PGS TS phamvanbui DIURETICS RAS INHIBITION (1)

LỢI TIỂU LỢI TIỂU KẾT HỢP ARB BỆNH THẬN MẠN PGS TS Phạm Văn Bùi BV Nguyễn Tri Phương ĐH YK Phạm Ngọc Thạch GS Thỉnh giảng ĐH Likuk, Belgium 13 Target-organ damage precedes clinical events Risk factors: diabetes, obesity, smoking, age Vasoconstriction Vascular hypertrophy Endothelial dysfunction Atherosclerosis Apoptosis Arrhythmia LVH Heart failure Fibrosis MI Vascular disease Hypertension Pro-thrombotic state Stroke Death Cognitive dysfunction Decreased GFR Proteinuria/albuminuria Renal failure Glomerulosclerosis Adapted from: Chung O & Unger T., Am J Hypertens 1999;12:150S–156S Risk of CV Mortality Doubles With Each 20/10 mmHg BP Increase • Meta-analysis of 61 prospective, observational studies/10y • million adults aged 40–69 y with BP > 115/75 mmHg (w/o previous vascular disease) • 12.7 million person-years 10 8-fold Fold increase in relative CV risk 4-fold 2-fold 1-fold 115/75 135/85 155/95 SBP/DBP (mmHg) 175/105 Lewington et al Lancet 2002;360:1903–1913 12.000THA/ Veterans Affairs Centers , USA F-U: 15 năm Each 10 mmHg Decrease in SBP Reduces CV Risk by 30-40% • Meta-analysis of 61 prospective, observational studies10y • million adults aged 40–69 y with BP > 115/75 mmHg (w/o previous vascular disease) • 12.7 million person-years 10 mmHg decrease in mean SBP 30% reduction in risk of IHD and other vascular disease mortality 40% reduction in risk of stroke mortality Lewington et al Lancet 2002;360:1903–1913 Each mmHg Decrease in SBP Reduces CV Risk by 7–10% • Meta-analysis of 61 prospective, observational studies10y • million adults aged 40–69 y with BP > 115/75 mmHg (w/o previous vascular disease) • 12.7 million person-years mmHg decrease in mean SBP 7% reduction in risk of IHD and other vascular disease mortality 10% reduction in risk of stroke mortality Lewington et al Lancet 2002;360:1903–1913 TẠI SAO KẾT HỢP DIURETICS + RAAS BLOCKADE • Giảm liều lợi tiểu • Giảm huyết áp nhanh • Đối kháng phản ứng hoạt hóa RAAS • Giảm phản ứng phụ Opie,(2013) Drugs for the heart Bernardo Rodriguez-Iturbe(2009) ERA-EDTA Congress, Milan, 2009 Liệu pháp kết hợp ưu tiên chọn lựa bệnh thận mạn • RAS blockers: chọn lựa BTM • THA/ BTM → ARB-based SPC dung nạp tốt • Có nhiều lựa chọn thường ARB/CCB ARB/HCTZ Cần cân nhắc cẩn thận / BN BTM Samir G Mallat Cardiovasc Diabetol 2012;11(32):1-12.; Mancia G J Hypertens 2009, 27(11):2121–2158 ; K/DOQI Am J Kidney Dis 2004, 43(5 Suppl 1):S1–S290 Hạ áp hiệu suốt 24 n = 329 BN THA nhẹ-vừa t= 16 tuần Sự thay đổi HA tâm thu (mmHg) -4 -8 -12 -16 -20 12 16 20 24 Thời gian sau dùng thuốc (giờ) DIOVAN 160 mg (tuần thứ 4)§ DBP 95 mmHg and 20 mmHg Co- DIOVAN 160/12.5 mg (n=258) DIOVAN 160 mg (n=261) Thay đổi HA tâm trương trung bình (mmHg) HATTh Thay đổi HA tâm thu trung bình (mmHg) –5 –10 –15 –20 –25 –20.7* –30 –35 * p[...]...