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PubMed2001

Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack.

BACKGROUND: Blood pressure is a determinant of the risk of stroke among both hypertensive and non-hypertensive individuals with cerebrovascular disease. However, there is uncertainty about the efficacy and safety of blood-pressure-lowering treatments for many such patients. The perindopril protection against recurrent stroke study (PROGRESS) was designed to determine the effects of a blood-pressure-lowering regimen in hypertensive and non-hypertensive patients with a history of stroke or transient ischaemic attack. METHODS: 6105 individuals from 172 centres in Asia, Australasia, and Europe were randomly assigned active treatment (n=3051) or placebo (n=3054). Active treatment comprised a flexible regimen based on the angiotensin- converting-enzyme inhibitor perindopril (4 mg daily), with the addition of the diuretic indapamide at the discretion of treating physicians. The primary outcome was total stroke (fatal or non-fatal). Analysis was by intention to treat. FINDINGS: Over 4 years of follow up, active treatment reduced blood pressure by 9/4 mm Hg. 307 (10%) individuals assigned active treatment suffered a stroke, compared with 420 (14%) assigned placebo (relative risk reduction 28% [95% CI 17-38], p<0.0001). Active treatment also reduced the risk of total major vascular events (26% [16-34]). There were similar reductions in the risk of stroke in hypertensive and non-hypertensive subgroups (all p<0.01). Combination therapy with perindopril plus indapamide reduced blood pressure by 12/5 mm Hg and stroke risk by 43% (30-54). Single-drug therapy reduced blood pressure by 5/3 mm Hg and produced no discernable reduction in the risk of stroke. INTERPRETATION: This blood-pressure-lowering regimen reduced the risk of stroke among both hypertensive and non-hypertensive individuals with a history of stroke or transient ischaemic attack. Combination therapy with perindopril and indapamide produced larger blood pressure reductions and larger risk reductions than did single drug therapy with perindopril alone. Treatment with these two agents should now be considered routinely for patients with a history of stroke or transient ischaemic attack, irrespective of their blood pressure.

Aged↗

PubMed1985

Regression of left ventricular hypertrophy in hypertension: comparative effects of three different drugs.

We examined the effect of three antihypertensive agents with differing modes of action on blood pressure, heart rate, plasma catecholamines, plasma renin activity, and echocardiographic left ventricular mass. Twenty-six patients were studied; nine were treated with nifedipine, a calcium antagonist, nine were treated with timolol, a nonselective beta-blocker, and eight were treated with indapamide, a diuretic with some probable calcium antagonist properties. All drugs reduced blood pressure satisfactorily; the reduction of systolic blood pressure was not significantly different among the three drugs, but timolol reduced diastolic blood pressure by a greater amount than did either indapamide or nifedipine. Left ventricular (LV) mass was reduced equally by all three drugs. However, there were markedly different effects on the other parameters measured. Heart rate was reduced to a greater extent by timolol than by the other two drugs. Plasma renin activity was reduced by timolol, unchanged by nifedipine, and increased by indapamide. There were no significant changes in either adrenaline or noradrenaline with any of the three drugs. We conclude that these data do not support the hypothesis that the sympathetic nervous system is primarily responsible for left ventricular hypertrophy, and suggest that reduction of left ventricular mass with antihypertensive agents is not the property of any one class of drug.

Adult↗

PubMed2006

Managing hypertension in high-risk patients: lessons and promises from the STRATHE and ADVANCE trials.

