1. Perindopril 10 mg po daily is the recommended initial treatment. It is an ACE inhibitor which is recommended as first line treatment for hypertension in patients with diabetes according to guidelines. 2. The patient should be followed up with basic screening including potassium and creatinine levels within one week of starting treatment, then every 3 months to monitor for side effects of the ACE inhibitor such as hyperkalemia and worsening renal function. 3. Additional monitoring of renal function and potassium is needed due to the patient's risk factors of obesity and diabetes which increase

1. HTN
The Silent Killer
New Data about ACEI
at least 12 % of world total mortality
ADA 2013 guidelines
BHS 2011 guidelines
Dr Ihab SulimanDr Ihab Suliman
Consultant CardiologistConsultant Cardiologist
25-4-201325-4-2013

2. Leading risks for
premature death
3
5
4
2
1
CholesterolCholesterol
AlcoholAlcohol
Tobacco UseTobacco Use
HYPERTENSIONHYPERTENSION
OverweightOverweight
(World Health Organization 2002)

3. HTN: KEY CONTRIBUTOR TO DIABETESHTN: KEY CONTRIBUTOR TO DIABETES
COMPLICATIONSCOMPLICATIONS
Framingham Study: DM ⊕ HTN vs DM alone
Relative Risk
of
Complication
Total mortality ↑ 72%
CVD events ↑ 57%
• HTN → 44% of deaths and 41% of CVD events in DM!
‒ ↑ risk of nephropathy/retinopathy/neuropathy 60-100%
Hypertension 2011; 57:891 Lancet 2012; 380:601

4. HTN PREVALENCE: GENERALHTN PREVALENCE: GENERAL vsvs DMDM
POPULATIONSPOPULATIONS
north american data UTAHnorth american data UTAH
BP ≥ 140/90
General population 30%
• Age ≥ 60y 67%
• White 29%
• Black 41%
• Hispanic 26%
Persons with DM 67% 76%
BP ≥ 130/80
---
---
---
---
---
---
 HTN is more than twice as common in DM!
JACC 2012; 60:599 Diabetes Care 2011; 34:1597 Am J Med 2009; 122:443
Utah State Health Department, 2012

5. BackgroundBackground
•
EachEach 22 mmHg rise in systolic blood pressuremmHg rise in systolic blood pressure
associated with increased risk of mortality:associated with increased risk of mortality:
– 7%7% from heart diseasefrom heart disease
– 10%10% from stroke.from stroke.

6. HTN: DOMINANT CONTRIBUTOR TO GLOBALHTN: DOMINANT CONTRIBUTOR TO GLOBAL
MORTALITYMORTALITY
Increases RR by 2.0-4.0 fold for:Increases RR by 2.0-4.0 fold for:
• CAD, stroke, HF, PADCAD, stroke, HF, PAD
• Renal failure, AF, dementia,Renal failure, AF, dementia, ↓↓ cognitioncognition
Attributable risk for HTN:Attributable risk for HTN:
• StrokeStroke 62%62% • MI• MI 25%25%
• CKDCKD 56%56% • Premature death• Premature death 24%24%
• HFHF 49%49%
Aftermath:Aftermath:
• Shortens lifespan 5yShortens lifespan 5y
• $93.5 billion/y in U.S.$93.5 billion/y in U.S.
CirculationCirculation 2012; 125:e122012; 125:e12 JJ HumHum HypertensionHypertension 2008; 22:632008; 22:63 HypertensionHypertension 2007; 50:10062007; 50:1006

7. Properly MeasuredProperly Measured
 Cuff SizeCuff Size
 BilateralBilateral
 Confirm with ManualConfirm with Manual
 No recent caffeine or SmokingNo recent caffeine or Smoking

8. How many BP readings?How many BP readings?
1.1. 3 – in sinus3 – in sinus
rhythmrhythm
2.2. more if theremore if there
are multipleare multiple
ectopics or AFectopics or AF

