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Hipertension arterial en tiempos de crisis
1. Tratamiento de la
hipertensión arterial en
tiempos de crisis
• Dr. Martin Velarde
• MASVH MASVC MAAVA
• CARDIOLOGO CLINICO 2015
2. ■ Prevalencia:
. ~ 40% de la población adulta.
. Un billón de hipertensos en el mundo.
■ . Desigualdad en el control entre países
. Aéreas rurales y zona de bajo ingreso peor.(PURE)
. 85 con riesgo cardiovascular añadido
■ Aumento en comorbilidades : DM , Obesidad……
.Alta tasa de abandono al tratamiento
. Aumento en el daño a órgano blanco aunado al envejecimiento.
Venezuela : seguimos con pobre control.
Sources: Gaziano TA, et al. J hypertens 2009;27:1472-1477;Mendis S, Puska S, Puska P, Worrving B,editors. Global atlas on cardiovascular disease prevention and control. Genova .Switzerland: World Health
organization; 2011.
La Hypertensiòn
3.
4. 4
Dedicated to the Assessment, Prevention, and Control of Hypertension Globally
The WHL is a charitable organization comprised of national and regional hypertension societies
High Blood Pressure: Why Prevention and Control are
Urgent and Important – A 2014 Fact Sheet From the World
Hypertension League and the International Society of
Hypertension
“High Blood Pressure: Why Prevention and Control are Urgent and
Important – A 2014 Fact Sheet from the World Hypertension League
and the International Society of Hypertension. The Journal of
Clinical Hypertension.
http://onlinelibrary.wiley.com/doi/10.1111/jch.12372/abstract
5. Silva H, Hernández-Hernández R et al, Am J Ther, 2009
Hypertension
Treatment and Control
83.3
23.9
76.1
61.0
28.8
12.0
46.7
71.1
Almos
Almost 80 % of
hypertensives in Latin
America are not in
control
6. Cardiovascular Drug Use for Secondary
Prevention Among Patients
With CHD or Stroke, by Nation Economic Status
CV drug category High-income (%) Upper-middle income
(%)
Lower-middle income
(%)
Low-income (%) Overall
Antiplatelets 62.0 24.6 21.9 8.8 25.3
Beta blockers 40.0 25.4 10.2 9.7 17.4
ACE inhibitors or ARBs 49.8 30.0 11.1 5.2 19.5
BP-lowering agents 73.8 48.4 37.4 19.2 41.8
Statins 66.5 17.6 4.3 3.3 14.6
7. ELEGIR ENTRE
Tiacida
I-ECA ARA II Βeta
bloqueador
Calcio
Antagonista*
Tratamiento de la Hipertensión, no complicada
sin factores de riesgo adicionales con cifras de
PA <160/100mmHg
ARA II MEJOR TOLERADOS CON ALTA ADHERENCIA (ESH 2013)
10. 3Nixon RM et al. Int J Clin Pract May 2009; 63: 766-75
Objetivo: Comparar la eficacia antihipertensiva en términos de
PAS y PAD entre los diferentes ARAII en HTA esencial
Metodología: revisión sistemática de 31 estudios (13.110 pacientes)
de diseño similar publicados entre 1997 y 2008
Todos los estudios incluidos fueron aleatorizados, doble ciego,
De grupos paralelos para el tto de la HTA (PAD: 90-115 mmHg)
11. Systolic Blood Pressure (SBP) Reduction with Valsartan is
Superior to Losartan and Comparable to Other ARBs
Drug and dose
Candesartan 8 mg
Candesartan 16 mg
Candesartan 32mg
Irbesartan 150 mg
Irbesartan 300 mg
Losartan 50 mg
Losartan 100 mg
Olmesartan 20 mg
Olmesartan 40 mg
Telmisartan 40 mg
Telmisartan 80 mg
Valsartan 80 mg
Valsartan 160 mg
Valsartan 320 mg
n
142
329
821
531
261
369
1733
145
199
275
233
321
3661
3091
Estimate and 95% CI
–10.04 (–13.89, –6.19)
–12.70 (–15.32, –10.07)
–15.28 (–17.75, –12.80)
–11.75 (–13.91, –9.54)
–15.98 (–18.89, –13.10)
–9.93 (–12.69. –7.14)
–12.01 (–13.78, –10.25)
–10.88 (–15.63, –6.05)
–13.98 (–18.53, –9.44)
–13.98 (–16.64, –11.23)
–16.50 (–19.26, –13.76)
–11.52 (–14.39, –8.70)
–15.32 (–17.09, –13.63)
–15.85 (–17.60, –14.12)
–18 –14 –10 –6
Changes in SBP (mmHg)
Nixon et al.
