MANAGEMENT DELL IPERTENSIONE NEL VERY OLD FRAIL: PRESENTAZIONE DEL DOCUMENTO CONGIUNTO EUGMS-ESH

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1 MANAGEMENT DELL IPERTENSIONE NEL VERY OLD FRAIL: PRESENTAZIONE DEL DOCUMENTO CONGIUNTO EUGMS-ESH Giovambattista Desideri Unità Operativa e SS di Geriatria Università degli Studi Dell Aquila

2 An Expert Opinion From the European Society of Hypertension European Union Geriatric Medicine Society Working Group on the Management of Hypertension in Very Old, Frail Subjects Athanase Benetos, Christopher J. Bulpitt, Mirko Petrovic, Andrea Ungar, Enrico Agabiti Rosei, Antonio Cherubini, Josep Redon, Tomasz Grodzicki, Anna Dominiczak, Timo Strandberg, Giuseppe Mancia Hypertension 2016; 67:

A systematic analysis for the Global Burden of Disease Study: Risk Fattori di rischio classificati secondo il loro peso sulla factors ranked by attributable

3 A systematic analysis for the Global Burden of Disease Study: Risk Fattori di rischio classificati secondo il loro peso sulla factors ranked by attributable burden of disease, 2010 salute globale in ogni regione, 2010 Regions are ordered by mean life expectancy Stephen S Lim et al, The Lancet Volume 380, 2013:

4 Age-related estimate of prevalence of hypertension in the US population Fields LE et al, Circulation, 2004

5 Lifetime risk (95% CI) of 12 different cardiovascular diseases in people with hypertension or normal BP from index age 30 years Rapsomaniki E et al. Lancet 2014; 383:

Treatment of hypertension in patients 80 years and older: the lower the better? A meta-analysis of randomized controlled trials Stroke Ictus All Mortalità Mortality. gen.

6 Treatment of hypertension in patients 80 years and older: the lower the better? A meta-analysis of randomized controlled trials Stroke Ictus All Mortalità Mortality. gen. CV Mortalità Mortality CV CV Eventi events CV Coronary Eventi coron. events CHF Insuff. card. Treatment vs. Placebo RR (95% CI) EWPHE SHEP-P SHEP STOP Syst-Eur Keep Antihypertensive drugs away from very old people.the instrument of geriatric assessment should be included in future biomedical trials with elderly patients. Età>80 aa N=1566 Peter Oster, Gu nter Schlierf - Lancet 1999 Gueyffier F et al., Lancet 1999; 353:793

7 Treatment of hypertension in patients 80 years and older: the lower the better? A meta-analysis of randomized controlled trials Treatment vs. Placebo Stroke All Mortality CV Mortality CV Events Coronary Events CHF EWPHE SHEP-P SHEP STOP Syst-Eur HYVET Pilot HYVET Coope 1986 age>80 aa N= RR (95% CI) Bejan-Angoulvant T et al, J Hypertens 2010, 28:

8 Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document M J. Hypertens 2009; 27:

9 Canadian Hypertension Education Program BP target in the very elderly <150 mm/hg

10 N Eng J Med 2015

11 Systolic Blood Pressure in the Two Treatment Groups over the Course of the Trial: SPRINT average BP difference of 14.8 mm Hg N Eng J Med 2015

12 Use of Major Antihypertensive Medications in SPRINT % D(+56%) 67.0 BB CCB RASblockers 76.7 Alpha 1 - blockers No. drugs average No. drugs final 4 n I S I S I S I S I S I S I S 0 I: intense treatment; S: standard treatment The SPRINT Research Group, NEJM,2015,373,2103

13 Systolic Blood Pressure in the Two Treatment Groups over the Course of the Trial: SPRINT primary composite outcome: myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. N Eng J Med 2015

14 Systolic Blood Pressure in the Two Treatment Groups over the Course of the Trial: SPRINT N Eng J Med 2015

15 A Randomized Trial of Intensive versus Standard Blood- Pressure Control: The SPRINT Research Group N Eng J Med 2015

16 A Randomized Trial of Intensive versus Standard Blood- Pressure Control: The SPRINT Research Group N Eng J Med 2015

17 JAMA. doi: /jama Published online May 19, 2016.

18 Incidence of Cardiovascular, Renal, and Mortality Outcomes by Treatment Group * * * * JAMA. doi: /jama Published online May 19, 2016.

Relative Risk SPRINT 1 SPRINT elderly 2 STROKE A B C D E F G Does hypertension still represent a risk factor for stroke? 1.50 1.25 1.00 0.75-16 -14-12 2 SPRINT NEJM 2015 1 Williamson JD et al. JAMA.

19 Relative Risk SPRINT 1 SPRINT elderly 2 STROKE A B C D E F G Does hypertension still represent a risk factor for stroke? SPRINT NEJM Williamson JD et al. JAMA. May 19, SBP differences between randomized groups (mm Hg) 0.50 A = CA vs placebo; B = ACE I vs placebo; C = intensive Tx vs less intensive; D = ARB vs placebo; E = ACE-I vs CA; F = CA vs diuretic or β-blocker; G = ACE-I vs diuretic and β-blocker. Blood Pressure Lowering Treatment Trialists Collaboration. Lancet 2003

20 Incidence of Cardiovascular, Renal, and Mortality Outcomes by Treatment Group * * * * JAMA. doi: /jama Published online May 19, 2016.

