HTN & DM

1. Role of ACEIs/CCBs
combinations
in
Optimizing HYPERTENSION TREATMENT
of DM/CKD/LVH patients
CARDIO-METABOLIC RISK REDUCTION
DR./ADEL ELNAGGAR
Endocrinologist
Dr.Erfan & Bagedo General Hospital

2. HTN/DM SPOT LIGHTS
HTN guidelines
ACEIs/CCBs clinical outcomes
(initiation benefits)
Summary/Home message

4. Pre-Diabetes
•Impaired fasting glucose (IFG)
•FPG 100-125mg/dL
•Impaired glucose tolerance (IGT)
•PPBG 140-199mg/dL
•HbA1c 6-6.5%

6. ?Prehypertension
● NOT a DISEASE category
–Should encourage lifestyle
modification as this group has an
increased risk of becoming
hypertensive
● NOT candidates for drug therapy
(unless compelling indications ie
DM etc goal <130/80)

9. INSULIN RESISTANCE
METABOLIC SYNDROME
&
ADULT OBESITY
Central obesity (waist circumference)
IGT or IFG
High lipid profile
LDL-HDL/CHOLESTEROL/TRIGLYCERIDES
HIGH BP more than 130/90

10. CARDIO-METABOLIC RISK
REDUCTION???? 4-stops

11. Blood Pressure Reductions as Little as 2 mmHg
Reduce the Risk of Cardiovascular Events by up to
10%
Meta-analysis of 61 prospective, observational studies conducted by
Lewington et al involving one million adults with no previous vascular disease
at baseline.
2 mmHg decrease
in mean SBP
10% reduction in
risk of stroke
mortality
7% reduction in
risk of IHD
mortality
Lewington S, et al. Lancet. 2002;360:1903–1913

12. Every 1% reduction in HbA1c
can reduce long-term
DIABETES COMPLICATIONS1
*p<0.0001
1. Adapted from Stratton IM et al. BMJ 2000;321:405–412.
37%
21%
14%
Microvascular
complications*
Deaths related
to diabetes*
Myocardial
infarction*

13. Benefits of weight neutral/reduction
regimens in management of
type 2 diabetes
1. Anderson and Konz. Obes Res 2001;9(Suppl. 4):326S–334S
2. Anderson et al. J Am Coll Nutr 2003;22:331–9
BP, blood pressure; CV, cardiovascular; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-
density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides

16. Attributable mortality in millions (total: 55,861,000)
Developing region
Developed region
0 87654321
Adapted from Ezzati et al. Lancet 2002;360:1347–60
Global Mortality year 2000
Impact of Hypertension and Other Health Risk Factors

17. CV Mortality Risk Doubles with Each
20/10 mm Hg BP Increment*
CV
mortality
risk
SBP/DBP (mm Hg)
0
1
2
3
4
5
6
7
8
115/75 135/85 155/95 175/105
*Individuals aged 40-70 years, starting at BP 115/75 mm Hg.
CV, cardiovascular; SBP, systolic blood pressure;
DBP, diastolic blood pressure
Lewington S et al. Lancet 2002; 60:1903-1913. JNC 7. JAMA. 2003;289:2560-2572

18. USA
53.1
Canada
41.0
Mexico
21.8
Germany
33.6
Greece
49.5
England
29.2
Egypt
33.5
South Africa*
47.6
Japan*
55.7
Taiwan
18.0
China
28.8
Updated from Kearney et al. J Hypertens 2004; 22: 11–19
Turkey
19.8
Worldwide Blood Pressure Control in
Treated Hypertensive Patients

19. Hypertension: the facts
World Health Organization: World Health Day 2013. http://www.paho.org/hipertension/?lang=en

22. Barriers to hypertension Care
Clinical Practice
Therapeutic Regimen
(poly-pharmacy/complex)
Disease Process
Patient Adherence

25. Medical Education & Information – for all Media, all Disciplines, from all over the World
Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension
The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357
Definitions and classification of office BP levels (mmHg)*
Category Systolic Diastolic
Optimal <120 and <80
Normal 120–129 and/or 80–84
High normal 130–139 and/or 85–89
Grade 1 hypertension 140–159 and/or 90–99
Grade 2 hypertension 160–179 and/or 100–109
Grade 3 hypertension ≥180 and/or ≥110
Isolated systolic hypertension ≥140 and <90
* The blood pressure (BP) category is defined by the highest level of BP, whether systolic or diastolic. Isolated systolic
hypertension should be graded 1, 2, or 3 according to systolic BP values in the ranges indicated.
Hypertension:
SBP >140 mmHg ± DBP >90 mmHg

27. Diabetic hypertension
ESH/ESC guidelines
• To reach diabetic hypertension goals, combination
therapy is most often required
• Evidence indicates that combinations including an
ACE inhibitors or ARBs in Type 2 diabetes provide
Reno_protection benefits
• In patients with type 2 diabetes, treatment should
be initiated when BP is high-normal
ESH/ESC Guidelines. J Hypertens 2007;25:1105 -1187

28. 0
25
50
75
100
125
150
175
200
225
250
SBP (mm Hg)
CVMortality
(deaths/10,000person-years)
No diabetes
Diabetes
120 120–139 140–159 160–179 180–199 200
Adapted from Stamler J et al. Diabetes Care. 1993;16:434-444.
Association of Systolic Blood Pressure (SBP) and
CV Death in Type 2 Diabetes

