Prise en charge de l’HTA des patients diabétiques de type II. Choix et perspectives.

Pr. Jean Jacques Mourad

Centre d’Excellence ESH en HTA, CHU Avicenne, AP-HP et Université Paris 13, Bobigny, France

Liens d’intérêts

www.transparence.sante.gouv.fr

Conférence rétribuée par les Laboratoires Servier

Arthur Guyton's computer model of the cardiovascular system.

John E. Hall Am J Physiol Regul Integr Comp Physiol 2004;287:R1009-R1011

Mr S. 52 ans

• Boucher salarié dans un centre commercial

• HTA détectée à 48 ans : atenolol 100mg/j

• Bilan OMS normal, Acide urique limite sup,

• FDR associés : Tabagisme modéré (7 cig/j) – 18 paquets.années Surpoids (BMI 29,1 kg/m²)

• Diagnostic de DNID posé il y a un an. HbA1c 9,5%. Metformine 2g/j

• PAS habituellement entre 140-150 mmHg

«J’ai lu sur internet que le diabète fait mourir prématurément »

- C’est vrai??

- Pouvez-vous faire quelque chose?

« Diabetic men and women 50y and older lived on average 7.5 &

8.2 years less than their nondiabetic

equivalents. »

Arch Int Med 2007;167:1145.

N Engl J Med 2018;379:633-44.

Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes

271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of age, sex, and county.

SUIVI MOYEN : 5.7 ANS

N Engl J Med 2018;379:633-44.

Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes

Contrôle tensionnel?

Lancet 2007;370:829

Lancet 2007;370:829

Lancet 2007;370:829

Lancet 2007;370:829

N Engl J Med. 2014 ;371:1392-406

American Diabetes Association guidelines

In ADVANCE, the active blood pressure intervention arm (a single-pill, fixed-dose combination of perindopriland

indapamide) showed a significant reduction in the risk of the primary composite end point (major macrovascular or

microvascular event) and significant reductions in the risk of death from any cause and of death from cardiovascular causes

(15). The baseline blood pressure among the study subjects was 145/81 mmHg. Compared with the placebo group, the

patients treated with a single-pill, fixed-dose combination of perindopril and indapamide experienced an average reduction

of 5.6 mmHg in SBP and 2.2 mmHg in DBP. The final blood pressure in the treated group was 136/73 mmHg, not quite the

intensive or tight control achieved in ACCORD. Recently published 6-year follow-up of the ADVANCE–Post-Trial Observational Study (ADVANCE-ON) reported that the

reductions in the risk of death from any cause and of death from cardiovascular causes in the intervention group were

attenuated, but remained significant.

American Diabetes Association. Diabetes Care. 2017;40 (suppl.1):S75-87.

Trithérapie recommandée en prévention

primaire

BB Bloqueurs du

SRAA

Thiazidiques InCa

NICE, HAS, ESH

2 arbitrages

1- Choix du bloqueur du SRA

Choix de la classe : IEC/ARA2, mais aussi

spironolactone, béta-bloquant et aliskiren

Choix de la molécule : Durée d’action réelle,

facilité de titration (gamme)

Privilégier les molécules éprouvées aux

dosages testés dans les études

Aucune indication élective pour les ARA2

qui ne soit pas partagée avec les IEC

JAMA Intern Med. Published online March 31, 2014

-13%

JAMA Intern Med. Published online March 31, 2014

NS

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004136.pub3/epdf/standard

-16%

+12% (ns)

Circulation. 2017;135:2088–2090

« Logic dictates that practice guidelines should recognize the unique cardiovascular benefits of ACEIs and their preferential use compared with ARBs. Were such advice to be given, the predicted impact on lives saved would be profound. »

AC/AHA 2018

2. Choix du diurétique

2- choix du diurétique

“If diuretic treatment is to be initiated or changed, offer a

thiazide-like diuretic, such as chlortalidone (12.5–25.0 mg once daily) or indapamide (1.5 mg modified-release once daily or 2.5

mg once daily) in preference to a conventional thiazide diuretic

such as bendroflumethiazide or hydrochlorothiazide”.