Pharmacological treatment of hypertension represents a cost-effective way of preventing cardiovascular and renal complications. To benefit maximally from antihypertensive treatment, blood pressure should be brought to below 140/90 mmHg in every hypertensive patient, and even lower (< 130/80 mmHg) if diabetes or renal disease co-exists. Such targets cannot usually be reached using monotherapies. This is especially true in patients who present with a high cardiovascular risk. The co-administration of two agents acting by different mechanisms considerably increases the blood pressure control rate. Such combinations are not only efficacious, but are also well tolerated, and some fixed low-dose combinations even have a placebo-like tolerability. This is the case for the preparation containing the angiotensin-converting enzyme inhibitor perindopril (2 mg) and the diuretic indapamide (0.625 mg), a fixed low-dose combination that has been shown in controlled trials to be more effective than monotherapies in reducing albuminuria, regressing cardiac hypertrophy and improving the stiffness of large arteries. Using this combination to initiate antihypertensive therapy has been shown in a double-blind trial (Strategies of Treatment in Hypertension: Evaluation; STRATHE) to normalize blood pressure (< 140/90 mmHg) in significantly more patients (62%) than a sequential monotherapy approach based on atenolol, losartan and amlodipine (49%) and a stepped-care strategy based on valsartan and hydrochlorothiazide (47%), with no difference between the three arm groups in terms of tolerability. An ongoing randomized trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; ADVANCE) is a study with a 2 x 2 factorial design assessing the effects of the fixed-dose perindopril-indapamide combination and of the intensive gliclazide modified release-based glucose control regimen in type 2 diabetic patients, with or without hypertension. A total of 11 140 patients were randomly selected. Within the first 6 weeks of treatment (run-in phase), the perindopril-indapamide combination lowered blood pressure from 145/81 +/- 22/11 mmHg (mean +/- SD) to 137/78 +/- 20/10 mmHg. Fixed-dose combinations are becoming more and more popular for the management of hypertension, and are even proposed by hypertension guidelines as a first-line option to treat hypertensive patients.

Adrenergic beta-Antagonists↗

PubMed2003

Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.

Adult↗

PubMed1999

Concluding remarks. Pursuit of the optimal outcome in hypertension.

Achieving the optimal outcome in hypertensive patients requires the selection and use of appropriate strategies to lower the blood pressure and reduce the patient's risk of cardiovascular events such as stroke and coronary heart disease. It also requires ongoing monitoring of the patient to ensure that the desirable end-points of treatment are being met, and that the heart, kidneys and other sites are being effectively protected from potential complications. Current guidelines on the treatment of hypertension continue to emphasise the use of low dose diuretics as appropriate first-line therapy whenever pharmacological intervention is indicated, except where there are positive indications (e.g. coexisting congestive heart failure or diabetic nephropathy) for other classes of drugs. Diuretics have repeatedly been shown to reduce the morbidity and mortality associated with hypertension, both in the elderly and in younger adults, and their combination with other antihypertensive agents (when clinically indicated) permits the use of lower total dosages. The thiazide-related diuretic indapamide has been reported to have a number of advantages over the thiazides, including minimal or no adverse influence on plasma lipids and glucose metabolism, or on kidney function in patients with renal insufficiency. It has also been found to produce regression of left ventricular hypertrophy, which is now accepted as an important objective of antihypertensive therapy. The recently developed sustained release (SR) formulation of indapamide allows use of a lower daily dosage of the drug, thereby improving its efficacy:safety ratio in comparison with immediate release formulations. Clinical studies have confirmed the efficacy of indapamide SR 1.5 mg daily in lowering elevated blood pressure, and this formulation can be considered an appropriate choice whenever a diuretic is indicated for the treatment of hypertension, including elderly hypertensives and, because of its metabolic 'neutrality', hypertensive patients with diabetes.

Age Factors↗

PubMed1999

Perindopril 2mg/indapamide 0.625mg. Fixed low-dose combination.

Low-dose drug combinations have been proposed in International Guidelines for use in patients with hypertension. The fixed low-dose combination of perindopril 2mg with indapamide 0.625mg combines an angiotensin converting enzyme (ACE) inhibitor with a non-thiazide diuretic. Coadministration of perindopril and indapamide did not have any clinically significant effects on the pharmacokinetic profile of either agent in healthy volunteers. In experimental models of hypertension, perindopril/indapamide restored endothelial function, improved microvascular density, reduced left ventricular and aortic hypertrophy, and reversed renal end-organ damage. Once daily oral perindopril 2mg/indapamide 0.625mg normalised blood pressure (BP) in 83.6% of elderly patients with essential hypertension (diastolic BP was reduced to < or =90mm Hg) and 81.7% of those with isolated systolic hypertension (systolic BP was reduced to <160mm Hg) after approximately 1 year of treatment. BP normalisation was sustained in 79.8% of patients throughout the study. Fixed low-dose perindopril/indapamide had a tolerability profile similar to that of placebo in clinical trials; most adverse events were of mild to moderate severity. Coadministration of the 2 agents reduced the incidence of hypokalaemia seen with indapamide alone.

