«Ενότητα Υπέρταση» «Τριπλοί συνδυασμοί αντιυπερτασικών φαρμάκων» Ρήγας Καλαϊτζίδης

«Ενότητα Υπέρταση» «Τριπλοί συνδυασμοί αντιυπερτασικών φαρμάκων» Ρήγας Καλαϊτζίδης Νεφρολόγος Νεφρολογική Κλινική Πανεπιστημιακού Νοσοκομείου Ιωαννίνων 7η Επιστημονική Διημερίδα: Πρόληψη & Θεραπεία των Kαρδιομεταβολικών Παραγόντων Κινδύνου: Σύγχρονές απόψεις 11-12 Σεπτεμβρίου 2015, Ξενοδοχείο Du Lac, Ιωάννινα

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Increased blood pressure (red arrow) is the second leading risk attributed to 17.8% of global deaths.. J Clin Hypertens (Greenwich). 2015:1 3

Κατευθυντήριες οδηγίες για την υπέρταση ESH-ESC 2013 Διουρητικά θειαζιδικού τύπου β-αποκλειστές Ανταγωνιστές ΑΤ1 υποδοχέων α-υποδοχείς Ανταγωνιστές Ca 2+ AMEA Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007; 28:1462-1536.

2013 ESH/ESC Guidelines for the management of arterial hypertension. 2013 ESH/ESC Guidelines

2013 ESH/ESC Guidelines for the management of arterial hypertension Prompt initiation of drug treatment is recommended in individuals with grade 2 and 3 hypertension With any level of CV risk, a few weeks after or simultaneously with initiation of lifestyle changes.

Τριπλή αντιϋπερτασική θεραπεία 50yrs The use of initial single-pill combination antihypertensive therapy has been present since 1966 with the single-pill combination of reserpine, hydrochlorothiazide, and hydralazine widely available and used. Arch Intern Med. 1996;156:1969 1978.

Γιατί χρειαζόμαστε τριπλή αντι-υπερτασική θεραπεία;

suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in some combinations. Diuretics (including thiazides, chlorthalidone and indapamide), Beta-blockers Calcium antagonists Angiotensin converting enzyme (ACE) inhibitors Angiotensin receptor blockers ESH guidelines 2013, 5.2.2 page 1309

JNC 2009 Nα αποφεύγεται η ιεραρχία «ranking» 1o, 2o,3o αντι-υπερτασικό Φ 5.2.1.8 Should antihypertensive agents be ranked in order of choice? ESH guidelines 2013,

Compelling and possible contra-indications to the use of antihypertensive drugs Στις μεγάλες δόσεις οι μονοθεραπείες προκαλούν προβλήματα ESH guidelines 2013

O συνδυασμός 2 κατηγοριών αντιυπερτασικών οδηγεί σε μεγαλύτερη πτώση της ΑΠ Αποτελεσματικότητα Wald et al. Am J Med 2009

2013 ESH/ESC Guidelines Choice of antihypertensive drugs Αll drug classes with mechanisms of action partially or totally different from those of the existing three drug regimens can lower BP in at least some resistant hypertensive individuals Arch Intern Med 1991; 151:1786 1792.

Ποιον συνδυασμό θα διαλέξουμε;

Journal of Human Hypertension (2015), 1 5

ACE/ARB ACE /ARB

Ποιοι είναι οι τριπλοί συνδυασμοί αντιυπερτασικών φαρμάκων;

Στην Ελλάδα amlodipine, valsartan, and hydrochlorothiazide amlodipine, olmesartan and hydrochlorothiazide amlodipine, peridropril and indapamide

Management of hypertension with fixed-dose triple-combination treatments Complementary mechanism of combination antihypertensive therapy