9. DefinitionsDefinitions
Stage 1 hypertensionStage 1 hypertension::
CBPCBP >>140/90140/90 andand ABPM or HBPMABPM or HBPM
>>135/85 mmHg135/85 mmHg
Stage 2 hypertension:Stage 2 hypertension:
CBPCBP >>160/100 160/100 andand ABPM or HBPM daytimeABPM or HBPM daytime
>>150/95 mmHg150/95 mmHg
Severe hypertension:Severe hypertension:
C SBPC SBP >>180 180 oror C DBPC DBP >>110 mmHg110 mmHg

10. Offer drug treatment to:Offer drug treatment to:
 stage 1 hypertension, aged <80 and meet identifiedstage 1 hypertension, aged <80 and meet identified
criteriacriteria
 stage 2 hypertension at any agestage 2 hypertension at any age
If <40 with stage 1 hypertension and without evidence ofIf <40 with stage 1 hypertension and without evidence of
TOD, CVD, CKD or diabetes, consider:TOD, CVD, CKD or diabetes, consider:
 specialist evaluation of secondary causes of hypertensionspecialist evaluation of secondary causes of hypertension
Initiating drug treatmentInitiating drug treatment

11. Choosing drugs for patients newly diagnosedChoosing drugs for patients newly diagnosed
with hypertensionwith hypertension
BHS Guidelines (2011)BHS Guidelines (2011)
Younger than 55 years
55 years or older
Or black patients
of any age
A C
A+C
A+C+D
Add
•further diuretic therapy
•Or alpha blocker
•Or Beta Blocker
•Consider seeking specialist advice
Abbreviations:
A: ACE-I (or
ARB if ACE
intolerant)
C: CCB
D: thiazide
type diuretic
Step 1
Step 2
Step 3
Step 4

13. Baseline characteristics of study population (n=158 998)
Trial Year N Active Control FU, HT, SBP, Age, Incidence
treatment years % mm Hg years rate, control
RENAAL 2001 1513 Losartan Placebo 3.1 97 153 60 66.0
IDNT 2001 1715 Irbesartan Amlo or placebo 2.9 100 159 59 54.0
LIFE 2002 9193 Losartan/HCTZ Atenol/HCTZ 4.8 100 174 67 19.5
ALLHAT 2002 33 357 Lisinopril Diur or Amlo 5.0 100 146 67 28.5
ANBP-2 2003 6083 Enalapril HCTZ 4.1 100 168 72 17.1
SCOPE 2003 4937 Candesartan Placebo 3.7 100 166 76 29.0
Pilot HYVET 2003 1283 Lisinopril Diuretic 1.1 100 182 84 55.4
JMIC B 2004 1650 Lisinopril or enal Nifedipine 2.3 100 146 65 6.2
VALUE 2004 15 245 Valsartan Amlodipine 4.3 100 155 67 24.8
MOSES 2005 1352 Eprosartan Nitrendipine 2.5 100 152 68 31.0
ASCOT-BPLA 2005 19 257 Amlo/perindopril Atenolol/BTZ 5.5 100 164 63 15.5
JIKEI HEART 2007 3081 Valsartan Non-ARB 2.81 88 139 65 6.2
ADVANCE 2007 11 140 Perindopril/Indap Placebo 4.3 69 145 66 19.8
HYVET 2008 3845 Indap/perindopril Placebo 2.1 90 173 84 59.3
PRoFESS 2008 20332 Telmisartan Placebo 2.5 74 144 66 29.1
TRANSCEND 2008 5926 Telmisartan Placebo 4.6 77 141 67 25.2
CASE-J 2008 4703 Candesartan Amlodipine 3.3 100 163 64 11.1
HIJ-CREATE 2009 2049 Candesartan Non-ARB 4.0 100 135 65 14.3
KYOTO HEART 2009 3031 Valsartan Non-ARB 2.9 100 157 66 7.2
NAVIGATOR 2010 9306 Valsartan Placebo 6.1 78 140 64 11.5
OVERALL 4.3 91 153 67 23.3