Int J Clin Pract 2009;63:766–75
Meta-regression analysis of 31 randomized controlled trials (n=13,110 patients) with at least one
angiotensin receptor blocker (ARB) arm. The meta-analysis adjusted for the influence of different
baseline BP between studies. Studies ranged in duration from 6–12 weeks.
Data are from baseline to follow-up
12. Conclusiones
Meta-análisis previos han demostrado que los ARA II
Tienen eficacia antihipertensivas similares
Valsartán 160mg y 320 mg es más efectivo que losartán
100mg estadísticamente significativo
Entre valsartán y el resto de los ARA II (olmesartán,
candersartán, irbesartán, la eficacia
antihipertensiva fue similar
3Nixon RM et al. Int J Clin Pract May 2009; 63: 766-75
19. Hypertension Treatment Significantly Reduced Mortality and
Morbidity
0
10
20
30
40
50
60
0 1 2 3 4 5
Years
EstimatedCumulative
IncidenceofAllMorbidEvents(%)
VA Cooperative Study Group – Estimated Cumulative Incidence of
All Morbid Events Over 5 Years
Veterans Administration Cooperative Study Group on antihypertensive agents JAMA 1970;213(7):1143-1152.
Control - Placebo
Active Treatment Groups -
Diuretic-based regimen
and hydralazine
20. Tengamos precaución con :
. Suspender Betabloqueantes (rebote)
. Clonidina ( rebote)
. Evitar combinación IECA + ARA
. Diuréticos a dosis alta (moduretic)
.Evitar Nifedipina de acción rápida.
21. The Human Side of Failed Hypertension Treatment
Michael A. weber, MD;1 Suzanne Oparil, MD2
From the state university of New York, Downstate College of Medicine, Brooklyn, NY; and university of Alabama, Birmingham, AL.
2013
22. ■ CDC
■ PAHO
■ Ministries Of Health
■ Physicians
■ Pharmacists,
■ Pharmacologists
■ Epidemiologists
March 2013 Miami LAC Workshop Attendees
Society Representation:
- American Heart Association
- Barbados Drug Service
- InterAmerican Society of
Cardiology
- Latin American Federation of
Obstetrics and Gynecology
- Latin American Society of
Hypertension
- Society of Latin American
Nephrology and Hypertension
23. From 2001 To 2009.
■ Hypertension Control Rate Nearly Doubled From 44% To 80%
■ Hypertension Registy Increase From 349,937 To 652,763 Persons .
■ Controlled Hypertension Tripled From 171.000 To 531,000.
●USA : 60% CONTROL
Six Care Proceses Implemented.
■ Evidence Based Guideline Development
■ Hypertension Registry Creation
■ Performance Measure Distribution
■ Successful Practice Dissemination
■ Single Pill Combination Therapy Promotion
■ Non-physician BP Visit Creation
Results From Kaiser Permanente
Jaffe MG et al JAMA. 2013;310(7): 699-705 doi: 10.1001/jama 2013.108769
24. FROM THE WORLD HYPERTENSION LEAGUE
Hypertension Prevention and Control in Latin América and the Caribbean
Pedro Ordunez, MD, PhD; Ramón Martínez, Mark L. Niebylski, PhD,MBA,MS; Norm R. Campbell, MD
From the Pan American Health Organization, Washington,DC; the World Hypertension League, Corvallis, MT; and the Libin Cardiovascular Institute, Calgary;
AB, Canada
28. 0
2
4
6
8
10
12
14
16
Proportionofpatientswithfirstevent(%)
Composite of CV death, stroke and MI
Losartan
Atenolol
LIFE: Primary Composite Endpoint
Study Month0 6 12 18 24 30 36 42 48 54 60 66
Losartan 4605 4524 4460 4392 4312 4247 4189 4112 4047 3897 1889 901
Atenolol 4588 4494 4414 4349 4289 4205 4135 4066 3992 3821 1854 876
Adjusted Risk Reduction 13.0%, p=0.021
Unadjusted Risk Reduction 14.6%, p=0.009
Dahlöf B et al Lancet 2002;359:995-1003.