πλεονεκτήματα χορήγησης συνδυασμού αντιϋπερτασικών φαρμάκων Χορήγηση μικρών δόσεων ενέργειες Αποφυγή άσκοπης αλλαγής φαρμάκων λιγότερες ανεπιθύμητες Γρήγορη επίτευξη στόχων σε άτομα με βλάβη οργάνωνστόχων ή πολύ υψηλά επίπεδα ΑΠ Έτοιμος συνδυασμός βελτίωση συμμόρφωσης

πλεονεκτήματα χορήγησης συνδυασμού αντιϋπερτασικών φαρμάκων Αποφυγή των πολλαπλών δόσεων Μείωση των επισκέψεων στον γιατρό Μείωση του κόστους;

Control rate Single-pill combination better than free combination Single-pill combination Free combination Monotherapy 68% Έλεγχος της ΑΠ 59% 59% Days to control Egan BM, Bandyopadhyay D, Shaftman SR, Wagner CS, Zhao Y, Yu-Isenberg KS. Hypertension. 2012;59:1124-1131. 30

Διατήρηση της ΦΑ MANAGED CARE / DECEMBER 2013

Hypertension drug treatment adherence (Fung 2007) συμμόρφωση MANAGED CARE / DECEMBER 2013

Better Compliance with Antihypertensive Drugs Leads to a Lower Risk of Hospitalization

Figure 3. Mean sitting DBP (A) and SBP (B) by treatment and week. David A. Calhoun et al. Hypertension. 2009;54:32-39 Copyright American Heart Association, Inc. All rights reserved.

Effects of demographics on the antihypertensive efficacy of triple therapy with amlodipine, valsartan, and hydrochlorothiazide for moderate to severe hypertension Current Medical Research & Opinion Volume 29, Number 8 August 2013

Triple Antihypertensive Therapy With Figure 4. Between-treatment comparisons for change from baseline to end point in mean sitting BP (mm Hg) by baseline MSSBP. Data presented are least-square mean changes. Amlodipine, Valsartan, and Hydrochlorothiazide David A. Calhoun et al. Hypertension. 2009;54:32-39 Copyright American Heart Association, Inc. All rights reserved.

Effects of demographics on the antihypertensive efficacy of triple therapy with amlodipine, valsartan, and hydrochlorothiazide for moderate to severe hypertension (age<65, age >65) Current Medical Research & Opinion Volume 29, Number 8 August 2013

Effects of demographics on the antihypertensive efficacy of triple therapy with amlodipine, valsartan, and hydrochlorothiazide for moderate to severe hypertension(βμι>30kg/m2) ΒΜΙ>30kg/m2 Incidence of any adverse event in patients who received at least one dose of study drug Current Medical Research & Opinion Volume 29, Number 8 August 2013

Drugs Aging (2013) 30:549 560

Am J Cardiovasc Drugs (2014) 14:137 145

Ambulatory blood pressure with triple-drug combination perindopril/indapamide/amlodipine Daytime blood pressure control was reached by 79.8 % of patients. Nighttime blood pressure control was reached by 51.0 % of patients..

Clin Drug Investig (2014) 34:701 708

The post hoc analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MRControlled Evaluation (ADVANCE) trial extends our data on the use of antihypertensive combinations to help achieve BP goals Hypertension. 2014;63:259 264.

Effects of the combination of perindopril and indapamide (randomized study drugs) with calcium channel blockers (CCBs) at any visit (nonstudy drug) on major cardiovascular (CV) events and death compared with participants on placebo who never receivedccbs.

Σε ποιους ασθενείς θα δώσουμε τριπλή αντιυπερτασική αγωγή;

2013 ESH/ESC Guidelines for the management of arterial hypertension

patients that require a third medication to achieve control tend be have worse kidney function.