14. Comparison of morbidity/mortality trials
in hypertension/high risk patients
Trial Treatmen
t
Total mortality CV mortality MI
HYVET Perindopril/indapamide RRR = 21% RRR = 27% RRR = 28%
vs placebo p = 0.019 p = 0.029 p = 0.45
ADVANC
E
Perindopril/indapamide RRR = 14% RRR = 18% RRR = 14%
vs control p = 0.025 p = 0.027 p = 0.02
ASCOT Amlodipine/perindopril RRR = 11% RRR = 24% RRR = 13%
vs b-blocker/thiazide p = 0.02 p = 0.001 p = 0.007
ONTAR
GET
Telmisartan vs ramipril NS NS Ramipril > telmisartan
RRR = 7% in favour of
ramipril
ONTAR
GET
Telmisartan+Ramipril vs Ramipril > combination Ramipril > combination Ramipril > combination
ramipril RRR = 7% in favour of RRR = 4% in favour of RRR = 8% in favour of
ramipril NS ramipril NS ramipril
TRANSC
END
Telmisartan vs placebo Placebo > telmisartan RRR = 21% in favour
RRR = 3% in favour of of telmisartan NS
placebo NS
VAL
UE
Valsartan vs amlodipine Amlodipine > valsartan Amlodipine > valsartan Amlodipine > valsartan
RRR = 4% in favour RRR = 1% in favour RRR = 19% in favour
amlodipine amlodipine of amlodipine
NS NS p = 0.02
LI
FE
Losartan/HCTZ vs NS NS Atenolol > losartan
Atenolol /HCTZ RRR = 7% in favour of
atenolol
ACCOMP
LISH
Benazepril/amlodipine vs NS NS RRR = 22% p = 0.04
benazepril/HCTZ

15. Circulation
2006
Neutral effect of ARBs on mortality,
MI increase
ARBs vs comparators
(11 trials, n=55 050)
RRR, %
+8%
ACE inhibitors vs comparators
(39 trials, n=150 943)
RRR, %
-6%
-9%
**
* -12%
** -14%
**
*
Adapted from: Strauss MH, Hall AS.
Circulation. 2006;114:838-854.
*
+1% +1%
-8%
*P=0.03; **P=0.0005; ***P<0.00001

16. Bangalore S, Kumar S, Messerli F.
BMJ. 2011;342:d2234.

17. Dose-Dependent AntihypertensiveDose-Dependent Antihypertensive
Efficacy and Tolerability of CoversylEfficacy and Tolerability of Coversyl
in a Large, Observational,12-Week,in a Large, Observational,12-Week,
General Practice-Based Study.General Practice-Based Study.
George TsoukasGeorge Tsoukas11
, Sanjiv Anand, Sanjiv Anand22
and Kwang Yangand Kwang Yang33
for thefor the
CONFIDENCECONFIDENCE InvestigatorsInvestigators
1.1. McGill University Health Centre, Montreal, Quebec, CanadaMcGill University Health Centre, Montreal, Quebec, Canada
2.2. Dr Georges-L. Dumont Regional Hospital, Moncton, New Brunswick, CanadaDr Georges-L. Dumont Regional Hospital, Moncton, New Brunswick, Canada
3.3. University of British Columbia, Surrey, British Columbia, CanadaUniversity of British Columbia, Surrey, British Columbia, Canada

18. Perindopril efficacy Results in Overall
Population
Strong Efficacy is consistent across the entire
groups

19. Perindopril results in Severe HTN
Population
Powerful BP reduction needed to achieve
Target Blood pressure

21. High tissue ACE AffinityHigh tissue ACE Affinity

22. Trough/Peak ratio: What does itTrough/Peak ratio: What does it
mean?mean?

23. 6-week run-in period of
active BP-lowering with
perindopril-indapamide
Registration
Randomization
N = 11,140
Optimal Therapy
+
+
Intensive glucose
control
Optimal Therapy +
+
Standard
glucose control
Optimal Therapy +
Placebo
+
Intensive glucose
control
Optimal Therapy
+
Placebo
+
Standard glucose
control
END OF FOLLOW-UP (average (5.5 years)
2 x 2 factorial multicenter, randomized control trial with 5-6 years followup
Patients were all allowed other Preventive Therapy including: other Blood Pressure Lowering Drugs, Lipid
Lowering Drugs, Glucose Lowering Drugs, Anti-platelets
ADVANCE - Lancet 2007; 370: 829–40
COVERSYL- NATRILIXCOVERSYL- NATRILIX

