Πανελλήνιa Σεμινάρια Ομάδων Εργασίας Ελληνική Καρδιολογική Εταιρεία Θεσσαλονίκη, 16-18/2/2017 Έναρξη & Στόχοι Θεραπείας Αρτηριακής Υπέρτασης Δρ. Παναγιώτης Χ. Σταφυλάς Καρδιολόγος - ESH Hypertension Specialist Medical Coordinator of European ehealth projects
Σύγκρουση συμφερόντων Grant/ Financial support: Speaker/Honoraria/ research grants: With the companies: European Commission AstraZeneca, Boehringer, Menarini, Novartis, Servier HIM SL (Spain), HIM SA (Belgium), MRI LP (Greece)
CDC US 2014 Lewington et al. Lancet 2002.
The most important modifiable RF for CHD, stroke, HF, CKD WHO estimates: 80% of CVD and t2dm, and 40% of cancer could be avoided if major risk factors were eliminated. CDC US 2014 WHO Strategy for Chronic Disease (WHO, 2008).
The lower the better vs the J-Curve hypothesis CV Disease Πόσο χαμηλά? 115/75 mmhg? 0 mmhg Blood Pressure 200 mmhg
2013 ESH/ESC Guidelines for the management of arterial hypertension Definitions and classification of office BP levels (mmhg)* Hypertension: SBP >140 mmhg ± DBP >90 mmhg Category Systolic Diastolic Optimal <120 and <80 Normal 120 129 and/or 80 84 High normal 130 139 and/or 85 89 Grade 1 hypertension 140 159 and/or 90 99 Grade 2 hypertension 160 179 and/or 100 109 Grade 3 hypertension 180 and/or 110 Isolated systolic hypertension 140 and <90 * The blood pressure (BP) category is defined by the highest level of BP, whether systolic or diastolic. Isolated systolic hypertension should be graded 1, 2, or 3 according to systolic BP values in the ranges indicated. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
Η μείωση της αρτηριακής πίεσης μειώνει τον καρδιαγγειακό κίνδυνο, τόσο σε μελέτες με υψηλότερη όσο και με χαμηλότερη ΣΑΠ Ettehad et al. Lancet 2015
Η μείωση της αρτηριακής πίεσης μειώνει τον καρδιαγγειακό κίνδυνο, τόσο σε μελέτες με υψηλότερη όσο και με χαμηλότερη ΣΑΠ 123 RCTs 613.815 patients Every 10mmHg SBP reduction: -27% stroke -28% HF -17% CHD -13% total mortality Ettehad et al. Lancet 2015
Έναρξη θεραπείας σε ασθενείς με ΑΥ σταδίου 1 140 159 / 90 99 mmhg ΜΑ (BPLTTC+new) Patient level + aggregated data 15.266 patients Average BP reduction 3.6/2.4 mmhg Sundstrom et al. Ann Intern Med 2014
Καμία μελέτη σε «ηλικιωμένους» με κριτήριο εισαγωγής ΣΑΠ<160 mmhg Mancia et al. J Hypertens 2009
Σε διαβητικούς ασθενείς, η έναρξη θεραπείας σε ΣΑΠ 140 mmhg υπερτερεί έναντι των χαμηλότερων επιπέδων έναρξης 40 RCTs 100.345 t2dm Significant benefits if start 140 mmhg Stroke, albuminuria ( <140 mmhg) Emdin et al. JAMA 2015
2013 ESH/ESC Guidelines for the management of arterial hypertension Initiation of lifestyle changes and antihypertensive drug treatment Other risk factors, asymptomatic organ damage or disease High normal SBP 130 139 or DBP 85 89 Blood pressure (mmhg) Grade 1 HT SBP 140 159 or DBP 90 99 Grade 2 HT SBP 160 179 or DBP 100 109 Grade 3 HT SBP 180 or DBP 110 No other RF No BP intervention Lifestyle changes for several months Then add BP drugs targeting <140/90 Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 1 2 RF Lifestyle changes No BP intervention Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 3 RF Lifestyle changes No BP intervention Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 OD, CKD stage 3 or diabetes Lifestyle changes No BP intervention Lifestyle changes BP drugs targeting <140/90 Lifestyle changes BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 Symptomatic CVD, CKD stage 4 or diabetes with OD/RFs Lifestyle changes No BP intervention Lifestyle changes BP drugs targeting <140/90 Lifestyle changes BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 BP, blood pressure; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; DBP, diastolic blood pressure; HT, hypertension; OD, organ damage; RF, risk factor; SBP, systolic blood pressure. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
Ποιοι είναι οι στόχοι της θεραπείας?
