Ε. Τριανταφυλλίδη Επιμελήτρια Α Καρδιολογίας. Β Πανεπιστημιακή Καρδιολογική Κλινική Νοσοκομείο ΑΤΤΙΚΟΝ

Transcript

1 Κριτική θεώρηση των μεγάλων μελετών και των καλών μεταναλύσεων ως εργαλείου ενδείξεων για τεκμηρίωση συστάσεων στα καρδιαγγειακά νοσήματα Αρτηριακή υπέρταση Ε. Τριανταφυλλίδη Επιμελήτρια Α Καρδιολογίας Β Πανεπιστημιακή Καρδιολογική Κλινική Νοσοκομείο ΑΤΤΙΚΟΝ

2 There is no conflict of interest

3 Αρτηριακή υπέρταση: επιπτώσεις Αθηρωμάτωση αγγείων Υπερτροφία αριστερής κοιλίας Στεφανιαία νόσος Οξύ έμφραγμα του μυοκαρδίου Καρδιακή ανεπάρκεια Κολπική μαρμαρυγή Ανεύρυσμα θωρακικής αορτής Παροδικό ΑΕΕ Ισχαιμικό ΑΕΕ Ενδοεγκεφαλική αιμορραγία Άνοια Χρόνια νεφρική ανεπάρκεια Αμφιβληστροειδοπάθεια Σεξουαλική δυσλειτουργία

4

5 Αρτηριακή υπέρταση: επίπτωση 25% του πληθυσμού της γης είναι υπερτασικοί (30% έως το 2025). Η επίπτωση παραμένει σχεδόν σταθερή στις αναπτυγμένες χώρες ενώ αυξάνεται στις οικονομικά αναπτυσσόμενες χώρες (διαφορά ποσοστών και μεγέθους πληθυσμού). Τα υψηλά ποσοστά υπέρτασης συμβάλλουν στην παρατηρούμενη έξαρση των καρδιαγγειακών νοσημάτων παγκοσμίως.

6

7

8

9

10 In medicine, clinicians initially formed guidelines to suggest a safe direction when managing difficult clinical situations. GUIDELINES experienced guides marked the best and safest paths for hikers to take by placing The original term for practice guidelines was borrowed from a mountain-climbing technique in which ropes (lines) along the way.

11

12 Major inclusion criteria: 1. A RCT major study in hypertension (they are less subject to bias than other study designs and represent the gold standard for determining efficacy and effectiveness) 2. The study had at least 2000 participants (larger study populations are needed to obtain interpretable results). 3. The study was multicentre. 4. Studies which reported the effects of the studied interventions on important health outcomes: Overall, cardiovascular disease (CVD) related and CKD-related mortality MI, HF, hospitalization for heart failure, stroke Coronary and carotid, renal, and lower extremity revascularization End-stage renal disease, doubling of Cr level, halving of GFR.

13

14

15

16

17 α-blockers, dual α1-+β-blocking agents (carvedilol), vasodilating β-blockers (nebivolol), central α2-adrenergic agonists (clonidine), direct vasodilators (hydralazine), aldosterone receptor antagonists (spironolactone), adrenergic neuronal depleting agents (reserpine), and loop diuretics (furosemide)

18 Epidemiology and Total Cardiovascular Risk

19

20

21

22

23 Ο πληθυσμός, ο οποίος δεν πληροί κανένα στόχο είναι συγκριτικά πολύ μεγαλύτερος, οπότε η προσπάθεια πρέπει να στραφεί στην αναγνώριση του και στην σωστή αντιμετώπιση του

24

25

26 The main studies, which were quoted by JNC-8 to show no benefit of the lower BP goal, were the JATOS (Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients) and VALISH (Valsartan in Elderly Isolated Systolic Hypertension Study). Neither included patients in the age 60 to 65 year range (JATOS age 65 to 85 years, VALISH age 70 to 84 years); JATOS had a target BP value of 140 to 159 mm Hg for the moderate BP control arm, different from the 140 to 150 mm Hg range of the JNC-8 panel recommendations; In both studies the observed rate of cardiovascular events was much lower than predicted, suggesting that the studies were underpowered to show benefit of a target of <140 mm Hg; and the studies were of relatively short duration (JATOS 2 years, VALISH 2.85 years). Also, both were in a Japanese cohort, which could limit the generalizability of the findings.

