{"id":1041,"date":"2016-05-04T14:53:20","date_gmt":"2016-05-04T14:53:20","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1041"},"modified":"2017-08-21T10:55:17","modified_gmt":"2017-08-21T10:55:17","slug":"primary-care-corner-with-geoffrey-modest-md-chlorthalidone-is-better-than-hctz-for-hypertension","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/04\/primary-care-corner-with-geoffrey-modest-md-chlorthalidone-is-better-than-hctz-for-hypertension\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Chlorthalidone is Better Than HCTZ for Hypertension"},"content":{"rendered":"<p><strong>\u00a0By Dr. Geoffrey Modest<\/strong><\/p>\n<p>A recent analysis of 24-h ambulatory blood pressure monitoring (ABMP) compared hydrochlorothiazide (HCTZ) with chlorthalidone, finding poor overall\u00a0blood pressure control with HCTZ (see\u00a0Pareek AK.\u00a0J Am Coll Cardiol 2016;67:379).<\/p>\n<p>Details:<\/p>\n<ul>\n<li>54 Indian\u00a0outpatients with stage 1 hypertension (140-159\/90-99 mmHg,\u00a0diagnosed at office visits and confirmed by 24-h ABPM) were randomized to chlorthalidone 6.25mg vs HCTZ 12.5mg vs a sustained released HCTZ (HCTZ-CR) 12.5mg. Followed for\u00a012-weeks [they chose the 6.25mg dose of chlorthalidone, since studies have found it to be 1.5-2.0 x more effective than HCTZ and have a much longer duration of action]<\/li>\n<li>Mean age 46,\u00a050% female, BMI 27, BP 148\/93, 10% current smokers<\/li>\n<li>ABPM was done at baseline, 4\u00a0weeks, 12 weeks<\/li>\n<\/ul>\n<p>Results:<\/p>\n<ul>\n<li>Significant decrease in daytime\u00a0systolic and diastolic blood.\u00a0at week 12:\n<ul>\n<li>HCTZ decreased 7.16\/4.73<\/li>\n<li>Chlorthalidone decreased 12.11\/8.4<\/li>\n<li>HCTZ-CR decreased 7.88\/6.32<\/li>\n<\/ul>\n<\/li>\n<li>But at week 12 of nighttime blood pressures\n<ul>\n<li>HCTZ decreased 4.87\/3.62<\/li>\n<li>Chlorthalidone decreased 10.17\/6.82<\/li>\n<li>HCT-CR decreased 12.66\/10.10<\/li>\n<\/ul>\n<\/li>\n<li>And<strong> NO DIFFERENCE when look at office based blood pressures<\/strong>: all were about 15\/8 mmHg lower<\/li>\n<li>Adverse events: few and not major. Hypokalemia in 2 on HCTZ-CR, 1 on HCTZ and 1 on chlorthalidone; increased uric acid in 3 on HCTZ-CR, 4 on HCTZ, and 2 on chlorthalidone. no diffs in lipids<\/li>\n<\/ul>\n<p>So, this brings up several issues:<\/p>\n<ul>\n<li>HCTZ is the most commonly prescribed antihypertensive in the world, and had &gt;134.1 million prescriptions in 2008, and more than 48 million are written for monotherapy.<\/li>\n<li>There are essentially <strong>no clinical\u00a0outcome data on HCTZ 12.5 mg<\/strong>, a very commonly used dose now\u00a0and one supported by the\u00a0JNCs (e.g. JNC8 &#8220;recommends\u00a0thiazide or thiazide-like diuretics&#8221;, and for HCTZ, &#8220;using 12.5 to 25 mg\/d as initial dose, or chlorthalidone 12.5mg\/d&#8221;). The old studies finding actual\u00a0clinical efficacy for thiazides\u00a0were done using\u00a0much higher doses\u00a0(and, of note, in a few studies using the 50-100mg dosages of HCTZ, there were\u00a0increases in primary cardiac arrests). In\u00a0the MRFIT study in the early 1980s both\u00a0chlorthalidone and HCTZ were used, and in the course of\u00a0the study those on HCTZ were switched to chlorthalidone because of increased cardiovascular mortality\u00a0in the HCTZ group.<\/li>\n<li>There are even some data that combinations of other antihypertensives with low dose HCTZ are\u00a0inferior to combinations with calcium-channel blockers (CCBs): e.g. the\u00a0ACCOMPLISH trial found\u00a0that there was a morbidity\/mortality advantage of the combination benazepril\/amlodipine over benazepril\/HCTZ<\/li>\n<li>There are med adherence data suggesting that HCTZ is among the worst (e.g., see Friedman O. Am J Med 2010: 123; 173)<\/li>\n<li>I sent out another article by Messerli several years ago, which looked at data on 24-hour ABPM by several different antihypertensives, also finding that HCTZ fared poorly (see\u00a0Messerli F. J Am Coll Cardiol 2011; 57: 590). This meta-analysis\u00a0found that HCTZ in doses of 12.5 to 25mg had 1\/2 the blood pressure reduction\u00a0of ACE-I, ARBs, b-blockers, and CCBs (6.5\/4.5 mmHg, vs, respectively, 12.9\/7.7, 13.3\/7.8, 11.2\/8.5, 11.0\/8.1) though<strong> in-clinic BP recordings\u00a0all have about the same BP reduction<\/strong>.