Curiosare tra le raccomandazioni delle nuove linee guida sull ipertensione arteriosa

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1 Curiosare tra le raccomandazioni delle nuove linee guida sull ipertensione arteriosa Stefano Taddei Dipartimento di Medicina Clinica e Sperimentale Università di Pisa

2 2013 ESH/ESC Hypertension Guidelines Historical Perspective 2003 Guidelines 2007 Guidelines 2009 Reappraisal ESH 2013 Guidelines J Hypertens 2013;31: Eur Heart J 2013 June 14 Blood Pressure 2013 June 15

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4 2013 ESH/ESC Hypertension Guidelines Table of contents 1. Introduction 2. Epidemiological aspects 3. Diagnostic evaluation 4. Treatment approach 5. Treatment strategies 6. Treatment strategies in special conditions 7. Treatment of associated risk factors 8. Follow-up 9. Improvement of blood pressure control in hypertension 10. Hypertension disease management 11. Gaps in evidence and need for future trials Appendix 1 Appendix 2 Acknowledgements References

5 2013 ESH/ESC Hypertension Guidelines Table of contents 1. Introduction 2. Epidemiological aspects 3. Diagnostic evaluation 4. Treatment approach 5. Treatment strategies 6. Treatment strategies in special conditions 7. Treatment of associated risk factors 8. Follow-up 9. Improvement of blood pressure control in hypertension 10. Hypertension disease management 11. Gaps in evidence and need for future trials Appendix 1 Appendix 2 Acknowledgements References

6 2007 ESH/ESC Hypertension Guidelines General hypertensive population High / very high CV risk (DM / CVD / CKD) Threshold BP Target BP 140/90 mmhg < 140/90 mmhg 130/80 mmhg < 130/80 mmhg BP threshold / targets flexible according to CV risk level

7 Achieved SBP in Uncomplicated Hypertension SBP (mmhg) % BP Benefit OS HDFP AUS MRC FEV Zanchetti, Grassi, Mancia J Hypert 2009; 27: 923 -Mancia et al., J Hypert 2009; 27: 2121

8 Achieved SBP in Trials Diabetes 170 Benefit No benefit SBP (mmhg) Active treatment HOT UKPDS S. Eur ADV ABCD IDNT SHEP HOPE PROG REN HT NT IDNT NAV ACRD AM predm Zanchetti, Grassi, Mancia, J Hypertens 2009; 27: , Mancia et al., J Hypertens 2009; 27: 2121

9 Achieved SBP in Trials Diabetes Previous CVD Stroke CHD SBP (mmhg) Active treatment Benefit No benefit SBP (mmhg) Benefit No benefit Benefit No benefit Active treatment HOT UKPDS S. Eur ADV ABCD IDNT SHEP HOPE PROG REN HT NT IDNT NAV ACRD AM predm 100 PATS ACC PROG PROF HOPE CAM-AM EU TR PREV CAM-EN ACT PEA Zanchetti, Grassi, Mancia, J Hypertens 2009; 27: , Mancia et al., J Hypertens 2009; 27: 2121

10 2013 ESH/ESC Hypertension Guidelines Target SBP < 130 mmhg at high / very high CV risk No clear / consistent evidence of CV event reduction also by subgroup / post-hoc data analysis No beneficial effects on risk of ESRD in nephropathic patients Although mainly based on post-hoc approach, suspicion of a possible J curve phenomenon

11 2013 ESH/ESC Hypertension Guidelines Blood pressure goals in hypertension A SBP < 140 mmhg recommended/considered, regardless the level of risk Low/moderate risk (IB) Diabetes (IA) Diabetic/nondiabetic CKD (IIaB) Patients with CHD/previous stroke or TIA (IIaB) A DBP < 90 mmhg recommended

12 Elderly patients (> 65 - < 80 Years)

13 Elderly patients (> 65 - < 80 Years) Per quali livelli di pressione arteriosa è raccomandato iniziare il trattamento?

14 BP at randomization in antihypertensive treatment trials in th elderly Recruitment BP criteria Mean BP at randomization Trial SBP (mmhg) DBP (mmhg) SBP (mmhg) DBP (mmhg) EWPHE or Coope/warrende r >170 or > SHEP >160 and < STOP-1 >180 or > MRC-elerly and < Syst-Eur and < Syst-China and < SCOPE* or HYVET and < YATOS >160 and < *In SCOPE 50% of patients pretreated with low dose thiazides Zanchetti, Grassi, Mancia, J Hypertens 2009; 27:

15 2013 ESH/ESC Hypertension Guidelines Elderly patients with SBP < 160 mmhg represent a relevant number in trials showing beneficial effects of antihypertensive drug treatment

16 2013 ESH/ESC Hypertension Guidelines Elderly hypertensive patients In ELDERLY HYPERTENSIVE PATIENTS drug treatment is recommended when SBP 160 mmhg Evidence Class Level I A may be considered (in those aged < 80 years) if SBP mmhg, provided treatment is well tolerated IIb C

17 Elderly patients (> 65 - < 80 Years) Quali livelli di pressione arteriosa è raccomandato raggiungere con il trattamento?

