Spironolactone withdrawal
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Spironolactone Withdrawal: Implications and Outcomes
Spironolactone Withdrawal in Dilated Cardiomyopathy
Relapse Rates and Cardiac Function
Spironolactone withdrawal in patients with dilated cardiomyopathy who have shown improved ejection fraction (EF) is associated with a high relapse rate. A study involving 70 patients found that 58% of those who discontinued spironolactone experienced a relapse, compared to only 13% in the continuation group. Relapse was defined by a significant reduction in left ventricular ejection fraction (LVEF), increased left ventricular end-systolic volume index (LVESVi), elevated NT-proBNP levels, or clinical signs of heart failure . These findings suggest that discontinuing spironolactone can lead to deterioration in cardiac function and symptom aggravation.
Study Design and Safety Considerations
Another study aimed to evaluate the safety of spironolactone withdrawal in heart failure patients with improved ejection fraction (HFiEF). This study will randomize 60 patients into two groups: one continuing spironolactone and the other withdrawing it. The primary outcome is the proportion of patients with a decline in LVEF by 10% or more. Secondary outcomes include changes in LVEF, renal function, and adverse clinical events such as death or re-hospitalization . This trial will provide further evidence on whether spironolactone should be maintained in patients with HFiEF.
Effects on Hypertension and Renal Function
Hemodynamic Changes
In patients with essential hypertension, spironolactone treatment led to minor adjustments in systemic and renal circulation. During treatment, body weight and plasma volume decreased, while plasma renin activity (PRA) and plasma aldosterone (PA) levels increased significantly. After withdrawal, body weight and plasma volume increased, and PRA and PA levels fell. Mean arterial blood pressure (MAP) increased in most patients after discontinuation . These findings indicate that spironolactone withdrawal can reverse some of the beneficial hemodynamic effects observed during treatment.
Hyperandrogenic Skin Disorders
Long-Lasting Effects
Spironolactone is effective in treating hyperandrogenic skin disorders such as hirsutism, acne, and alopecia. A study involving 63 women with polycystic ovary syndrome (PCOS) found that spironolactone treatment led to significant improvement in skin symptoms. Notably, 38 patients experienced prolonged benefits even 33.7 months after discontinuation, while 20 patients relapsed 17.5 months post-withdrawal . This suggests that spironolactone can have long-lasting effects even after cessation, although some patients may experience a relapse.
Opiate Withdrawal
Attenuation of Withdrawal Symptoms
Spironolactone has been shown to attenuate the somatic signs of opiate withdrawal by blocking mineralocorticoid receptors (MR). In a study on rats, spironolactone pretreatment reduced the physical signs of withdrawal induced by naloxone in morphine-treated animals. However, it did not significantly alter brain stress system responses such as noradrenaline turnover or hypothalamus-pituitary-adrenocortical (HPA) axis activity . This indicates that MR signaling plays a role in modulating the somatic symptoms of opiate withdrawal.
Metabolic Acidosis in Cirrhosis
Reversible Effects
In patients with alcoholic cirrhosis, spironolactone treatment can lead to hyperchloremic metabolic acidosis. A study involving six patients found that spironolactone therapy significantly decreased serum bicarbonate levels, which returned to baseline upon drug withdrawal. Serum potassium levels also increased during treatment and normalized after cessation . These findings highlight the need for careful monitoring of metabolic parameters in cirrhotic patients on spironolactone.
Conclusion
Spironolactone withdrawal can have significant implications depending on the condition being treated. In heart failure and dilated cardiomyopathy, withdrawal is associated with high relapse rates and deterioration in cardiac function. In hypertension, it can reverse beneficial hemodynamic changes. For hyperandrogenic skin disorders, spironolactone shows long-lasting effects even after discontinuation, although some patients may relapse. In opiate withdrawal, it helps attenuate somatic symptoms, and in cirrhosis, it can cause reversible metabolic acidosis. These findings underscore the importance of weighing the benefits and risks before discontinuing spironolactone therapy.
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