Fourth Mediterranean Congress Innovative Scenario in Internal Medicine Presidente - Chiar.mo Prof. Giuseppe Licata Palermo, 06-07 Giugno 2014 I SESSIONE IPERTENSIONE ARTERIOSA - BASI BIOPATOLOGICHE E TERAPIA PERSONALIZZATA Luci ed ombre delle Linee Guida Claudio Ferri Università dell Aquila Cattedra e Scuola di Medicina Interna Dipartimento MeSVA U.O.C. di Medicina Interna e Nefrologia Ospedale San Salvatore
Luci ed ombre delle Linee Guida
Luci ed ombre delle Linee Guida Ombra La stratificazione del rischio Come viene valutato in atto il paziente iperteso?
ESC guidelines. Eur Heart J. 2012; 33, 1635 1701 SCORE chart: 10-year risk of fatal cardiovascular disease (CVD) in countries at high CVD risk SCORE chart: 10-year risk of fatal cardiovascular disease (CVD) in countries at low CVD risk
Luci ed ombre delle Linee Guida
Luci ed ombre delle Linee Guida I concetti base che sfuggono alle carte
Luci ed ombre delle Linee Guida I concetti base che sfuggono alle carte 1. L attrazione temporale dei fattori di rischio (variabile diacrona e non sincrona)
The attraction concept: Predictive value of the prevalence of components of MetS on incident MetS (Logistic regression) from examination 4 to examination 6 (Prevalence from 23.5% to 40.6%) Variables Significance Odds Ratio 95% CI N = 3078, age = 51.6±9.9 Large waist circumference <0.0001 4.40 5.12 Hypertriglyceridemia <0.0001 3.44 5.10 HDL <0.0001 4.21 4.87 Hyperglycemia <0.0001 2.56 3.89 Blood pressure <0.0001 3.25 3.76 Age 0.9937 <0.0001 1.00 1.03 M F -2.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 Odds Ratio Franco OH. et al, Circulation 2009,120(20):1943-1950
Luci ed ombre delle Linee Guida I concetti base che sfuggono alle carte 1.L attrazione temporale dei fattori di rischio (variabile diacrona e non sincrona) 2.L impatto nel tempo (diacronia) diurno/notturno
Duration of exposure (daily) to RFs for CVD Rate Ratio (95% CI) Men (n=54 668, 1180 deaths) Exposed currently 1.23 (1.03-1.47) Self-report 1-2 h/d 1.23 (0.91-1.67) 3-4 h/d 1.35 (0.96-1.90) >4 h/d 1.13 (0.84-1.51) Smoking reported by spouse <20 cigarettes/d 1.37 (1.04-1.79) 20 cigarettes/d 1.15 (0.86-1.53) >20 cigarettes/d 1.12 (0.77-1.63) Age <65 y at baseline 1.42 (1.10-1.83) No heart disease at baseline 1.32 (1.04-1.66) Heart disease at baseline 1.07 (0.80-1.42) Women (n=80 549, 426 deaths) Exposed currently 1.19 (0.97-1.45) Self-report 1-2 h/d 0.70 (0.45-1.10) 3-4 h/d 1.21 (0.85-1.74) >4 h/d 1.28 (1.01-1.62) Smoking reported by spouse <20 cigarettes/d 1.22 (0.86-1.72) 20 cigarettes/d 1.14 (0.83-1.57) 21-39 cigarettes/d 1.02 (0.66-1.60) 40+ cigarettes/d 1.28 (0.81-2.01) Age <65 y at baseline 1.24 (0.89-1.71) No heart disease at baseline 1.15 (0.91-1.47) Heart disease at baseline 1.17 (0.82-1.67) CVD and correct spouse selection Rate Ratio (95% CI) Men: Spousal subcohort (n=58 530; 1299 deaths) Exposed to current smoker 1.48 (1.21-1.80) Exposed to former smoker 0.97 (0.79-1.20) Years exposed to cigarette smoke 1-12 1.14 (0.80-1.63) 13-21 1.13 (0.80-1.59) 22-29 1.14 (0.84-1.56) 30+ 1.25 (1.01-1.53) Pack-years of exposure 1-5 1.25 (0.91-1.71) 6-14 1.33 (1.01-1.75) 15-27 1.13 (0.84-1.51) 28+ 1.10 (0.86-1.42) Women: Spousal subcohort (n=99 621; 572 deaths) Exposed to current smoker 1.16 (0.91-1.48) Exposed to former smoker 1.08 (0.90-1.29) Years exposed to spousal cigarette smoke 1-14 0.84 (0.59-1.20) 15-25 0.99 (0.73-1.33) 26-33 1.20 (0.91-1.58) 34+ 1.20 (0.98-1.46) Pack-years of exposure to spousal cigarette smoke 1-12 0.83 (0.60-1.13) 13-25 1.12 (0.86-1.46) 26-33 1.09 (0.84-1.42) 34+ 1.26 (1.01-1.57) Steenland K et al. Circulation.1996; 94: 622-628
