1.
Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial.
Raman, SV, Hor, KN, Mazur, W, He, X, Kissel, JT, Smart, S, McCarthy, B, Roble, SL, Cripe, LH
Orphanet journal of rare diseases. 2017;(1):39
Abstract
BACKGROUND Cardiomyopathy is a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD). We recently showed in a 12-month double-blind randomized controlled trial that adding eplerenone to background medical therapy was cardioprotective in this population. The objective of this study was to evaluate the safety and efficacy of longer-term eplerenone therapy in boys with DMD. RESULTS Eleven subjects (phase 1 baseline median [range] age: 13 [7 - 25] years) from the original 12-month trial at a single participating center were enrolled. Importantly, those who entered the extension study who had been on eplerenone previously were significantly older than those who had originally been on placebo (median age 10.5 vs. 18.0 years, p = 0.045). During an additional 24-month open-label extension study, all boys received eplerenone 25 mg orally once daily to treat preclinical DMD cardiomyopathy, defined as evident myocardial damage by late gadolinium enhancement cardiac magnetic resonance (LGE) with preserved ejection fraction (EF). The threshold for potassium level, the primary safety measure, was not exceeded in any non-hemolyzed blood sample. Over 24 months, left ventricular (LV) systolic strain, a more sensitive marker whose more negative values indicate greater contractility significantly improved (median change -4.4%, IQR -5.8 to -0.9%) in younger subjects whereas older subjects' strain remained stable without significant worsening or improvement (median change 0.2%, IQR -1.1 to 4.3%). EF and extent of myocardial damage by LGE remained stable in both groups over 2 years. CONCLUSIONS Eplerenone offers effective and safe cardioprotection for boys with DMD, particularly when started at a younger age. Eplerenone is a useful clinical therapeutic option, particularly if treatment is initiated earlier in life when cardiac damage is minimal. TRIAL REGISTRATION http://ClinicalTrials.gov identifier NCT01521546. Registered 26 January 2012.
2.
Influence of spironolactone therapy on thiamine blood levels in patients with heart failure.
Rocha, RM, Silva, GV, de Albuquerque, DC, Tura, BR, Albanesi Filho, FM
Arquivos brasileiros de cardiologia. 2008;(5):324-8
Abstract
BACKGROUND The nonpharmacological management of heart failure (HF) has been understudied. The importance of micronutrients such as thiamine has long been known since its deficiency is associated with the development of high-output HF. OBJECTIVE We studied the relationship between adding to ACE inhibition further aldosterone suppression with spironolactone and thiamine blood levels (pmol/ml). METHODS A total of 22 patients (pts) with HF (NYHA III/IV) were divided in two groups [group I-spironolactone 25mg/qd (n=11) and group II - no spironolactone (n=11)]. Thiamine levels were determined using the erythrocyte transketolase activity. The groups were compared regarding food intake, demographics, furosemide doses and thiamine blood levels using Mann-Whitney and student's T-test. The proportions were analyzed with Chi-square and Kruskal-Wallis tests to associate thiamine with demographics and furosemide doses as dependent variables. RESULTS Group I and II were similar regarding food intake, daily furosemide doses (110.9+/-30.2 and 105.5+/-26.9 mg, respectively; p>0.05), demographics (etiology, age, hypertension, diabetes, smoking, alcohol abuse, dyslipidemia and adjuvant drug HF treatment). Pts in group I showed significantly higher thiamine levels when compared to pts in group II (277.2+/-89.8 and 154.7+/-35.7, respectively) (p<0.001). None of the dependent variables cited above were associated with thiamine. CONCLUSION In a cohort of ambulatory HF patients on high dose of loop diuretics, the use of spironolactone is associated with higher thiamine blood levels. The significance of this finding remains to be established by future studies with prospective design and larger sample sizes.
3.
Randomized, placebo-controlled trial of the effects of drospirenone-estradiol on blood pressure and potassium balance in hypertensive postmenopausal women receiving hydrochlorothiazide.
Preston, RA, Norris, PM, Alonso, AB, Ni, P, Hanes, V, Karara, AH
Menopause (New York, N.Y.). 2007;(3 Pt 1):408-14
Abstract
OBJECTIVE Drospirenone (DRSP), a spironolactone analog with aldosterone antagonist activity, is a novel progestogen developed for use as hormone therapy in postmenopausal women in combination with 17beta-estradiol (E2). DRSP/E2 lowers blood pressure when used alone in hypertensive postmenopausal women or when administered concomitantly with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. DRSP/E2 has not been studied in combination with the widely prescribed hydrochlorothiazide (HCTZ). We investigated the effects of 3 mg DRSP/1 mg E2 versus placebo on blood pressure and potassium balance when added to existing therapy with 25 mg HCTZ in postmenopausal women with established stage I hypertension. DESIGN This was a single-center, double-blind, randomized, placebo-controlled, two-treatment, two 4-week treatment period crossover study in 36 postmenopausal women with stage I hypertension maintained on 25 mg HCTZ. The endpoint was a change from baseline in systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring. Safety monitoring included serum potassium (mEq/L) and adverse events. RESULTS Mean systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring were reduced significantly, by -7.2 and -4.5 mm Hg, respectively, with DRSP/E2 as compared with placebo. The decrease in potassium with HCTZ was 0.2 mEq/L less with DRSP/E2 than placebo, suggesting a potassium-sparing effect. The most frequently observed adverse events with DRSP/E2 were vaginal bleeding and breast tenderness, which were attributable to the hormone therapy. CONCLUSIONS DRSP/E2 substantially lowers systolic and diastolic blood pressure when added to existing antihypertensive therapy with HCTZ in hypertensive postmenopausal women. In addition, DRSP/E2 has a potassium-sparing effect that counteracts HCTZ-induced potassium loss.