<\/li>\n<li>One really\u00a0big concern is that if we are only checking the daytime clinic blood pressure, low dose HCTZ seems to work\u00a0fine, as it was in the above study, but the night-time efficacy is pretty bad (which is a real concern, especially given the high incidence of cerebrovasular and cardiovascular events in the early am!!)<\/li>\n<li>Unfortunately in the US we have more limited choices than in the study: chlorthalidone is only available as 25mg (and, from my experience, the pills are way too small to cut further) and there is no\u00a0extended release form for HCTZ<\/li>\n<li>One\u00a0caveat here is that the vast majority of the anti-HCTZ articles involve Franz Messerli, who is a renowned hypertension researcher over the years, but there is always a little twinge of concern when the conclusions are largely related to one person (though\u00a0a study by Freis ED in 1986 &#8211;see Magee PF, Freis ED. Hypertension 1986; 8: 135 (supplement 2) &#8212; did conclude: &#8220;12.5 mg of HCTZ per day has no significant antihypertensive effect&#8221;). And the meta-analysis above did include\u00a0studies done by\u00a0other investigators (e.g. a Mayo Clinic study: Finkielman JD. Am J Hypertens. 2005; 18: 398)<\/li>\n<li>So, what should one do?\n<ul>\n<li>I have stopped using HCTZ 12.5-25 as an initial agent for hypertension for several years now, since the Messerli articles came out, and since there are so many good alternatives with 24-hour efficacy. And\u00a0the Ontario study on medication adherence showed such low medication adherence rates. I am also\u00a0really concerned that the good clinic-based blood pressure readings on low-dose HCTZ may be creating a delusion of its actual\u00a0effectiveness, both for us and patients.<\/li>\n<li>I initially tried chlorthalidone as first-line therapy, but the 25 mg tablet causes too much hypokalemia (there were a recent study showing that it really is no worse than HCTZ 25 mg, but I have had several patients on chlorthalidone 25mg with pretty striking hypokalemia)<\/li>\n<li>In terms of pharmacokinetics, I think amlodipine is the best. It does well in the 24-hour ABPM studies, and there are other studies showing less blood pressure variability with it over ACE-I\/ARB\u00a0for example. And there have been several studies on blood pressure variability showing an increase in strokes in those on meds with more variability (includign ACE-I). If a person is on an ACE-I\/ARB and needs a second agent, I usually will try a CCB instead of the combo pill with HCTZ<\/li>\n<li>I would be happy to try chlorthalidone if it were available in the lower doses, and the above study with only 6.25mg looks pretty good to me. By the way, Messerli et al really single out HCTZ as the bad one, not indapamide. So that may be an option, though I have not used it.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: Chlorthalidone is Better Than HCTZ for Hypertension [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/04\/primary-care-corner-with-geoffrey-modest-md-chlorthalidone-is-better-than-hctz-for-hypertension\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-1041","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1041","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=1041"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1041\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=1041"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=1041"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=1041"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}