Duration of exposure (daily) to RFs for CVD Rate Ratio (95% CI) Men (n=54 668, 1180 deaths) Exposed currently 1.23 (1.03-1.47) Self-report 1-2 h/d 1.23 (0.91-1.67) 3-4 h/d 1.35 (0.96-1.90) >4 h/d 1.13 (0.84-1.51) Smoking reported by spouse <20 cigarettes/d 1.37 (1.04-1.79) 20 cigarettes/d 1.15 (0.86-1.53) >20 cigarettes/d 1.12 (0.77-1.63) Age <65 y at baseline 1.42 (1.10-1.83) No heart disease at baseline 1.32 (1.04-1.66) Heart disease at baseline 1.07 (0.80-1.42) CVD and correct spouse selection Rate Ratio (95% CI) Men: Spousal subcohort (n=58 530; 1299 deaths) Exposed to current smoker 1.48 (1.21-1.80) Exposed to former smoker 0.97 (0.79-1.20) Years exposed to cigarette smoke 1-12 1.14 (0.80-1.63) 13-21 1.13 (0.80-1.59) 22-29 1.14 (0.84-1.56) 30+ 1.25 (1.01-1.53) Pack-years of exposure 1-5 1.25 (0.91-1.71) 6-14 1.33 (1.01-1.75) 15-27 1.13 (0.84-1.51) 28+ 1.10 (0.86-1.42) Women (n=80 549, 426 deaths) Exposed currently 1.19 (0.97-1.45) Self-report 1-2 h/d 0.70 (0.45-1.10) 3-4 h/d 1.21 (0.85-1.74) Nicotina >4 h/d 1.28 (1.01-1.62) Smoking reported by Polonio-210 spouse <20 cigarettes/d Composti organici 1.22 volatili (0.86-1.72) 20 cigarettes/d Gas tossici 1.14 (0.83-1.57) 21-39 cigarettes/d 1.02 (0.66-1.60) Catrame e condensato 40+ cigarettes/d 1.28 (0.81-2.01) Age <65 y at baseline Acetato di cellulosa 1.24 (0.89-1.71) No heart disease at baseline 1.15 (0.91-1.47) Heart disease at baseline 1.17 (0.82-1.67) Women: Spousal subcohort (n=99 621; 572 deaths) Exposed to current smoker 1.16 (0.91-1.48) Exposed to former smoker 1.08 (0.90-1.29) Years exposed to spousal cigarette smoke 1-14 0.84 (0.59-1.20) 324 tonnellate 15-25 0.99 (0.73-1.33) 1872 milioni di Bq 26-33 1.20 (0.91-1.58) 34+ 1800 tonnellate 1.20 (0.98-1.46) Pack-years 21,6 tonnellate of exposure to spousal cigarette smoke 1-12 0.83 (0.60-1.13) 1440 tonnellate 13-25 1.12 (0.86-1.46) 12240 tonnellate 26-33 1.09 (0.84-1.42) 34+ 1.26 (1.01-1.57) ITALIA 13 milioni di fumatori = 72 miliardi di cicche x anno Steenland K et al. Circulation.1996; 94: 622-628
Luci ed ombre delle Linee Guida I concetti base che sfuggono alle carte 1.L attrazione temporale dei fattori di rischio (variabile diacrona e non sincrona) 2.L impatto nel tempo (diacronia) diurno/notturno 3.L impatto nel tempo (diacronia) inteso come lungo periodo
Conen D et al. Ann Intern Med. 2011; 154(11): 719 726 NIH-PA Author Manuscript Duration of exposure (years) to RFs for Conen PAD et al. Duration of cessation of exposure to RFs for PAD Pag
Luci ed Ombre delle Linee Guida Luce L ingresso degli anziani veri
SBP (mmhg) SBP (mmhg) SBP (mmhg) SBP (mmhg) Achieved SBP in Trials 160 150 140 Uncomplicated HT 190 180 146 170 Elderly Benefit Benefit No benefit 130 120 110 130 130 138 137 160 150 140 130 150 162 143 167 156 151 151 144 145 138 100 OS HDFP AUS MRC FEV 120 EW SHEP MRC S. China SCOPE CW STOP S. Eur HYVET JATOS 170 160 Diabetes Benefit No benefit 160 150 Stroke 150 Previous CVD CHD Benefit No benefit Benefit No benefit 150 140 130 145 145 144 139 153 134 134 132 128 140 143 141 133 140 130 120 143 132 136 135 128 124 136 122 130 124 129 120 119 110 110 HOT UKPDS S. Eur ADV ABCD IDNT SHEP HOPE PROG REN HT NT IR IDNT NAV ACRD AM predm 100 PATS ACC PROG PROF HOPE CAM-AM EU TR PREV CAM-EN ACT PEA Zanchetti A, Grassi G and Mancia G, J Hypertens 2009; 27: 923-934 and Mancia et al., J Hypertens 2009; 27: 2121
No. of events per 100 patients Incidence of Morbidity / Mortality in HYVET 8 All stroke 5 Fatal stroke 7 6-30% 4-39% 5 4 3 2 1 0 7 p = 0.055 3 p = 0.046 Heart failure 2 1 0 30 Total mortality Placebo 173/91 160/84 (mmhg) Active treatment 173/91 144/78 (mmhg) 6 5 4 20 p < 0.0001-64% p = 0.019-21% 3 2 1 0 0 1 2 3 4 Follow-up (yr) 10 0 0 1 2 3 4 Follow-up (yr) Goal SBP < 150 mmhg Beckett et al, N Eng J Med 2008; 358: 10
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 150-140 mmhg (IA) This is the case also in individuals older than 80 ys, provided they are in good physical/mental conditions (IB) Any evidence in favour of lower BP targets?
