Giovambattista Desideri Università degli Studi dell’Aquila ... · Exceptional Longevity in Men - Modifiable Factors Associated With Survival and Function to Age 90 Years: Physicians’

Giovambattista DesideriUniversità degli Studi dell’Aquila

Dipartimento di Medicina Interna e Sanità Pubblica

Approccio terapeutico all’anziano iperteso:

quanto e come trattare

Approccio terapeutico all’anziano iperteso:

quanto e come trattare

Simposio SIGG-SIGGIpertensione arteriosa: gli

aspetti peculiari nell’anziano

Simposio SIGG-SIGGIpertensione arteriosa: gli

aspetti peculiari nell’anziano

Exceptional Longevity in Men - Modifiable Factors Associated With Survival and Function to Age 90 Years: Physicians’ Health Study

Yates LB, et al. Arch Inter Med 2009;168(3):284-290

2357 healthy men (mean age, 72 years)

Yates LB, et al. Arch Inter Med 2009;168(3):284-290

2357 healthy men (mean age, 72 years)

Exceptional Longevity in Men - Modifiable Factors Associated With Survival and Function to Age 90 Years: Physicians’ Health Study

Modificato da: Prospective Studies Collaboration. Lancet 2002;360:1903-1913

Mo

rtalità

per

ictu

s(r

isch

io a

sso

luto

e 9

5%

CI)

Pressione sistolica usuale (mm Hg)

50-59 anni

60-69 anni

70-79 anni

80-89 anni

Fasce di età:

256

128

64

32

16

8

4

2

1

0120 140 160 180

Mo

rtalità

per

card

iop

ati

a isc

hem

ica

(ris

chio

ass

olu

toe 9

5%

CI)

Pressione sistolica usuale (mm Hg)

256

128

64

32

16

8

4

2

1

0120 140 160 180

50-59 anni

60-69 anni

70-79 anni

80-89 anni

Fasce di età:

40-49 anni

La mortalità per ictus e cardiopatia ischemica aumenta con l’aumentare dei valori pressori

Ipertensione

Meccanismi di danno cognitivo nel paziente iperteso

Demenza vascolare

Demenza degenerativaDemenza degenerativa

Funz

ioni

cogn

itive

no demenza

demenza

soglia

no demenza

demenza

soglia ictus

morte morte

White matter lesions

Mortalità totaleSHEP 213:242SYST-EUR 123:137SYST-CHINA 61:82Totale 397:461Eterogeneità: p=0,38

Mortalità cardiovascolareSHEP 90:112SYST-EUR 59:77SYST-CHINA 33:44Totale 182:233Eterogeneità: p=0,82

N° di endpoint Odds ratios RiduzioneStudio Trattati: Controlli e IC e DS

Trattamentopeggiore

1.00.5 1.5

17% DS 62p = 0.008

25% DS 82p = 0.005

Staessen JA et al. Lancet 2000; 355: 865–872

Trattamentomigliore

Mortalità totale e cardiovascolare nei pazienti più anziani con ipertensione sistolica isolata

Gueyffier F et al., Lancet 1999; 353:793

MortalitMortalitàà gen.gen.

MortalitMortalitàà CVCV

Eventi coronEventi coron..

IctusIctus

InsuffInsuff. card.. card.

EventiEventi CVCV

EWPHEEWPHESHEPSHEP--PPSHEPSHEPSTOPSTOPSystSyst--EurEur

1.00.80.2 0.4 0.6 1.2 1.4 1.6 1.8RR (95% CI)RR (95% CI)

TrattamentoTrattamento vs. Placebovs. Placebo

EtEtàà>>8080 aaaaN=1566N=1566

Prevenzione del rischio CV nel “grande vecchio” iperteso: metanalisidi trial in “doppio cieco”

Gueyffier F et al., Lancet 1999; 353:793




IctusIctus


EventiEventi CVCV

EWPHEEWPHESHEPSHEP--PPSHEPSHEPSTOPSTOPSystSyst--EurEur

1.00.80.2 0.4 0.6 1.2 1.4 1.6 1.8RR (95% CI)RR (95% CI)



Prevenzione del rischio CV nel “grande vecchio” iperteso: metanalisidi trial in “doppio cieco”

Keep Antihypertensive drugs away from very old people

….The instrument of geriatric assessment should be included in future biomedical trials with elderly patients.

