Εμαηνκηθεπκέλε ρνξήγεζε ζπλδπαζκέλεο αληηππεξηαζηθή αγωγή

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1 32 Ο Παλειιήλην Καξδηνινγηθό Σπλέδξην Θεζ/λίθε 22/10/011 Εμαηνκηθεπκέλε ρνξήγεζε ζπλδπαζκέλεο αληηππεξηαζηθή αγωγή Κ.Τζηνύθεο A Παλεπηζηεκηαθή Καξδηνινγηθή Κιηληθή Ιππνθξάηεην Γ.Ν.Α

2 Points for discussion How low to decrease BP Choice of Monotherapy Choice of Combinations

3 BP lowering and CV benefit For each 10mmHg decrease for SBP and 5 mmhg decrease for DBP the risk for CAD and stroke is decreased by 22% και 41% respectively The lower the better Law et al, BMJ 2009

4 ONTARGET: Adjusted risk of outcome events achieved by SBP divided into deciles. Journal of Hypertension 2009;27(7):

5 INVEST JACC 2009;54(20):

6 Reduction of BP and CV risk The role of Target organ damage Not the lower the better but the earlier the better

7 Daytime or night time BP? Blood pressure variability

8 Increased nighttime blood pressure or nondipping profile for prediction of cardiovascular outcomes. Review article Our findings suggest that nocturnal BP including the phenotype of isolated nocturnal hypertension is better associated with CV target organ damage and 'hard end points' as compared with the nondipping pattern Tsioufis C, et al. J Hum Hypertens. 2011;25(5):281-93

9 Comparative prognostic role of nighttime blood pressure and nondipping profile on renal outcomes. These findings underline the importance of nocturnal BP phenotypes, retrieved by ambulatory BP measurements, on age-dependent progressive kidney function decline and question whether, to what extent and in whom the reduced nocturnal BP or reverse nondipping BP profile to a normal pattern will be of benefit Tsioufis C, et al Am J Nephrol 2011;33:277-88

10 BP variability and CV risk Mancia et al, J Hypertens 2001: BPV and TOD Rothwell et al, Lancet 2010: BPV is an independent and strong predictor of CV events Zhang et al, Hypertension 2011: Antihypertensive drugs not all equal to reduce BPV

11 Points for discussion How low to decrease BP Monotherapy

12 2007 ESH Guidelines First choice treatment Diuretics * ACE-inhibitors Calcium antagonists Angiotensin receptor antagonists Beta-blockers * * Not to be initially preferred in patients at high risk of developing diabetes The BB/Diuretic combination should not be used in patients with MS or at high risk of diabetes

13 Choice of antihypertensive drugs Each drug class has contraindications as well favorable effects in specific clinical settings. The choice of drug(s) should be made according to this evidence.

14 Καξδην-αγγεην-λεθξν-πξνζηαζία ΥΑΚ Πρόληυη, σποζηροθή ACEI, ARB Προηγούμενο ΕΜ BB, ACEI, ARB Σηηθάγτη προζπαθείας BB, CA Καρδιακή ανεπάρκεια Diuretics, BB, ACEI, Κολπική μαρμαρσγή Πρόληυη σποηροπών ACEI, ARB Έλεγτος ζστνόηηηας BB, μη δισδροπσριδίνες Νεθξηθή δπζιεηηνπξγία ACEI, ARB ARB,Antialdost.ant

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17 OLMESARTAN VASCULAR PROTECTION Explained by : a unique binding to AT1 receptor resulting in a high affinity and strong selectivity for AT1 receptor vs AT2 receptor (Mire et al, 2005) An activation of ACE2 enzyme expression leading to an increase of Ang 1-7 implicated in BP decreasing, antiremodelling and antiinflammatory effect (Agata et al. 2006) Supported by : A strong inflammatory effect - EUTOPIA Study (Fliser, 04) A complete reversion of vascular remodelling -VIOS Study A decrease of atherosclerotic plaque volume, as much as the volume is important - MORE Study The first ARB evaluating its efficacy on all steps of the vascular continuum 17

18 EUTOPIA study: olmesartan reduced serum inflammatory markers Fliser D et al. Circulation. 2004;110:

19 VIOS study: effect of olmesartan or atenolol on wall-to-lumen ratio Smith R et al. J Am Soc Hypertension. 2008;2;

20 Olmesartan and nephroprotection in DM Reduced microalbuminuria de Pablos-Velasco P.L. et al., J Hypertens; 2005

21 ... another important issue Prevention of diabetes mellitus in high risk patients LIFE -25% SCOPE -20% CHARM -22%

22 Β αλαζηνιείο θαη θαξδηνπξνζηαζία ζηνπο ππεξηαζηθνύο αζζελείο Οι β αναζηολείς τρηζιμοποιούμενοι έφς 1-2 έηη μεηά από ΕΜ ήηαν 2 θορές πιο αποηελεζμαηικοί ζε καρδιοπροζηαζία ζε ζτέζη με ηοσς β αναζηολείς ή ηα άλλα ανηισπερηαζικά ζε άλλες καηαζηάζεις BMJ 2009;338:b1665

23 Beta-Blockers in Hypertension Plusses Adequate BP reduction CV event reduction - Placebo-controlled trials - Comparison trials Effective protection against CHD/CHF (primary prevention) Superior CHD protection in CAD patients Treatment of angina / CHF Minuses Dysmetabolic effects Protection against subclinical OD Side effects Less central BP reduction? Less prevention of stroke? Less BP reduction / CVD protection in the elderly?

