{"id":131932,"date":"2022-11-09T12:04:50","date_gmt":"2022-11-09T17:04:50","guid":{"rendered":"https:\/\/cardiologynownews.org\/?p=131932"},"modified":"2022-11-09T12:12:09","modified_gmt":"2022-11-09T17:12:09","slug":"brightn-baxdrostat-an-aldosterone-synthase-inhibitor-showed-dose-related-reductions-in-blood-pressure-in-safely-and-effectively-lowers-blood-pressure-in-patients-with-resistant-hypertension-compar","status":"publish","type":"post","link":"https:\/\/cardiologynownews.org\/?p=131932","title":{"rendered":"BrigHTN: Baxdrostat, an aldosterone synthase inhibitor,  showed dose-related reductions in blood pressure and safely and effectively lowers blood pressure in patients with resistant hypertension"},"content":{"rendered":"<p>Key Points<\/p>\n<ul>\n<li>In a Phase 2 randomized trial, baxdrostat, a highly potent and selective aldosterone synthase inhibitor, had dose-related reductions in blood pressurein patients with resistant hypertension compared to placebo, without any serious adverse events.<\/li>\n<\/ul>\n<p><!--more--><\/p>\n<p>Difficult to control hypertension is associated with elevated cardiovascular risk.\u00a0 Spironolactone, a mineralocorticoid receptor antagonist, is recommended by current guidelines for treatment of resistant hypertension.\u00a0 Baxdrostat has been shown in Phase 1 trials to selectively inhibit aldosterone synthase and thereby reduce aldosterone levels without significantly affecting cortisol levels. \u00a0\u00a0On November 7, 2022 during the American Heart Association 2022 Late-Breaking Science Session on Resistant Hypertension, Dr. Mason Freeman presented the Phase 2 results of BrgHTN, simultaneously published in the <em>New England Journal of Medicine.<\/em><sup>1<\/sup><\/p>\n<p>In this multicenter trial funded by CinCor Pharma, 275 patients on three or more antihypertensive medications (including at least one diuretic) with a blood pressure &gt;=130\/80 averaged over three seated measurements 5 minutes apart were randomized in a parallel fashion to once daily baxdrostat 0.5mg (n=69), baxdrostat 1 mg (n=70), baxdrostat 2mg (n= 67), or placebo (n=69) and followed for 12 weeks.\u00a0 Patients with systolic pressure &gt;= 180 mmHg, diastolic pressure &gt;=110mm Hg, estimated glomerular filtration rate of &lt;45 ml\/min\/1.73 m<sup>2<\/sup>, or poorly controlled diabetes were excluded.\u00a0 If patients were on spironolactone at baseline, it was stopped four weeks prior to randomization.\u00a0 In addition, patients had to be at least 70% compliant with their medication regimen based on pill counts during a single blind run-in period prior to randomization. The primary endpoint was change in blood pressure from baseline for each study drug dose compared to placebo.<\/p>\n<p>Overall, participants were in their 60s with a slight male predominance, about 25% were Black and 40% Hispanic or Latino.\u00a0 Over 90% of patients were on an ACE inhibitor or angiotensin receptor blocker.<\/p>\n<p>The trial was stopped early because it met the criteria for overwhelming efficacy.\u00a0 By week 12, the least-squares mean systolic blood pressure decreased in a dose dependent manner: -20.3 mm Hg in the 2mg group, -17.5 mm Hg in the 1mg group, -12.1 mm Hg in the 0.5mg group, and -9.4 mm Hg in the placebo group.\u00a0 There was a significant difference in blood pressure drop between the 2-mg group and the placebo group (-11mm Hg, 95% confidence interval [CI] \u221216.4 to \u22125.5, P&lt;0.001) as well as between the 1-mg group and the placebo group (-8.1 mm Hg, 95% CI -13 to -2.8, P=0.003), but not between the 0.5mg group and the placebo group.\u00a0 There were no deaths or episode of adrenal insufficiency.\u00a0 Two patients in the intervention arm had the study drug temporarily held for potassium &gt; 6.0 mmol\/L; the values normalized on recheck and the medication was restarted without any recurrence of hyperkalemia.<\/p>\n<p>In conclusion, baxdrostat 2mg significantly lowered blood pressure in patients with resistant hypertension compared to placebo.\u00a0 The secondary analysis showed that baxdrostat reduced aldosterone levels and increased plasma renin activity without changing cortisol levels.\u00a0 \u201cWe have beautiful biomarker evidence, not only of blood pressure lowering, but the mechanism by which the blood pressure reduction is occurring,\u201d said Dr. Freeman.\u00a0 \u00a0\u201cWe believe that baxdrostat has the potential to treat disorders associated with aldosterone excess, including primary hyperaldosteronism.\u201d<\/p>\n<p>The authors point out that there has not been a new class of anti-hypertensive medication approved in the United States since 2007.\u00a0 Baxdrostat is a promising novel agent that may safely reduce blood pressure among those that are the hardest to treat.\u00a0 The effect of this medication on cardiovascular outcomes and the safety of this medication in those with chronic kidney disease will be the subject of future studies.\u00a0 Phase 3 trials are planned for 2023.<\/p>\n<ol>\n<li>Freeman MW, Halvorsen Y-D, Marshall W, et al. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. N Engl J Med [Internet] 2022;1\u201311. Available from: http:\/\/www.nejm.org\/doi\/10.1056\/NEJMoa2213169<\/li>\n<\/ol>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Key Points In a Phase 2 randomized trial, baxdrostat, a highly potent and selective aldosterone synthase inhibitor, had dose-related reductions in blood pressurein patients with resistant hypertension compared to placebo, without any serious adverse events.<\/p>\n","protected":false},"author":40603,"featured_media":131933,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[875,169,8],"tags":[876,45,47,72,185],"ppma_author":[1029],"class_list":{"0":"post-131932","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-aha-2022","8":"category-hypertension","9":"category-news","10":"tag-aha-2022","11":"tag-conference","12":"tag-featured","13":"tag-hypertension","14":"tag-news","15":"author-leah-kosyakovsky"},"authors":[{"term_id":1029,"user_id":40603,"is_guest":0,"slug":"leah-kosyakovsky","display_name":"Leah Kosyakovsky","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/864bde69f6f1f80e91e4a97f0a0ba8daa64c2bb702be09ed787444c7dfa045bb?s=96&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/131932","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/users\/40603"}],"replies":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=131932"}],"version-history":[{"count":2,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/131932\/revisions"}],"predecessor-version":[{"id":131935,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/131932\/revisions\/131935"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/media\/131933"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=131932"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=131932"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=131932"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=131932"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}