Professional Documents
Culture Documents
Dr. Tarek El Zawawy gy, Alex. University y Professor of Cardiology, CardioAlex Conference 2010
Case Study
Mr. SB is a 40 y year old male, smoker, active, with no
significant past medical history & on no medication, with confirmed elevation in BP on repeated visits.
Symptoms:
Headache Visual Vi l di disturbances. t b
Family History:
Father With 20 years of Hypertension & IHD Hypertensive Brother at the age of 51.
Past P t History: Hi t
Treatment for mental depression for 3 years
ECG: voltage g criteria for LVH Chest X-Ray: Normal heart size, 0 Lung Pathology Urine alysis: Normal
Laboratory Findings:
Na 140, K 3.9, 39 Cl 102, FBS 115, OGTT 160 BUN 15, Creatinine 1.1, Cholesterol 270 (LDL 210, HDL 45),] Triglycerides 250, Hct 42
Q2: How do you classify this patient according to ESC-ESH risk stratification?
Low added risk
Specific Drug Indications Any effective antihypertensive drug or combination bi ti ACEI or ARB or CCB or thiazide or combination
<130/80
Yes
-blocker and ACEI or ARB -blocker and ACEI or ARB -blocker and ACEI or ARB ACEI or ARB and -blocker and aldo antagonist and thiazide or loop diuretic and hydral/nitrate (blacks)
* diabetes, CKD, CAD or equivalent weight loss if appropriate, healthy diet, exercise, smoking cessation and alcohol moderation evidence supports ACEI or ARB, CCB, or thiazide as first-line if anterior MI is present, if HTN persists, if LVD or HF is present, if diabetic adapted from Rosendorff C, et al. Circulation 2007;115:published online
14
Lifestyle y Modifications
Weight reduction Restriction of sodium intake Reduction in dietary fat and cholesterol Avoidance of tobacco Restriction of alcohol consumption Use of biofeedback, relaxation techniques Regular physical exercise
Lifestyle Modification
M difi ti Modification Weight reduction Adopt DASH eating plan Dietary sodium reduction Physical activity Moderation of alcohol consumption A Approximate i t SBP reduction d ti (range) 520 mmHg/10 kg weight loss 814 mmHg 28 mmHg 49 mmHg 24 mmHg
Q4: With regards to pharmacological treatment the ideal anti hypertensive is... treatment, is
With Effective BP control regardless of other attributes
Stage 1 Thiazide-type diuretics for most May consider ACE most. inhibitor, ARB, -blocker, CCB, or combination
If not at goal, optimise dosages or add additional drugs until goal BP is achieved. C Consider id consultation lt ti with ith h hypertension t i specialist i li t
*BP goal <140/90 mmHg or <130/80 mmHg for those with diabetes or chronic kidney disease Chobanian et al. JAMA 2003;289:256072
18
PAI-1/ thrombosis
Ang II
Myocyte growth
Collagen
Burnier M, Brunner HR. Lancet. 2000;355:637-45. B Brown NJ, NJ Vaughn V h DE. DE Adv Ad I Intern t M Med d. 2000;45:419-29. 2000 45 419 29
Stroke H Hypertension t i
Fibrosis Fib i Remodeling Apoptosis GFR Proteinuria Aldosterone release Glomerular sclerosis
Heart Failure MI
Death
Renal Failure
*Preclinical Preclinical data. LV=left ventricular; MI=myocardial infarction; GFR=glomerular filtration rate.
Q5: RAAS Blockade is the future of Hypertension Management Do we use ACEi or ARBs? Management.