18 Achieved SBP in Trials Elderly Benefit No benefit SBP (mmhg) Active treatment EW SHEP MRC S. China SCOPE CW STOP S. Eur HYVET JATOS 18559a M Zanchetti, Grassi, Mancia, J Hypertens 2009; 27: , Mancia et al., J Hypertens 2009; 27: 2121

19 Incidence of Morbidity / Mortality in HYVET 8 All stroke 5 Fatal stroke No. of events per 100 patients % 4 p = p = Heart failure p < % p = Total mortality -39% -21% Placebo 173/91 160/84 (mmhg) Active treatment 173/91 144/78 (mmhg) Goal SBP < 150 mmhg Follow-up (yr) Follow-up (yr) HYVET -Beckett, NEJM 2008; 358: 10

20 2013 ESH/ESC Hypertension Guidelines Target BP in the elderly In elderly pts (>65 ys of age) there is solid evidence to recommend reducing SBP to mmhg (IA) This is the case also in individuals older than 80 ys, provided they are in good physical/mental conditions Any evidence in favour of lower BP targets?

21 2013 ESH/ESC Hypertension Guidelines BP targets in the elderly Evidence Class Level IIb C In fit elderly pts <80 ys old a SBP TARGET <140mmHg may be considered if treatment is well tolerated

22 2013 ESH/ESC Hypertension Guidelines Choice of antihypertensive drugs - Conclusions from 2013 (and 2003 and 2007) Guidelines The main benefits of antihypertensive treatment are due to lowering BP per se and are largely independent of the drug employed Although meta-analyses occasionally claim superiority of one class for some outcomes this largely depends on selection bias of trials. The largest meta-analyses do not show clinically relevant between-class differences

23 2013 ESH/ESC Hypertension Guidelines Choice of antihypertensive drugs - Conclusions from 2013 (and 2003 and 2007) Guidelines The main benefits of antihypertensive treatment are due to lowering BP per se and are largely independent of the drug employed Although meta-analyses occasionally claim superiority of one class for some outcomes this largely depends on selection bias of trials. The largest meta-analyses do not show clinically relevant between-class differences Current Guidelines reconfirm that the following drugs classes are all suitable for initiation and maintenance of antihypertensive treatment either as monotherapy or in some combinations with each other (IA) Diuretics (thiazides / chlorthalidone / indapamide) Beta-blockers Calcium antagonists ACE-inhibitors Angiotensin receptor blockers

24 Algoritmo BHS/NICE (UK) NICE/BHS,

25 Effect of ACE-I and ARBs on total mortality ( patients) Van Vark C et al, Eur Heart 2011

26 Effect of ACE-I and ARBs on total mortality ( patients) Van Vark C et al, Eur Heart 2011

27 Effect of ACE-Is or ARBs on outcomes ( patients) 0,11 % 0,9 * * 0,11 % 0,9 0,11 % 0,9 0,11 * * % 0,9 * 0,7 0,7 0,7 0,7 0,5 0,5 0,5 0,5 Composite outcome Cardiovascular death Myocardial infarction Stroke 0,11 % 0,9 * 0,11 % 0,9 * 0,11 % 0,9 * * 0,7 0,7 0,7 ACE-Is 0,5 0,5 0,5 ARBs All-cause death New heart failure onset New diabetes onset * outcome significantly reduced as compared to placebo Savarese G et al, JACC 2013

28 Effect of ACE-Is or ARBs on outcomes ( patients) 0,11 % 0,9 * * 0,11 % 0,9 0,11 % 0,9 0,11 * * % 0,9 * 0,7 0,7 0,7 0,7 0,5 0,5 0,5 0,5 Composite outcome Cardiovascular death Myocardial infarction Stroke 0,11 % 0,9 * 0,11 % 0,9 * 0,11 % 0,9 * * 0,7 0,7 0,7 ACE-Is 0,5 0,5 0,5 ARBs All-cause death New heart failure onset New diabetes onset * outcome significantly reduced as compared to placebo Savarese G et al, JACC 2013

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30 2013 ESH/ESC Hypertension Guidelines Drugs to be preferred in specific conditions

31 2007 ESH/ESC Guidelines Criteri di scelta tra monoterapia e terapia di associazione Lieve incremento pressorio Rischio CV basso/moderato Obiettivo pressorio convenzionale Scegliere tra Marcato incremento pressorio Rischio CV elevato o molto elevato Obiettivo pressorio più ambizioso Monoterapia a basso dosaggio Se non si riesce ad ottenere l obiettivo pressorio Associazione di 2 farmaci a basso dosaggio Raggiungere il dosaggio pieno Modifica del farmaco iniziando a basso dosaggio Raggiungere il dosaggio pieno dell associazione Aggiungere un terzo farmaco a basso dosaggio Associare tra loro 2-3 farmaci a dosaggio pieno 22 Monoterapia a dosaggio pieno Se non si riesce ad ottenere l obiettivo pressorio Associare tra loro tre farmaci a dosaggio pieno