Beneficial Effects of BP Reduction < 140 mmhg SBP in Elderly Patients (age > 65 years) of Event HR HR (95% CI) p Strokes 0.56 (0.41-0.75) < 0.001 All CV events 0.53 (0.41-0.69) < 0.001 All cardiac events 0.49 (0.31-0.77) 0.002 CV deaths 0.64 (0.45-0.91) 0.013 All deaths 0.2 0.5 1 2 Felodipine (BP 139.7 / 81.2 mmhg) 0.51 (0.33-0.81) Placebo (BP 145.5 / 83.6 mmhg) 0.004 Zhang et al., Eur Heart J 2011; 32: 1500
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
Luci ed Ombre delle Linee Guida Luce ed Ombra Il trattamento
2013 ESH/ESC Hypertension Guidelines Monotherapy vs. drug combination strategies to achieve target BP Mild BP elevation Low/moderate CV risk Choose between Marked BP elevation High/very high CV risk (IIbC) Single agent Two-drug combination Switch to different agent Previous agent at full dose Previous combination at full dose Add a third drug Full dose monotherapy Two drug combination at full doses Switch to different twodrug combination Three drug combination at full doses Moving from a less intensive to a more intensive therapeutic strategy should be done whenever BP target is not achieved.
2013 ESH/ESC Hypertension Guidelines Drugs to be preferred in specific conditions Condition Other ISH (elderly) Metabolic syndrome Diabetes mellitus Pregnancy Blacks Asymptomatic organ damage LVH Asymptomatic atherosclerosis Microalbuminuria Renal dysfunction Clinical CV event Previous stroke Previous myocardial infarction Angina pectoris Heart failure Aortic aneurysm Atrial fibrillation, prevention Atrial fibrillation, ventricular rate control ESRD/proteinuria Peripheral artery disease Drug Diuretic, calcium antagonist ACE inhibitor, ARB, calcium antagonist ACE inhibitor, ARB Methyldopa, BB, calcium antagonist Diuretic, calcium antagonist ACE inhibitor, calcium antagonist, ARB Calcium antagonist, ACE inhibitor ACE inhibitor, ARB ACE inhibitor, ARB Any agent effectively lowering BP BB, ACE inhibitor, ARB BB, calcium antagonist Diuretic, BB, ACE inhibitor, ARB, mineralocorticoid receptor antagonists BB Consider ARB, ACE inhibitor, BB or mineralocorticoid receptor antagonist BB, non-dihydropyridine calcium antagonist ACE inhibitor, ARB ACE inhibitor, calcium antagonist
Luci ed Ombre delle Linee Guida Luci ed Ombre 1.Ombra: E necessario e le Linee Guida solo in parte lo fanno superare la cardiocentricità nella stratificazione del rischio cardiovascolare 2.Luce: E qualificante il prolungato focus sul paziente anziano vero, che attualizza al mondo reale le Linee Guida 3.Ombra e Luce: La pressione normale alta andrebbe trattata sempre, mentre è molto qualificante l approccio terapeutico. Tuttavia, se si vuole implementare realmente il controllo, è necessario generale degli algoritmi più improntati al decisionismo
Luci ed Ombre delle Linee Guida Luci ed Ombre 1.Ombra: E necessario e le Linee Guida solo in parte lo fanno superare la cardiocentricità nella stratificazione del rischio cardiovascolare 2.Luce: E qualificante il prolungato focus sul paziente anziano vero, che attualizza al mondo reale le Linee Guida 3.Ombra e Luce: La pressione normale alta andrebbe trattata sempre, mentre è molto qualificante l approccio terapeutico. Tuttavia, se si vuole implementare realmente il controllo, è necessario generale degli algoritmi più improntati al decisionismo
Luci ed Ombre delle Linee Guida Luci ed Ombre 1.Ombra: E necessario e le Linee Guida solo in parte lo fanno superare la cardiocentricità nella stratificazione del rischio cardiovascolare 2.Luce: E qualificante il prolungato focus sul paziente anziano vero, che attualizza al mondo reale le Linee Guida Ombra e Luce: E molto qualificante l approccio terapeutico. Tuttavia, se si vuole implementare realmente il controllo, è necessario generale degli algoritmi più improntati al decisionismo