ỨC CHẾ MEN CHUYỂN VÀ CHẸN THỤ THỂ ANGIOTENSINE TRONG ĐIỀU TRỊ TĂNG HA Ở BN CÓ BỆNH ĐM VÀNH PGS.TS Trương Quang Bình ĐH Y Dược - TPHCM Angiotensinogen Angiotensin I Angiotensin II Adrenalin release Inflammatory responses Na + , H 2 O reabsorption ACE inhibition Renin inhibition Selective AT 1 - receptor blockade Vasopressin release Aldosterone production AT 1 AT 2 ACE Renin Bradykinin degradation The Renin-Angiotensin System Alternative pathways AT 3 AT 4 ? ACE-inhibitors in high risk patients ≥55 years of age: HOPE trial - 9,297 patients - Documented CAD or DM + 1 RF - No history of CHF or LV dysfunction The HOPE investigators. N Engl J Med 2000;342:145-153. CV death, AMI or stroke RRR 28% (14-30) EUROPA: results Perindopril 8mg Placebo ans 0 2 4 6 8 10 12 14 0 1 2 3 4 5 CV death, AMI or resuscitated cardiac arrest Annual event rate (placebo) : 2.4 % RRR: 20% [95% CI : 9 - 29] p = 0.0003 Lancet 2003; 362: 782-88 • 12 218 patients with stable CAD • no CHF Review the clinical hypetensive trials Bertrand Michel (2010) • Morbidity-mortality trials conducted from 2000 to June 2010 • Trials including mainly hypertensive patients • All-cause mortality: a prespecified end point or reported in the principal study publication Michel E. BERTRAND, MD, FRCP (London), FESC, FACC, FAHA Lille University Heart Hospital, Lille, France 21 trials: all-cause mortality reduction? Study All-cause mortality HR P 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 RENAAL IDNT ALLHAT LIFE INVEST ANBP-2 SCOPE VALUE JMIC-B ASCOT-BPLA MOSES JIKEI HEART ONTARGET PRoFESS ACCOMPLISH TRANSCEND HYVET ADVANCE KYOTO HEART HIJ-CREATE 1.03 (0.83-1.29) 1.04 (0.77-1.40) 1.00 (0.94-1.08) 0.88 (0.77-1.01) 0.98 (0.89-1. 08) 0.92 (0.76-1.12) 0.96 (0.81-1.14) 1.03 (0.94-1.13) 0.74 (0.35-1.58) 0.90 (0.81-0.99) 1.08 (0.74-1.57) 1.04 (0.61-1.76) 1.02 (0.93-1.11) 1.02 (0.92-1.13) 0.90 (0.75-1.07) 1.05 (0.91-1.22) 0.79 (0.65-0.95) 0.86 (0.75-0.98) 0.68 (0.40-1.17) 1.17 (0.83-1.66) 0.88 0.57 0.90 0.07 0.72 0.27 NS 0.45 0.40 0.03 0.72 0.75 NS 0.55 0.08 0.49 0.02 0.03 0.33 0.36 Active treatment better Control better n = 194.621 HR: 0.97 95% CI: 0.94-1.00, P = 0.031 Study All-cause mortality HR P 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 RENAAL IDNT ALLHAT LIFE INVEST ANBP-2 SCOPE VALUE JMIC-B ASCOT-BPLA MOSES JIKEI Heart ONTARGET PRoFESS ACCOMPLISH TRANSCEND HYVET ADVANCE KYOTO HEART HIJ-CREATE NAVIGATOR 1.03 (0.83-1.29) 1.04 (0.77-1.40) 1.00 (0.94-1.08) 0.88 (0.77-1.01) 0.98 (0.89-1. 08) 0.92 (0.76-1.12) 0.96 (0.81-1.14) 1.03 (0.94-1.13) 0.74 (0.35-1.58) 0.90 (0.81-0.99) 1.08 (0.74-1.57) 1.04 (0.61-1.76) 1.02 (0.93-1.11) 1.02 (0.92-1.13) 0.90 (0.75-1.07) 1.05 (0.91-1.22) 0.79 (0.65-0.95) 0.86 (0.75-0.98) 0.68 (0.40-1.17) 1.17 (0.83-1.66) 0.90 (0.77-1.05) 0.88 0.57 0.90 0.07 0.72 0.27 NS 0.45 0.40 0.03 0.72 0.75 NS 0.55 0.08 0.49 0.02 0.03 0.33 0.36 NS Individually, significant reduction in all-cause mortality has been demonstrated in 3 trials only