ΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ ΚΑΙ ΑΝΤΑΓΩΝΙΣΤΕΣ ΑΛΔΟΣΤΕΡΟΝΗΣ ΣΠΥΡΟΜΗΤΡΟΣ ΓΕΩΡΓΙΟΣ MD, FESC. E.Α Κ/Δ Γ.Ν.ΚΑΤΕΡΙΝΗΣ

Transcription

1 ΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ ΚΑΙ ΑΝΤΑΓΩΝΙΣΤΕΣ ΑΛΔΟΣΤΕΡΟΝΗΣ ΣΠΥΡΟΜΗΤΡΟΣ ΓΕΩΡΓΙΟΣ MD, FESC. E.Α Κ/Δ Γ.Ν.ΚΑΤΕΡΙΝΗΣ

2

3 Aldosterone is a mineralocorticoid hormone synthesized by the adrenal glands that has several regulatory functions to help the body maintain normal volume status and electrolyte balance. Studies have shown significantly higher levels of aldosterone secretion in patients with congestive heart failure compared with normal patients. elevate blood pressure, cause left ventricular hypertrophy promote cardiac fibrosis NAPI,VASCULAR,2011

4

5 Mineralocorticoid receptors present in the heart and aldosterone is produced by the diseased myocardium. The latter effect is mediated by the induction of aldosterone synthase (CYP11B2) by angiotensin II in the failing ventricle Binding of angiotensin II will lead to higher secretion of aldosterone Aldosterone causes an upregulation of angiotensinconvertingenzyme mrna expression, leading to increased levels of angiotensin II SILVESTRE,CIRC 1999,MIZUNO CIRC2001, NAPI,VASCULAR,2011

6 Activatable mineralocorticoid receptors are also present in coronary artery and aortic vascular smooth muscle cells These receptors can be activated by aldosterone as well as by angiotensin II Activation of these receptors may also contribute to the increased incidence of stroke and coronary events in patients with primary aldosteronism compared to matched patients with primary hypertension JAFFE,CIRC,2005

7 Direct effects of aldosterone on the heart cardiac hypertrophy and fibrosis, proarrhythmia with chronic pressure overload, the transition from hypertrophy to HF Patients with higher serum concentrations of markers of collagen synthesis (procollagen type I carboxy-terminal peptide, procollagen type I amino-terminal peptide, and procollagen type III amino-terminal peptide) had higher rates of death and hospitalization. Lin,J M CELL CARD 2000,OURVARD,CIRC 2005, RALES

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26 It is essential that serum potassium and creatinine be checked one to two weeks after starting spironolactone or eplerenone and periodically thereafter. Patients with poor renal function are particularly at risk for hyperkalemia. Increasing age More severe HF Diabetes mellitus Underlying renal dysfunction Volume depletion Higher baseline plasma potassium concentration Spironolactone dose 50 mg/day Higher ACE inhibitor or angiotensin II receptor blocker dose Combined use of ACE inhibitors and angiotensin II receptor blockers Concomitant beta blocker use Use of potassium supplements or potassium-containing salt substitutes Use of nonsteroidal anti-inflammatory drugs EPHESUS, the four independent baseline predictors of hyperkalemia (serum potassium 6.0 Meq/L) glomerular filtration rate (egfr) <60 ml/min per 1.73 m2, history of diabetes mellitus, serum potassium >4.3 meq/l, and prior use of antiarrhythmics

27 If the egfr is 50 ml/min per 1.73 m2, we suggest starting with spironolactone 25 mg/day and after four weeks increasing to 50 mg/day if serum potassium is <5.0 meq/l. A switch to eplerenone (25 mg/day and after four weeks increasing to 50 mg/day if serum potassium is <5.0 meq/l) is recommended if endocrine side effects occur. If the egfr is 30 to 49 ml/min per 1.73 m2, the initial dose of spironolactone should be 25 mg on alternate days (or 12.5 mg/day) and after four weeks increasing to 25 mg daily if the serum potassium is <5.0 meq/l. A switch to eplerenone (25 mg on alternate days and after four weeks 25 mg/day if serum potassium is <5.0 meq/l) is recommended if endocrine side effects occur. As in the EPHESUS and EMPHASIS-HF trials, if the serum potassium level is 5.5 to 5.9 meq/l, the dose should

28 Other endocrine effects Spironolactone and eplerenone compete for the mineralocorticoid receptor with aldosterone The endocrine side effects of spironolactone (gynecomastia, breast pain, menstrual irregularities, impotence, and decreased libido) result from nonselective binding to androgen and progesterone receptors Eplerenone has greater specificity than spironolactone for the mineralocorticoid receptor resulting in a lower incidence of endocrine side effects