21 Incidence of Cardiovascular and Mortality Outcomes by Frailty Status and Gait Speed * * * * * * JAMA. doi: /jama Published online May 19, 2016.

Baseline Characteristics of Participants Aged 75 Years or Older: SPRINT trial Distribution of frailty index (FI) in SPRINT participants at randomization JAMA.

22 Baseline Characteristics of Participants Aged 75 Years or Older: SPRINT trial Distribution of frailty index (FI) in SPRINT participants at randomization JAMA. doi: /jama Published online May 19, Williamson JD et al. JAMA 2016 N. M. Pajewski et al. J Gerontol A Biol Sci Med Sci 2016;71:

23 BP in SPRINT elderly patients (n= 2636) age >-75. mean 79.9 years( Williamson, JAMA 2016) Intensive Standard Baseline SBP On-treatment SBP Baseline DBP On-treatment mean of three blood-pressure measurements at an office visit while the patient was seated and after 5 minutes of quiet rest; the measurements were made with the use of an automated measurement system

24 Definizione di ipertensione con i livelli di pressione arteriosa (BP) clinica e al di fuori dell ambiente medico 2013 ESH-ESC Guidelines, J Hypertens 2013

25 AUTOMATED vs MANUAL OFFICE BP(353 HTs) Filipovsky et al (Blood Pressure, 2016) SBP DBP AUTOMATED (mmhg) MANUAL(mmHg) DELTA(mmHg)

26 Equating SPRINT to conventional BP values /targets is erroneous and probably harmful to patients (very low on-treatment BP)

27 SPRINT Trial What news for elderly patients? Patients with or at high risk for CVD have reduced CVD with more intensive BP control In the analysis of fit to frail SPRINT subjects, most subjects were still fit or less fit - so it is hard to extrapolate to truly frail patients Frail patients had higher rates of falls, injurious falls and hospitalization We still don t have the cognitive data! We need these data before extrapolating SPRINT to those over 75 who are frail, have diabetes, or are nursing home residents

Antihypertensive treatment strategies in the

treating physician, and based on monitoring of the

28 Antihypertensive treatment strategies in the elderly Recommendations Class Level In frail elderly patients, it is recommended to leave decisions on antihypertensive therapy to the treating physician, and based on monitoring of the clinical effects of treatment. I C 2013 ESH-ESC Guidelines, J Hypertens 2013

29 Treatment of hypertension in patients 80 years and older: the lower the better? A meta-analysis of randomized controlled trials 36% CVD 30% CVD No CVD No CVD 11% CVD Bejan-Angoulvant T et al, J Hypertens 2010, 28:

30 With advancing age, physiologic reserves are increasingly being used to maintain homeostasis

31 CV event rates and mortality according to achieved SBP and DBP in patients with stable CAD: an international cohort study - CLARIFY Vidal-Petiot et al. Lancet august 2016

32 CV event rates and mortality according to achieved SBP and DBP in patients with stable CAD: an international cohort study - CLARIFY.Together with previous literature, our study suggests caution when treating patients with coronary artery disease with antihypertensive drugs.. Searching the maximum protection for each mmhg blood pressure reduction Vidal-Petiot et al. Lancet august 2016

33 Vidal-Petiot et al. Lancet august 2016

34 ESH/ESC 2013: Scelta dei farmaci antipertensivi La maggior parte del beneficio del trattamento antipertensivo è legato alla riduzione della pressione di per sè ed è largamente indipendente dal farmaco impiegato. Ampie metanalisi non evidenziano rilevanti differenze cliniche tra le varie classi di farmaci. Diuretici (tiazidici, clortalidone e indapamide), betabloccanti, calcioantagonisti, ACE-inibitori, ARB sono tutti impiegabili e raccomandati per l inizio e il mantenimento della terapia antipertensiva sia in monoterapia che in associazione. Alcuni farmaci devono essere considerati di prima scelta in specifiche condizioni in quanto utilizzati in trial che hanno valutato quelle specifiche condizioni o perché maggiormente efficaci in determinati tipi di danno d organo I IIa A C 2013 ESH-ESC Guidelines, J Hypertens 2013

35 Guidelines recommendations for combining antihypertensive drugs and the available evidence for prognostic improvement Diuretics LIFE b-blockers FEVER ELSA SCOPE Angiotensin receptor blockers (ARBs) PROGRESS VALUE a-blockers ADVANCE HYVET INVEST ASCOT Angiotensin-converting enzyme (ACE) inhibitors ACCOMPLISH Calcium channel blockers (CCBs) Mancia G. et al 2009 Reappraisal of guidelines on hypertension management J Hypertens. 2009, 27: Mancia G. et al 2007 Guidelines for the management of hypertension J Hypertens. 2013;25:

36 Superiorità della combinazione amlodipina/perindopril rispetto alla combinazione atenololo/diuretico tiazidico nel prevenire gli eventi nello studio ASCOT-BPLA Dahlo f B, et al. Lancet 2005; 366:

37 Ipertensione nel grande anziano: una malattia diversa con target diversi?

38 Ipertensione nel grande anziano: una malattia diversa con target diversi?

Hypertension Update Clinical Controversies Regarding Age and Race

Hypertension Update Clinical Controversies Regarding Age and Race Allison Helmer, PharmD, BCACP Assistant Clinical Professor Auburn University Harrison School of Pharmacy July 22, 2017 DISCLOSURE/CONFLICT