{"id":1067,"date":"2016-06-10T15:23:13","date_gmt":"2016-06-10T15:23:13","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1067"},"modified":"2017-08-21T10:53:45","modified_gmt":"2017-08-21T10:53:45","slug":"primary-care-corner-with-geoffrey-modest-md-heart-failure-guidelines-the-new-meds","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/06\/10\/primary-care-corner-with-geoffrey-modest-md-heart-failure-guidelines-the-new-meds\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Heart Failure Guidelines: The New Meds"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>The Am Heart Assn\/Am\u00a0College of Cardiol just published their updated 2016 guidelines on the pharmacological therapy of heart failure (HF),\u00a0focusing on the\u00a0newer therapies (see\u00a0doi:10.1161\/CIR.0000000000000435\/-\/DC1)<\/p>\n<p>Details:<\/p>\n<ul>\n<li>Meds for Stage C (symptomatic)\u00a0HF with reduced ejection fraction (HFrEF). Clinical strategy is to use one of these meds\u00a0in combo with evidence-based b-blocker and aldosterone antagonist in\u00a0appropriate patients.<\/li>\n<li>ACE-I\u00a0(Level A evidence): reduces morbidity and mortality in patients with any stage of symptomatic HF (also in asymptomatic, as an aside), with or without coronary artery disease (CAD). Associated with hypotension; renal insufficiency;\u00a0elevated K;\u00a0angioedema in &lt;1%, though higher in women and black patients.<\/li>\n<li>ARBs\u00a0(Level A evidence): thought to help also with decreasing angiotensin II production (which continues despite\u00a0ACE-I\u00a0through alternative enzymatic pathways). ARBs\u00a0reduce\u00a0mortality, esp in ACE-I intolerant patients (they have the same adverse effects, though less cough, presumably because of the\u00a0ACE-I associated bradykinin increases).\u00a0[They do point out that an ARB should be used in those intolerant of ACE-I for cough or angioedema, but\u00a0commenting that they be used in caution in those who develop angioedema with ACE-I; and I\u00a0have personally sent a patient to the ICU twice with severe angioedema, first from an\u00a0ACE-I, then\u00a0from an ARB.\u00a0So I am really cautious to the point of avoiding ARBs if at all possible in ACE-I associated angioedema]. ACE-I may have some advantage over ARBs\u00a0in their\u00a0beneficial vasodilatory effects through the kininase inhibition.<\/li>\n<li>ARNI(Level\u00a0B\u00a0evidence &#8212; moderate quality from 1 or more RCTs): a combo of an ARB and neprilysin, an enzyme that degrades natriuetic peptides, bradykinin, adrenomedullin, and other vasoactive peptides. Valsartan\/sacubitril vs enalapril was associated with 20% decrease in composite of cardiovascular death or HF hospitalization\u00a0(see\u00a0McMurray JJ. N Engl J Med. 2014;371:993). ARNIs are\u00a0also associated with renal insufficiency, hypotension. And they should not be given within 36 hours of last dose of ACE-I, since they can lead to angioedema (because both ACE\u00a0and neprilysin affect bradykinin). Also, should<strong> not use ARNI in setting of patient with any\u00a0history of angioedema<\/strong>.\u00a0No head-to-head comparison of ARB\u00a0and ARNI<\/li>\n<li>Ivabradine\u00a0(Level\u00a0B\u00a0evidence &#8212; moderate quality from 1 or more RCTs): lowers heart rate by a direct effect on the sinoatrial node, with heart rate lowering being the posited mechanism of action for improving HF. one RCT (the SHIFT trial, Swedberg K. Lancet 2010; 376: 875)showed reduction in HF hospitalizations. The target of treatment was lowering the heart rate, BUT only 23% of the patients were on the\u00a0optimal dose of b-blockers<\/li>\n<\/ul>\n<ul>\n<li>One confusing thing in this guideline is that, though they promote ACE-I and ARB with strong ratings (both Level A evidence), they\u00a0pretty clearly highlight the one positive study of\u00a0valsartan\/sacubitril\u00a0and do seem to push the ARNI, albeit with caveats about the angioedema (e.g., stating:\u00a0&#8220;In patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality&#8221;).\u00a0One general concern of mine is that ARNIs do have a pretty wide effect on major enzyme systems (i.e., shotgun vs targeted bullet), which does raise\u00a0the concern about other adverse effects, those not detected in the short-term 27-month N Engl J Med study above. This study\u00a0did find twice as many\u00a0patients\u00a0developed angioedema (19 vs 10 patients, in a study of 8442 patients, though statistically nonsignficant). Would that number increase with more prolonged use? What about the long-term effects of\u00a0all the other vasoactive\/other\u00a0enzymes which are inhibited by neprilysin? [i.e., those general enzyme systems are likely there for a reason&#8230;.]<\/li>\n<li>Ivabradine has a somewhat lower recommendation: it &#8220;can be beneficial to reduce HF hospitalizations for patients with symptomatic (NYHA class II-III) stable chronic HFrEF (LVEF&lt;35%)&#8230;\u00a0on a beta blocker at maximum tolerated\u00a0dose&#8221; and who are in sinus rhythm\u00a0with\u00a0a resting\u00a0heart rate of &gt;=70.<\/li>\n<li>The committee chairs had no conflicts of interest reported, though 6 of the 15 committee members did.<\/li>\n<\/ul>\n<p>So, how should this change practice?<\/p>\n<ul>\n<li>It is important to remember and acknowledge the baseline: the use of ACE-I, ARB, b-blockers and aldosterone antagonists has so dramatically improved the prognosis and function of patients with HFrEF over the past couple of decades, such that many of my\u00a0patients, even with symptomatic HF\u00a0and severely reduced EF are living long and active lives.<\/li>\n<li>The data on valsartan\/sacubitril is indeed impressive (including the 20% decrease in mortality on subgroup analysis), though given how well patients are doing with optimized older medical therapy, and given the somewhat shotgun effects that this new\u00a0drug combo has on several important enzyme systems, I personally am not ready to use it until more and longer-term data is available (though I would really consider it in patients with suboptimal functional improvement with ACE-I\/ARBs).<\/li>\n<li>In terms of ivabradine, I am less enthusiastic because of the study limitations. This was also\u00a0short term trial (23 months), and a\u00a0significant majority\u00a0were not on full-dose b-blockers. Given the strong data supporting the use of b-blockers, I would primarily promote them. I would consider ivabradine in those not tolerant of b-blockers, though\u00a0keeping in mind that in the SHIFT trial\u00a0there was a 15% higher\u00a0rate of atrial\u00a0fibrillation, and more symptomatic bradycardia and visual side-effects<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: Heart Failure Guidelines: The New Meds  [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/06\/10\/primary-care-corner-with-geoffrey-modest-md-heart-failure-guidelines-the-new-meds\/\">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-1067","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\/1067","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=1067"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1067\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=1067"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=1067"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=1067"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}