Htn the silent killer25 4-2013

HTN The Silent Killer

New Data about ACEI at least 12 % of world total

mortalityADA 2013 guidelinesBHS 2011 guidelinesDr Ihab SulimanDr Ihab Suliman

Consultant CardiologistConsultant Cardiologist

25-4-201325-4-2013

Leading risks for premature death

3

5

4

2

1

CholesterolCholesterol

AlcoholAlcohol

Tobacco UseTobacco Use

HYPERTENSIONHYPERTENSION

OverweightOverweight

(World Health Organization 2002)

HTN: KEY CONTRIBUTOR TO DIABETES HTN: 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; 57:891Lancet 2012; 380:601

HTN PREVALENCE: GENERAL HTN PREVALENCE: GENERAL vsvs DM DM POPULATIONSPOPULATIONS

north american data UTAHnorth american data UTAHBP 140/90

General population

30%

• Age 60y 67%

• White 29%

• Black 41%

• Hispanic 26%

Persons with DM

67% 76%

BP 130/80

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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

BackgroundBackground• Each Each 22 mmHg rise in systolic blood mmHg rise in systolic blood

pressure associated with increased pressure associated with increased risk of mortality:risk of mortality:– 7%7% from heart disease from heart disease

– 10%10% from stroke. from stroke.

HTN: DOMINANT CONTRIBUTOR TO HTN: DOMINANT CONTRIBUTOR TO GLOBAL MORTALITYGLOBAL MORTALITY

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, cognition cognition

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:e12 2012; 125:e12 JJ HumHum HypertensionHypertension 2008; 22:63 2008; 22:63 HypertensionHypertension 2007; 2007; 50:100650:1006

Properly MeasuredProperly Measured

Cuff SizeCuff Size

Bilateral Bilateral

Confirm with Manual Confirm with Manual

No recent caffeine or SmokingNo recent caffeine or Smoking

How many BP How many BP readings?readings?

1.1. 3 – in sinus 3 – in sinus rhythmrhythm

2.2. more if more if there are there are multiple multiple ectopics or ectopics or AFAF

DefinitionsDefinitionsStage 1 hypertensionStage 1 hypertension::CBP CBP >>140/90 140/90 and and ABPM or HBPM ABPM or HBPM

>>135/85 mmHg 135/85 mmHg

Stage 2 hypertension:Stage 2 hypertension: CBP CBP >>160/100 160/100 and and ABPM or HBPM ABPM or HBPM

daytime daytime >>150/95 mmHg150/95 mmHg

Severe hypertension:Severe hypertension: C SBP C SBP >>180 180 or or C DBP C DBP >>110 mmHg110 mmHg

Offer drug treatment to:Offer drug treatment to: stage 1 hypertension, aged <80 and meet stage 1 hypertension, aged <80 and meet

identified criteriaidentified criteria stage 2 hypertension at any age stage 2 hypertension at any age

If <40 with stage 1 hypertension and If <40 with stage 1 hypertension and without evidence of TOD, CVD, CKD or without evidence of TOD, CVD, CKD or diabetes, consider:diabetes, consider:

specialist evaluation of secondary causes specialist evaluation of secondary causes of hypertensionof hypertension

Initiating drug Initiating drug treatmenttreatment

Choosing drugs for patients newly diagnosed Choosing drugs for patients newly diagnosed with hypertensionwith hypertension

BHS Guidelines (2011)BHS Guidelines (2011)

Younger than 55 years55 years or olderOr 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

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

Comparison of morbidity/mortality trialsin hypertension/high risk patients

Trial Treatment

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

ADVANCE

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

ONTARGET

Telmisartan vs ramipril NS NS Ramipril > telmisartanRRR = 7% in favour oframipril

ONTARGET

Telmisartan+Ramipril vs Ramipril > combination Ramipril > combination Ramipril > combinationramipril RRR = 7% in favour of RRR = 4% in favour of RRR = 8% in favour of

ramipril NS ramipril NS ramipril

TRANSCEND

Telmisartan vs placebo Placebo > telmisartan RRR = 21% in favourRRR = 3% in favour of of telmisartan NSplacebo NS

VALUE

Valsartan vs amlodipine Amlodipine > valsartan Amlodipine > valsartan Amlodipine > valsartanRRR = 4% in favour RRR = 1% in favour RRR = 19% in favouramlodipine amlodipine of amlodipineNS NS p = 0.02

LIFE

Losartan/HCTZ vs NS NS Atenolol > losartanAtenolol /HCTZ RRR = 7% in favour of

atenolol

ACCOMPLISH

Benazepril/amlodipine vs NS NS RRR = 22% p = 0.04benazepril/HCTZ

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

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

Dose-Dependent Antihypertensive Dose-Dependent Antihypertensive Efficacy and Tolerability of Coversyl Efficacy 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 Yang and Kwang Yang33 for the for the

CONFIDENCECONFIDENCE Investigators Investigators1.1. 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

Perindopril efficacy Results in Overall Population

Strong Efficacy is consistent across the entire groups

Perindopril results in Severe HTN Population

Powerful BP reduction needed to achieve Target Blood pressure

High tissue ACE AffinityHigh tissue ACE Affinity

Trough/Peak ratio: What does it Trough/Peak ratio: What does it mean?mean?