24. ADVANCE Collaborative Group. Lancet. 2007;370:829-
840.

25. HYVET, an internationalHYVET, an international
trialtrial
The trial:
International, multicenter, randomized, double-blind, placebo-
controlled
Inclusion criteria: Exclusion criteria:
Aged 80 or more, Standing SBP <140 mm Hg
Systolic BP 160-199 mm Hg Stroke in last 6 months
+ diastolic BP <110 mm Hg, Dementia
Informed consent Need for daily nursing care
Primary end point:
All strokes (fatal and nonfatal)

26. Total mortality
(21% reduction)
Placebo
P=0.02
Natrilix SR+COVERSYL
Numberofeventsper100patients
Follow-up (years)
Beckett N, et al. NEJM 2008;358:1887-1898.
This result is at odds with findings from previous trials

27. CaseCase
 55 years old obese Diabetic with Type 2 DM,55 years old obese Diabetic with Type 2 DM,
SBP is consistently above 150 mmHg, the bestSBP is consistently above 150 mmHg, the best
initial treatment will be ???initial treatment will be ???
 1-HCTZ 12.5 mg po daily.1-HCTZ 12.5 mg po daily.
 2-Atenolol 50 mg po daily.2-Atenolol 50 mg po daily.
 3-Perindoril 10 mg po daily3-Perindoril 10 mg po daily

28.  Perindopril 10 mg po daily is chosenPerindopril 10 mg po daily is chosen
 You FU the patient byYou FU the patient by
 A-POTASSIUMA-POTASSIUM
 B-RENINB-RENIN
 C-CREATININEC-CREATININE
 D-ECGD-ECG
 E— A&CE— A&C
 F-A,B,C,DF-A,B,C,D

29.  E— A&CE— A&C
 The patient after starting Lisinopril will be seenThe patient after starting Lisinopril will be seen
after with Basic Screenafter with Basic Screen
 A- one week then 3 monthyA- one week then 3 monthy
 B- every 3 monthsB- every 3 months
 C- within 3 days then 3monthsC- within 3 days then 3months

30.  A- one week then 3 monthyA- one week then 3 monthy

31.  45 years old male with DM , Prior history of45 years old male with DM , Prior history of
IHD, Last echo report EF 45%, SBP 155,IHD, Last echo report EF 45%, SBP 155,
Creatinine 140, potassium 4, started onCreatinine 140, potassium 4, started on
Perindopril 10 mg po daily, after 3 month on aPerindopril 10 mg po daily, after 3 month on a
routine visit SBP 115, creatinine 155, potassiumroutine visit SBP 115, creatinine 155, potassium
is 4.5 , No chest Pain or SOB, the next step willis 4.5 , No chest Pain or SOB, the next step will
be ????be ????

32.  A- DIC perindopril & Start Amlor .A- DIC perindopril & Start Amlor .
 B- refer to cardiology.B- refer to cardiology.
 C-No change & BC-No change & B
 D- DIC Perindopril& start ARBsD- DIC Perindopril& start ARBs
 E- Start AliskirenE- Start Aliskiren

33.  70 years old female with no prior active cardiac70 years old female with no prior active cardiac
problems, Informed in a private clinic aboutproblems, Informed in a private clinic about
being Hypertensive, 3 separate visits, SBP 160-being Hypertensive, 3 separate visits, SBP 160-
170 ,what is the next step??170 ,what is the next step??
 A-life style modfication.A-life style modfication.
 B-single agent anti hypertensiveB-single agent anti hypertensive
 C- combination of two anti hypertensive agents.C- combination of two anti hypertensive agents.
 D- a diagnosis of HTN cannot be made at thisD- a diagnosis of HTN cannot be made at this
time.time.

34.  C- combination of two anti hypertensive agents.C- combination of two anti hypertensive agents.

35. Recommendations: Hypertension/Blood PressureRecommendations: Hypertension/Blood Pressure
ControlControl
Screening and diagnosisScreening and diagnosis
 Blood pressure should be measured atBlood pressure should be measured at
every routine visitevery routine visit
 Patients found to have elevated bloodPatients found to have elevated blood
pressure should have blood pressurepressure should have blood pressure
confirmed on a separate day (B)confirmed on a separate day (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S28-S29.

