Interpretation of Blood Pressure in Epidemiological Studies and Clinical Trials
Wilmer W Nichols, Michael F O'Rourke, Elazer R Edelman, Charalambos Vlachopoulos in McDonald's Blood Flow in Arteries, 2022
The modern era was revolutionized by the SHEP study, initiated by the U.S. NHLBI. SHEP established the importance of systolic blood pressure lowering in older patients with isolated systolic hypertension (ISH), with greatest reduction in stroke (reduced by 37 percent) and cardiac failure (reduced by 54 percent) and lesser (27 percent) reduction in myocardial infarction and coronary death. Active treatment was chlorthalidone (diuretic), with a β-blocker added if target blood pressure was not achieved. The comparator was placebo. SHEP’s results were decisive but led to another query: Were newer more expensive antihypertensive drugs, i.e. ACEIs, CCBs, α-blockers or ARBs, better than the older therapy with diuretics and β-blockers? The NHLBI ALLHAT trial was designed to answer this question and reported in late 2002. Findings (ALLHAT Collaborators, 2002) are consistent with the view that pressure reduction is all important and that the newer drugs (ACEIs, CCBs) have no special advantage for first-line treatment. Most ALLHAT patients did eventually require a cocktail of two or more drugs to achieve blood pressure control.
Diabetes mellitus and cardiovascular disease in the elderly
Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich in Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Other agents are also useful for treatment of hypertension in diabetes. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack (ALLHAT) trial included over 33,000 patients among whom over 35% had type 2 diabetes (100). This large trial compared a thiazide diuretic (chlorthalidone), calcium channel blocker (amlodipine), and ACE inhibitor (lisinopril). Because chlorthalidone was at least as effective as the other agents in preventing cardiovascular events and is less costly, ALLHAT supports the use of this agent as first-line therapy for hypertension. In general, the drugs recommended for first-line treatment of hypertension are calcium channel blockers, ACE inhibitors or angiotensin receptor blocker, and diuretics (101).
Sodium Intake and Hypertension
Austin E. Doyle, Frederick A. O. Mendelsohn, Trefor O. Morgan in Pharmacological and Therapeutic Aspects of Hypertension, 2020
Hypertensitivity reactions are the more serious side effects and are independent of dose. The other side effects are all dose dependent, and their incidence is reduced markedly if the dose of the thiazide is kept small. Doses of chlorothiazide of 500 mg daily or chlorthalidone of 25 mg daily have 70% of the antihypertensive action which can be achieved by larger doses, but have a lower incidence of complications. A dose of 2000 mg of chlorothiazide induces a maximal diuretic effect, but induces a much higher incidence of side effects than 500 mg. Further dose increases increase side effects with little extra therapeutic action (Figure 27).
Novel therapeutic approaches in the management of chronic kidney disease: a narrative review
Published in Postgraduate Medicine, 2023
Panagiotis Theofilis, Aikaterini Vordoni, Rigas G. Kalaitzidis
Diuretics have been a first-class antihypertensive agent since 1960. Their efficacy in the prevention of cardiovascular morbidity and mortality has been confirmed in longitudinal studies and meta-analyses. While loop diuretics are the main pharmacologic option in patients with advanced CKD (estimated GFR (eGFR)<30 ml/min/1.73 m2) [20], thiazide-like diuretics may be of importance. Chlorthalidone and indapamide have a longer duration of action compared to hydrochlorothiazide, with a similar safety profile [20]. In 2021, chlorthalidone was found to be effective in treating hypertensive patients with advanced CKD [21]. The response to chlorthalidone treatment could also be augmented in patients who are already on loop diuretics. Therefore, among patients with advanced CKD and receiving loop diuretics, initiation of chlorthalidone treatment at doses lower than 12.5 mg thrice weekly can be suggested [22]. It should be stated, however, that the use of chlorthalidone has been associated with hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia in patients with advanced CKD [21].
Established and recent developments in the pharmacological management of urolithiasis: an overview of the current treatment armamentarium
Published in Expert Opinion on Pharmacotherapy, 2020
Mohamed Abou Chakra, Athanasios E. Dellis, Athanasios G. Papatsoris, Mohamad Moussa
There is a lack of data regarding adverse, long-term side effects of thiazides used for kidney stone prevention. However, the side effect profile of thiazide diuretics has been well studied in the setting of hypertension. Thiazide‐related side effects are more common with longer‐acting compounds, such as chlorthalidone and metolazone. Among the thiazide‐type diuretics, indapamide has the least significant metabolic derangements. Side effects may include hypokalemia, hypomagnesemia and hyperuricemia [54]. A large, prospective, cohort study (12,550 non diabetic adults [45‐ to 64‐ years old] who did not have diabetes concluded that subjects with hypertension who were taking thiazide diuretics were not at greater risk for the subsequent development of diabetes [55]. Adverse effects of thiazide and thiazide‐like diuretics on male sexual function are decreased libido, erectile dysfunction, and difficult ejaculation [56,57]. In addition, hydrochlorothiazide can cause photosensitivity [58]. There is a lack of data on the metabolic effects of thiazides used to prevent recurrent calcium nephrolithiasis. It remains unclear if metabolic effects occur and increase the risk of cardiovascular disease in otherwise healthy patients with recurrent nephrolithiasis on thiazide prophylaxis [59]. Thiazide prescription is associated with decreased urinary citrate, this is caused by thiazide‐induced hypokalemia, which would stimulate citrate reabsorption in the proximal tubules [60,61].
Drug treatment of hypertension in older patients with diabetes mellitus
Published in Expert Opinion on Pharmacotherapy, 2018
Srikanth Yandrapalli, Suman Pal, Christopher Nabors, Wilbert S. Aronow
In the elderly diabetic patients with hypertension, thiazide diuretics, ACEIs, ARBs, and CCBs are all effective and should be considered as first-line therapies to reduce CV morbidity and mortality [1,103,104]. Elderly hypertensive diabetics can have a multitude of CV comorbidities at which times appropriate antihypertensives should be used which will provide additional CV benefit. Diuretics are an important initial therapy in most cases and should be used for appropriate volume control in diastolic HF patients. Hydrochlorothiazide and chlorthalidone are inexpensive thiazide diuretics and generally well-tolerated in the lower doses which are currently recommended. In hypertensive diabetic patients with persistent albuminuria >300 mg/day or chronic kidney disease stages 1 and 2, initial treatment with ACEIs or ARBs should be considered [1,105,106]. ACEIs and ARBs should be carefully up-titrated in clinical practice to prevent hyperkalemia especially in patients with renal dysfunction [48].
Related Knowledge Centers
- Edema
- Hydrochlorothiazide
- Nephrotic Syndrome
- Renal Tubular Acidosis
- Hypertension
- Heart Failure
- Thiazide-Like Diuretic
- Liver Failure
- Diabetes Insipidus
- Kidney Stone Disease