Sacubitril/valsartan

In the largest HF trial ever conducted; more than 8400 patients randomized

(PARADIGM-HF)

Indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II‐IV) and reduced ejection fraction.

Usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB.

Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Use is contraindicated in patients with a history of angioedema related to previous angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy.

Use did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and ejection fraction of 45% or higher ( Solomon SD).

Use is contraindicated with concomitant use of ACE inhibitors, and should not be administered within 36 hours of switching from or to an ACE inhibitor.

Contraindicated with concomitant use of aliskiren in patients with diabetes.

May cause angioedema, and when associated with laryngeal edema may be fatal.

Associated with a higher rate of angioedema in Black patients and in patients with a prior history of angioedema.

Lowers blood pressure and may cause symptomatic hypotension, and patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients are at greater risk.

Among patients with heart failure with reduced ejection fraction hospitalized for acute decompensated heart failure, the initiation of sacubitril-valsartan therapy lead to a greater reduction in the NT-pro BNP concentration than enalapril therapy (VelasquezEJ).

In patients with HFrEF treatment with sacubitril-valsartan, the reduction in NT-pro BNP was weakly yet significantly correlated with improvements in markers of cardiac volume and function at 12 months.

Treatment with HFrEF with sacubitril-vasaltran, compared with enlapril, did not significantly reduce central aortic stiffness (Cesar AS).

Volume or salt depletion prior to administration should be corrected.

Decreases in renal function may be anticipated in susceptible individuals.

Treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria, progressive azotemia and, rarely, acute renal failure and death.

May increase blood urea and serum creatinine levels in patients with bilateral or unilateral renal artery stenosis.

In patients who are elderly, volume-depleted, those on diuretic therapy, or with compromised renal function, concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors, may result in worsening of renal function, including possible acute renal failure.

Hyperkalemia may occur and monitoring serum potassium may be required.

Concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium.

ARBs: Avoid use with an ARB, because the drug contains the angiotensin II receptor blocker valsartan.

Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists.

Most commonly observed adverse events: are hypotension (18%, 12%), hyperkalemia (12%, 14%), cough (9%, 13%) dizziness (6%, 5%) and renal failure/acute renal failure (5%, 5%).