(48M-70%)) (68M-31%)) (31M-46%)) The Minority of Patients Achieve BP Control on Monotherapy Patients with BP control (%) 40 39 30 20 20 10 0 BP < 140/90 mmHg Dickerson et al Lancet 1999:353:2008–2013 BP < 135/85 mmHg Monotherapy for hypertension is not effective in controlling BP in many patients 80 Cumulative % of patients with BP controlled (BP 20/10 mm Hg above target BP • ESH : initial combination therapy advised for "high-risk" patients Lisa Nainggolan Heartwire © 2011 Medscape Combination Therapy Beats Monotherapy as... Treatment: ACCELERATE(RCT): • First study : combination therapy helps patients to achieve BP goals faster than does initial monotherapy w/ fewer side effects • Combination therapy: the first choice to start treatment in patients w/ BP>150/90 mm Hg despite lifestyle changes • Use of a combination antihypertensive therapy, with a RAS blocker combined with either a calcium-channel blocker or long-acting... disease Dementia Cardiac arrest Hiroshi Ito Mebio 2005; 22: 125-8 Combination therapy means more consistent effect, regardless of underlying causes of hypertension (ISN Canada, 2011) RAS Na+ + Na RAS ACEI/ARB CCB DIURETIC RAS +++ ++ + ACEI/ARB + CCB ++++ ACEI/ARB + Diuretic ++++ ACEI/ARB CCB DIURETIC + Na ++ ++ ++ ACEI/ARB + CCB ++++ ACEI/ARB + Diuretic ++++ ACEI/ARB CCB DIURETIC + +++ +++ ACEI/ARB +... 0.71 to 0.81 p < 0.0001 24 20 10 0 Chronic disease (9 studies**) 11,925 / 8,317 pts Hypertension (4 studies) •With single-pill combination therapy v/s free-drug regimens •** two studies in patients with tuberculosis, four in hypertension, one in HIV disease and two in diabetes Bangalore et al Am J Med 2007;120:713–719 Patients who are adherent are at lower CV risk Relative risk of a CV event 100% 90%... Hg) at five years 66 Percent 60 49 40 26 20 0 1 1 11 or or 2 2 1 or 2Any or more Number of Prescribed Drugs Cushman et al J Clin Hypertens 2002;4:393-404 © Theodore Kurtz, MD all rights reserved © Theodore Kurtz, MD all rights reserved Hypertension  Multifactorial disorder - Many mechanisms involved - Multiple drugs often required to control BP  More than just high blood pressure - Often occurs as part... 9,666) Medium (40-79%) (n = 7,624) High (>=80%) Adherence (n = 1,516) 400 Italian primary care physicians :18,806 newly diagnosed hypertensive patients 35 years old during 20002001 Mazzaglia et al Circulation 2009;120:1598-1605 Adherence to antihypertensive agents and BP control in chronic kidney disease • Schmitt và c/s: N/c hồi cứu 7227 BN BTM ở Cincinnati Veterans Affairs Medical Center θ = ít nhất... cardiovascular disease and diabetes  Current therapies are often inadequate - Designed to attack only single mechanisms - Fail to address associated metabolic risk factors © Theodore Kurtz, MD all rights reserved Concept of Metabolic Domino effect in metabolic syndrome Lifestyle habit Postprandial Hyperglycemia Hyperlipidemia Hypertension Sympathetic nerve system Renin-angiotensin system Macro angiopathy... BTM • → Phòng ngừa xuất hiện/nặng thêm CVD Thuốc lựa chọn hàng đầu: → Giảm áp → Giảm đạm niệu Lợi ích lâu dài cho Tim mạch-thận khi ↓đạm niệu Leticia Buffet, et al US Pharmacist © 2012 TẠI SAO KẾT HỢP DIURETICS + RAAS BLOCKADE • Giảm liều lợi tiểu • Giảm huyết áp nhanh hơn • Đối kháng phản ứng hoạt hóa RAAS • Giảm phản ứng phụ Opie,(2013) Drugs for the heart