KHỞI TRỊ TĂNG HA Ở
NGƯỜI CAO TUỔI:
CHỨNG CỨ LIÊN QUAN
ĐẾN THUỐC LỢI TiỂU
PGS TS Trương Quang Bình
ĐHYD TP HCM
Systolic BP:
highly predictive of stroke risk
Stroke mortality*
Age at risk
256
80-89 y
128
70-79 y
64
60-69 y
32
50-59
16
8
4
2
1
0
120
* Floating absolute risk and 95% confidence interval.
SBP, systolic blood pressure.
1. Lewington S et al. Lancet. 2002;360:1903-1913.
140
160
180
Usual systolic BP (mm Hg)
4
Hypertension sub-type According to Age
Franklin SS, et al. Circulation 1997;96: 308-15.
Reflected waves due to stiffer arteries from periphery
increase pulse wave velocity & Systolic BP
1. O’Rourke M. Hypertension. 1995;26:2-9
6
Older patients have a low level of renin activity
Supine plasma renin
activity
(PRA)
and
aldosterone plasma level
as a function of age in
healthy
normotensive
people receiving an ad
libitum sodium diet.
1. Belmin et al. Drugs Aging. 1994;5(5):391-400.
7
Tieán trieån cuûa taêng HA
B. Williams. 2007 Number
Amlodipine has Shown CV Protective Efficacy in
Landmark Studies
PREVENT1
825 CAD patients (≥ 30%); multicentre,
randomized, placebo-controlled
CAMELOT2
1,991 CAD patients (≥ 20%); double-blind,
randomized study vs placebo and enalapril
20 mg
ASCOT-BPLA/CAFE3,4
19,257 HTN patients; multicentre,
randomized, prospective study vs atenolol
ALLHAT5
18,102 HTN patients; multicentre,
randomized, prospective study vs lisinopril
Primary outcome: no difference in mean 3-y coronary
angiographic changes vs placebo
35% ↓hospitalization for heart failure + angina
33% ↓revascularization procedures
Primary outcome: 30%↓in CV events vs placebo
41% ↓hospitalization for angina
27% ↓coronary revascularization
Primary outcome: 10%↓in non-fatal MI and fatal CHD
16% ↓total CV events and procedures
30% ↓new-onset diabetes
27% ↓stroke
11% ↓all-cause mortality
4.3 mmHg ↓central aortic pressure
Primary outcome: no difference in composite of fatal
CHD and non-fatal MI vs lisinopril
6% ↓combined CVD
23% ↓stroke
1. Pitt et al. Circulation. 2000;102:1503–1510; 2. Nissen et al. JAMA. 2004;292:2217–2226; 3. Dahlof et al. Lancet.
2005;366:895–906; 4. Williams et al. Circulation. 2006;113:1213 –1225; 5. Leenen et al. Hypertension.2006;48:374–384.
A = ACE-inh or ARB, C = CCB, D = thiazide type diuretic
11
12
Cumulative Event Rates for All-Cause
Mortality by ALLHAT Treatment Group
ALLHAT
.3
Cumulative Mortality Rate
.25
HR (95% CI)
p value
A/C
0.96 (0.89-1.02)
0.20
L/C
1.00 (0.94-1.08)
0.90
.2
Chlorthalidone
Amlodipine
Lisinopril
.15
.1
.05
0
0
Number at risk:
Chlor
15,255
Amlo
9,048
Lisin
9,054
1
14,933
8,847
8,853
2
14,564
8,654
8,612
3
4
Years to Death
14,077
8,391
8,318
12,480
7,442
7,382
5
6
7
7.185
4,312
4,304
3,523
2,101
2,121
4288
217
144
13
Cumulative Event Rates for Heart Failure
by ALLHAT Treatment Group
ALLHAT
Cumulative CHF Rate
.15
HR (95% CI)
p value
A/C
1.38 (1.25-1.52)
<.001
L/C
1.19 (1.07-1.31)
<.001
.12
Chlorthalidone
Amlodipine
Lisinopril
.09
.06
.03
0
0
Number at risk:
Chlor
15,255
Amlo
9,048
Lisin
9,054
1
2
14,528
8,535
8,496
13,898
8,185
8,096
3
4
Years to HF
13,224
7,801
7,689
11,511
6,785
6,698
5
6,369
3,775
3,789
6
3,016
1,780
1,837
7
384
210
313
HYVET Trial: Study Design
3845 patients > 80 years with continual hypertension and systolic blood pressure ≥
160 mm Hg prior to randomization
Prospective. Randomized. Double Blind. Placebo-Controlled. Mean follow-up 1.8yrs
R
Active Treatment
1.5 mg Indapamide (SR)
n=1933
Placebo
Matching Dose
n=1912
2 yrs. follow-up
Primary Endpoint: fatal and non-fatal strokes
Secondary Endpoints: death from: stroke, cardiovascular
causes, cardiac causes and any cause
N Engl J Med 2008;358/ACC 2008
Thiazide diuretics / CCB combination is recommended
for older hypertensive patients
ESH/ESC guidelines suggest a diuretic or a CCB may be
particularly useful for elderly patients
Mancia G et al. Eur Heart J. 2013;34:2159-2219.
2013
19
Thiazide diuretics / CCB combination is recommended
for older and black hypertensive patients
JNC8 panel report recommends a CCB or a thiazide-type diuretic, alone or in combination for patients over 60
Initiate thiazide –
type diuretic or
CCB, alone or in
combination
James PA et al. JAMA. 2014;311(5):507-520.
2014
20
2015
21
Hypertension Canada CHEP Guidelines
for the Management of Hypertension
2016
Indapamide is more potent than HCTZ & chlorthalidone
at reducing systolic blood pressure
Roush meta-analysis (2015)1
Indapamide is significantly more potent than HCTZ at reducing systolic blood
pressure, which is not the case with chlorthalidone
-9.5
-13.1
-14.6
Systematic review and
meta-analysis; head-tohead RCTs comparing
HCTZ vs indapamide (10
RCTS, n=813) and HCTZ
vs chlorthalidone (3
RCTS, n=70).
-3.6 mm Hg, (NS)
54%
-5.1 mm Hg, (95% CI; -8.7 to -1.6), P=0.004
Roush et al. Hypertension. 2015;65:1041-1046.
24
Indapamide has a better metabolic profile…
Indapamide
Lipid & glucose neutral1
Chlorthalidone
High risk of new onset diabetes2
43%
higher risk
1. Ambrosioni E, Safar M, Degaute JP, et al. J Hypertens. 1998;16:1677-1684; 2. ALLHAT Collaborative Research Group JAMA. 2002;288:2981-2997.
25