Σε ανεπίπλεκτους υπερτασικούς, η μείωση της ΣΑΠ<140 mmhg συνοδεύεται από μείωση του καρδιαγγειακού κινδύνου Zanchetti et al. J Hypertens 2009
Καμία μελέτη δεν δείχνει όφελος από τη μείωση της ΣΑΠ<140 mmhg σε ηλικιωμένους υπερτασικούς Zanchetti et al. J Hypertens 2009
Καμία μελέτη σε διαβητικούς ασθενείς δεν έδειξε σημαντικά κλινικά οφέλη από τη μείωση της ΣΑΠ<130 mmhg, αλλά δυο μελέτες έδειξαν όφελος σε επίπεδα ΔΑΠ μεταξύ 80 85 mmhg Zanchetti et al. J Hypertens 2009
ACCORD Results are Mixed Target SBP<120 mmhg vs <140 mm Hg in 4,700 participants with type 2 diabetes at high risk for CVD events Outcome Intensive Events (%/yr) Standard Events (%/yr) HR (95% CI) P CVD (Primary) 208 (1.87) 237 (2.09) 0.88 (0.73-1.06) 0.20 Cardiovascular Deaths 60 (0.52) 58 (0.49) 1.06 (0.74-1.52) 0.74 Total Stroke 36 (0.32) 62 (0.53) 0.59 (0.39-0.89) 0.01 N Engl J Med. 2010;362:1575-85
ACCORD Adverse Events Adverse Events Intensive N (%) Standard N (%) P value Serious AE 77 (3.3) 30 (1.3) <0.0001 Hypotension 17 (0.7) 1 (0.04) <0.0001 Syncope 12 (0.5) 5 (0.2) 0.10 Bradycardia or Arrhythmia 12 (0.5) 3 (0.1) 0.02 Hyperkalemia 9 (0.4) 1 (0.04) 0.01 Renal Failure 5 (0.2) 1 (0.04) 0.12 egfr ever <30 ml/min/1.73m 2 99 (4.2) 52 (2.2) <0.001 Any Dialysis or ESRD 59 (2.5) 58 (2.4) 0.93 Dizziness on Standing 217 (44) 188 (40) 0.36 N Engl J Med. 2010;362:1575-85
Οι μελέτες σε ασθενείς με καρδιαγγειακά συμβάματα (AEE, ΣΝ) δίνουν αντικρουόμενα αποτελέσματα Zanchetti et al. J Hypertens 2009
Νεφρική νόσος Δεν υπάρχουν επαρκή δεδομένα σχετικά με το στόχο Οι διαθέσιμες μελέτες δείχνουν ότι δεν υπάρχει όφελος από τη μείωση της ΣΑΠ<130 mmhg, ενώ παράλληλα αυξάνονται οι επιπλοκές (επιδείνωση egfr) Οι ασθενείς με πρωτεϊνουρία πιθανόν να οφελούνται περισσότερο από χαμηλότερα επίπεδα αρτηριακής πίεσης Mancia et al. 2013 ESH/ESC Guidelines ACCORD. N Engl J Med. 2010
2013 ESH/ESC Guidelines for the management of arterial hypertension Blood pressure goals in hypertensive patients Recommendations SBP goal for most Patients at low moderate CV risk Patients with diabetes Consider with previous stroke or TIA Consider with CHD Consider with diabetic or non-diabetic CKD SBP goal for elderly Ages <80 years Initial SBP 160 mmhg SBP goal for fit elderly Aged <80 years SBP goal for elderly >80 years with SBP 160 mmhg DBP goal for most DB goal for patients with diabetes <140 mmhg 140-150 mmhg <140 mmhg 140-150 mmhg <90 mmhg <85 mmhg SBP, systolic blood pressure; CV, cardiovascular; TIA, transient ischaemic attack; CHD, coronary heart disease; CKD, chronic kidney disease; DBP, diastolic blood pressure. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
JNC8 2014 Evidence-based guideline James et al. JNC8. JAMA 2014
Comparisons to Other Guidelines BP Goal JNC-8 ASH/ISH ESC/ESH CHEP Age < 60 <140/90 Age 60-79 <150/90 <140/90 Age 80+ <150/90 Diabetes <140/90 <140/90 <140/85 <130/80 CKD <140/90 <140/90 <140/90 <140/90 Adapted from Salvo M et al. Ann Pharmacother 2014;48:1242-8.