NICE Guidelines 2011

European Heart Journal (2018) 39, 3021–3104

Hydrochlorothiazide use and risk of non-melanoma skin cancer: A nationwide case-control study from Denmark.

Arnspang S, JAAD 2017

Hydrochlorothiazide use and risk of non-melanoma skin cancer: A nationwide case-control study from Denmark.

Arnspang S, JAAD 2017

Hydrochlorothiazide use is strongly associated with risk of lip cancer

Pottegard A, JIM 2017

Pottegard A, JIM 2017

Hydrochlorothiazide use is strongly associated with risk of lip cancer

Quels objectifs tensionnels ?

Primary & Secondary outcomes

ACCORD Study

Intensive

Events (%/yr)

Standard

Events (%/yr) HR (95% CI) P

Primary 208 (1.87) 237 (2.09) 0.88 (0.73-1.06) 0.20

Total Mortality 150 (1.28) 144 (1.19) 1.07 (0.85-1.35) 0.55

Cardiovascular Deaths 60 (0.52) 58 (0.49) 1.06 (0.74-1.52) 0.74

Nonfatal MI 126 (1.13) 146 (1.28) 0.87 (0.68-1.10) 0.25

Nonfatal Stroke 34 (0.30) 55 (0.47) 0.63 (0.41-0.96) 0.03

Total Stroke 36 (0.32) 62 (0.53) 0.59 (0.39-0.89) 0.01

Also examined Fatal/Nonfatal HF (HR=0.94, p=0.67), a composite of fatal coronary events, nonfatal MI and unstable angina (HR=0.94, p=0.50) and a composite of the primary outcome, revascularization and unstable

angina (HR=0.95, p=0.40)

N Engl J Med. 2010 ;362(17):1575-85

Hypertension. 2018;72:323-330

N Engl J Med 2018;379:633-44.

Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes

Références -HbA1c : 53 mmol/mol (7%)

-PAS : 140 mmHg -LDL : 2,5 mmol/l (1g/l)

Circulation. 2011;123:2799-2810

CV mortality Total mortality

MI Stroke

Adverse effects Renal outcomes

Une PAS entre 130 et 135 mmHg est acceptable

13 trials

2018 ESC/ESH Guidelines for The management of arterial hypertension

European Heart Journal (2018) 00, 1–98

Résumé

Titration dynamique et sécurisée des molécules efficaces

- PAS entre 130 and 135 mmHg

bloqueur du SRAA+ Thiazidique (HCTZ?) + DHP si nécessaire

Efficacité démontrée des IEC sur la mortalité et les événements coronaires

Dose maximale des BSRA pour la protection tissulaire

Doses maximales tolérées des thiazidiques et DHP pour atteindre l’objectif de PAS

- Statines pour la très grande majorité des hypertendus diabétiques

- Aspirine ?

BMJ 2018;363:k4209

BMJ 2018;363:k4209

Lancet Oncol. 2010 July ; 11(7): 627–636.

Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups(7.2% vs 6.0%, risk ratio [RR] 1.08, 95% CI 1.01–1.15; p=0.016). When analysis was limited to trials where cancer was a prespecified endpoint, the RR was 1.11 (95% CI 1.04–1.18, p=0.001). Among specific solid organ cancers examined, only new lung-cancer occurrence was significantly higher in patients randomly assigned to receive ARBs than in those assigned to receive control (0.9% vs 0.7%, RR 1.25, 1.05–1.49; p=0.01). No statistically significant difference in cancer deaths was observed (1.8% vs 1.6%, RR 1.07, 0.97–1.18; p=0.183). Interpretation— This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis.

Lancet Oncol. 2010 July ; 11(7): 627–636.