Peter Oster, Gunter Schlierf - Lancet 1999

Beckett NS et al. N Engl J Med 2008;358:1887-1898

Treatment of Hypertension in Patiens 80 years of Age or Older: HYVET study

-30%

-39%-23%

HF: - 64%

-21%

PAS – 14.5±18.5 mmHgPAD – 6.8±10.5 mmHg

Placebo20% target

PAS – 29.5±15.4 mmHgPAD – 12.9±9.5 mmHg

Treatment20% target

Bejan-Angoulvant T et al, J Hypertens 2010, 28:1366–1372




IctusIctus


EventiEventi CVCV

EWPHEEWPHESHEPSHEP--PPSHEPSHEPSTOPSTOPSystSyst--EurEurHYVET PilotHYVET PilotHYVETHYVETCoopeCoope 19861986

1.00.80.2 0.4 0.6 1.2 1.4 1.6 1.8RR (95% CI)RR (95% CI)



Treatment of hypertension in patients 80 years and older: the lowerthe better? A meta-analysis of randomized controlled trials

Turnbull F, et al. BMJ 2008;336:1121-1123

Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials

Blood Pressure Lowering Treatmen Trialists’ Collaboration: 31 trials, 190.606 participants

Law, M R et al. BMJ 2009;338:b1665

DBP SBP

Reduction in incidence of coronary heart disease (CHD) events and stroke in relation to reduction in diastolic and systolic blood pressure according to drug dose, number of drugs, pretreatment diastolic blood pressure, and age. *Blood pressure reductions are more uncertain and hence also reductions in disease incidence (147 randomized trials)

Reappraisal of European guidelines on hypertension management: aEuropean Society of Hypertension Task Force document

J. Hypertens 2009; 27: 2121-2158

In the elderly antihypertensive treatment is highly beneficial. Theproportional benefit in patients aged more than 65 years is no less than thatin younger patients.

In the elderly, outcome trials have only addressed patients with an entry SBP at least 160mmHg, and in no trial in which a benefit was shown achieved SBP averaged less than 140mmHg…. but common sense considerations suggest that also in the elderly drug treatment can be initiated when SBP is higher than 140mmHg, and that SBP can be brought to below 140mmHg, provided treatment is conducted with particular attention to adverse responses, potentially more frequent in the elderly.

Treatment of hypertension in patients 80 years and older: the lowerthe better? A meta-analysis of randomized controlled trials

Bejan-Angoulvant T et al, J Hypertens 2010, 28:1366–1372

Target Blood Pressure for Treatment of Isolated Systolic Hypertension in the Elderly. Valsartan in Elderly Isolated Systolic Hypertension Study

Ogihara T, et al. Hypertension. 2010;56:196-202

3260 patients, aged 70 to 84 years with ISH, (160 to 199 mm Hg)PAS >140 <150 mmHg

PAS <140 mmHg

Target Blood Pressure for Treatment of Isolated Systolic Hypertension in the Elderly. Valsartan in Elderly Isolated Systolic Hypertension Study

Ogihara T, et al. Hypertension. 2010;56:196-202

Primary end point: composite of SD, fatal and nonfatal stroke, fatal and nonfatal MI, HF death, other CV death,unplanned hospitalization because of CV diseases, and renal dysfunction.

Exp. inc. of primary outcome: 21.4 (strict) 29.1 (moderate) per 1000 pts/yrObs. Inc. of primary outcome: 10.6 (strict) 12.0 (moderate) per 1000 pts/yr

14215 M14215 M

Does Evidence Support an Aggressive Systolic Blood Pressure Target in the Elderly?

Zanchetti A, et al. J. Hypertens 2009; 27: 923-934

(1) Not a single trial was specifically conducted in elderly hypertensive patients with systolic BP <160 mm Hg;

(2) In none of the available placebo-controlled trials did systolic BP fall below 140 mm Hg in the treated group

(3) In none of the available placebo-controlled trials was140 mm Hg the prespecified BP target of treatment.