36. Recommendations: Hypertension/Blood PressureRecommendations: Hypertension/Blood Pressure
ControlControl
Treatment (1)Treatment (1)
 Patients with a blood pressure (BP)Patients with a blood pressure (BP)
>120/80 mmHg should be advised on>120/80 mmHg should be advised on
lifestyle changes to reduce BP (B)lifestyle changes to reduce BP (B)
 Patients with confirmed BP ≥140/80Patients with confirmed BP ≥140/80
mmHg should, in addition to lifestylemmHg should, in addition to lifestyle
therapy, have prompt initiation and timelytherapy, have prompt initiation and timely
subsequent titration of pharmacologicalsubsequent titration of pharmacological
therapy to achieve BP goals (B)therapy to achieve BP goals (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S29.

37. Recommendations: Hypertension/Blood PressureRecommendations: Hypertension/Blood Pressure
ControlControl
 Lifestyle therapy for elevated BP (B)Lifestyle therapy for elevated BP (B)
 Weight loss if overweightWeight loss if overweight
 DASH-style dietary pattern includingDASH-style dietary pattern including
reducing sodium, increasing potassiumreducing sodium, increasing potassium
intakeintake
 Moderation of alcohol intakeModeration of alcohol intake
 Increased physical activityIncreased physical activity
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S29.

38. Recommendations: Hypertension/BloodRecommendations: Hypertension/Blood
Pressure ControlPressure Control
 Pharmacological therapy for patients with diabetes andPharmacological therapy for patients with diabetes and
hypertension (C)hypertension (C)
 A regimen that includes either an ACE inhibitor orA regimen that includes either an ACE inhibitor or
angiotensin II receptor blocker; if one class is not tolerated,angiotensin II receptor blocker; if one class is not tolerated,
substitute the othersubstitute the other
 Multiple drug therapy (two or more agents at maximalMultiple drug therapy (two or more agents at maximal
doses) generally required to achieve BP targets (B)doses) generally required to achieve BP targets (B)
 Administer one or more antihypertensive medicationsAdminister one or more antihypertensive medications
at bedtime (A)at bedtime (A)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S29.

39. Recommendations: Hypertension/Blood PressureRecommendations: Hypertension/Blood Pressure
ControlControl
 If ACE inhibitors, ARBs, or diuretics are used,If ACE inhibitors, ARBs, or diuretics are used,
kidney function, serum potassium levels should bekidney function, serum potassium levels should be
monitored (E)monitored (E)
 In pregnant patients with diabetes and chronicIn pregnant patients with diabetes and chronic
hypertension, blood pressure target goals of 110–hypertension, blood pressure target goals of 110–
129/65–79 mmHg are suggested in interest of129/65–79 mmHg are suggested in interest of
long-term maternal health and minimizing impairedlong-term maternal health and minimizing impaired
fetal growth; ACE inhibitors, ARBs, contraindicatedfetal growth; ACE inhibitors, ARBs, contraindicated
during pregnancy (E)during pregnancy (E)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S29.

40. © 2008, American Heart
Association. All rights
reserved.
• Blood pressure remaining above goal in spite
of concurrent use of 3 antihypertensive agents
of different classes.
• Ideally, 1 of the 3 agents should be a
diuretic & all agents should be prescribed at
optimal dose amounts.
Resistant Hypertension

41. Conclusion
 HTN is a silent killer responsible for significant
proportion of mortality and morbidity.
 Effective lowering of BP and choice of
Antihypertensive Rx is equally important.

42. ‫ينفعنا‬ ‫ما‬ ‫يعلمنا‬ ‫أن‬ ‫ا‬ ‫نسأل‬،
‫علمنا‬ ‫بما‬ ‫ينفعنا‬ ‫،وأن‬
‫علما‬ ‫وأ‬
‫النهاية‬ ‫وفي‬‫النهاية‬ ‫وفي‬