24 Not all beta-blockers are equal Vasodilatation has haemodynamic/metabolic benefits

25 Vasodilator BBs - Favourable Effects Less bradycardia Aortic stiffness Central BP Less NOD than classical BBs (GEMINI) NOD similar to placebo (SENIORS) Less adverse effects on HbA1 c / lipid profile Greater antiproteinuric effect Improvement of coronary flow reserve in HT Reduction of death / hospitalization in CHF ESH Task Force Document, J Hypertens 2009

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28 Malacco.2010

29 29 Review by Malacco

30 Η ζέζε ηεο ζπλδπαζκέλεο Αληηππεξηαζηθήο αγωγήο ζήκεξα Γηαηί ρξεηαδόκαζηε ζπλδπαζκό θαξκάθωλ

31 Advantages of combinations Efficacy Safety/Tolerability Compliance

32 Ο ζπλδπαζκόο 2 αγωγώλ είλαη 5 θνξέο πην απνηειεζκαηηθόο ζηε κείωζε ηεο ΣΑΠ από ην δηπιαζηαζκό ηεο δόζεο 1 θαξκάθνπ Μετα-ανάλυση 42 μελετών σε υπερτασικούς Wald et al. Ann Int Med 2009

33 Different Classes of Drugs have Different Sites of Action BP = Cardiac output = X Total peripheral resistance Heart rate X Stroke volume Arterial pressure Venous pressure β-blockers Diuretics CCBs ARBs ACEIs Different, but complementary mechanism of action Beevers, et al. BMJ 2001;322:912 6;

34 Single-Pill Combinations Have Several Advantages Versus Free Combinations of Two or More Antihypertensive Drugs Single pill Free Simplicity of treatment + Compliance + Efficacy + + Tolerability +* Price + Flexibility +** ++ *Lower doses generally used in single-pill combinations **An increasing number of single-pill combinations are becoming available with a range of doses + = potential advantage Burnier, et al. Am J Hypertens 2006;19:1190 6;

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36 Adherence to treatment ARBs exhibited better tolerability than ACEi the best medications are of little value unless they are taken

37 Combination Antihypertensive Therapies 1950 s 1960 s 1970 s 1980 s 1990 s- 2000s Ser-Ap-Es (reserpine/hydralazine/ hydrochlorothiazide) Methyldopa/thiazide ACE inhibitor/thiazide Butiserpine (reserpine/butalbital) Hyphex (hexamethonium/hydralazine) Hypotensin A, B, & C (pentolinium/hydralazine/resperine) Renir (reserpine/ephedrine) Verapene (rauwolfia/veratrum) Thiazide/K + -sparing diuretic b blocker/thiazide Clonidine/thiazide ACE inhibitor/ccb ARB/thiazide//CCB DRI/ARB/thiazide/ /CCB Low-dose b blocker/thiazide

38 There are many possible combinations of hypertension drugs Diuretics b-blockers ARBs a-blockers CCBs ACEIs Preferred combinations Less frequently used/combination used as necessary Task Force for ESH ESC. J Hypertens 2007;25: ;

39 The CCB-ARB combination targets two key pathways: synergy for decreasing oedema Fogari R et al. J Hum Hypertens. 2007;21: Gustafsson D. J Cardiovasc Pharmacol. 1987;10 Suppl 1:S

40 AMLO/OLME : Mean change in SeBP from baseline to week 8 HYPERTENSION CLASS SUBGROUPS

41 AMLO/OLME : Mean change in SeBP from baseline to week 8 AGE SUBGROUPS

42 AMLO/OLME : Mean change in SeBP from baseline to week 8 BMI SUBGROUPS

43 AMLO/OLME : Mean change in SeBP from baseline to week 8 DIABETICS SUBGROUPS

44 AMLO/OLME in hypertensive patients with metabolic syndrome: OLAS study effect on BP/UAE/Adiponectin Derived from text in Martinez-Martin FJ et al. J Hypertens. 2008;26:S331.

45 OLAS study AMLO/OLME combination therapy: effect on inflammatory markers Martinez-Martin FJ et al. J Hypertens. 2008;26:S331.

46 RAS blocker diuretic or RAS blocker calcium antagonist combinations

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

48 Future Medicine Personalized Medicine

49 Evidence based medicine Experience Individualized medicine Medicine is an art based on science