Σύγτρονη θεραπεία της ανθεκτικής σπέρτασης

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1 Σύγτρονη θεραπεία της ανθεκτικής σπέρτασης Κώζηας Τζιούθης Α Παν/κή Καρ/κή Κλινική Ιπποκράηειο Γ.Ν.Α.

2 Resistant or Refractory to treatment Hypertension Office BP>140/90 or 130/80 mm Hg in patients with diabetes or chronic kidney disease and Patient prescribed 3 or more antihypertensive medications at optimal doses, including if possible a diuretic or Office BP at goal but patient requiring 4 or more antihypertensive medications

3 Uncontrolled vs Resistant Uncontrolled Hypertension Hypertension

4 Prevalence of Resistant Hypertension Exact prevalence of resistant hypertension is unknown Small studies estimate the prevalence at approximately 5% in general practice and 50% or higher in nephrology clinics, depending on the severity of the underlying chronic renal disease In a large US study (NHANES), the estimated prevalence of resistant hypertension was 8.9% of all adults with hypertension and 12.8% of all drug-treated hypertensive adults in the US Specialized Referral Centers 10-15% True Resistant HTN on optimal Rx 3-5%

5 The Phenotype of Resistant Hypertension Patient Characteristics Associated With Resistant Hypertension Older age High baseline BP Obesity Excessive dietary salt ingestion Chronic kidney disease Diabetes Left ventricular hypertrophy Black race Female sex

6 Resistant Hypertension Diagnosis Diet Drugs Devices

7 Resistant hypertension: diagnostic and treatment recommendations 1 st step: Confirm resistance-exclude Pseudoresistance Is patient adherent with prescribed regimen? Obtain home, work, or ambulatory blood pressure readings to exclude white coat effect Circulation 2008;117:

8 Resistant hypertension: diagnostic and treatment recommendations 2 nd step: Identify and Reverse Contributing Lifestyle Factors Obesity Physical inactivity Excessive alcohol ingestion High salt, low fiber diet Circulation 2008;117:

9 Circulation 2008;117: Resistant hypertension: diagnostic and treatment recommendations 3 rd step: Discontinue or Minimize Interfering Substances Non-steroidal anti-inflammatory agents Sympathomimetics (diet pills, decongestants) Stimulants Oral contraceptives Licorice Ephedra

10 Resistant hypertension: diagnostic and treatment recommendations 4 th step: Screen for Secondary Causes of Hypertension Obstructive sleep apnea (snoring, witnessed apnea, excessive daytime sleepiness) Primary aldosteronism (elevated aldosterone/renin ratio) Chronic kidney disease (creatinine clearance <30 ml/min) Renal artery stenosis (young female, known atherosclerotic disease, worsening renal function) Pheochromocytoma (episodic hypertension, palpitations, diaphoresis, head ache) Cushing s syndrome (moon facies, central obesity, abdominal striae, inter-scapular fat deposition) Aortic coarctation (differential in brachial or femoral pulses, systolic bruit) Circulation 2008;117:

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12 Resistant Hypertension Diagnosis Diet Drugs Devices

13 Impact of Lifestyle Changes on BP Lifestyle Changes BP Drop Hypocaloric Diet 5-20 mmhg/10 kg «DASH» Diet 8-14 mmhg Salt Restriction (6 g NaCl/day) 2-8 mmhg Physical Exercice (at least 30 /day) 4-9 mmhg Moderate alcohol consumption 2-4 mmhg

14 Resistant Hypertension Diagnosis Diet Drugs Devices

15 Treatment of resistant hypertension the role of diuretics 90% of pts with Resistant hypertension have expanded plasma volume An appropriate diuretic (dose and type according to kidney function) to decrease volume overload is a cornerstone of therapy Chlorothalidone 25mg daily provided greater ambulatory BP reduction especially during overnight compared to hydrochlorothiazide 50 mg

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17 Treatment of resistant hypertension The role of aldosterone blockers ASCOT trial: spironolactone as fourth line antihypertensive agent for uncontrolled BP I addition to an average of 3 drugs resulted in a BP drop of 21.9/9.5 mmhg that was unaffected by age, sex, smoking and diabetic status

18 Pharmacologic Treatment Addition of Spironolactone in patients with Resistant Arterial Hypertension (ASPIRANT) A randomized, double-blind, placebo controlled trial 25 mg Spironolactone for 8 weeks resulted in a significant decrease in office SBP (by -5.6mm ), in 24h SBP (by 9.8mmHg) and in nighttime SBP (by -8.6mmHg) Jan Vaclavik, et al, Hypertension 2011;57:

19 Resistant Hypertension - ESH Recommendations - Optimize antihypertensive treatment with at least 3 (or better 4) tolerated drugs including a diuretic and an antialdosterone drug (if clinically possible, e.g after reevaluating renal function and the potential risk of hyperkaliemia) Schmieder,...Tsioufis. J Hypertens. 2012;30:

20 Circulation 2008;117: Resistant hypertension: diagnostic and treatment recommendations 5 th step:pharmacologic Treatment Maximize diuretic therapy, Include possible addition of mineralocorticoid receptor antagonist Use of loop diuretics in patients with chronic kidney disease and/or patients receiving potent vasodilators (e.g., minoxidil)

21 Circulation 2008;117: Resistant hypertension: diagnostic and treatment recommendations 5 th step:pharmacologic Treatment Combine agents with different mechanisms of action

