Come ridurre il rischio di ictus e di infarto miocardico nell ipertensione arteriosa

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Flavio Santi
6 anni fa
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1 Come ridurre il rischio di ictus e di infarto miocardico nell ipertensione arteriosa Paolo Verdecchia, F.E.S.C., F.A.C.C. Hospital of Assisi. Department of Medicine Via Valentin Müller, Assisi PG verdec@tin.it

2 DISCLOSURE INFORMATION Paolo Verdecchia Negli ultimi due anni ho avuto i seguenti rapporti anche di finanziamento con soggetti portatori di interessi commerciali in campo sanitario: Boehringer-Ingelheim, Bayer, BMS-Pfizer-Daiichi-Sankyo

3 In epidemiologia, più bassa è la PA, più basso è il rischio sia di infarto miocardico sia di ictus cerebrale

4 BP and Mortality from Coronary Artery Disease The lower, the better Meta-analysis from 61 studies, 1 million individuals and deaths Ischaemic heart disease mortality (floating absolute risk and 95% CI) Systolic blood pressure Age at risk (year) Diastolic blood pressure Age at risk (year) Usual systolic blood pressure (mmhg) Usual diastolic blood pressure (mmhg) Lancet 2002; 360:

Meta-analysis from 61 studies, 1 million individuals and 120 000 deaths Stroke mortality (floating absolute risk and 95% CI) 256 128 64 32 16 BP and Mortality from Stroke The lower, the better 8 4

5 Meta-analysis from 61 studies, 1 million individuals and deaths Stroke mortality (floating absolute risk and 95% CI) BP and Mortality from Stroke The lower, the better 8 4 Systolic blood pressure Age at risk (year) Diastolic blood pressure Age at risk (year) Usual systolic blood pressure (mmhg) Usual diastolic blood pressure (mmhg) Lancet 2002; 360:

6 ...ed è vera anche la reverse epidemiology : Quanto più scende la pressione arteriosa, tanto più diminuisce il rischio di eventi cardiovascolari...

7 The degree of BP Reduction is a Major Determinant of the Benefit. A meta-regression analysis The greater the BP reduction, the greater the expected benefit (reduced risk of events) Staessen J et al. Hypert Res 2005

8 Effects of Antihypertensive Treatment on CV Complications % - 52% - 38% - 38% - 35% - 35% - 21% - 21% CHF Stroke LVH CV deaths Combined results of 17 randomized, placebo-controlled 3- to 5-year trials. BP decreased by 10-12/5-6 mmhg on active treatment vs placebo - 16% - 16% CHD Moser M et al. J Am Coll Cardiol 1996; 27:

9 Le linee-guida fanno differenza tra infarto e ictus? No 2016 European Guidelines on CVD Prevention in Clinical Practice. Eur Heart J 2018;37:

10 In alcune specifiche condizioni sono preferibili alcuni tipi di farmaci European Guidelines on CVD Prevention in Clinical Practice. Eur Heart J 2018;37:

11 Eppure c è evidenza che i farmaci antiipertensivi non sono tutti uguali nel proteggere dall IMA e dall ictus.

12 A parità di abbassamento pressorio, gli ACE-inibitori sono più efficaci del Calcio-antagonisti per la prevenzione della cardiopatia coronarica Verdecchia P, et al Hypertension 2005

13 A parità di abbassamento pressorio, i Calcio-antagonisti sono più efficaci degli ACE-inibitori per la prevenzione dell ictus cerebrale Verdecchia P, et al Hypertension 2005

14 E questo è vero anche per quanto riguarda lo scompenso cardiaco ccongestizio

15 Odds Ratio for Congestive Heart Failure ACE Inhibitors or Angiotensin Receptor Blockers DREAM Calcium Channel Blockers MIDAS VHAS INSIGHT ALLHAT/CCB-D ALLHAT/ACE-D CAPPP UKPDS39 LIFE TRANSCEND ANBP2 HOPE IDNT/ARB-PLB PART-2 DIABHYCAR STOP2/ACE-BB Camelot/ACE-PLB PEACE RENAAL EUROPA NORDIL CONVINCE IDNT/CCB-PLB SHELL INVEST STOP2/CCB-BB ASCOT ACTION FEVER Camelot/CCB-PLB SYST-EUR.4.2 NICS SYST-China STONE PREVENT Systolic Blood Pressure Difference Between Randomized groups (mmhg) Verdecchia P et al. Eur Heart J Mar;30(6):