Number
at Risk
28
29. 24
1. VALUE
2. VALIANT
3. NAVIGATOR
4. Val-HeFT
5. JIKEI HEART
6. KYOTO HEART
7. VART
27. HIJ-CREATE
28. E-COST
29. HOPE-3*
30. 4C*
31. I-PRESERVE
32. IDNT
33. ACTIVE-I*
34. NID-2
35. SUPPORT*
36. COLM*
37. OSCAR*
38. ORIENT
39. MOSES
8. VALISH*
9. NAGOYA-HEART*
10. V-CARD*
11. ONTARGET
12. PRoFESS
13. TRANSCEND
14. HALT-PKD*
*Expected enrolment‡Ongoing and completed
randomized controlled
trials with death or hard
CV events as or part of
the primary endpoint
¶Valid as of December 2009
15. NCT00490958*
16. LIFE
17. OPTIMAAL
18. ELITE II
19. RENAAL
20. NCT00090259*
21. VA NEPHRON-D*
22. CHARM
23. SCOPE
24. SCAST*
25. CASE-J
26. ACCOST
Numberofpatients
Valsartan Telmisartan Losartan Candesartan Irbesartan Olmesartan Eprosartan
57,046
53,247
25,019
36,940
6,777
1,405
15,693
1
2
5
4
3
7
8
6
11
12
14
13
20
21
18
16
17
25
26
28
22
23
39
36
35
37
38
34
33
32
31
27
1Julius et al. 2004; 2Pfeffer et al. 2003; 3Califf et al 2008; 4Cohn et al. 2001; 5Mochizuki et al. 2007; 6Sawada et al 2009
7Narumi et al. 2009 [abstract at ESC]; 8http://clinicaltrials.gov (NCT00151229); 9http://clinicaltrials.gov (NCT00129233)
10http://clinicaltrials.gov (NCT00140790); 11ONTARGET Investigators 2008; 12Yusuf et al 2008; 13TRANSCEND Investigators 2008
14http://clinicaltrials.gov (NCT00283686); 15http://clinicaltrials.gov (NCT00490958); 16Dahlöf et al. 2002; 17Dickstein et al. 2002
18Pitt et al. 2000; 19Brenner et al. 2001; 20http://clinicaltrials.gov (NCT00090259); 21Fried et al 2009; 22Pfeffer et al 2003
23Papademetriou et al. 2004; 24http://clinicaltrials.gov (NCT00120003); 25Ogihara et al. 2008
26http://clinicaltrials.gov (NCT00108706); 27Laufs et al. 2008; 28Suzuki et al. 2005; 29http://clinicaltrials.gov (NCT00468923)
30http://clinicaltrials.gov (NCT00139386); 31Massie et al 2008; 32Lewis et al. 2001; 33http://clinicaltrials.gov (NCT00249795)
34http://clinicaltrials.gov (NCT00535925); 35http://clinicaltrials.gov (NCT00417222); 36Ogihara et al 2009; 37Ogawa et al 2009
38Imai et al. 2009 (Abstract F-FC313 at ASN 2009); 39Schrader et al. 2005
15
19
29
30
9
10
60,000
50,000
40,000
30,000
20,000
10,000
0
EL CONTINUO CARDIOVASCULAR
# ESTUDIOS CON ARA2
30. Advance Publication by J-STAGE
Angiotensin II Receptor Blocker, Valsartan,increases
Myocardial Blood Volume and Regresses Hypertrophy
In Hypertensive Patients
Hiroshi Komatsu, MD;Satoshi Yamada,MD;Hiroyuki Iwano,MD;Masako Okada,MD;
Hisao Onozuka,MD*;Taisei Mikami,MD*;Shinobu Yokoyama,AA**;Mamiko Inoue,BA**;
Sanae Kaga,BA**;Mutsumi Nishida,PhD**; Chikara Shimizu,MD**;
Kazuhiko Matsuno,MD**;Hiroyuki Tsutsui,MD
Conclusions: Valsartan,an angiotensin II receptor blocker, corrected the decreased MBV in association with regression of LVH in petients with HT
32. Amlodipina: mecanismo antioxidante
NH2
+
+
O2
-
ONOO-
HO-
H2O2
estabilización
Amlodipina
-100 veces más potente antioxidante que otros calcioantagonistas
-Tan potente antioxidante como lovastatina y más que captopril
Mason RP. Am J Hypertens 1998; 11: A245
33. Tasadeeventosacumulativa
20% Reducción de
Riesgo
Tiempo hasta 1er Evento (días)
IECA / HCTZ
CA / IECA
650
526
0.10
0.08
0.06
0.04
0.02
0.00
0.16
0.14
0.12
1400120010008006004002000
ACCOMPLISH: Resultado Principal( Kaplan Melier)
34. ASCOT-BPLA: puntos finales
Dahlöf B, et al. Lancet. 2005;366:895-906.