32. ESHESC 2013 guidelines:
recommendations for BP goals1
A SBP goal <140 mmHg:
a) is recommended in patients at low–moderate CV risk;
b) is recommended in patients with diabetes;
c) should be considered in patients with previous stroke or TIA;
d) should be considered in patients with CHD;
e) should be considered in patients with diabetic or non-diabetic CKD
CHD: coronary heart disease; CKD : chronic kidney disease: CV: cardiovascular;
DBP: diastolic blood pressure; SBP: systolic blood pressure; TIA: transient ischaemic attack;
ESH: European Society of Hypertension; ESC: European Society of Cardiology
1Mancia et al. Eur Heart J 2013;34:2159–219

33. From: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the
Panel Members Appointed to the Eighth Joint National Committee (JNC 8)
Comparison of Treatment Goals between Guidelines

37. Medical Education & Information – for all Media, all Disciplines, from all over the World
Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension
The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357
Lifestyle changes for hypertensive patients
* Unless contraindicated. BMI, body mass index.
Recommendations to reduce BP and/or CV risk factors
Salt intake Restrict 5-6 g/day
Moderate alcohol intake Limit to 20-30 g/day men,
10-20 g/day women
Increase vegetable, fruit, low-fat dairy intake
BMI goal 25 kg/m2
Waist circumference goal Men: <102 cm (40 in.)*
Women: <88 cm (34 in.)*
Exercise goals ≥30 min/day, 5-7 days/week
(moderate, dynamic
exercise)
Quit smoking

40. Hypertension

41. DM HTN
CVD CKD

44. Corrao et al. J Hypertens. 2011;29:610-618.
Coronary events
Cerebrovascular events
Hazardratioreduction(%)†
Very low
(reference)
–24% –23
Intermediate
–16%
–21%
Low
–10
0
–20
–30
–40
–50
–37% –36%
Persistence category
Continuing use
†Estimates are adjusted for gender, age, initial antihypertensive regimen,
number of different classes of antihypertensive medications dispensed during
follow-up, use of other drugs during follow-up, and categories of Charlson
comorbidity index score.
* At least 1 episode of no prescription coverage for > 90 days.
Adherence level
Discontinuing use*
(reference)
High
Effect of compliance with antihypertensive medications
on the risk of cardiovascular outcomes
44

45. Evolution of guidelines on fixed-dose
combinations
“The use of fixed-dose combinations may be advantageous…”
“Where they are no more expensive, such formulations may be preferable since they
have advantages in terms of compliance”
“When BP is more than 20/10 mm Hg above goal, consideration should be given to
initiating therapy with two drugs, either in separate prescriptions or in fixed-dose
combinations”
Fixed-dose combinations… allow administration of two agents within a single tablet,
thus optimizing compliance”
“Fixed-dose combinations reduce the number of tablets to be taken, and this has some
advantages on compliance”
“Whenever possible, use of single-tablet combinations should be preferred, because
simplification of treatment causes advantages for compliance to treatment”
“The guidelines favor the use of combinations of two antihypertensive drugs at fixed
doses in a single tablet, because… improves adherence… and increases the rate of
BP control”
1999 WHO/ISH
2003 WHO/ISH
2003 JNC 7
2003 ESH/ESC
2007 ESH/ESC
2009 ESH/ESC
2013 ESH/ESC
45

46. •efficacy
•Micro albuminuria reduction
•Cost benefit
•CV outcomes
????? Anti-HTN choice

51. Difference between ACE inhibitors and ARBs
on mortality reductions in recent meta-analyses
51
1. van Vark LC, et al. Eur Heart J. 2012;33(16):2088-2097. 2. Lv J, et al. Cochrane Database Syst Rev. 2012;12:CD004136. 3. Baker WL, et al. Ann
Intern Med. 2009;151(12):861-871. 4. Savarese G, et al. J Am Coll Cardiol.15;61(2):131-142. 5. Hara et al. Am J Cardiol. 2014;114(1):1-8

52. ACEi plus CCB
Synergy at the clinical level
Less edema!!
Meta analysis:
25 trials
17,206 pts
CCB+ACEi: 54% less edema
CCB+ARB: 21% less edema
Makani H, et al. Am J Med 2011

54. 55
Amlodipine/perindopril:
Beyond brachial blood pressure control
Williams et al.
Circulation.
2006;113(9):1213-1225
O’Brien et al.
J Hypertens.
2009;27(4):876-885.
Dahlöf et al.
Lancet.
2005;366(9489):895-906.
Rothwell et al.
Lancet Neurol.
2010;9(5):469-480.

55. More effective reduction in blood pressure
variability with amlodipine/perindopril
Watson et al. J Hypertens. 2014;32(e-suppl 1):e125.9C.06.56
Visit-to-visit variability of systolic blood pressure (SBP) in ASCOT-BPLA patients treated exclusively with either
amlodipine/perindopril or β-blocker/thiazide for at least 6 months.
Difference in baseline SBP (mm Hg, 95% CI) = -1.6 (-2.7 to -0.0056)
Difference in final SBP (mm Hg, 95% CI) = -0.6 (-1.6 to 0.4), P=0.2216
n=1 372 n=2 319

56. ASCOT-Variability:
Amlodipine/perindopril lowers blood
pressure variability

57. CHOICES MODULES OF THERAPIES FOR MANAGEMENT
OF TYPE 2 DM
4 RIGHTS MODULE

59. CARDIO-METABOLIC RISK
REDUCTION???? 4-stops

60. Institute of Medicine Report, November 2010
Thank you
DR./ ADEL EL NAGGAR