Animals↗

PubMed2005

A meta-analytical approach to the efficacy of antihypertensive drugs in reducing blood pressure.

INTRODUCTION: Hypertension constitutes a veritable public health issue. Several classes of drugs are available for the treatment of hypertension. The objective of this meta-analytical approach was to assess the efficacy of antihypertensive drugs most commonly used in France in reducing clinical SBP and DBP. METHODS: The antihypertensive drugs selected were hydrochlorothiazide, indapamide sustained release (SR), furosemide and spironolactone for diuretics; amlodipine and lercanidipine for calcium channel antagonists; atenolol for beta-adrenoceptor antagonists (beta-blockers); enalapril and ramipril for ACE inhibitors; and candesartan cilexetil, irbesartan, losartan, and valsartan for angiotensin II receptor antagonists. The trials selected were published between 1973 and 2004, evaluated monotherapy with trial drugs as fixed-dosage or with dosage increase, and assessed blood pressure reduction between 2 and 3 months. The analysis method used was based on the calculation of the sum weighted for the trial size. RESULTS: A total of 72 trials (comprising 9094 patients) were selected and analyzed. No trial evaluating furosemide or spironolactone satisfied the inclusion criteria for this analysis. For SBP, the reduction was more marked with diuretics, calcium channel antagonists, and ACE inhibitors. Of all the drugs studied, indapamide SR gave the greatest SBP reduction (-22.2 mm Hg). Evaluated therapeutic classes had a similar magnitude of effect on DBP, i.e. reduction between -11.4 mm Hg with beta-adrenoceptor antagonists and -10.3 mm Hg with angiotensin II type 1 receptor antagonists. CONCLUSION: Indapamide SR 1.5 mg appeared to be the most effective drug for a significant reduction in SBP within 2-3 months, which is an essential element in optimizing cardiovascular prevention among hypertensive patients. The clinical application of these results should take into consideration all the limitations discussed in this analysis.

Adrenergic beta-Antagonists↗

PubMed1999

Effect of binders on anti hypertensive drugs.

Tablets of antihypertensive drugs, Indapamide, Methyldopa and Clonidine have been prepared and their physico-chemical properties were determined. The effect of various binders viz. starch, acacia, sodium carboxymethyl cellulose (sod. CMC), gelatin and lactose on the properties of these tablets were studied. Formulations of tablets of indapamide, methyldopa and clonidine prepared in combination with acacia, lactose and sod. CMC, respectively result in the best flow properties, minimum percentage fines, low angle of repose and compressibility. The tablets prepared from these granules possess all quality features including a good dissolution profile. Gelatin, sod. CMC and starch have less effective granule formation leading to poor quality of tablets in case of Indapamide, Methyldopa and Clonidine, respectively.

Antihypertensive Agents↗

PubMed2002

[Management of hypertensive patients with left ventricular hypertrophy].

CARDIOVASCULAR RISK OF LEFT VENTRICULAR HYPERTROPHY: Because of the rhythmic, mechanical and ischemic risk related to it, the left ventricular hypertrophy (LVH) is considered to be a major independent risk factor for cardiovascular disease which should be screened for and treated early. In patients with type 2 diabetes, left ventricular hypertrophy is mainly due to high blood pressure, but also to reduced elasticity of the large vessels, defective vasomotricity and dysfunction of the arterial endothelium. Obesity, elevated blood viscosity, hyperinsulinism and/or autonomous cardiac neuropathy can also have a favoring effect. THE LIVE STUDY: Is the first multicentric European study comparing the efficacy of a thiazide-like diuretic, slow-release indapamid, with a converting enzyme inhibitor, enalapril 20 mg, on the reduction of the left ventricular mass index (LVMI) in hypertensive subjects with LVH. The study involved a randomized centralized reading of the echocardiograms as well as a randomized and blinded reading at the end of the study. DEMONSTRATED SUPERIORITY OF INDAPAMID SR: The LIVE study clearly demonstrated the superiority of indapamid SR over enalapril 20 mg in reducing the LVMI in hypertensive subjects with LVH while the blood pressure lowering effect was comparable for the two treatments.

