Linee guida ipertensione ASH 2014:
quale ruolo per la terapia di
Associazione
Massimo Salvetti
Clinica Medica – Università di Brescia
Ezzati et al, N Engl J Med September 5, 2013
Years of life lost to cardiovascular disease up to 95 years of age associated with
hypertension at index ages 30
www.thelancet.com Vol 383 May 31, 2014
Blood pressure control in Europe
Age- and gender adjusted hypertension control by country
(Patients aged 35-64 yrs; 140/90 mmHg thereshold)
70
60
Population
Treated hypertensives
50
40
(%)
30
20
10
0
USA
Canada
Italy
Spain
Adapted from Wolf-Maier K. et al. Hypertension 2004;43:10-17
England
Germany
Sweden
(< 140/90 mm Hg)
Grassi et al, European Heart Journal 2011
7860 treated hypertensive patients followed by non-specialist or specialist physicians
Serial cross-sectional study of five Health Survey for England surveys based on nationally
representative samples of non-institutionalised adults (aged ≥16 years)
- 4540 people (1961 men and 2579 women, mean age was 46 years)
Blood pressure control (<140/90 mmHg)
www.thelancet.com Vol 383 May 31, 2014
Richard J McManus, Jonathan Mant, www.thelancet.com Vol 383 May 31, 2014
Clinic blood pressure levels in the overall population sample and in subgroups of
patients followed by general practitioners or in hypertension centres
“…BP control rates among treated hypertensive patients were reported in three
surveys performed by general practitioners and only in one study performed in
hypertension centres, with an overall BP control rate of 37.0% among treated
hypertensive patients…”
J Hypertens 2012
“…The success of treating hypertension has been limited, and despite
well-established approaches to diagnosis and treatment, in many
communities fewer than half of all hypertensive patients have
adequately controlled blood pressure. …”
“…These guidelines have been written to provide a straightforward
approach to managing hypertension in the community…”
The Journal of Clinical Hypertension, published online ahead of print, Dec 17, 2013
- “…For hypertension, the treatment goal for SBP
usually is less than 140 mmHg and for DBP less
than 90 mmHg…”
- “…some experts still recommend less than
130/80mmHg if albuminuria is present in
patients with chronic kidney disease.…
- in people aged 80 or more “…a target of less
than 150/90mmHg is now recommended…”
Clinical Practice Guidelines for the Management of Hypertension in the Community
A Statement by the American Society of Hypertension
and the International
Society of Hypertension.
“…Most patients will require more than one
antihypertensive drug to maintain blood
pressure control…”
(ASH Guidelines)
“…most patients require the combination of
at least two drugs to achieve BP control…”
(ESH ESC Guidelines)
13. DRUG TREATMENT OF HYPERTENSION
“…In patients with stage 2 hypertension (blood
pressure 160/100mmHg), drug treatment should
be started immediately after diagnosis, usually
with a two-drug combination…”
Clinical Practice Guidelines for the Management of Hypertension in the Community
A Statement by the American Society of Hypertension
and the International
Society of Hypertension.
Monotherapy vs. drug combination
2013 ESH/ESC Guidelines for the management of arterial hypertension
ASH 2014
Hypertension
Guidelines
ASH 2014
Hypertension
Guidelines
“…when more than one drug is prescribed, the
use of a combination product with two
appropriate medications in a single tablet can
simplify treatment for patients……”
J Clin Hypertens 2014 Jan;16(1):14-26
Possible combinations of classes of antihypertensive drugs
“…Combinations of two antihypertensive drugs
at fixed doses in a single tablet may be
recommended and favoured, because reducing
the number of daily pills improves adherence
which is low in patients with hypertension…”
2013 ESH/ESC Guidelines for the management of arterial hypertension
Compliance to Treatment Related to
Daily Number of Pills Prescribed
Compliance to
treatment (%)
(%)
70
60
50
40
30
20
10
0
1
2
3
8
Average number of daily pills
Mancia G et al. Am J Hypertens 1997; 10: 153S-158S
Persistence with antihypertensive therapy regimens;
single-pill combination therapy vs free-drug combinations
(Sherrill 2011).
