Difficult to Control HTN: It is not all the same. Structured approach to evaluation and treatment

Transcription

1 Difficult to Control HTN: It is not all the same. Structured approach to evaluation and treatment Dmitri Vasin M.D. Nephrologist and ASH certified clinical hypertension specialist Bremerton, WA, USA

2 Johnson Am J Hyperten 2005;18:431-40

3 Johnson Am J Hyperten 2005;18:431-40

4 Concept Great majority of difficult to treat hypertension can be controlled by using agents proven to improve outcomes (not just decrease BP) at least in some subpopulations of patients Option for discontinuing ineffective medications (for both BP and other end points, like proteinuria, tachycardia, etc.)

5 Components of HTN Renin-Angiotensin-Aldosterone system Aldosterone, renin-independent (AT II independent escape) Volume overload Sympathetic hyperactivity Endothelial dysfunction/nitric oxide deficiency Uric acid (at least early on) Other mechanisms

6 Renin-Angiotensin-Aldosterone System (-) Renin~60% Non-renin ~40% Chymase t-pa Cathepsin G Tonin Angiotensinogen Angiotensin I Non-ACE Angiotensin II ACE Bradykinin Nitric Oxide Inactive kinins BP Ellis ML et al. Pharmacotherapy. 1996;16: Carey RM et al. Hypertension. 2000;35: Siragy et al. Semin Nephrology 2004;24: AT 1 AT 2 Vasoconstriction Aldosterone secretion Catecholamine release Proliferation Hypertrophy Vasodilation Inhibition of cell growth Cell differentiation Injury response Apoptosis Bradykinin increase

7 All Hypertension Is Not The Same Renin-Angiotensin- Aldosterone (RAAS) Dependent About 70% of HTN More common in younger and caucasians Responds to RAAS inhibiting drugs: ACEI, ARB, beta-blockers, DRI Higher risk for MI More likely to respond to life style modifications PRA >0.65 ng/ml/h Direct Renin >5 µu/ml Volume Dependent About 30% of HTN More frequent in elderly and African Americans Responds to diuretics and peripheral vasodilators: CCB, Hydralazine, Minoxidil, alpha-blockers Lower risk for MI Less likely to respond to life style modifications PRA <0.65 ng/ml/h Direct Renin <5 µu/ml Laragh, AJH 2003;16:407

8 Renin-Angiotensin-Aldosterone System RAAS is probably contributing to HTN if: PRA>0.65 in absence of RAAS blockade PRA>6.5 (and especially >15) in presence of RAAS blockade by ACEI or ARBs Additional blockade of RAAS by combination therapy (ACEI + DRI, ACEI + BB, ACEI + DRI + BB) can be considered for patients with very high renin, above 15

9 Volume Overload -1 Obtain History and PE for clues to presence of fluid overload: increased DOE, PND, high salt intake; increased JVP, positive HJR, crackles, S3, edema (least reliable) BNP testing: Target 50-70, in very obese 30-50; or lowest tolerated (above the target) by labs (creatinine increase >20%, BUN/Cr >40, CO2 >28) or hypotensive symptoms. The lowest tolerated BNP level should be targeted during follow up Consider decreasing/weaning diuretics if BNP <30, especially in patient with tachycardia, orthostatic symptoms or PRA >6.5 untreated/>15 treated

10 Volume Overload -2 Spironolactone ( mg/day) if Aldosterone is not suppressed (<5). Check K+ in 3-6 weeks If BNP is high and Aldosterone is <5 minimize salt intake as much as possible, use thiazides or loop diuretics as below; trial of Spironolactone still may be warranted Thiazides ( mg Indapamide, mg Chlorthalidone) added if spironolactone is not sufficiently effective; Metalozone preferred if Cr >2.0 Check K+ in 2-4 weeks Loop diuretics for patients with Cr >3.0. Furosemide dose 20xCr b.i.d., morning and lunch. Torsemide may be better, q.d. dosage (5-10 mg q.d.), especially in patients with edema above the thigh level

11 RAAS inhibition: Practicalities Add DRI to ACEI if Renin >6.5 and/or aldosterone >15 Change ARB to DRI Recheck aldosterone in 1 month; if still >15 consider adding Aldosterone Antagonist (Spironolactone or Eplerenone)

12 Sympathetic Hyperactivity -1 Tachycardia, labile BP, palpitations, sweating, flushing, tremors, headaches. Rule out Pheo if all or most of the above present Carvedilol b.i.d. or q. hs (if morning dose is not well tolerated) Alternatively Labetalol 100 b.i.d., titrate to 300 b.i.d. If HR >70 add Metoprolol, titrate to achieve HR ~60. If BP still not controlled consider increasing Labetalol to 600 b.i.d. or adding another agent

13 Sympathetic Hyperactivity - 2 HR>70 on 50 mg/day of Carvedilol consider adding low dose Verapamil or Diltiazem in patient <70 years old and no conduction abnormalities on ECG For patients with labile hypertension and hypotensive symptoms on therapy consider Pseudopheochromocytoma

14 Endothelial Dysfunction For patients with uncontrolled BP (and especially uncontrolled CHF) on optimal (ACEI, DRI, Carvedilol, AA, optimal BNP, statin) or maximal tolerated therapy consider Hydralazine plus nitrate Hydralazine mg b.i.d t.i.d and nitrate in any sustained formulation (ISMO, ISDN, Nitropatch, etc.)

15 Causes of Failure Again and Again for a patient on 3+ well matched agents, including diuretic: #1 - insufficient diuresis #2 - non-compliance #3 - empiric trial of AA before you give up! Also, look for: Intake of agents that increase BP: decongestants, stimulants, weight loss products, estrogens, licorice containing products Alcohol intake > 2 drinks for males, >1 for females?stress - Pseudopheochromocytoma