In: Post TW, ed. Table 2. August P. Angiotensin Converting Enzyme Inhibitors and Receptor Blockers in Pregnancy. Furthermore, discontinuation was observed in 15-25% of patients (5). A dramatic effect on mortality in patients that did not receive or discontinued therapy with RAASi was reported by a Swedish registry (6). In addition and more importantly, patients who did receive medication, were frequently underdosed, because these patients were at increased risk for concomitant adverse events (2-4). Use of angiotensin converting-enzyme inhibitors and angiotensin receptor blockers in CKD. The increasing longevity of humans results in a higher number of elderly patients’ presenting with multiple chronic diseases such as hypertension, diabetes, and chronic kidney disease (CKD). 29, 2020 - Profs. 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. Franzosi MG, Santoro E, Zuanetti G, et al. Hence, Zannad emphasised that patients be maintained on RAASi medication when they are at risk of hyperkalaemia, thereby offering patients a life-saving therapy. McMurray JJV, et al., N Engl J med. Renin-angiotensin-aldosterone system inhibitors (RAASi) are the cornerstone of treatment of heart failure with reduced ejection fraction (HFrEF). Cooper WO, Hernandez-diaz S, Arbogast PG, et al. Clinical pharmacokinetics and pharmacodynamics of Aliskiren. 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. 10. Packham DK, et al., N Engl J Med. 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] . Lecture - Apr. 2014;7:51-58, 9. Pitt B, et al., Eur Heart J 2011;32:820-828. Lisbon 2017. Harel Z, Gilbert C, Wald R, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. The DIAMOND study is designed to further support the use of Veltassa ® to effectively control high blood potassium levels, thereby enabling optimal RAASi therapy in HF patients. Definition of Hyperkalemia. Patiromer DDIs. In: Post TW, ed. Palmer BV. Many factors affect potassium homeostasis.2 Table 1. Townsend RR. 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. Effect of Enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. UpToDate. These increased risks of mortality are similar for all types of RAASi. Therefore, discontinuation of RAASi is not needed when levels are below this line and only dose reduction or temporary dose reduction should be considered. 2020. Only potassium levels above 5.5 mmol/L increase the risk of mortality (7), meaning that there is not much concern when potassium levels are elevated but stay below 5 mmol/L. Normally, angiotensin II constricts efferent vessels and thereby increases the GFR. We balanced our views on efficacy with the safety data. ACE inhibitors antagonize the conversion of angiotensin I to angiotensin II, thereby reducing the GFR!References:[2][8][13][14][15][16]. 2014;34:333-339, 20. Enabling and optimising RAASi therapy for cardio-renal patients by controlling potassium levels Organized by Vifor Pharma SESSION INFORMATION. 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. POINTER: While the RASI method is an integral part Valsartan, candesartan, losartan, irbesartan, References:[1][2][3][4][5][6][7][7][8][9], 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:[8][11][12]. A common side effect of ACE inhibitors is a bradykinin-induced cough, which may necessitate switching to an alternative therapy (e.g. 22, 2018 - John Deanfield, Francesco Cosentino, Filip Knop - Online CME, 10' education - June 5, 2018 - Stefano Taddei, Cees Tack, Massimo Volpe - Online CME, 10' education - Mar. 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. Shionoiri H. Pharmacokinetic drug interactions with ACE inhibitors. Do not combine direct renin inhibitors with ACE inhibitors or ARBs, especially in patients with diabetes or pre-existing kidney disease!References:[17][18][19][20][21], , which increases the retention of water and sodium, Contraindications for ACE inhibitors and ARBs, : GFR is already decreased and further reduction may lead to. 12. Renin angiotensin aldosterone system inhibitors/antagonists/blockers (RAASi) are a cornerstone in treatment of patients with cardiovascular diseases especially in those with heart failure (HF) due to their proven effect on surrogate and hard endpoints. Methods for Improvement Consultants © 2015 RASI Chart What is it? In: Post TW, ed. hypertension or heart failure) have been relatively low (0.4–8.1% [3,20]) while data on the patterns of RAASi therapy following hyperkalemia in CKD in routine clinical settings are limited. Cagnoni F, Njwe CA, Zaninelli A, et al. - PLoS Biol 2020, Literature - Sep. 28, 2020 - Mayl JJ et al. - J Am Coll Cardiol 2020, 5' education - Oct. 7, 2020 - Aernoud Fiolet, MD and prof. Jan Hein Cornel, MD, PhD, 10' education - Oct. 20, 2020 - Prof. Richard Hobbs, MD, 5' education - Jan. 15, 2020 - Thomas Gaziano, MD, Literature - Nov. 4, 2019 - Alexander M et al, - BMJ 2019, Literature - Dec. 15, 2020 - Castañer O, et al. failure receiving a sub-optimal dose of RAASi therapy. Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. Notably, the high rates of RAASi use indicate that the patients were well-treated at baseline. Shirazian S, et al., Am J Med Sci. Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP. SZC DDIs. He showed that RAASi are frequently omitted or discontinued in clinical practice, although HF guidelines strongly recommend the use of RAASi for several indications. ... Impact of Novel K+ Binders on RAASi Therapy. - Eur Heart J. mmol/l) alongside standard treatment with insulin -glucose and salbutamol. Aliskiren: Drug Information. Bicket DP. 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. These adverse events comprised mainly persistent and consistent hyperkalaemia and/or worsening renal function. 2015;17:1032-1041, 7. The selection is not exhaustive. A second study showed similar results for patients with stage 3-4 CKD, HF and diabetes and remarkably, mortality rates were almost comparable for patients who received reduced doses and those who discontinued. Reported percentages of RAASi therapy (single or dual) discontinuation due to hyperkalemia from randomized trials of various patient groups (e.g. He showed that RAASi are frequently omitted or discontinued in clinical practice, although HF guidelines strongly recommend the use of RAASi for several indications. But what if there was a better way to lower potassium levels so that these patients could reach those target doses? Hyperkalaemia can be prevented by monitoring potassium levels, which can be done by e.g. Raebel MA, et al., Pharmacoepidemiology and drug safety 2007;16:55-64. Phillips CO, et al., Arch intern med. Ayatollahi A, Toossi P, Younespour S, Robati R. Serum angiotensin converting enzyme in pemphigus vulgaris. For a vast majority of the HFpEF patients, a RAASi‐based therapy is used. Target Audience and Goal Statement. They are particularly important in the treatment of hypertensive diabetic patients, as they prevent the development of diabetic nephropathy. 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. Roett MA, Liegl S, Jabbarpour Y. Diabetic nephropathy - the family physician's role. In: Post TW, ed. Unfortunately, it has been shown that measurements of potassium are not regularly executed in common practice (9). Pitt B, et al., N Engl J Med 2003;348:1309-1321, 18. However, when alternative definitions of RAASi exposure were investigated (such as only including patients in receipt of RAASi over the duration of the follow-up period, or intervals where a RAASi therapy had been prescribed), the association pattern between serum potassium levels and the likelihood of RAASi discontinuation was preserved. These problems increase morbidity and mortality in the elderly. Prof. Zannad explained the implementation of RAAS inhibitors (RAASi) for the treatment of HF in clinical practice and their clinical impact. Renin-angiotensin-aldosterone system inhibitors (RAASi) are of prognostic benefit in patients with heart failure with reduced ejection fraction (HFrEF) and post myocardial infarction (MI) left ventricular systolic dysfunction (LVSD) and as such should be continued wherever possible for these indications. 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). Multidisciplinary Approach to Managing Chronic Hyperkalemia. Discontinuation and reinitiating medication can be guided by an algorithm, for instance as used in EMPHASIS-HF (8). The selection is not exhaustive. Gheorghiade M, et al., Congest heart fail. Share this page with your colleagues and friends: 10' education - Feb. 11, 2020 - Prof. Deepak Bhatt, MD - Online CME, 10' education - Feb. 4, 2020 - Jorge Plutzky, MD - Online CME, 10' education - Jan. 16, 2020 - Prof. Børge Nordestgaard, MD, 10' education - Dec. 10, 2020 - Prof. Subodh Verma, MD, 10' education - Dec. 3, 2020 - Prof. Eduard Montanya, MD, 10' education - Dec. 1, 2020 - Prof. Naveed Sattar, MD, 10' education - Mar. - Circ Heart Fail 2020, 10' education - Aug. 27, 2018 - Burkert Pieske, MD - Berlin, Germany - Online CME, Slides (presentation) - Aug. 27, 2018 - Carolyn Lam, MD - Singapore, 10' education - Aug. 27, 2018 - Barry Borlaug - Rochester, MN, USA - Online CME, Literature - Dec. 8, 2020 - Elbatreek MH, et al. 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 Presently, RAASi treatment is frequently discontinued due to the risk of hyperkalaemia (elevated blood potassium levels). Add favourite. 2014;371:993-1004, 16. The risk doubled compared with patients receiving the therapy, regardless of having renal insufficiency. 2015 Jan 15;372(3):222-31. 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. Standards of Medical Care in Diabetes 2016. Acute Versus Chronic Hyperkalemia 3, 4 2007;167:1930-1936, 14. Safety. or other drugs that increase potassium level: preferably in controlled setting) is recommended to avoid severe. Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination. Potassium levels quickly rise after induction of RAASi, but the risk of hyperkalaemia is low if you monitor potassium properly. - J Am Coll Cardiol. 2012;18:9-17, 4. Major Side Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers. 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. 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