Adrenergic alpha-Antagonists↗

PubMed2002

[Arterial hypertension in elderly individuals].

EMERIAU STUDY IN ELDERLY HYPERTENSIVE PATIENTS: This multicenter, randomized, double-blind European study was conducted in 524 elderly patients of mean aged 72 years in three parallel treatment arms (indapamid SR 1.5 mg, amlopidine 5 mg hydrochlorothiazide 25 mg). The study demonstrated an equivalent antihypertensive effect for the three treatment arms and with a mean reduction in diastolic pressure of 23 mmHg. In the indapamid SR group, the rate of normalization was higher, both for elevated systolic-diastolic pressure and elevated systolic pressure, alone. HYVET STUDY: This is an ongoing randomized, double-blind trial designed to confirm the beneficial effect of antihypertensive treatment with indapamid SR in very elderly patients (> 80 years old).

Age Factors↗

PubMed1999

Left ventricular hypertrophy regression: the LIVE trial.

Left ventricular hypertrophy (LVH) is a clinical condition associated with an increased risk of vascular events. Several trials have been done to evaluate the action of different antihypertensive treatments on the regression of LVH IN HYPERTENSIVE PATIENTS. The efficacy of diuretics in the reduction of LVH is controversial. The LIVE study (Left Ventricular Hypertrophy Regression: Indapamide Versus Enalapril) is a European, prospective, double-blind, randomised, controlled trial aimed to compare the efficacy of indapamide 1.5 mg daily with that of enalapril 20 mg daily in the reduction of LVH in hypertensive patients (systolic blood pressure > 160 and < 210 mmHg) with LVH (left ventricular mass index 120 g/m2 in men and > 100 g/m2 in women) after 1 year of treatment. The assessment of LVH was done by echocardiography. A blind randomised reading of the echo recordings was performed at the end of the study by an independent Core Echocardiography Committee with three readers. Preliminary data are available from this trial. These data confirm the antihypertensive efficacy of indapamide and its efficacy in the reduction of left ventricular mass through a progressive action over 1 year.

Antihypertensive Agents↗

PubMed2003

Clinical role of Natrilix SR in the treatment of at-risk hypertensive patients.

Although recent trials have shown that antihypertensive treatment can bring about a reduction in stroke, coronary heart disease, heart failure and renal disease, the situation is no longer improving. This is due to the fact that the percentage of hypertensive patients with satisfactory blood pressure is still very poor. International guidelines on hypertension indicate the importance of assessing the absolute risk of patients and the use of a lower dose of drugs to improve the efficacy-tolerability profile. Diuretics used at lower dosage than in the past are effective in reducing morbidity and mortality and continue to be drugs of first choice in the treatment of hypertension. Indapamide sustained release (Natrilix SR) 1.5 mg has an antihypertensive effect equivalent to indapamide immediate release 2.5 mg with a 50% reduction in incidence of serum potassium levels <3.4 mmol/l. Natrilix SR has proved to have a neutral effect both on lipid and glucose profiles and to reduce microalbuminuria in diabetic hypertensive patients. Recent multicentre European clinical trials have shown that Natrilix SR decreases diastolic blood pressure to <90 mmHg in about 75% of patients treated for 1 year. In elderly patients with isolated systolic hypertension, Natrilix SR has been proven to be as effective as amlodipine 5 mg and significantly more effective than hydrochlorothiazide 25 mg. Natrilix SR produces regression of left ventricular hypertrophy which, in the Left ventricular hypertrophy: Indapamide Versus Enalapril study was greater than that induced by enalapril. Natrilix SR represents an appropriate choice not only as a first-line drug in many hypertensive patients but also in at-risk patients like the elderly, subjects with other cardiovascular risk factors, target organ damage, diabetes, or impaired renal function.

Delayed-Action Preparations↗

PubMed2005

[Cardiac glycosides in complex treatment of patients with heart failure and supraventricular arrhythmias].