16 I sartani sono più efficaci degli ACEinibitori nella prevenzione dell ictus cerebrale

17 The risk of stroke is 8% lower with angiotensin receptor blockers than with ACE-Inhibitors Study Publication Year OR (95% CI) Events, ARBs Events, ACEi ARB vs. ACEI ELITE (0.31, 6.33) 4/352 3/370 ELITE-II (0.77, 3.48) 18/ /1574 OPTIMAAL (0.83, 1.35) 140/ /2733 DETAIL (0.34, 3.47) 6/120 6/130 VALIANT/Val (0.69, 1.04) 180/ /4909 ONTARGET/Tel (0.79, 1.05) 369/ /8576 Fixed Effect Model (I 2 = 0.0%, p = 0.478) 0.93 (0.84, 1.03) 717/ /18292 Random Effect Model 0.93 (0.84, 1.03) ARB+ACEI vs. ACEI VALIANT/Val+Cap (0.71, 1.06) 183/ /4909 ONTARGET/Tel+Ram (0.80, 1.07) 373/ /8576 Fixed Effect Model (I 2 = 0.0%, p = 0.602) 0.91 (0.81, 1.02) 556/ /13485 Random Effect Model 0.91 (0.81, 1.02) Overall Estimate Fixed Effect Model (I 2 = 0.0%, p = 0.670) Random Effect Model Heterogeneity between groups: p = (0.85, 0.99) 1273/ (0.85, 0.99) 1384/ Favors 1 st Listed Favors 2 nd Listed Reboldi P, Mancia G. Verdecchia P, et al. J Hypertens :

18 A parità di riduzione pressoria, l ictus cerebrale viene prevenuto molto più che l infarto miocardico Il caso del diabete mellito

19 Relative Risk of Stroke Relative Risk of Acute Myocardial Infarction ABCD/Norm IDNT/ARB-CCB ABCD/HYP ABCD/HYP IDNT/ARB-CCB ATLANTIS/ ACTION-Diab STOP2/ACE-CCB-Diab ALLHAT/ACE-CCB-Diab UKPDS39 DETAIL ALLHAT/ACE-D-Diab IDNT/ARB-PLB CAPPP-Diab DIABHYCAR ADVANCE STOP2/ACE-BB-Diab RENAAL ALLHAT/CCB-D-Diab INSIGHT-Diab EUROPA-Diab MOSES-Diab INVEST-Diab STOP2/CCB-BB-Diab LIFE-Diab HOT-DM More vs Less ASCOT-Diab SHEP-Diab HOPE-Diab PROGRESS-Diab ABCD-H More vs Less STOP2/CCB-BB-Diab DETAIL ABCD-N More vs Less UKPDS39 ABCD/Norm ABCD-H More vs Less INVEST-Diab ATLANTIS/5 ADVANCE IDNT/ARB-PLB ASCOT-Diab ACTION-Diab JMIC-B-Diab LIFE-Diab ACCORD BP UKPDS 38 FACET DIABHYCAR HOPE-Diab EUROPA-Diab RENAAL STOP2/ACE-BB-Diab HOT-DM More vs Less IDNT/CCB-PLB JMIC-B-Diab UKPDS ACCORD 38 BP IDNT/CCB-PLB STOP2/ACE-CCB-Diab FACET CAPPP-Diab SYST-EUR-Diab ABCD-N More vs Less Reboldi GP, Verdecchia P, Angeli F et al, Journal of Hypertension, 2011 Diastolic BP difference between randomised groups, mmhg

20 SPRINT

21 SPRINT: Primary Outcome Hazard Ratio = 0.75 (95% CI: 0.64 to 0.89) Standard (319 events) Intensive (243 events) Median follow-up = 3.26 years Number Needed to Treat (NNT) to prevent a primary outcome = 61

23 Come porre lo studio SPRINT nel contesto degli altri studi di confronto tra target pressori diversi?

25 Verdecchia P et al. Hypertension 2016; 68:

26 Verdecchia P et al. Hypertension 2016; 68:

27 Circulation Research 2017;120:27-29

28 Grazie per la vostra attenzione

29 Knot at -34 mmhg 1.05 ( ) p= Knot at -7 mmhg Reference Knot at 20 mmhg 1.20 ( ) p= Knot at -21 mmhg 1.09 ( ) p= Knot at -6 mmhg Reference Knot at 10 mmhg 1.04 ( ) p= Wald Chi-Square DF p-value Nonlinear Wald Chi-Square DF p-value Nonlinear Knot at 20 mmhg 1.42 ( ) p< Knot at 10 mmhg 1.18 ( ) p< Knot at -34 mmhg 0.84 ( ) p= Knot at -7 mmhg Reference Knot at -21 mmhg 0.79 ( ) p= Knot at -6 mmhg Reference Wald Chi-Square DF p-value Wald Chi-Square DF p-value Nonlinear Nonlinear Conclusions. In patients with CAD and initially free from CHF, a BP reduction from baseline over the examined BP range had little effect on the risk of MI and predicted a lower risk of stroke. An increase in SBP from baseline increased the risk of stroke and MI. A treatment-induced BP reduction over the explored range was safe in these patients. Verdecchia P et al. Hypertension. 2015;65:108-14

30 Il risultato non cambia anche considerando i valori pressori assoluti...

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