Μεγάλη ηλικία

Influence of albuminuria on bloοd pressure response to antihypertensive therapy Flack, Vasc Risk Manag 2007

These drug Combinations have been shown to be effectiv safe and well tolerat by most patients Triple-drug Double- and triple-drug combination therapy of hypertensive patients with diabetes mellitus, chronic kidney disease and cardiovascular disease. Expert Rev. Cardiovasc. Ther. 11(9), 1115 1124 (2013)

The most common treatment-emergent adverse events (3%) reported by patients administered the triple combination Dizziness (9.9%) ankle edema (7.7%) Headache (6.4%) Fatigue (4.2%) Nasopharyngitis (3.5%) muscle spasms (3.1%) nausea (3.0%) Oparil, Clin Ter. 2010;32:1252 1269

Number of antihypertensive medications required to achieve BP goals in major clinical trials over the past decade >2.8 drugs Κhosla N, Kalaitzidis R et al Med Clin North Am 2009

Συμφωνούμε αλλά τι γίνεται με το κόστος ; The American Heart Association projects that direct medical costs of treating hypertension in the U.S. Will increase from $70 billion in 2010 (in 2008$) to over $200 billion in 2030, the cost of hypertension as a risk factor for cardiovascular disease (a portion of the costs of complications associated with hypertension, HF coronary heart disease stroke and other cardiovascular disease will increase from $131 billion in 2010 to $389 billion in 2030 Heidenreich 2011

The single-pill V/A/H therapy is a cost-effective antihypertensive choice for the treatment of moderate to severe hypertension, compared to its dual components. Cost Effectiveness and Resource Allocation (2015) 13:10

Change from baseline in health care costs in patients with hypertension using either a single-pill combination or free-drug combination.

Conclusions: This study constitutes the first pharmacoeconomic comparison of single-pill triple antihypertensive therapies.the study demonstrated that V/A/H combination was a cost-effective choice for the treatment of moderate to severe hypertension in the Greek health-care setting. Journal ofhypertension Volume33,e-Supplement1,2015

Marques da Silva et al. Health and Quality of Life Outcomes (2015) 13:24 This study showed that OLM/AML/HCTZ reduced blood pressure and significantly increased blood pressure control whilst improving patients HRQoL. Achieving blood pressure control, amount of concomitant medication and dosage strength of antihypertensive impacted on patients HRQoL

Current Medical Research & Opinion Vol. 30, No. 12, 2014, 2415 2422

Trends in awareness, treatment, and control of high blood pressure, 1976 2000*

Patients not achieving BP goal (%) Approximately 70% of Patients* Who Receive Treatment Do Not Reach BP Goal 60% 70% 72% 79% 81% Approximately 50 % of Patients Treated for hypertension BP goal <140/90 mmhg England Germany Italy Sweden Spain Wolf-Maier et al. Hypertension 2004;43:10 17

Patient education has been demonstrated to result in improved blood pressure control Ιατρική θεραπευτική αδράνεια Ann Intern Med. 2006;145(3):165

Συμπεράσματα Ο τριπλός συνδυασμός των αντιυπερτασικών φαρμάκων αισιοδοξεί να επιτύχει μεγαλύτερα ποσοστά ρύθμισης της ΑΠ και να μειώσει τα καρδιαγγειακά συμβάματα Η μείωση του αριθμού των χαπιών σε ένα βοηθάει στην βελτίωση της συμμόρφωσης σε υπερτασικούς με συννοσηρότητες Ο τριπλός συνδυασμός των αντιυπερτασικών φαρμάκων σε ένα χάπι επιτυγχάνει υψηλότερα ποσοστά συμμόρφωσης και υψηλότερα ποσοστά επίτευξης του στόχου της ΑΠ

Συμπεράσματα H θεραπευτική αγωγή με την χρήση ενός μόνο χαπιού κοστίζει λιγότερο Η βελτίωση της συμμόρφωσης με τον τριπλό συνδυασμό των αντιυπερτασικών φαρμάκων έχει την δυνατότητα όχι μόνο να σώσει ζωές αλλά και να μειωθεί το συνολικό κόστος για την υγεία που αυξάνεται από όσους έχουν μη ρυθμισμένη ΑΠ

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