The authors of the article studied potential of various drug combinations (atenolol + enalapril + indapamide, and celanid + enalapril + indapamide) in complex treatment of patients with heart failure (HF) and supraventricular arrhythmias. The subjects were 106 patients, of whom 74 had coronary heart disease, of whom 51 had old myocardial infarction, and 18 had undergone coronary artery bypass grafting. Dilatation cardiomyopathy was found in 8, aortomitral valvular disease--in 18, and combined mitral valvular disease--in 6 patients. 36 subjects had permanent atrial fibrillation, 48--a paroxysmal form of ciliary arrhythmia, 22--paroxysms of atrial tachycardia. NYHA functional class (FC) II HF was diagnosed in 64 patients, NYHA FC III HF--in 42 patients. According to what treatment regimen was applied, the patients were divided into two groups, comparable in the main clinical and functional characteristics. Two-month therapy resulted in improvement of hemodynamics, increase of activity tolerance and improvement of life quality in both groups. The combination celanide + enalapril + indapamide in individual doses was effective in FC II-III HF with supraventricular arrhythmias. The cost of treatment with celanid is lower.

Aged↗

PubMed1980

[Ambulatory treatment of hypertension].

In an open study 30 hypertensive outpatients have been treated with Indapamide in a dosage of 2,5 mg daily in the morning for eight weeks. In the course of this treatment a highly significant decrease of blood pressure could be observed. The antihypertensive effect came up gently in the beginning. Indapamide has been well tolerated by all patients. The rate of adverse reactions was low. Syncopal episodes did not occur. The biochemical data monitored (fasting glucose level, creatinine, urea, potassium, sodium, calcium, chloride) did not show any significant deviation. According to the present data Indapamide may be used as basic medication in the treatment of genuine hypertension. The gentle effect in the beginning prevents syncopal episodes, however a sufficient period of treatment, at least eight weeks, is needed to assess the success of the therapy.

Administration, Oral↗

PubMed1995

Post-stroke antihypertensive treatment study. A preliminary result.

Post-stroke Antihypertensive Treatment Study (PATS) was a randomized, double-blind and placebo-controlled trial, which aimed at determining whether antihypertensive treatment could reduce the risk of fatal and nonfatal stroke incidence in patients with a history of stroke or transient ischemic attack (TIA). 5,665 patients were randomized by a sealed envelope system. Systolic blood pressure (SBP) ranged from 80 to 280 mm Hg and diastolic (DBP) from 50 to 150 mmHg. The average SBP was 154 mmHg and average DBP 93 mmHg. The mean age was 60 years. Among the patients, women accounted for 28%. In 71% the latest stroke was ischemic. Average follow-up approximated to 2 years. The three-year average SBP was 149 mmHg for the placebo group and 144 mmHg for the indapamide treatment group, and the three-year DBP was 89 mmHg and 87 mmHg respectively. The three-year first incidence of fatal and nonfatal stroke was 12.3 per 100 patients placebo treatment and 9.4 per 100 with indapamide. The relative risk by proportional hazards regression analysis was 0.71 (P = 0.0009). For deaths from all causes, the relative risk was 0.91. (P > 0.05). The findings of this trial indicate that in patients with a history of stroke or TIA, blood pressure reduction of 5/2 mmHg with 2.5 mg indapamide reduced the first incidence of fatal and nonfatal stroke by 29%, with three-year absolute benefit of 29 events per 1000 participants.

Aged↗

PubMed1996

[Value of diuretics in hypertension].

Diuretics still remain a cornerstone in the treatment of hypertension. Adverse effects such as disorders of the carbohydrate and lipid metabolism as well as development of hypokalemia or hypomagnesemia are obviously directly correlated to the administered dosage. Therefore, there is increasing agreement for low-dose drug therapy. In contrast to hydrochlorothiazide treatment, metabolic disorders are less commonly encountered with indapamide therapy. A pronounced diuretic efficacy is linked to the combined use of diuretics which act on different segments of the nephron (for example administration of a loop diuretic together with a thiazide). In chronic renal failure indapamide appears to be superior to hydrochlorothiazide considering preservation of renal function. In contrast to thiazides, indapamide is the therapy of choice in patients with diabetes.

