Epstein M, et al., Am J manag care 2015;21:S212-S220, 6. ARBs), while angioedema and hyperkalemia may occur in both ARBs and ACE inhibitor use. Table 2. 2. Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP. Clinicians often struggle to optimize guideline-directed medical therapy in patients with heart failure and frequently lower RAASi therapies in response to episodes of hyperkalemia, which translates into an increased risk for poor outcomes. 2014;34:333-339, 20. hypertension or heart failure) have been relatively low (0.4â8.1% [3,20]) while data on the patterns of RAASi therapy following hyperkalemia in CKD in routine clinical settings are limited. 14-09-2017 18:30 - 20:00 1 viewers. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. ACE inhibitors antagonize the conversion of angiotensin I to angiotensin II, thereby reducing the GFR!References:. ... Impact of Novel K+ Binders on RAASi Therapy. Data of the ESC heart failure registry revealed that while ACEi or ARBs were quite frequently prescribed by practitioners, MRAs were not offered to ~30% of the eligible HF patients with reduced ejection fraction (HFrEF) (1). He showed that RAASi are frequently omitted or discontinued in clinical practice, although HF guidelines strongly recommend the use of RAASi for several indications. The proportion of the population that is elderly (age â¥65 years) is growing across the world. Angiotensin-converting enzyme inhibitors (ACE inhibitors) are a group of medicines that are mainly used to treat certain heart and kidney conditions; however, they may be used in the management of other conditions such as migraine and scleroderma.. Shionoiri H. Pharmacokinetic drug interactions with ACE inhibitors. Renin-Angiotensin System Inhibition in the Treatment of Hypertension. - J Am Heart Assoc. In fact, these diseases are by definition mostly asymptomatic. 2013;15:1173-1184, 3. Di Tano G, et al., Eur J Heart Fail. Hence, Zannad emphasised that patients be maintained on RAASi medication when they are at risk of hyperkalaemia, thereby offering patients a life-saving therapy. John Deanfield, Jan Danser and Murray Epstein, 10' education - Apr. 2015 Jul 14;314:151-61. Clinical pharmacokinetics and pharmacodynamics of Aliskiren. RAASi before starting therapy and between 1 and 2 weeks thereafter as well as after each dose increase to stress the importance of potassium level monitoring during treatment [25, 31] . ACE inhibitors and ARBs are commonly used in the treatment of patients with hypertension, heart failure with reduced ejection fraction, certain types of chronic kidney disease, and patients who have suffered a myocardial infarction. In this study the adjusted incidence rates of hyperkalemia in CKD patients with and without RAASi therapy were 8.22 and 1.77 per 100 patient-months, respectively.2 Interestingly, RAASis seem to induce hyperkalemia even in patients receiving maintenance dialysis,10 most likely due to their effect on gastrointestinal potassium secretion. Literature - Sep. 7, 2020 - Mehta A et al., - J Am Coll Cardiol. The selection is not exhaustive. We balanced our views on efficacy with the safety data. Ayatollahi A, Toossi P, Younespour S, Robati R. Serum angiotensin converting enzyme in pemphigus vulgaris. failure receiving a sub-optimal dose of RAASi therapy. Definition of Hyperkalemia. They are particularly important in the treatment of hypertensive diabetic patients, as they prevent the development of diabetic nephropathy. Read our disclaimer. Valsartan, candesartan, losartan, irbesartan, References:, Acute kidney injury is a potential side effect of all types of RAAS inhibitors, especially in patients with pre-existing kidney disease or in combination with NSAIDs!References:. 2015 Jan 15;372(3):222-31. Notably, the high rates of RAASi use indicate that the patients were well-treated at baseline. Moreover, this algorithm provides information about how frequently potassium levels should be checked. 