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Dr. Abdul Rab Shaikh

AMSTANSCILIFE

Kearney PM et al. Lancet 2005; 365:217-223.

Global burden of hypertension in the adult population

Year Overall, % (95% CI)

Men, % (95% CI)

Women, % (95% CI)

2000 26.4(26.0-26.8)

26.6(26.0-27.2)

26.1(25.5-26.6)

2025 29.2(28.8-29.7)

29.0(28.6-29.4)

29.5(29.1-29.9)

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

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

Poor Compliance and Persistence with Antihypertensive Treatment

Years after first prescription

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Van Wijk et al. J Hypertens 2005;23:2101–7

Multiple Antihypertensive Drugs Required to Achieve Target BP

Dahlöf B et al. Lancet. 2005;366:895–906.

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.

JNC-7

Guidelines

NIH P u b l i c a t i o n N o . 0 3 - 5 2 3 3 December 2003

ESH-ESC

Guidelines

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

ESH–ESC: Algorithm for Treatment of Hypertension

Task Force for ESH–ESC. J Hypertens 2007;25:1105–87

BP Regulation: The Two Key Vasoconstrictor Systems

Mutually reinforcing actions combine to regulate BP

Grassi. J Hypertens 2001;19:1713–16

CCB-ARB : 2 Key BP Effector PathwaysOn Sympathetic Nervous System

CCB-ARB : 2 Key BP Effector PathwaysOn Renin-Angiotensin-Aldosterone System

Neutralizing Counter-regulatory Mechanismsto Minimize Elevations in Blood Pressure

CCB-ARB: Synergy of Counter-regulation

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

Interaction of CCBs and ARBs on Vascular and Renal Function,

SNS and RAS Activity

Amlodipine/Valsartan

BP lowering efficacy & get to goal rates

Amlodipine/Valsartan

Efficacy on Non- responders to Monotherapy

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.

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.

The (EX-FAST) Study

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..

Conclusion:

Amlodipine/Valsartan

Efficacy across Different Grades of Hypertension

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.

Conclusion:

Category Mean BP Reduction (mmHg)Diastolic BP

Reduction (mmHg)

Mild -20 -17

Moderate -30 -18

Severe -36 -29

SBP 180mmHg -43 -26

Amlodipine/Valsartan

Safety & Tolerability

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.

Conclusion:

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

Multiple-mechanism therapy results in a greater BP reduction than seen with its single-mechanism components 1,2

Advantages of Multiple-mechanism Therapy

1Sica. Drugs 2002;62:443−622Quan et al. Am J Cardiovasc Drugs 2006;6:103−13

Thank You

HYPERTENSION

AMLODIPINEVALSARTAN

HYPER TENSION