高血压欧洲新指南和小剂量联合用药PPT课件

Dose titration
100
Therapeutic effect
Percent maximum effect
80 Critical dose
60
Toxic effect
40
Optimal dose
20
0
0
1
10
100
1000
Dose arbitrary units
10000
Percentage of patients with AE
0
"Second" drug alone
-5
-10
-5
Systolic Diastolic
Combination
Law et al, BMJ 2003
Percent of ALLHAT participants who achieved their goal blood pressure (SBP/DBP < 140/90 mmHg)
Effects of two different drugs on BP separately and in combination
(119 randomized placebo controlled trials)
Placebo-subtracted BP response. mmHg
"First" drug alone
-blood pressure normalization in only a fraction of
hypertensive patients
-each drug class cannot be given to each patient
-dose-dependent side-effects for most antihypertensive
Achieved BP: <140/90 mmHg 80
60 39
% 40
20
0
During monotherapy
(diuretic, -blocker, ACE inhibitor or Ca antagonist)
Dickerson et al, Lancet, 1999
Sequential monotherapy and dose ranging strategy:yes,but… !
New European Guidelines and The Role of Low-dose Combinations
Bernard Waeber Lausanne, Switzerland
Goals of treatment
-BP < 140/90 mmHg in all hypertensive patients < 130/80 mmHg in hypertensive patients with diabetes or renal disease
100
Percent
80
% Controlled (<140/90 mmHg)
60
On 1 drug
40
On 2 drugs
20
On 3 drugs
On >4 drugs 0
0 6 12 24 36 48 60
Cushman et al, J Clin Hypertens, 2002
A multifactorial trial design to assess combination therapy in hypertension
-Control of all cardiovascular risk factors
ESH - ESC Guidelines, J Hypertens 2003
Patient 1
Patient 2
Patient 3
Sympathetic nervous system Renin-angiotensin system Total body sodium
20
N°of trials :
59
15
96
10
62
5
96
44
0
-5
Half Standard Twice
standard
dose standard
dose
dose
-blockers ACE inhibitors Thiazides
Calcium antagonists AT1-receptor blockers
512 patients with esential hypertension
4 weeks
HCTZ mg/d
0
3 x 4 factorial trial double-blind treatment
6.25
25 Frishman et al, Arch Intern Med, 1994
Law et al, BMJ 2003
Sequential monotherapy
Percentage of patients with normal blood pressure
Drug A
Drug B
Drugs C
0
20
40
60
80 100 %
BP control rate during antihypertensive monotherapy
Drug A
Dຫໍສະໝຸດ Baiduug B
Drugs A + B
0
20
40
60
80 100 %
Combination therapy: rationale
-Combination of drugs lowering blood pressure by different mechanisms antihypertensive efficacy -Complementary actions of drugs from different classes prevention of counter-balancing mechanisms antihypertensive efficacy -Lower doses generally needed when two drugs are combined incidence of side-effects
agents
-time consuming approach
possible
discouragement of the patient and … of the doctor!
Combination therapy
Percentage of patients with normal blood pressure