22, 2018 - Filippo Crea, Angelyn Bethel, Eduard Montanya - Online CME, 10' education - Nov. 24, 2020 - Prof. Francesco Cosentino, MD, 3' education - Dec. 15, 2020 - Prof. van der Meer, MD, PhD, Literature - Dec. 8, 2020 - Unlu O, et al. Using ACE inhibitors appropriately. Methods for Improvement Consultants © 2015 RASI Chart What is it? Therefore, discontinuation of RAASi is not needed when levels are below this line and only dose reduction or temporary dose reduction should be considered. The goal of this activity is to have increased knowledge about the changes in renal function associated with renin-angiotensin-aldosterone system inhibitor (RAASi) therapy and how to manage RAASi therapy and associated hyperkalemia. - J Am Coll Cardiol 2020, 10' education - Dec. 9, 2019 - Prof. Kausik Ray, MD, 10' education - Sep. 30, 2019 - Prof. Wouter Jukema, Literature - Dec. 1, 2020 - Giustino G, et al. Stamp LK, Chapman PT. SZC DDIs. - Eur Heart J. Lisbon 2017. Bicket DP. A common side effect of ACE inhibitors is a bradykinin-induced cough, which may necessitate switching to an alternative therapy (e.g. You give aggressive therapy, you do lab testing, you bring them back to the clinic to prevent worsening of those particular diseases per se. Polónia J. Interaction of antihypertensive drugs with anti-inflammatory drugs. An unmet need exists for new hyperkalemia management guidelines that effectively incorporate classification and monitoring for hyperkalemia, optimization of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, and use of the newer potassium (K +) binders. Safety. The study will evaluate the potential of Veltassa to improve outcomes by enabling heart failure patients, with or without chronic kidney disease, to be treated with renin-angiotensin-aldosterone system inhibitors (RAASi) therapy in accordance with HF treatment guidelines. Causes of Hyperkalemia. *“Dose reduction or discontinuation is not always needed, as hyperkalaemia is just a very expected adverse event of RAASi”*. Dürrenmatt Hall. Franzosi MG, Santoro E, Zuanetti G, et al. However, said Zannad, ‘dose reduction or discontinuation is not always needed, as hyperkalaemia is just a very expected adverse event of RAASi’. In a retrospective study, the frequency of underdosing of RAASi was independent of risk factors such as chronic kidney disease (CKD) and diabetes, and was noted in about two third of patients. In: Post TW, ed. In: Post TW, ed. The benefits of RAAS Inhibition Heart failure and CKD patients treated at guideline target doses of RAAS inhibition consistently have better clinical outcomes than patients who are treated with lower doses or who discontinue treatment1-13 However, their preventive value needs to be investigated. In: Post TW, ed. Gout and its comorbidities: implications for therapy. Do not combine direct renin inhibitors with ACE inhibitors or ARBs, especially in patients with diabetes or pre-existing kidney disease!References:, , which increases the retention of water and sodium, Contraindications for ACE inhibitors and ARBs, : GFR is already decreased and further reduction may lead to. - J Am Coll Cardiol. 10. Palmer BV. 9, 2018 - VBWG at ACC, Orlando, FL, USA - Prof. Mardi Gomberg-Maitland, Falls Church, VA, USA - Online CME, 5' education - Aug. 29, 2017 - ESC 2017, Barcelona, Spain - Prof Nazzareno Galiè - Bologna, Italy, Literature - June 6, 2017 - Kylhammar D, et al. Standards of Medical Care in Diabetes 2016. Potassium levels quickly rise after induction of RAASi, but the risk of hyperkalaemia is low if you monitor potassium properly. N Engl J Med 2004;351:585-592. Maggioni AP, et al., Eur J Heart Fail. Unfortunately, it has been shown that measurements of potassium are not regularly executed in common practice (9). Cagnoni F, Njwe CA, Zaninelli A, et al. Effect of Enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The risk doubled compared with patients receiving the therapy, regardless of having renal insufficiency. Gheorghiade M, et al., Congest heart fail. Write comment. - J Am Coll Cardiol. Mann JF, Hilgers KF. 13. This activity is intended for nephrologists, cardiologists, and primary care physicians. A dramatic effect on mortality in patients that did not receive or discontinued therapy with RAASi was reported by a Swedish registry (6). 19, 2020 - Prof. Jan Danser, PhD, Literature - Oct. 26, 2020 - Everett BM et al. Comparable results have also been shown with eplerenone for HFrEF patients (8). Zannad F, et al., N Engl J Med 2011;364:11-21, 19. A common side effect of ACE inhibitors is a bradykinin-induced cough, which may necessitate switching to an alternative therapy (e.g. Hyperkalaemia can be prevented by monitoring potassium levels, which can be done by e.g. 2020, 10' education - Nov. 24, 2020 - Anthony Fauci, MD. In the nearby future, new potassium binders may optimise RAASi therapy, by allowing uptitration of the dose of RAASi. Target Audience and Goal Statement. Reeder GS. 2014;7:51-58, 9. RAASi therapy was comprised of