14215 M14215 M


J. Hypertens 2009; 27: 2121-2158

Bottom blood pressure or bottom cardiovascular risk?How far can cardiovascular risk be reduced?

Zanchetti A. J Hypertens 2009; 27:1509-1520

Elderly Hypertensive Patients

Cumulative incidence of CVD adjusted for the competing risk of death for men and women according to aggregate RFs burden at 50 years of age

Lloyd Jones DM et al Circulation 2006;113:791-798

Two-steps in hypertension induced vascular damage

Life: 0 10 20 30 40 50 60 70 80...years

Early step:Endothelial Abnormalities

Late step:Atherosclerotic plaque

Early step:Subclinical damage

Late step:Cardiovascular event

Dogma Disputed: Can Aggressively Lowering Blood Pressure inHypertensive Patients with Coronary Artery Disease Be Dangerous?

Messerli F, et al. Ann Intern Med. 2006;144:884-893





Antihypertensive treatment in patients with cerebrovascular disease: thelower the better? The SMART study

Muller M, et al. J Hypertens 2010; 28:1498–1505

high pCBF (highest two tertiles; <47 ml/min per 100 ml)

low pCBF (highest two tertiles; >47 ml/min per 100 ml)..


J. Hypertens 2009; 27: 2121-2158

In the elderly antihypertensive treatment is highly beneficial. Theproportional benefit in patients aged more than 65 years is no less than thatin younger patients.

In the elderly, outcome trials have only addressed patients with an entry SBP at least 160mmHg, and in no trial in which a benefit was shown achieved SBP averaged less than 140mmHg…. but common sense considerations suggest that also in the elderly drug treatment can be initiated when SBP is higher than 140mmHg, and that SBP can be brought to below 140mmHg, provided treatment is conducted with particular attention to adverse responses, potentially more frequent in the elderly.

Sodium Reduction and Weight Loss in the Treatment of Hypertension in Older Persons: ARandomized Controlled Trial of Nonpharmacologic Interventions inOnline article andrelated contentthe Elderly (TONE)

Welthon PK, et al. AMA. 1998;279(11):839-846 (

The 2007 ESH/ESC guidelines conclusion that diuretics, ACEinhibitors, calcium antagonists,angiotensin receptor antagonists, and β-blockers can all be considered suitable for initiation ofantihypertensive treatment, as well as for its maintenance, can thus be confirmed.

The choice of the drugs to employ should thus not be guided by age.Thiazide diuretics, ACE inhibitors,calcium antagonists, angiotensin receptor antagonists, and β-blockerscan be considered for initiation andmaintenance of treatment also in theelderly.

J. Hypertens 2009; 27: 2121-2158


Thiazide Thiazide diuretics diuretics

ACEACE--II

CCBCCB

ARBsARBsßß--blockersblockers

αα--blockersblockers

Effects of different regimens to lower blood pressure on major CVevents in older and younger adults: meta-analysis of randomised trials



Effects of different regimens to lower blood pressure on major CVevents in older and younger adults: meta-analysis of randomised trials



Onder G, et al. JAGS 50:1962–1968, 2002

Adverse Drug Reactions as Cause of Hospital Admissions: Results from the Italian Group of Pharmacoepidemiologyin the Elderly(GIFA)

ARBs 0.57(0.46-0.72) p<0.0001

ACE inhibitors 0.67(0.56-0.80) p<0.0001

CCBs 0.75(0.62-0.90) p=0.002

Placebo 0.77(0.63-0.94) p=0.009

Β blockers 0.90(0.75-1.09) p=0.30

Diuretics Referent

0.50 0.70 0.90 1.26

Odds ratio of incident diabetes Incoherence=0.000017

Elliott WJ et al Lancet 2007;369:201-07

Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis Results of 22 clinical trials