22 Ο ζσνδσαζμός 2 αγωγών είναι 5 θορές πιο αποηελεζμαηικός ζηη μείωζη ηης ΣΑΠ από ηο διπλαζιαζμό ηης δόζης 1 θαρμάκοσ Μετα-ανάλυση 42 μελετών σε υπερτασικούς Wald et al. Ann Int Med 2009

23 ACEI + ARBs DRI +ACEI/ ARBs RAAS /Ca Metabolic syndrome Young elderly RAAS/D Heart failure Evidence of carotid atherosclerosis DM RAAS + D + Ca

24 Novel anti-hypertensive drugs Endothelin receptor antagonists (darusentan) Novel targets: Angiotensin II Type 2 receptor, Neutral endopeptidase, (pro-) Renin receptor Aldosterone synthase, Renalase

25 Resistant hypertension: diagnostic and treatment recommendations 6 th step:refer to Specialist Refer to hypertension specialist if blood pressure remains uncontrolled after 6 months of treatment Circulation 2008;117:

26 Resistant Hypertension Diagnosis Diet Drugs Devices

27 Resistant hypertension: diagnostic and treatment recommendations 7 th step: Interventional Approach Baroreceptor stimulation Therapy Catheter-Based Renal Sympathetic Denervation

28 Renal Sympathetic Activity Mechanoreceptors chemoreceptors Krum H et al. Circulation 2011

29 45 patients were treated with catheter-based renal denervation

30 Results: Office BP Reduction 3 Months * p < % CI Tsioufis et al, ESC Meeting 2012

31 Comparison of Office Systolic BP Reductions at 3 Months Krum H. et al, Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. The Lancet 2009;373;

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34 A 42-Year-Old Female with True Severe Resistant Hypertension OBP: 175/105mmHg, 85 bpm ΑΒPM :145/85mmHg Currently on 7 antihypertensive drugs: Olmesartan/HCTZ 20/25mg OD Lercanidipine 20mg OD Betaxolol 20mg OD Diltiazem 300mg OD Spironolactone 100mg OD Terazosin 2mg BID Other drugs: ASA 100mg/clopidogrel 75 mg

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37 A 42-Year-Old Female with True Severe Resistant Hypertension at 1 month post RSD Office BP= 145/90 mmhg 24h SBP :130 mmhg 24h DBP : 74 mmhg

38 A 42-Year-Old Female with True Severe Resistant Hypertension at 3 months post RSD Office BP= 140/85 mmhg 24h SBP :128 mmhg 24h DBP : 74 mmhg

39 CV Mortality Risk Doubles with Each 20/10 mmhg Increment in SBP/DBP CV mortality risk Severe RH 8 6 8X risk X risk 2X risk 4X risk 115/75 135/85 155/95 175/105 SBP/DBP (mmhg) Lewington et al. Lancet 2002;360: *Individuals aged years

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41 Renal sympathetic denervation Current indications Severe Resistant hypertension office BP 160 systolic or 100 mmhg diastolic ( 150/95 mmhg in type 2 diabetes) despite treatment with 3 antihypertensive drugs of different types, including one diuretic.

42 Clinical egfr<45 ml/min per 1.73 m 2 DM-I exclusion criteria history of a recent MI, unstable angina, or a cerebrovascular accident within 6 months, Pregnacy Anatomic ESH : Renal sympathetic denervation Schmieder Tsioufis. J Hypertens 2012;30: History of renal artery intervention (balloon angioplasty or stenting) Renal artery irregularities (stenosis >30%, aneurusm) multiple renal arteries (>20mm in diameter) main renal arteries of less than 4 mm in diameter or less than 20 mm in length

43 Alternative approaches for RSD Over 61 companies working in the area of RSD Radiofrequency: eg. St Jude Medical Vessix Medical Covidien Boston Scientific High Frequency Ultrasound: eg. Kona Medical Cardiosonics Cryotherapy: Radiation: Neurotoxins directly injected

44 Renal Sympathetic Denervation The Greek experience in the Hippocratio Hospital Clinical and pre-clinical EnligHTN I (FIM) Global Simplicity Registry Chemical ablation (Prof. Stefanadis)

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46 Unmet needs in RDN Randomized blinded studies Use of 24-h ABPM to enroll patients and to assess BP reduction Comparison of RDN efficacy and safety when using different procedures Long-term maintenance of efficacy and safety Impact in morbidity and mortality reduction Cost-benefit balance studies Standardized certification of RDN centers Schmieder Tsioufis. J Hypertens 2012;30:

47 Pay attention.. Not all patients will be candidates for intervention 80% of all resistant hypertensive patients are responders RSD is primarily being done for better BP control and not for reducing the number of antihypertensive drugs

48 Renal nerve ablation ESH:TODAY RECOMMENDATIONS Careful selection of candidates for RNA in Hypertension Excellence Centers Perform the procedure in very experienced hospital centers by well trained interventionalists Use devices which have demonstrate efficacy and safety in clinical studies Schmieder Tsioufis. J Hypertens 2012;30:837-41

49 RSD therapy Patient initially diagnosed with resistant hypertension by general practitioner/internist/cardiologist/nephrologist Referral or self-referral Hypertension specialist Hypertension Center (preferably Hypertension Excellence Center) Resistant hypertension confirmed and intensify therapy (After exclusion of pseudoresistance, white-coat resistance, contributing lifestyle factors/substances and secondary hypertension) Controlled Hypertension Resistant hypertension not confirmed Standard conservative therapy Resistant Hypertension Not controlled Consider for RSD Re-evaluation and implementation of current eligibility criteria (anatomical and clinical) for RSD therapy Patient s eligibility for RSD confirmed Patient s eligibility for RSD not confirmed Specialized catheterization laboratory Center for RSD

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