Aims
To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 ...diabetes mellitus.
Methods
In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30–70 years, with stage I hypertension and diabetes
mellitus
, were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (
N
= 47) or 50 mg of losartan (
N
= 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion.
Results
Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan (
P
< 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group (
P
< 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group (
P
= 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment.
Conclusions
Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes
mellitus
and hypertension.
Trial registration
Clinical trials registration number: NCT00971165
To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension.
The PREVER-prevention trial was a randomized, parallel, ...double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30-70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo once a day. The main outcomes were the percentage of participants who achieved an optimal level of BP.
A total of 372 participants were randomly allocated to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05). The mean net reduction in SBP and DBP for the diuretic group compared with placebo was 2.8 mmHg (95% CI 1.1 to 4.5) and 1.1 mmHg (95% CI -0.09 to 2.4), respectively. Most participants in the active treatment group (74.5%) and in the placebo group (80.7%) continued to have BP in the prehypertension range or progressed to hypertension.
Low-dose diuretic therapy increased the probability of individuals with prehypertension to achieve optimal BP but most of those treated continued to have a BP in the prehypertension range or progressed to having overt hypertension.
Background
Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension ...(PREVER‐Prevention) trial aimed to evaluate the efficacy and safety of a low‐dose diuretic for the prevention of hypertension and end‐organ damage.
Methods and Results
This randomized, parallel, double‐blind, placebo‐controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new‐onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38–0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm (P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow‐Lyon voltage and voltage‐duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02).
Conclusions
A combination of low‐dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension.
Clinical Trial Registration
URL: http://www.ClinicalTrials.gov, www.ensaiosclinicos.gov. Unique identifiers: NCT00970931, RBR‐74rr6s.
To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension.
In a randomized, double-blind, ...controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 333) or 50 mg of losartan (N = 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated.
The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 ± 40.4 versus 16.2 ± 26.7 mg, P = 0.09).
Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP.
NCT00971165.
Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently ...demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted.
This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, 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 subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution.
The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil.
ClinicalTrials.gov: NCT00971165.
Blood 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.
This 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.
The 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.
Clinical Trials NCT00970931.
Abstract Background: Among the various pathologies that affect the elderly, Heart Failure (HF) stands out. Recently, an attempt has been made to verify the existence of cognitive impairment ...associated with HF. Objectives: To compare the cognitive performance of elderly people with heart failure with that of age-matched individuals without this pathology. Check the existence of marked impairment in some cognitive functions in the clinical group. Methods: The sample consisted of 78 elderly people, whose inclusion criterion was the presence of HF and no HF (control group); age over 60 years, both sexes, and any level of education. The control group consisted of 37 individuals (with a median age of 68 years – Interquartile range of 12) and the HF group, with 41 individuals (with a median age of 67 years – Interquartile range of 11). The subjects were matched in terms of education level, with a predominance of elderly people with 0 to 4 years of education (65.9% in the Clinical Group and 59.5% in the Control Group). Eleven neuropsychological tests covering cognitive functions were used: attention, language, memory, mood, and executive function. Statistical analysis was performed using SPSS software, version 23, with a significance level of 5%. The Chi-square test and the Mann-Whitney test were applied. Results: The results showed significant differences between the groups, mainly in executive functions, which include the ability to plan, switch, and recall previously stored information. Conclusion: Our study showed differences between the cognitive performance of elderly people with HF and elderly people without HF. The main alteration was found in the so-called executive functions, attention, and memory.
Abstract Background: Among the various pathologies that affect the elderly, Heart Failure (HF) stands out. Recently, an attempt has been made to verify the existence of cognitive impairment ...associated with HF. Objectives: To compare the cognitive performance of elderly people with heart failure with that of age-matched individuals without this pathology. Check the existence of marked impairment in some cognitive functions in the clinical group. Methods: The sample consisted of 78 elderly people, whose inclusion criterion was the presence of HF and no HF (control group); age over 60 years, both sexes, and any level of education. The control group consisted of 37 individuals (with a median age of 68 years – Interquartile range of 12) and the HF group, with 41 individuals (with a median age of 67 years – Interquartile range of 11). The subjects were matched in terms of education level, with a predominance of elderly people with 0 to 4 years of education (65.9% in the Clinical Group and 59.5% in the Control Group). Eleven neuropsychological tests covering cognitive functions were used: attention, language, memory, mood, and executive function. Statistical analysis was performed using SPSS software, version 23, with a significance level of 5%. The Chi-square test and the Mann-Whitney test were applied. Results: The results showed significant differences between the groups, mainly in executive functions, which include the ability to plan, switch, and recall previously stored information. Conclusion: Our study showed differences between the cognitive performance of elderly people with HF and elderly people without HF. The main alteration was found in the so-called executive functions, attention, and memory.
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