amlodipina perindopril mejor atenolol tiazida mejor
0.50 0.70 1.00 1.45
Primarios
IM No-fatal (incl silente) + EAC fatal
Secundarios
IM No-fatal (exc. Silente) + EAC fatal
Total coronarios
Total CV (eventos y procedimientos)
All-cause mortalidad
Cardiovascular mortalidad
ACV Fatal y no fatal
IC Fatal y no fatal
Terciarios
IM Silente
Angina Inestable
Angina Cronica estable
Enf arterial Periferica
Arritmias de riesgo de vida
Nuevos casos diabetes mellitus
Nuevos casos insuf renal
Post hoc
PF Primario + proced coronarios
Muerte CV + IM + ACV
2.00
Unadjusted HR (95% CI)
0.90 (0.79-1.02)
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)
1.27 (0.80-2.00)
0.68 (0.51-0.92)
0.98 (0.81-1.19)
0.65 (0.52-0.81)
1.07 (0.62-1.85)
0.70 (0.63-.078)
0.85 (0.75-0.97)
0.86 (0.77-0.96)
0.84 (0.76-0.92)
37. AMLODIPINA/VALSARTAN: reducción de la PAS
en pacientes con HTA st 2 Estudio EX-EFFeCTS
Destro et al. J.AmSocHypertens 2008:2;294-302
BRA+BCC: Eficacia
38.
39.
40. –49.6*
–39.9
–43.6 –42.5
La terapia de combinación triple es superior a la terapia
de combinación doble en pacientes con hipertensión severa
n=168 n=155n=155
Lacourciere et.al. J Hypertens 2009;27(Suppl 4):S119
0
–10
–20
–30
–40
–50
n=168
ReduccióndelaPAS(mmHg)
Amlodipina/
Valsartán/
HCTZ
10/320/25 mg
Valsartán/
HCTZ
320/25 mg
Amlodipina/
Valsartán
10/320 mg
HCTZ/
amlodipina
25/10 mg
p<0.0001
p=0.0009
p<0.0001
Analisis post-hoc
Calhoun DA et al. Hypertension 2009;54:32–9
*p<0.0001 vs. todas las otras combinaciones
41. 48.3
54.1
44.8
70.8*
La Triple Terapia Lleva a Mas Pacientes a Alcanzar una Mayor
Tasa de Control de la HTA
* p<0.0001 versus todas las otras combinaciones
n=583 n=568n=559
80
70
60
50
40
30
20
10
0
n=561
TasadeControl(%)dePAS/PAD
(<140/90mmHg)
(N=2,271)
Mas pacientes con triple terapia alcanzaron el control de la PA que los que recibieron terapia dual
Valsartan/
HCTZ/
amlodipina
320 / 25 / 10
Valsartan/
HCTZ
320 / 25
Valsartan/
amlodipina
320 / 10
HCTZ/
amlodipina
25 /10
Calhoun-DA et al., Hypertension. 2009;54:32-39.
42. Amlodipine-Valsartan Combination Decreases Central
Systolic Blood Pressure More Effectively Than the
Amlodipine-Atenolol Combination
The EXPLOR Study
Pierre Boutouyrie, Assya Achouba, Patrick Trunet, Ste´phane Laurent,
for the EXPLOR Trialist Group
Hypertension 2010;55;1314-1322
El estudio fue diseñado para determinar si las ventajas de los BRAA en la
reducción de la PA central, sobre Atenolol permanecen significativas
cuando son combinados con Amlodipina
43. No diferencias en PA Braquial PAS central disminuyó más en el grupo A/V
(13.701.15 mm Hg ) Que el grupo A/A
(9.701.10 mm Hg). Diferencia 4 mmHg
ESTUDIO EXPLOR
Hypertension 2010;55;1314-1322
44. Exforge: Efecto en Edema Periférico Inducido por Amlodipina
8
10
6
4
2
0
8.7%
5.4%
Incidenciadeedema
periférico(%)
p=0.0138
3.0%
Placebo Amlodipina Exforge
38% diferencia
Datos agrupados de dos estudios con Exforge a dosis hasta de 10/320 mg y Amlodipina
hasta de 10 mg REDUCCION DE EDEMA PERIFERICO COMPROBADA
n=337 n=460 n=1,437
Philipp et al. Clin Ther 2007 (publicación por Internet, 2 April 2007)