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      Diuretics in primary hypertension – Reloaded

      editorial
      Indian Heart Journal
      Elsevier
      Diuretics, Hydrochlorothiazide, Chlorthalidone, Indapamide, Mortality, Cardiovascular outcome

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          Abstract

          Diuretics have long been cherished as drugs of choice for uncomplicated primary hypertension. Robust mortality and morbidity data is available for diuretics to back this strategy. Off-late the interest for diuretics has waned off perhaps due to availability of more effective drugs but more likely due to perceived lack of tolerance and side-effect profile of high-dose of diuretics required for mortality benefit. Low-dose diuretics particularly thiazide diuretics are safer but lack the mortality benefit shown by high-dose. However, indapamide and low dose chlorthalidone have fewer side-effects but continue to provide mortality benefit.

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          Most cited references29

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          2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

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            Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

            (2002)
            Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is unknown. To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002. A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers. Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15 255); amlodipine, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 years. The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure [HF], and peripheral arterial disease). Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P =.03) and lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone, and 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P<.001). For amlodipine vs chlorthalidone, secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI, 1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31). Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.
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              Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group.

              To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension. Multicenter, randomized, double-blind, placebo-controlled. Community-based ambulatory population in tertiary care centers. 4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black. --Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d. Primary. Nonfatal and fatal (total) stroke. Secondary. Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures. Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87. In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000.
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                Author and article information

                Contributors
                Journal
                Indian Heart J
                Indian Heart J
                Indian Heart Journal
                Elsevier
                0019-4832
                Sep-Oct 2016
                10 September 2016
                : 68
                : 5
                : 720-723
                Affiliations
                [0005]Cardiology, AIIMS, New Delhi, India
                Article
                S0019-4832(16)30414-X
                10.1016/j.ihj.2016.08.013
                5079206
                27773415
                41fa4f9c-62d2-44a3-b7f9-d4ea5f5a698c
                © 2016 Published by Elsevier B.V. on behalf of Cardiological Society of India.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Categories
                Editorial Review

                diuretics,hydrochlorothiazide,chlorthalidone,indapamide,mortality,cardiovascular outcome

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