There has been a major revolution in the management of heart failure with the introduction of ARNI (Sacubitril + Valsartan) which is now established to have significant benefits for patients suffering from HFrEF, NYHA class II to III. Its use has led to a significant reduction in the number of hospitalizations and improvement in QOL (Quality-of-Life) due to increase in the tolerance of the patients. This drug is a combination molecule comprising of ARB Valsartan together with Neprilysin inhibitor Sacubitril. Neprilysin is an endopeptidase inhibiting natriuretics while sacubitril ensures a prolonged circulatory life span of natriuretic peptides. The dual mechanism of the two drugs leads to diuresis, natriuresis and may also be accompanied by significant lowering of the blood pressure.

Most patients of heart failure, especially due to metabolic syndrome, diabetes, CAD, and cardiomyopathy, are often accompanied by rise in serum creatinine which may be due to pre-existing kidney disease such as diabetic glomerular disease, hypertensive nephrosclerosis or ischemic nephropathy. Mild CKD can also be attributed to other coincidental causes which have been so far undetected or unnoticed but becomes apparent when heart failure ensues. HF itself causes fall of GFR due to renal hypoperfusion from low cardiac output.

The dilemma that the Cardiologist faces when deciding to use ARNI, arises from the three probable side effects of this drug i.e., rise in creatinine, rise in potassium and fall of blood pressure. When the Cardiologist calls upon his Nephrologist colleagues to assist in the management of patients such as the case describe here in, the approach described below is recommended.

Male 38 years old, suffering from Cardiomyopathy since 4 years is in chronic heart failure, NYHA class II, edema, JVP elevated. BP 100/70, basal Rales liver+. Serum Cr 1.8 milgm %, urine shows occasional Casts, micro Alb 200 miligram/24 hrs, he is taking 100 mg furosemide daily. Diagnosis CRS type II CKD due to CHF.

The echocardiogram reveals EF 40%. The cardiologist would like to start ARNI. The Nephrologist would best advise him as follows.

The case is identified as HFrEF with CKD stage 3A (eGFR by EPI 46 ML/Min). It is advisable to admit the patient and get report of Serum Sodium, Potassium, chloride and bicarbonate. The drug is best avoided if serum potassium is more than 5.0 Meq/L. The patient should be weighed, and weight recorded when the drug is started. Furosemide should be withdrawn. ARNI should be started at dose of 25 mg BID, and then gradually titrated upwards watching the Cr. K+, daily and BP at least 4 Times a day in sitting position with close observation for adverse symptoms. Any increase of SK+ to more than 5 Meq/L would necessitate withdrawal of this drug and reinstatement after Potassium sparing measures as outlined below. Any reduction in GFR, more than 20% would also necessitate withdrawal of this drug. Experience, however has shown that severity of these Side effects is not very common when the dose is gently increased rather than rushing in to higher dose. It will also be noted that the patient will lose weight. BP in sitting position should be taken twice day should not be allowed to fall below 110 mm/Hg in young patients and 125mm/Hg in older individuals, i.e. above age 60 years.

In the prevention and management of ensuing hyperkalemia the only available Potassium Binding Resin in India is Calcium Polystyrene. It has immediate action and can be safely administered when potassium has suddenly gone up to between 5.1 and 6.0.Meq/L. When SK+ is beyond 6.0 Meq/L there should be immediate administration of other potassium reducing measures i.e. salbutamol inhalation, Calcium Gluconate IV inj. Glucose insulin drip and Soda bicarb infusion (if patient does not have pulmonary edema which may be aggravated by soda bicarb). Such a patient should be monitored in the ICU until potassium comes down below 5.1. Meq/L. It may appear to the reader that SK+ of 5.1 Meq/L is an over correction as lab value of 5.5 Meq/L are considered normal in non-CKD patients, but the CKD patients are much more prone to mild hyperkalemia in the range of 5.1 to 5.5 Meq/L than non-CKD patients. So better safe than sorry.

Calcium Polystyrene is an excellent drug, but it is often complicated by constipation and therefore should be administered with oral Mannitol, Sorbitol or Lactulose to ensure that the resin which acts in the gut passes out of the body and does not stagnate in the colon from where potassium may get reabsorbed. Moreover, more than a few days therapy of Calcium polystyrene given 15 gms one to three times a day or per rectum as a retention enema, can result in severe colonic injury, perforation or intestinal obstruction. Two new drugs i.e. Patiromer of and Sodium Zirconium Cyclosilicate are now available in the US and approved for chronic usage in patients who have chronic hyperkalemia either drug induced or by chronic renal pathology per se.

I have personal experience in 2 of my patients who are taking Patiromer 8 gms once or twice a day and doing very well on chronic long-term basis. I sincerely hope these two medications will soon be available in the India so that the ARNI would be useable in conjunction with these drugs to protect against hyperkalemia.