Antihypertensive Agents↗

PubMed2001

Antihypertensive drug prescription trends at the primary health care centres in Bahrain.

PURPOSE: To determine the antihypertensive drug prescribing pattern by primary care physicians in patients with uncomplicated essential hypertension; to identify whether such pattern of prescription is appropriate and in accordance with international guidelines for pharmacotherapy of hypertension; and to estimate the impact of such prescriptions on cost of treatment. METHODS: A prescription-based survey among patients with uncomplicated essential hypertension was conducted in seven out of a total of 18 health centres in Bahrain. The relevant data for our study was collected using cards, designed for chronically-ill patients. RESULTS: A total of 1019 male and 1395 female (62.9%) out of 3838 of the study population were on monotherapy, whereas 596 male and 828 female (37.1%) were on antihypertensive combination therapy. Among the monotherapy category, the various antihypertensive drugs used were as follows: beta-blockers (58.8%), angiotensin converting enzyme (ACE) inhibitors (14.2%), calcium channel blockers (11.1%), diuretics (8.1%) and alpha-methyldopa (7.0%). With respect to overall utilization pattern, beta-blockers were the most frequently prescribed (65.5%), diuretics ranked second (27.4%), followed by ACE inhibitors (20.6%), calcium channel blockers (19.9%) and alpha-methyldopa (8.5%). Within each class of antihypertensives used, the most frequently used individual agents were as follows: (a) among beta-blockers 97.7% used atenolol; (b) among the diuretics, indapamide (35.4%), hydrochlorothiazide (HCTZ) (32.7%), HCTZ in combination with triamterene (25.7%), and chlorthalidone (4.6%); (c) among the ACE inhibitors, captopril (44.9%), enalapril (29.7%), and lisinopril (19.0%); (d) among the calcium channel blockers, nifedipine (98.2%). Significant age- and gender-related differences in prescribing patterns were seen. Short-acting nifedipine monotherapy was inappropriately prescribed in a significant number of patients above the age of 50 years. ACE inhibitors accounted for approximately two-thirds of the total antihypertensive drug expenditure, although these drugs represent only one-fifth of overall antihypertensives used. There is a trend towards excessive use of expensive thiazide-like diuretics such as indapamide which seems to be unjustifiable practice, particularly in a study population free from diabetic hypertensive patients. CONCLUSIONS: The general pattern of antihypertensive utilization appears to be in accordance with the guidelines of WHO and the Joint National Committee issued in the 1990s. The trends of prescribing of antihypertensives were in favour of conventional ones such as the beta blockers and diuretics, and the introduction of newer classes of antihypertensives had a generally minimal impact on the prescribing profile. Almost two-thirds of the patients were treated with monotherapy. A disproportionately large percentage of antihypertensive drug cost was due to overt use of ACE inhibitors, and indapamide, instead of thiazide diuretics. The use of short-acting calcium channel blockers especially in the elderly is unjustifiable.

Adolescent↗

PubMed1991

Hyperlipidemia in hypertension: causes and prevention.

Hyperlipidemia is prevalent in hypertension, but the cause of this association is unknown. Treatment of hypertension with thiazide diuretics accentuates the hyperlipidemia, perhaps by causing potassium or sodium depletion. To assess the role of hypokalemia in thiazide hyperlipidemia, I measured lipid concentrations while using a spironolactone-thiazide regimen to prevent potassium wastage during the treatment of hypertension. Blood pressure decreased substantially, but hyperlipidemia occurred despite the maintenance of normal serum potassium. To test a role of sodium balance, I measured lipid levels during periods of sodium feeding and placebo therapy. Cholesterol levels decreased during sodium administration. Carrying this information to therapy, I participated in a multicenter comparison of enalapril and indapamide therapy in resistant hypertension. Both regimens caused minor metabolic effects, but indapamide provided superior antihypertensive potency. This evidence suggests that sodium feeding improves lipid metabolism, but sodium diuresis enhances an antihypertensive effect. Low-dose therapy combining a diuretic, such as indapamide, with a nondiuretic agent promises to improve metabolic tolerance and maximize hypertension control. This strategy optimally lowers overall cardiovascular risk.

Benzothiadiazines↗