27

28

29

30 Those patients for whom the recommendations had changed and who would no longer be eligible for initiation or intensification of treatment had an average 10-year risk of myocardial infarction or death of 8.5%, and when including stroke risk, of 28%. This number was estimated to be reduced to approximately 19% if those patients were treated to the JNC-7 guideline goals, equivalent to a number-needed-to-treat, for more than 10 years, of 10 to 11 patients to prevent 1 cardiovascular event. The higher SBP goal in individuals aged 60 years or older may reverse the decades-long decline in CVD, especially stroke mortality and might partially undo the remarkable progress in reducing cardiovascular mortality in Americans older than 60 years

31 What is missing from the evidence? The answer is a large, randomized controlled trial of those older than 60 years of age without diabetes or CKD comparing a higher and lower goal. Two such trials are underway: 1. SPRINT (Systolic Blood Pressure Intervention Trial) planned to randomize high-risk subjects >50 years of age to target SBP goals of <120 and <140 mm Hg 2. ESH-CHL-SHOT (Optimal Blood Pressure and Cholesterol Targets for Preventing Recurrent Stroke in Hypertensives) in which 7,500 subjects >65 years of age with prior stroke or transient ischemic attack will be randomized to 3 different target SBP goals: < mm Hg; < mm Hg; and <125 mm Hg. Both trials compare goals near the standard (140mmHg SBP) with lower goals. If they clearly show benefit from a lower goal, then the goal of 150 mm Hg may be less defensible. But if, like in the ACCORD trial, they fail to demonstrate any benefit of a lower goal, the issue will not be resolved.

32

33 The second recommendation is that of achieving systolic blood pressure levels below 140 mmhg in all hypertensive patients, including the elderly, and values below 130 mmhg in patients having diabetes and high/very-high-risk patients. Critical analyses of the results of available trials show that the evidence is scanty for both recommendations. Nonetheless, they can be accepted as prudent statements, as antihypertensive agents are very well tolerated and lowering systolic blood pressure below 130 mmhg appears well tolerated. However, wisdom should not be taken for evidence, and simple trials should be designed to look for more solid evidence in favour of current recommendations.

34 Intensive arm: more treatment-related adverse events (K, GFR, BP)

35

36 Intensive arm: more treatment-related adverse events (K, GFR, BP)

37

38

39 A meta-analysis of 15 trials of intensive BP lowering demonstrated risk reductions of % for major CV events, MI, and end-stage kidney disease and of 24 % for stroke, but with no clear effect on mortality. Intensive BP reduction did not increase the rate of drug discontinuation or the incidence of serious AEs, apart from hypotension, which occurred infrequently.

40 Συμπεράσματα Και οι δύο ομάδες κατευθυντηρίων οδηγιών (JNC-8, ESH 2013) θεωρούν ότι αν και η σχέση μεταξύ αρτηριακής πίεσης και καρδιαγγειακού κινδύνου είναι γραμμική, απουσιάζουν εκείνα τα αποδεικτικά στοιχεία, τα οποία αποδεικνύουν πραγματικό όφελος όταν η πίεση θεραπεύεται σε επίπεδα χαμηλότερα των 140/90 mmhg ειδικά σε ασθενείς υψηλού κινδύνου. However, until more solid RCT data are available, individualized treatment of high-risk patients may be prudent. Individual patient demographics, BP level, CV risk, comorbidities, and preference should influence the chosen treatment strategy. An optimal therapy regimen that lowers BP and CV risk while being tolerable will encourage patient adherence.