1- 42.1; P = 0.04). In a multiple linear regression model, adjusting for age, SBP and diabetes, the time rate index was strongly associated with ABI (P < 0.01). None of the other indexes of BP variability were associated with ABI in univariate and multivariate analyses.ConclusionTime rate index is a sensible method to measure BP variability by ABPM. Its performance for risk stratification of patients with hypertension should be explored in longitudinal studies.

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Section: Discussionmentioning

confidence: 99%

Association between different measurements of blood pressure variability by ABP monitoring and ankle-brachial index

Wittke

Fuchs

et al. 2010

BMC Cardiovasc Disord

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“…Chlorthalidone was chosen in face of its higher blood pressure-lowering efficacy and better performance in the prevention of major cardiovascular events than hydrochlorothiazide [24]. The association with amiloride aims to prevent the deleterious hypokalemia induced by diuretics [25,26]. If the intervention shows to be effective and well-tolerated, the early use of this association could be the basis for an innovative public health program to prevent hypertension in Brazil.…”

Section: Introductionmentioning

confidence: 99%

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

Fuchs

Moreira

et al. 2011

Trials

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BackgroundBlood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.MethodsThis is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.DiscussionThe early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.Trial RegistrationClinical Trials NCT00970931.

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“…In patients with heart failure, both enalapril and fosinopril have similar short-term effects on event-free survival, ejection fraction, functional capacity, and quality of life [ 58 ]. In patients on hydrochlorothiazide with uncontrolled blood pressure, enalapril was more effective than amiloride in lowering blood pressure [ 59 ]. In patients with mild-to-moderate hypertension, a fi xed-dose combination of enalapril and nitrendipine was well tolerated and effectively lowered blood pressure, with lower incidence of edema than with calcium channel blocker monotherapy [ 60 , 61 ].…”

Section: Enalaprilmentioning

confidence: 97%

Drugs Targeting RAAS in the Treatment of Hypertension and Other Cardiovascular Diseases

Balakumar

Jagadeesh

2015

Pathophysiology and Pharmacotherapy of Cardiovascular Disease

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Drugs with diversifi ed structure and class target the RAAS cascade at various levels. Beginning with the inhibition of renin from the juxtaglomerular cells of the kidney, it extends to the blockade of formation and actions of its principal component, Ang II, and its effector, aldosterone and its synthesis. Although all of them are very effi cacious in combating overactivation of RAAS, ACE inhibitors and ARBs stand out in the armamentarium of RAAS inhibitors. All of them are effective in lowering blood pressure but differ from each other in potency, pharmacokinetic properties and additional pharmacologic actions that are contributed by their unique functional groups. Therapeutic uses of RAAS blockers stem from the dynamics of the complex intertwined downstream signaling molecules that interact to contribute beyond blood pressure control. Thus, some of the ACE inhibitors and ARBs are also indicated in the treatment of heart failure, left ventricular dysfunction following myocardial infarction, and nephropathy in T2DM, reducing the risk of cardiovascular mortality, nonfatal myocardial infarction, and the risk of developing heart failure. Several studies have investigated the dual inhibition of the RAAS in hypertension and heart failure with an outcome of more adverse events without an increase in benefi t. While considering Ang II and aldosterone escape processes during ACE inhibitors and ARBs therapies, RAAS at the base level can be halted using aldosterone receptor antagonists for the management of hypertension and heart failure. InThe opinions expressed herein are those of GJ and do not necessarily refl ect those of the US Food and Drug Administration.

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Blood Pressure-Lowering Efficacy of Amiloride versus Enalapril as Add-On Drugs in Patients with Uncontrolled Blood Pressure Receiving Hydrochlorothiazide

Cited by 25 publications

References 31 publications

Association between different measurements of blood pressure variability by ABP monitoring and ankle-brachial index

Association between different measurements of blood pressure variability by ABP monitoring and ankle-brachial index

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

Drugs Targeting RAAS in the Treatment of Hypertension and Other Cardiovascular Diseases

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