1. Love Birds
To
Hatered
By
Dr. Abdul Rab Shaikh
SCILIFE AMSTAN

2. Global burden of hypertension in the
adult population
Year Overall, % Men, % Women, %
(95% CI) (95% CI) (95% CI)
2000 26.4 26.6 26.1
(26.0-26.8) (26.0-27.2) (25.5-26.6)
2025 29.2 29.0 29.5
(28.8-29.7) (28.6-29.4) (29.1-29.9)
Kearney PM et al. Lancet 2005; 365:217-223.

3. Prevalence in Pakistan
50 percent of the population over the age of 50 is hypertensive.
There are an estimated 12 million hypertensives in the country.
The National Health Survey of Pakistan, jointly conducted by the Pakistan
Medical Research Council (PMRC) in collaboration with the Federal
Bureau of statistics, Pakistan and the Department of Health ad Human
Services, Washington, USA revealed that only 3% of the hypertensive
population in Pakistan is adequately controlled.
Heartfile Newsletter," Vol.3, Issue1, March
2001

4. The ‘Rule of Halves’–the Need for Effective
Diagnosis and Treatment of Hypertension

5. Poor Compliance and Persistence with
Antihypertensive Treatment
Continuous Antihypertensive use
beyond first year (%)
Years after first prescription
Van Wijk et al. J Hypertens 2005;23:2101–7

8. Multiple Antihypertensive Drugs Required to
Achieve Target BP
Dahlöf B et al. Lancet. 2005;366:895–906.

9. Guidelines
JNC-7
 The relationship between BP and risk of CVD events is continuous, consistent
and independent of other risk factors. The higher the BP, the greater is the
chance of heart attack, heart failure, stroke, and kidney disease.
 Most patients with hypertension will require two or more antihypertensive
agents to achieve their BP goals. When BP is more than 20 mm Hg above systolic
goal or 10 mm Hg above diastolic goal, consideration should be given to initiate
therapy with 2 drugs, either as separate prescriptions or in fixed-dose
combinations.
NIH P u b l i c a t i o n N o . 0 3 - 5 2 3 3 December 2003

10. Guidelines
ESH-ESC
 More than one agent is necessary to achieve target BP in the majority
of patients
Treatment can be initiated with monotherapy or a combination of two
drugs at low doses Drug dose or number of drugs may be increased if
necessary
 A combination of two drugs at low doses preferred 1st step
 When Initial BP in grade 2–3 range
 Total CV risk high/very high
 Fixed combinations of two drugs simplify treatment/favor compliance
Task Force of ESH/ESC. J Hypertens 2007;25:1105–87

11. ESH–ESC: Algorithm for Treatment of
Hypertension
Task Force for ESH–ESC. J Hypertens 2007;25:1105–87

12. BP Regulation: The Two Key Vasoconstrictor
Systems
Mutually reinforcing actions combine to regulate BP
Grassi. J Hypertens 2001;19:1713–16

13. CCB-ARB : 2 Key BP Effector Pathways
On Sympathetic Nervous System

14. CCB-ARB : 2 Key BP Effector Pathways
On Renin-Angiotensin-Aldosterone System

15. Neutralizing Counter-regulatory Mechanisms
to Minimize Elevations in Blood Pressure

16. CCB-ARB: Synergy of Counter-regulation

17. Recommendations for Multiple-mechanism
Therapy: What the Treatment Guidelines Say:
ESH–ESC
 More than one agent is necessary to achieve target BP in the majority
of patients
 Treatment can be initiated with monotherapy or a combination of two
drugs at low doses
 Drug dose or number of drugs may be increased if necessary
 A combination of two drugs at low doses preferred 1st step when
 Initial BP in grade 2–3 range
 Total CV risk high/very high
 Fixed combinations of two drugs simplify treatment/favor compliance
Task Force of ESH/ESC. J Hypertens 2007;25:1105–87

18. Interaction of CCBs and ARBs on Vascular and
Renal Function,
SNS and RAS Activity

19. Amlodipine/Valsartan
BP lowering efficacy & get to goal rates

21. Amlodipine/Valsartan
Efficacy on Non- responders to Monotherapy

22. Efficacy of the combination of amlodipine and valsartan in
patients with hypertension uncontrolled with previous
monotherapy: the Exforge in Failure after Single Therapy
(EX-FAST) study.
 Randomized, double-blind, multicenter study, patients whose blood pressure
(BP) was uncontrolled by monotherapy were switched directly to
amlodipine/valsartan 5/160 mg (n=443) or 10/160 mg (n=451).
 After 16 weeks, BP control (levels <140/90 mm Hg or <130/80 mm Hg for
diabetics) was achieved in 72.7% of patients receiving amlodipine/valsartan 5/160
mg and in 74.8% receiving amlodipine/valsartan 10/160 mg.
 Incremental reductions from baseline in mean sitting systolic and diastolic BP
were significantly greater with the higher dose (20.0+/-0.7 vs 17.5+/-0.7 mm Hg.
Incremental BP reductions were also achieved with both regimens irrespective of
previous monotherapy, hypertension severity, diabetic status, body mass index,
and age.

23. The (EX-FAST) Study

24. Conclusion:
 These results provide additional support for the rationale of
combining antihypertensive drugs with complementary mechanisms
of action for the treatment of patients with hypertension.
 These data add to the literature indicating that combination therapy
lowers BP to a greater degree than monotherapy.
 Amlodipine/valsartan was found to be an effective and well-
tolerated strategy for BP control in a wide range of patients with
hypertension not previously controlled by use of a single
antihypertensive agent.
.

25. Amlodipine/Valsartan
Efficacy across Different Grades of
Hypertension

26. Conclusion:
 These data gives us more rationale of combination antihypertensive
therapies.
 Four categories of patients taken in this study from Mild, Moderate,
Severe to SBP more than or equal to 180mmHg.
 Amlodipine/ Valsartan was found to produce significant reduction of
BP mean as well as Diastolic BP.
Diastolic BP
Category Mean BP Reduction (mmHg)
Reduction (mmHg)
Mild -20 -17
Moderate -30 -18
Severe -36 -29
SBP 180mmHg -43 -26

27. Amlodipine/Valsartan
Safety & Tolerability

28. Conclusion:
 Great reduction in ankle edema seen in subjects taking amlo/val.
Combination compared with amlodipine monotherapy.
 Ankle edema reduction of more than 16 % seen in combination
versus montherapy.

29. Advantages of Multiple-mechanism Therapy
Multiple-mechanism therapy results in a greater BP reduction
than seen with its single-mechanism components 1,2
 Components with a different mechanism of action interact on
complementary pathways of BP control 1
 Each component can potentially neutralize counter-regulatory
mechanisms, e.g.
 Diuretics reduce plasma volume, which in turn stimulates the renin
angiotensin system (RAS) and thus increases BP; addition of a RAS
blocker attenuates this effect 1,2
 Multiple-mechanism therapy may result in BP reductions that are
additive 2
1Sica. Drugs 2002;62:443−62
2Quan et al. Am J Cardiovasc Drugs 2006;6:103−13

30. Thank You

31. HYPERTENSION
VALSARTAN
AMLODIPINE
HYPER
TENSION