ACEi
ARBs
The sites of action of ACE inhibition and AT1 receptor blockade in the renin-angiotensin system
Angiotensinogen
Renin
Chymase y trypsin peptidase
ACEIs
Angiotensin I
ACEACE -Kininase II
Bradykinin
Angiotensin II
NO
ARBs
Step of RAAS Blockade Bradykinin Metabolism Non ACE Pathway Activation
Receptor Level
Preserve ATII beneficial effect
ACEi
Interval I t l
Deprive the body from ATII beneficial effect
Dont Interfere
No Dry Cough
Prevent
Dry Cough
Non Activated
Activated
BP uncontrolled over time
24
ARBs
Combination Others therapy Persistence defined as prescription refill within 21 days of the target month
Diuretics
BBs
ACEIs
CCBs
Odds ratio of incident diabetes *17 trials enrolled patients with hypertension, three enrolled high-risk patients and one enrolled patients with heart failure (HF) ARB=angiotensin receptor blocker; ACE=angiotensin ACE=angiotensin-converting converting enzyme; CCB=calcium channel blocker
Q6: Are Drugs in the Same class Possessing the similar clinical benefits?
YES
NO
Pharmacological g differences
Selectivity on AT1 Receptor
30,000 ,
20000 10000
8500 1000 Valsartan Losartan irbisartan Candisartan Telmisartan 10,000 30 000 30,000
3,000
Valsartan is 30,000 , times more selective for AT1 receptors p than AT2
28
Clinical impact
Superior blood pressure control Proven efficacy in Endothelial dysfunction Evidence of Superior cardiovascular protection Evidence of Superior Renal protection
29
SBP
Mean change in B BP from bas seline to 8 week ks (mm Hg)
DBP
population SBP 160 and 200 mm Hg); *p<0.05 vs. baseline; p<0.05 vs. VALSARTAN 160 mg monotherapy; p<0.05 vs. DIOVAN 160 mg; Response= SBP <140 mmHg or decrease in SBP 20 mmHg after 8 weeks of treatment Lacourciere et al. Clin Ther 2005;27(7):1013 2005;27(7):1013-21 21
UPDATED #ITT
Evening administration
SBP DBP
#with
<10% decline in nocturnal relative to diurnal BP and SBP/DBP 140/90 and 179/109; *p<0.001 *p<0 001 vs vs. baseline Hermida et al. J Hypertens 2005;23(10):1913-1922
-15 -25 -35 35 2 4 6 Mean BP and 95% CI 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 Time after dose administration ( (hours)* )
DBP between 95 and 115 mm Hg at baseline, *intervals 2-24, n=21 (15 treated with valsartan 80 mg, 6 with 160 mg) intervals 26-48, n=10 (9 treated with valsartan 80 mg, 1 with 160 mg), hour 25-48 without dose Lasko et al. Blood Press Monit 2001;6(2):91-99
#sitting
VALSARTAN Reduces The Risk of Diabetes in Patients with High CV Risk on Monotherapy
Results from a 4.1-year study in 7,080 patients with HTN and high risk of cardiac events (VALUE study post-hoc analysis) study,
10 8 6 4 2 0 7.8% 9.9%
23% risk reduction d ti of NOD*
UPDATED Follow-up period: 4-6 (mean 4.2) years; Patients with BP<140/90 still receiving monotherapy at the end of the 6 months up-titration; *Valsartan vs. amlodipine, p=0.012, NOD=newonset diabetes Julius et al. Hypertension 2006;48:385-391
#Using a US healthcare claims database; *Unadjusted risk, valsartan vs. losartan (95% CI: 0.63-0.95); newonset diabetes identified as 2 outpatient diagnoses (7 days apart), 1 inpatient diagnosis, or 1 prescriptions for antidiabetic medication Weycker et al. J Clin Hypertens 2007; Suppl A (9):P-448
Ventricular Dilation
Heart Failure
JIKEI HEART 5
1. Julius et al. Lancet 2004; 363:202231; 2. Pfeffer et al. N Engl J Med 2003;349:1893906; 3. Cohn et al. N Engl J Med 2001; 345:166775 4. Califf et al. Am Heart J 2008;156:62332; 5. Mochizuki et al. Lancet 2007;369:14319; 6. Viberti et al. Circulation 2002;106:6728 7. Karalliedde et al. Hypertension 2008;51:161723; 8. SMART Group. Diabetes Care 2007;30:15813; 9. Hollenberg et al. J Hypertens 2007;25:19216
Summary
Central to the success of any antihypertensive regimen
Efficacy 24-hour BP control Compliance & persistence