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

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

HYVET, an HYVET, an international trialinternational trial

The trial:International, multicenter, randomized, double-blind, placebo-controlled

Inclusion criteria: Exclusion criteria:Aged 80 or more, Standing SBP <140 mm HgSystolic BP 160-199 mm Hg Stroke in last 6 months+ diastolic BP <110 mm Hg, DementiaInformed consent Need for daily nursing care

Primary end point: All strokes (fatal and nonfatal)

Total mortality(21% reduction)

Placebo

P=0.02

Natrilix SR+COVERSYL

Nu

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of

even

ts p

er

10

0 p

ati

en

t s

Follow-up (years)

Beckett N, et al. NEJM 2008;358:1887-1898.

This result is at odds with findings from previous trials

Case Case

55 years old obese Diabetic with 55 years old obese Diabetic with Type 2 DM, SBP is consistently Type 2 DM, SBP is consistently above 150 mmHg, the best initial above 150 mmHg, the best initial treatment will be ???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

Perindopril 10 mg po daily is chosenPerindopril 10 mg po daily is chosen You FU the patient by You 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

E— A&CE— A&C The patient after starting Lisinopril The patient after starting Lisinopril

will be seen after with Basic Screenwill be seen after 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

A- one week then 3 monthyA- one week then 3 monthy

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

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 Aliskiren E- Start Aliskiren

70 years old female with no prior active 70 years old female with no prior active cardiac problems, Informed in a private cardiac problems, Informed in a private clinic about being Hypertensive, 3 separate clinic about being Hypertensive, 3 separate visits, SBP 160-170 ,what is the next step??visits, SBP 160-170 ,what is the next step??

A-life style modfication.A-life style modfication. B-single agent anti hypertensive B-single agent anti hypertensive C- combination of two anti hypertensive C- combination of two anti hypertensive

agents.agents. D- a diagnosis of HTN cannot be made at D- a diagnosis of HTN cannot be made at

this time.this time.

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

Recommendations: Recommendations: Hypertension/Blood Pressure ControlHypertension/Blood Pressure Control

Screening and diagnosisScreening and diagnosis Blood pressure should be measured at Blood pressure should be measured at

every routine visitevery routine visit Patients found to have elevated blood Patients found to have elevated blood

pressure should have blood pressure pressure 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.


Treatment (1)Treatment (1) Patients with a blood pressure (BP) >120/80 mmHg Patients with a blood pressure (BP) >120/80 mmHg

should be advised on lifestyle changes to reduce BP should be advised on lifestyle changes to reduce BP (B)(B)

Patients with confirmed BP ≥140/80 mmHg should, in Patients with confirmed BP ≥140/80 mmHg should, in addition to lifestyle therapy, have prompt initiation addition to lifestyle therapy, have prompt initiation and timely subsequent titration of pharmacological and timely subsequent 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.


Lifestyle therapy for Lifestyle therapy for elevated BP (B)elevated BP (B)Weight loss if overweightWeight loss if overweightDASH-style dietary pattern DASH-style dietary pattern

including reducing sodium, including reducing sodium, increasing potassium intakeincreasing potassium intake

Moderation of alcohol intakeModeration of alcohol intake Increased physical activityIncreased physical activity


Recommendations: Recommendations: Hypertension/Blood Pressure Hypertension/Blood Pressure

ControlControl Pharmacological therapy for patients with Pharmacological therapy for patients with

diabetes and hypertension (C)diabetes and hypertension (C) A regimen that includes either an ACE A regimen that includes either an ACE

inhibitor or angiotensin II receptor blocker; if inhibitor or angiotensin II receptor blocker; if one class is not tolerated, substitute the otherone class is not tolerated, substitute the other

Multiple drug therapy (two or more Multiple drug therapy (two or more agents at maximal doses) generally agents at maximal doses) generally required to achieve BP targets (B)required to achieve BP targets (B)

Administer one or more antihypertensive Administer one or more antihypertensive medications at bedtime (A)medications at bedtime (A)



If ACE inhibitors, ARBs, or diuretics are If ACE inhibitors, ARBs, or diuretics are used, kidney function, serum potassium used, kidney function, serum potassium levels should be monitored (E)levels should be monitored (E)

In pregnant patients with diabetes and In pregnant patients with diabetes and chronic hypertension, blood pressure chronic hypertension, blood pressure target goals of 110–129/65–79 mmHg are target goals of 110–129/65–79 mmHg are suggested in interest of long-term suggested in interest of long-term maternal health and minimizing impaired maternal health and minimizing impaired fetal growth; ACE inhibitors, ARBs, fetal growth; ACE inhibitors, ARBs, contraindicated during pregnancy (E)contraindicated during pregnancy (E)


© 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

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.

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Htn the silent killer25 4-2013