Treatment of hypertension in the elderly. III. Response of isolated systolic hypertension to various doses of hydrochlorothiazide: results of a Department of Veterans Affairs cooperative study. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents

Wc, Cushman; Khatri, Ibrahim M.; Bj, Materson; Dj, Reda; Ed, Freis; Goldstein, Gérald; Ea, Ramírez; Fn, Talmers; Tj, White; Nunn, S

doi:10.1001/archinte.151.10.1954

Cited by 17 publications

(10 citation statements)

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“…The significance of diuretic‐related K + changes in the ALLHAT study is still unclear and awaits final analysis of study results. In other studies of thiazide diuretic therapy, 28 hypokalemia occurred at a higher rate but in a dose‐dependent fashion; for example, the fall in serum K + was 0.57 mmol/L (50‐mg hydrochlorothiazide group) vs. 0.17 mmol/L (25‐mg hydrochlorothiazide group). This latter study had only a 24‐week maintenance phase and, because of its short nature, would have been less likely to detect differences in clinical outcome relating to differences in serum K + values.…”

Section: Potassium and Arrhythmiasmentioning

confidence: 82%

Importance of Potassium in Cardiovascular Disease

Sica

Struthers

Cushman

et al. 2002

J of Clinical Hypertension

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The pivotal role of potassium (K+) in cardiovascular disease and the importance of preserving potassium balance have become clinical hot points, particularly as relates to new and emerging cardioprotective and renoprotective therapies that promote potassium retention. Although clinicians may be aware of the critical nature of this relationship, quite frequently there is some uncertainty as to the best way to monitor potassium levels in the face of a host of pathologic states and/or accompanying drug therapies that affect serum levels and/or total body potassium balance. Moreover, guidelines for monitoring of serum potassium levels are at best tentative and oftentimes are translated according to the level of concern of the respective physician. To address these uncertainties, an expert group was convened that included representatives from multiple disciplines. They attempted to reach consensus on the importance of K+ in hypertension, stroke, and arrhythmias as well as practical issues on maintaining K+ balance and avoiding K+ depletion. Because of the complexity of this topic, issues of hyperkalemia will be addressed in a forthcoming manuscript.

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Section: Potassium and Arrhythmiasmentioning

confidence: 82%

Importance of Potassium in Cardiovascular Disease

Sica

Struthers

Cushman

et al. 2002

J of Clinical Hypertension

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“…8 -10,14,22,24 -27,30,31 In addition, conflicting evidence exists regarding the added efficacy of 50 mg/d of HCTZ compared with 25 mg/d, 10,[32][33][34] although it has been shown that some patients require 50 mg/d to achieve blood pressure goals. 14,18 Thus, low dosages of chlorthalidone (12.5-25 mg/d) and HCTZ (12.5-25 mg/d) are generally preferred because these dosages are both safe and effective. 5-7,14,19 -21,24 -25,30 -32,35 As Table 1 demonstrates, reductions in blood pressure varied widely for both HCTZ (8 -35/7-17 mm Hg) and chlorthalidone (5.3-55/4.8 -27 mm Hg).…”

Section: Blood Pressure Loweringmentioning

confidence: 99%

Hydrochlorothiazide Versus Chlorthalidone in the Management of Hypertension

Neff¹,

Nawarskas²

2010

Cardiology in Review

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Thiazide diuretics are a mainstay for the treatment of hypertension. Although there are several thiazide diuretics currently available, hydrochlorothiazide (HCTZ) continues to be the most popular thiazide used for treating high blood pressure. This is despite several clinical trials that have used and documented the benefits of chlorthalidone for hypertension management. In terms of blood pressure lowering, both HCTZ and chlorthalidone appear to be very effective. Head-to-head studies have shown trends favoring chlorthalidone as a more effective blood pressure lowering agent compared with HCTZ, but statistical significance in this regard has not been consistently demonstrated. Also unclear is the relative benefits of these 2 drugs with regards to reducing clinical complications of hypertension, namely cardiovascular morbidity and mortality. Whereas there is more aggregate clinical trial data documenting the benefits of chlorthalidone compared with HCTZ in terms of hard clinical outcomes, these trials are not direct comparisons and can only be used to fuel the debate as to which of the 2 thiazides are better. From a safety perspective, hypokalemia is a risk with any of the thiazide diuretics and has been shown to be dose-related. However, at equipotent dosages, the incidence of hypokalemia between chlorthalidone and HCTZ appears comparable. The available evidence therefore supports both HCTZ and chlorthalidone as safe and effective drugs for treating hypertension. Although there are favorable trends both in terms of antihypertensive efficacy as well as clinical outcomes data with chlorthalidone compared with HCTZ, the results are not conclusive, and as such may not be enough to shift the treatment paradigm in favor of chlorthalidone, given the comfort level that most prescribers have with HCTZ. A head-to-head study looking at hard clinical outcomes, which may or may not ever be performed, may be the only way to resolve the ongoing debate as to which is the preferred thiazide for treating hypertension.

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“…51,52 Later studies revealed that 25 mg daily was nearly as effective as higher doses with less hypokalemia. 22,[53][54][55] Doses of HCTZ as low as 12.5 mg daily have significant antihypertensive effects in some patients but are not as effective as higher doses. 56 -58 In one study, 111 patients with hypertension were randomly assigned to placebo or 3, 6, 12.5, or 25 mg HCTZ for 6 weeks.…”

Section: Dose Responsementioning

confidence: 99%

“…Another study found reductions in SBP of 29, 21, 32, and 24 mm Hg in 51 elderly patients randomly assigned to 25 mg daily, 25 mg twice daily, 50 mg daily, and 50 mg twice daily, respectively. 55 Five important principles are evident with HCTZ dosing: (1) some patients will respond to doses of 12.5 mg daily, (2) doses Ͼ25 mg daily often lower BP only slightly more than does 25 mg (ie, a relatively flat dose response), (3) hypokalemia is dose related, and the risk increases with dose, 53,57,58 (4) there is a great deal of variability in response with some patients, requiring doses of 25 to 50 mg before substantial antihypertensive effects are observed, 22,52,53 and the reduction in BP is greater when baseline BP is highest.…”

Section: Dose Responsementioning

confidence: 99%

Hydrochlorothiazide Versus Chlorthalidone

2004

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Abstract-Thiazide diuretics are one of the preferred pharmacologic treatments for hypertension. Hydrochlorothiazide and chlorthalidone have been the 2 most commonly used diuretics in major clinical trials. Treatment guidelines and compendia often consider these 2 drugs interchangeable agents within the class of thiazide or thiazide-like diuretics. Many sources list them as equipotent. Despite these beliefs, there is some suggestion that cardiovascular outcomes are not necessarily the same with these 2 drugs. We conducted a literature search from 1960 to 2003 to identify studies that evaluated the pharmacokinetic and blood pressure-lowering effects of these 2 agents. There are significant pharmacokinetic and pharmacodynamic differences between these diuretics. Chlorthalidone is Ϸ1.5 to 2.0 times as potent as hydrochlorothiazide, and the former has a much longer duration of action. Whether these pharmacokinetic and pharmacodynamic features cause differences in outcomes is not known.

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Treatment of hypertension in the elderly. III. Response of isolated systolic hypertension to various doses of hydrochlorothiazide: results of a Department of Veterans Affairs cooperative study. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents

Cited by 17 publications

References 0 publications

Importance of Potassium in Cardiovascular Disease

Importance of Potassium in Cardiovascular Disease

Hydrochlorothiazide Versus Chlorthalidone in the Management of Hypertension

Hydrochlorothiazide Versus Chlorthalidone

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