Fixed-Dose Combinations Improve Medication
Compliance: A Meta-Analysis (retrospective trials)
Bangalore S et al, Am J Med 2007: 120: 713-719
“…Do not com bine ARBs w ith ACE inhibitors; each of
these drug types is beneficial in patients with kidney
disease, but in combination they may actually have adverse
effects on renal events…”
(ASH Guidelines)
“…The com bination of tw o antagonists of the RAS is
not recom m ended and should be discouraged…”
(ESH ESC Guidelines)
Clinical Practice Guidelines for the Management of Hypertension in the Community
A Statement by the American Society of Hypertension
and the International
Society of Hypertension
2
drugs
ASH 2014
Hypertension
Guidelines
2
drugs
3
drugs
ASH 2014
Hypertension
Guidelines
Possible combinations of classes of antihypertensive drugs
2013 ESH/ESC Guidelines for the management of arterial hypertension
4161 patients were randomly assigned to double-blind treatment with nebivolol
and valsartan fi xed-dose combination (5 and 80 mg/day, 5 and 160 mg/day, or
10 and 160 mg/day), nebivolol (5 mg/day or 20 mg/day), valsartan (80 mg/day or
160 mg/day), or placebo.
“…Interpretation Nebivolol and valsartan fixed-dose
combination is an eff ective and well-tolerated
treatment option for patients with hypertension…”
Lancet 2014
“…no evidence is available that different
choices should be m ade based on age or
gender (except for caution in using RAS blockers in
women with child bearing potential because of
possible teratogenic effects)…”
“…Rather than indulging in an all-purpose ranking,
the Task Force decided to confirm (with small
changes) the table published in the 2007 ESH/ESC
Guidelines, with the drugs to be considered in
specific conditions…”
2013 ESH/ESC Guidelines for the management of arterial hypertension
ESC ESC 2013 Guidelines - Drugs to be preferred in specific conditions
Ma allora? Le raccomandazioni
sono completamente differenti?
Guardiamo meglio
Clinical Practice Guidelines for the Management of Hypertension in the Community
A Statement by the American Society of Hypertension
and the International
Society of Hypertension.
Clinical Practice Guidelines for the Management of Hypertension in the Community
A Statement by the American Society of Hypertension
and the International
Society of Hypertension.
Clinical Practice Guidelines for the Management of Hypertension in the Community
A Statement by the American Society of Hypertension
and the International
Society of Hypertension.
Clinical Practice Guidelines for the Management of Hypertension in the Community
A Statement by the American Society of Hypertension
and the International
Society of Hypertension.
Clinical Practice Guidelines for the Management of Hypertension in the Community
A Statement by the American Society of Hypertension
and the International
Society of Hypertension.
Clinical Practice Guidelines for the Management of Hypertension in the Community
A Statement by the American Society of Hypertension
and the International
Society of Hypertension.