32 2007 ESH/ESC Guidelines Criteri di scelta tra monoterapia e terapia di associazione Lieve incremento pressorio Rischio CV basso/moderato Obiettivo pressorio convenzionale Scegliere tra Marcato incremento pressorio Rischio CV elevato o molto elevato Obiettivo pressorio più ambizioso Monoterapia a basso dosaggio Se non si riesce ad ottenere l obiettivo pressorio Associazione di 2 farmaci a basso dosaggio Raggiungere il dosaggio pieno Modifica del farmaco iniziando a basso dosaggio Raggiungere il dosaggio pieno dell associazione Aggiungere un terzo farmaco a basso dosaggio Associare tra loro 2-3 farmaci a dosaggio pieno Monoterapia a dosaggio pieno Se non si riesce ad ottenere l obiettivo pressorio Associare tra loro tre farmaci a dosaggio pieno

33 Associazioni omeopatiche Ramipril 2.5 mg / HTCZ 12.5 mg Perindopril 2.5 mg / Indapamide 0.625

34 2013 ESH/ESC Hypertension Guidelines Monotherapy vs. drug combination strategies to achieve target BP Incremento dose monoterapia

35 2013 ESH/ESC Hypertension Guidelines Possible combinations of antihypertensive drug classes Green/continuous: preferred Green/dashed: useful (with some limitations) Black/dashed: possible but less well tested Red/continuous: not recommended Only dihydropyridines to be combined with β-blockers (except for verapamil or diltiazem for rate control in AF) Thiazides + β-blockers increase risk of new onset DM ACEI + ARB combination discouraged (IIIA)

36 Meccanismi d azione dei farmaci antipertensivi Diuretici Calcio antagonisti Alfa-antagonisti SRA ACE-inibitori AT-1 antagonisti Beta-bloccanti Vasodilatatori SNS ACE-inibitori AT-1 antagonisti Beta-bloccanti Simpatomodulatori

37 Randomizzazione (Pazienti giàin trattamento 92%) Terapia a base di Valsartan VALUE: Disegno dello Studio Titolazione secondo target pressorio (<140/90 mmhg) V 80 mg A 5 mg Terapia a base di Amlodipina V 160 mg A 10 mg V 160 mg + HCTZ 12.5 mg A 10 mg + HCTZ 12.5 mg V 160 mg + HCTZ 25 mg A 10 mg + HCTZ 25 mg V 160 mg + HCTZ 25 mg + Agg. libera" A 10 mg + HCTZ 25 mg + Agg. libera" Mese * 72 Screening Randomizzazione *Visite ai pazienti ogni 6 mesi per 6 72 mesi. Fine della fase di aggiustamento posologico Julius S et al. Lancet. 2004

38 Andamento della Pressione Arteriosa mmhg PAS nel tempo, per gruppo di trattamento 4.3 mmhg Valsartan (N= 7649) Amlodipina (N = 7596) Basale Mesi (o visita finale) mmhg PAD nel tempo, per gruppo di trattamento 2.5 mmhg Valsartan (N= 7649) Amlodipina (N = 7596) Basale (o visita finale) Julius S et al. Lancet. Giugno 2004;363.

39 Assenza di effetto additivo tra i Calcio-Antagonisti e i Diuretici ±1.5 * p <0.05 vs placebo PA media 110 * 108.4±1.1 * 108.9±0.9 * 107.3± Placebo Nifedipina Clortalidone Nifedipina+ Clortalidone Salvetti et al, J Hypertens 1989

40 ALLHAT Study Farmaco Associazione Clortalidone Atenololo Razionale Amlodipina Atenololo Razionale Lisinopril Atenololo Non razionale Nello studio ALLHAT il controllo della PA è stato inferiore nel braccio trattato con lisinopril!

41 2013 ESH/ESC Hypertension Guidelines RAS Blocker plus CA or Diuretic (D) in ACCOMPLISH Only trial comparing two combinations in all patients ACEI+D inferior to ACEI+CA despite no BP difference Replication desirable because trials on CA-based vs D-based therapy have never shown a CA superiority Further information on which patients benefit more from one or the other treatment extremely important

42 Applicazione delle Linee Guida nella pratica clinica quotidiana 1. Le Linee Guida sono un discreto strumento culturale (un text book sull ipertensione) 2. La gestione del paziente deve però essere affidata alle qualità cliniche del medico che sono determinate dalla sapiente unione di: cultura, esperienza e buon senso.