Long term outcome of Aldosteronism after target treatments

Abstract

There exists a great knowledge gap in terms of long-term effects of various surgical and pharmacological treatments on outcomes among primary aldosteronism (PA) patients. Using a validated algorithm, we extracted longitudinal data for all PA patients diagnosed in 1997-2010 and treated in the Taiwan National Health Insurance. We identified 3362 PA patients for whom the mean length of follow-up was 5.75 years. PA has higher major cardiovascular events (MACE) than essential hypertension (23.3% vs 19.3%, p = 0.015). Results from the Cox model suggest a strong effect of adrenalectomy on lowering mortality (HR = 0.23 with residual hypertension and 0.21 with resolved hypertension). While the need for mineralocorticoid receptor antagonist (MRA) after diagnosis suggests that a defined daily dose (DDD) of MRA between 12.5 and 50 mg may alleviate risk of death in a U-shape pattern. A specificity test identified patients who has aldosterone producing adenoma (HR = 0.50, p = 0.005) also confirmed adrenalectomy attenuated all-cause mortality. Adrenalectomy decreases long-term all-cause mortality independently from PA cure from hypertension. Prescription corresponding to a DDD between 12.5 and 50 mg may decrease mortality for patients needing MRA. It calls for more attention on early diagnosis, early treatment and prescription of appropriate dosage of MRA for PA patients.

Figure 1. Flow diagram of selecting study subjects.

(Abbreviations: MRA, mineralocorticoid receptor antagonist; PA, primary aldosteronism) *Our study only enrolled patients who ever used MRA (belonging to the ATC class C03D) in the one year prior to or the two years following the first ICD-9-CM coding of PA, because this additional condition could assure high values for both sensitivity and the positive predictive value according to our validated report.

Figure 2. Future 10-year probability of mortality was lower among APA patients received adrenalectomy during follow up.

The simulation curves were depicted based on different scenarios of morbid conditions with regard to MRA, and adrenalectomy stratified by subsequent MACE.

Figure 3. Adjusted HRs for long-term risk of mortality among PA patients, based on comparison between adrenalectomy and non-adrenalectomy groups, and subgroup analysis with respect to premorbid risk that further adjusted for age and gender.

(Abbreviations: CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio; OP, operation; PA, primary aldosteronism).

Figure 4. The function curve with values of the logs of odds ratios from the GAM model with splines regarding MRA for our multilevel discrete-time event history analysis of risk of death among PA patients.

The curve was centered to have an average of zero over the range of the data. The dashed lines indicated approximated point-wise 95% CIs. (Abbreviations: CI, confidence interval; DDD, defined daily dose; GAM, generalized additive model; MRA, mineralocorticoid receptor antagonist; PA, primary aldosteronism) (The DDD of MRA is 0.17 (12.5 mg of spironolactone) and 0.66 (50 mg spironolactone).