Uso di combinazioni razionali
An olmesartan (OM) treat-to-target algorithm highlights
the benefits of combining an ARB with HCTZ
Week
0–3
3–6
OM
20 mg
OM
40 mg
6–9
9–12
OM/HCTZ OM/HCTZ
40/12.5 mg 40/25 mg
Change in BP (mmHg)
0
12–16
(extension phase)
OM/HCTZ
40/50 mg
● Potassium levels unchanged
-5,5
● Small, non-significant rise in glucose
-6,8
-10
-11,5
Baseline
OM/HCTZ
40/25
OM/HCTZ
40/50
Potassium
(mEq/L)
4.3±0.4
4.3±0.5
4.2±0.5
Glucose
(mmol/L)
5.7±1.4
6.0±1.7
6.0±1.9
-13,7
-16,9
-20
-18,4
-30
-30,3
SeDBP
SeSBP
-34,5
-40
Izzo et al. J Clin Hypertens 2007;9:36–44
Izzo et al. J Clin Hypertens 2007;9:45–8
Pooled incidence of peripheral edema and withdrawal due to edema with CCB’s
and CCB’s’RAS blockers
Makani H et al, Am J Med 2011
Alcune combinazioni
potrebbero offrire
particolari vantaggi
Effetto del trattamento con amlodipina/perindopril o con
atenololo/benflurazide sulla PA sistolica brachiale e centrale nello
studio CAFÉ
PAS Brachiale
Diff Media (AUC) = 0.7 (-0.4,1.7) mm Hg
Atenololo/benflurazide
Amlodipina/Perindopril
140
mm Hg
135
130
133.9
133.2
P=.07
125
125.5
121.2
120
P<.0001
PAS CENTRALE
Diff Media (AUC) = 4.3 (3.3, 5.4) mm Hg
115
0
Atenololo
Amlodipina
0.5
1
1.5
86
88
243
248
2
2.5
3
3.5
4
Tempo (Anni)
4.5
324 356 445 372 462 270
329 369 475 406 508 278
6
AUC
339 128 85
390 126 101
1031
1042
5
5.5
Williams Bet al. Circulation. 2006;113:1213-1225.
Combination therapies:
differential effects on central SBP
Favors 1st combination
- 10
CAFE
Amlodipine + Perindopril
EXPLOR
Valsartan + Amlodipine
-5
0
5 mmHg
- 4.3 [-5.4 to -3.3]
P<0.0001
- 3.9 [-7.1 to -0.8]
P=0.02
- 5.2 [-10.2 to -0.3]
P=0.004
Atenolol + HCTZ
Atenolol + Amlodipine
J-CORE
Azelnidipine + Olmesartan
HCTZ + Olmesartan
CAFE. 6 yrs
Williams et al. Circulation 2006
EXPLOR. 6 months Boutouyrie et al. Hypertension 2010
J-CORE 6 months Matsui et al. Hypertension 2009
ASCOT
Summary of primary and secondary end points
Primary
Non-fatal MI (incl silent) + fatal CHD
Unadjusted Hazard
ratio (95% CI)
0.90 (0.79-1.02)
Secondary
Non-fatal MI (exc. Silent) +fatal CHD
Total coronary end point
Total CV event and procedures
All-cause mortality
Cardiovascular mortality
Fatal and non-fatal stroke
Fatal and non-fatal heart failure
0.87 (0.76-1.00)
0.87 (0.79-0.96)
0.84 (0.78-0.90)
0.89 (0.81-0.99)
0.76 (0.65-0.90)
0.77 (0.66-0.89)
0.84 (0.66-1.05)
0.50
0.70
1.00
Amlodipine ± perindopril better
1.45
2.00
Atenolol ± thiazide better
“The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes
than the atenolol-based regimen. On the basis of previous trial evidence, these effects might not be
entirely explained by better control of blood pressure… Nevertheless, the results have implications with
respect to optimum combinations of antihypertensive agents”
Percentage of adults with controlled hypertension
among those treated, by survey year
www.thelancet.com Vol 383 May 31, 2014
Percentage of adults with controlled hypertension
among those treated, by survey year
80%
www.thelancet.com Vol 383 May 31, 2014
Linee Guida Ipertensione ASH 2014 e terapia di associazione
- Le nuove LG ASH sottolineano gli insoddisfacenti risultati ottenuti con le
strategie adottate sino ad ora
- Suggeriscono un approccio iniziale per la scelta dei farmaci differente
rispetto a quello delle Linee Guida ESH ESC 2013
- Esistono tuttavia anche diversi punti in comune fra le LG ASH e le ESH
ESC:
 Rimarcano la necessità di ricorrere ad una combinazione di farmaci
nella maggior parte dei pazienti ipertesi
 Suggeriscono terapia di combinazione fin dall’inizio se HT grado 2
 Indicano come preferenziale l’impiego di combinazioni fisse per
migliorare aderenza e persistenza
 Scoraggiano l’utilizzo del doppio blocco del RAS nella maggior parte
dei pazienti
 Suggeriscono una individualizzazione dei trattamenti