The effects of short-term omission of daily medication on the pathophysiology of heart failure

Aims: Pharmacological therapies for heart failure (HF) aim to improve congestion, symptoms, and prognosis. Failing to take medication is a potential cause of worsening HF. Characterizing the effects of short-term medication omission could inform the development of better technologies and strategies to detect and interpret the reasons for worsening HF. We examined the effect of planned HF medication omission for 48 h on weight, echocardiograms, transthoracic bio-impedance, and plasma concentrations of NT-proBNP. Methods and results: Outpatients with stable HF and an LVEF <45% were assigned to take or omit their HF medication for 48 h in a randomized, crossover trial. Twenty patients (16 men, LVEF 32 ± 9%, median NT-proBNP 962 ng/L) were included. Compared with regular medication, omission led to an increase in NT-proBNP by 99% (from 962 to 1883 ng/L, P < 0.001), systolic blood pressure by 16% (from 131 to 152 mmHg, P < 0.001), and left atrial volume by 21% (from 69 to 80 mL, P = 0.001), and reductions in transthoracic bio-impedance by 10% (from 33 to 30 Σ, P = 0.001) and serum creatinine by 8% (from 135 to 118 µmol/L, P = 0.012). No significant changes in body weight, heart rate, or LVEF were observed. Conclusions: The characteristic pattern of response to short-term medication omission is of increasing congestion but, in contrast to the pattern reported for disease progression, with a rise in blood pressure and improved renal function. In stable HF, weight is not a sensitive marker of short-term diuretic omission.