Will a lower SBP goal reduce the occurrence of CVD among high risk patients? Target SBP < 120 mmhg vs <140 mmhg
Major Inclusion Criteria 1. At least 50 years old 2. Systolic blood pressure (130-180 mmhg) SBP: 130 180 mm Hg on 0 or 1 medication SBP: 130 170 mm Hg on up to 2 medications SBP: 130 160 mm Hg on up to 3 medications SBP: 130 150 mm Hg on up to 4 medications 3. High CV Risk (one or more of the following) Presence of clinical or subclinical CVD (not stroke) Chronic Kidney Disease (CKD), defined as egfr 20 59 ml/min/1.73m 2 Framingham Risk Score for 10-year CVD risk 15% Not needed if eligible based on preexisting CVD or CKD Age 75 years
Major Exclusion Criteria 1. Stroke 2. Diabetes 3. Congestive heart failure (symptoms or EF < 35%) 4. Proteinuria >1g/d 5. CKD with egfr < 20 ml/min/1.73m 2 (MDRD) 6. Adherence flags
Systolic Pressures Mean # Meds Intensive: 3.2 3.4 3.5 3.4 Standard: 1.9 2.1 2.2 2.3 Average after 1 st year: 133.5 Standard vs. 119.3 Intensive, Delta = 14.2 N Engl J Med. 2010;362:1575-85
Primary outcome and death from any cause -25% -27% Number Needed to Treat (NNT) to prevent a primary outcome = 61 Number Needed to Treat (NNT) to Prevent a death = 90
Forest plot of primary outcome according to subgroups
Serious adverse events
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2016 CHEP Guidelines New recommended treatment targets Population SBP DBP High Risk < 120 mmhg NA Diabetes < 130 mmhg < 80 mmhg All others (incl. CKD) < 140 mmhg < 90 mmhg Χρησιμοποίηση αυτόματων ηλεκτρονικών πιεσομέτρων για την μέτρηση της ΑΠ στο ιατρείο και την παρακολούθηση κατ οίκον
Majority of US Hypertensive Patients Not at SBP Goal of <140 mm Hg: Goal Gap 81 90 91 100 101 110 111 120 121 130 131 140 141 150 151 160 161 170 171 180 181 190 191 200 201 210 211 220 221 230 231 240 241 250 14.0 12.0 10.0 Population (millions) 8.0 6.0 4.0 2.0 NOT MEETING GOAL 0.0 SBP = Systolic Blood Pressure Adapted from Whyte JL et al. J Clin Hypertens. 2001;3:211-216. ESH Newsletter 2011;12(3) SBP Range (mm Hg)
Συμπεράσματα Γενικός πληθυσμός: έναρξη 140/90 mmhg, στόχος <140/90 mmhg Διαβητικοί: έναρξη 140/90 mmhg, στόχος <140/85 mmhg (JNC8 <140/90 mmhg, CHEP <130/80 mmhg) Ηλικιωμένοι: έναρξη 160/90 mmhg, στόχος <140-150/90 mmhg (JNC8 >60 ετών, <150/90 mmhg) Υπερτασικοί ασθενείς υψηλού κινδύνου: εξατομίκευση του στόχου της θεραπείας Εναλλακτικές μέθοδοι μέτρησης της αρτηριακής πίεσης
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