Diff

eren

ces

inH

azar

d R

atio

s(H

R)

p=0.0168

HR=1

Aksnes et al Hypertension 2007;50:467-473

Never DMn=8697

New-onset DMn=1298

Baseline DMn=5.250

Heart Failureby 3 patient group

HR=1.41(1.06 to 1.87)

HR=2.79(2.40 to 3.25)

Total cardiac morbidityby 3 patient groups

p<0.0001

HR = 1.43 (1.16 to 1.77)

p=0.0008

HR = 2.20 (1.95 to 2.49)

P=0.0001

HR=1

Diff

eren

ces

inH

azar

d R

atio

s(H

R)

n=2833.3%

n=594.9%

n=4127.9%

Never DMn=8697

New-onset DMn=1298

Baseline DMn=5.250

n=4895.6%

n=1078.2%

n=56810.8%

Impact of new-onset diabetes on cardiac outcomes in the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) Trial

Van Wijk BLG et al. Hypertens 23:2101–2107

Rate and determinants of 10-year persistence withantihypertensive drugs

0.5 1.0 2.0

Diuretics

Beta-blockers

Alpha-blockers

Calcium channel blockers

ACE-inhibitors

ARBs

1.83 (1.81-1.85)

1.64 (1.62-1.67)

1.23 (1.20-1.27)

1.08 (1.06-1.09)

0.92 (0.90-0.94)

- +

(n = 445356)

Corrao G et al J Hypertens. 2008;26(4):819-24.

Cumulative Incidence of Discontinuation of Initial Antihypertensive Monotherapy over 1 Year (Lombardia Data-base)

Antihypertensive efficacy and safety of olmesartan medoxomil andramipril in elderly patients with mild to moderate essential hypertension: the ESPORT study

Malacco E, et al. J Hypertens 2010;28:2342-2350

1102 elderly hypertensivs (65–89 years)DBP, 90–109 mmHg and/or SBP, 140–179 mmHg)

Target nondiabetics<140/90 mmhg

Target diabetics<130/30 mmhg

Olm Ram Olm Ram Olm Ram



1102 elderly hypertensives (65–89 years)DBP, 90–109 mmHg and/or SBP, 140–179 mmHg)

Target nondiabetics<140/90 mmhg

Target diabetics<130/30 mmhg

Olm Ram



Olmesartan, an Angiotensin II Receptor Blocker, Restores Cerebral Hypoperfusion in Elderly Patients With Hypertension

Nagata R, et al. J Stroke Cerebrov Dis 2010; 19:236-240

Olmesartan, an Angiotensin II Receptor Blocker, Restores Cerebral Hypoperfusion in Elderly Patients With Hypertension

Nagata R, et al. J Stroke Cerebrov Dis 2010; 19:236-240

PAS/PAD 156.2±9.9/89.1±5.5 130.4±4.2/78.2±7.0

Death

Terminal HFDementia

ESRD

Endothelialdysfunction and

activation

Micro-albuminuria

CHFSecondary stroke

Nefrotic proteinuria

Macro-proteinuria

MI and Stroke

ATS, IVS

LV dilationCognitive

impairment

LV remodelling

Cardio-renal and cardio-cerebral continuum

CardiovascularRisk factors

Mod. from Dzau, Braunwald. Am Heart J 1991

Slow downSlow down - regressionPrevention



J. Hypertens 2009; 27: 2121-2158

olivus

J. Hypertens 2009; 27: 2121-2158

IPOTENSIONE E CADUTE

J. Hypertens 2009; 27: 2121-2158

J. Hypertens 2009; 27: 2121-2158

OLIVUS

Valish ha fallito

VEDI GILL NEJM 2010 SU FRAGILITA

Comparison between angiotensin-converting enzyme inhibitors andangiotensin receptor blockers on the risk of stroke: a meta-analysis

Reboldi G, et al. J Hypertens 2008

J. Hypertens 2009; 27: 2121-2158

MAZZAGLIA

E STAY ON TREATMENT

E noi di AQ

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Giovambattista Desideri Università degli Studi dell’Aquila ... · Exceptional Longevity in Men - Modifiable Factors Associated With Survival and Function to Age 90 Years: Physicians’