Safety and Tolerability of Neurohormonal Antagonism in Cardiac Amyloidosis

Abstract

Background: Drugs for neurohormonal antagonism are usually denied to patients with cardiac amyloidosis (CA) because of safety concerns.

Methods: Patients diagnosed with CA at a tertiary referral centre from 2009 to 2019 were enrolled. In the absence of contraindications, beta-blockers, angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB), and mineralocorticoid receptor antagonists (MRA) were started or up-titrated.

Results: 99 patients were evaluated (72% men, age 80 years [72,83], 33% light-chain and 67% transthyretin amyloidosis); 56% were started on or underwent up-titration of a beta-blocker, 25% of ACEi/ARB, and 39% of MRA; beta-blockers were then prescribed to 87% of patients, ACEi/ARB to 75%, and MRA to 63%, with median bisoprolol, ramipril, valsartan, and spironolactone daily equivalent doses of 2.5 mg, 5 mg, 80 mg, and 25 mg, respectively. Patients starting or starting/up-titrating a beta-blocker did not show a higher frequency of hypotension, fatigue, syncope, symptomatic bradycardia, need for pacemaker implantation, or HF hospitalization. Lower stroke volume and cardiac output (CO) predicted HF hospitalization regardless of amyloidosis type; lower left ventricular ejection fraction predicted hypotension, and lower CO and diastolic blood pressure predicted syncope. Patients who had an ACEi/ARB or MRA being started or up-titrated did not experience more adverse events than other patients.

Conclusions: ACEi/ARB and MRA can be safely used in CA, provided that no contraindications are present, treatment is started at a low dose and slowly up-titrated, and patients are monitored quite closely. Beta-blocker therapy is less tolerated in patients with AL amyloidosis and/or worse haemodynamic function.

Keywords: Cardiac Amyloidosis; Drugs; Neurohormonal Antagonism; Safety.