ACE inhibitors, ARBs, renin inhibitors and MRAs Furuland et al. Study treatment in this study refers to ZS or placebo, while RAASi therapies are considered background therapy and will not be provided by the study sponsor. Discontinuation and reinitiating medication can be guided by an algorithm, for instance as used in EMPHASIS-HF (8). or other drugs that increase potassium level: preferably in controlled setting) is recommended to avoid severe. hypertension or heart failure) have been relatively low (0.4â8.1% [3,20]) while data on the patterns of RAASi therapy following hyperkalemia in CKD in routine clinical settings are limited. Direct renin inhibitors may be considered in hypertensive patients if ACE inhibitors or ARBs are not well tolerated; however, they should never be used in combination with other RAAS inhibitors. 7, 2018 - Prof Guntram Schernthaner - Vienna, Austria - Online CME, Literature - Dec. 15, 2020 - You SC, et al. Who is At Risk for Hyperkalemia? Normally, angiotensin II constricts efferent vessels and thereby increases the GFR. 2014;371:993-1004, 16. Users of renin angiotensin aldosterone system inhibitors (RAASi) or diuretics have a slightly increased risk of acute kidney injury (AKI), new study findings in BMC Nephrology confirm. Methods: A patient-level simulation model was designed to fully characterise the natural history of CKD over a lifetime horizon, and predict the associations between serum potassium levels, RAASi use â¦ 11. Aliskiren: Drug Information. But what if there was a better way to lower potassium levels so that these patients could reach those target doses? Reninâangiotensinâaldosterone system inhibitors (RAASi) are now a standard treatment in most patients with cardiovascular disease, especially in those with heart failure (HF). 2015;17:1075-1083, 15. Use of angiotensin converting-enzyme inhibitors and angiotensin receptor blockers in CKD. The increasing longevity of humans results in a higher number of elderly patientsâ presenting with multiple chronic diseases such as hypertension, diabetes, and chronic kidney disease (CKD). Major congenital malformations after first-trimester exposure to ACE inhibitors. Written and peer-reviewed by physicians—but use at your own risk. heart failure with reduced ejection fraction, Heart failure with reduced ejection fraction, http://care.diabetesjournals.org/content/suppl/2015/12/21/39.Supplement_1.DC2/2016-Standards-of-Care.pdf, https://www.uptodate.com/contents/renin-angiotensin-system-inhibition-in-the-treatment-of-hypertension, http://www.cvphysiology.com/Blood%20Pressure/BP015, https://www.uptodate.com/contents/aliskiren-drug-information, https://www.uptodate.com/contents/angiotensin-converting-enzyme-inhibitors-and-receptor-blockers-in-acute-myocardial-infarction-clinical-trials, https://www.uptodate.com/contents/major-side-effects-of-angiotensin-converting-enzyme-inhibitors-and-angiotensin-ii-receptor-blockers, https://www.uptodate.com/contents/angiotensin-converting-enzyme-inhibitors-and-receptor-blockers-in-pregnancy, https://www2.kidney.org/professionals/kdoqi/guidelines_bp/guide_11.htm, Drug interactions (see “Interactions” below). Harel Z, Gilbert C, Wald R, et al. Many factors affect potassium homeostasis.2 Table 1. We list the most important adverse effects. 2020, 3' education - Sep. 7, 2020 - Prof. Renato D. Lopes, MD, PhD, 5' education - Aug. 27, 2017 - ESC 2017, Barcelona, Spain, 10' education - June 12, 2018 - Prof. Frank Visseren - Utrecht, The Netherlands - Online CME, 10' education - June 12, 2018 - Prof. Richard Hobbs - Oxford, UK - Online CME, 10' education - June 6, 2018 - Prof. Kees Hovingh - Amsterdam, The Netherlands - Online CME, 5' education - Nov. 23, 2020 - Prof. Deepak Bhatt, MD, 3' education - Oct. 27, 2020 - Prof. Kausik Ray, MD, 10' education - Oct. 26, 2020 - Prof. Ulrich Laufs, MD, 10' education - Nov. 3, 2020 - Prof. Erik Stroes, MD, 10' education - Nov. 9, 2020 - Prof. John Kastelein, MD, 3' education - Mar. Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. Shirazian S, et al., Am J Med Sci. Unfortunately, these events are frequently associated with HF (2-4). Townsend RR. McMurray JJV, et al., N Engl J med. Pitt B, et al., N Engl J Med 2003;348:1309-1321, 18. Renin-angiotensin-aldosterone system (RAAS) inhibitors are a group of drugs that act by inhibiting the renin-angiotensin-aldosterone system (RAAS) and include angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), and direct renin inhibitors.