Love Birds To Hatered By Dr. Abdul Rab ShaikhSCILIFE AMSTAN
Global burden of hypertension in the adult populationYear 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.
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, March2001
The ‘Rule of Halves’–the Need for EffectiveDiagnosis and Treatment of Hypertension
Poor Compliance and Persistence with Antihypertensive Treatment Continuous Antihypertensive use beyond first year (%) Years after first prescriptionVan Wijk et al. J Hypertens 2005;23:2101–7
Multiple Antihypertensive Drugs Required to Achieve Target BPDahlöf B et al. Lancet. 2005;366:895–906.
GuidelinesJNC-7 The relationship between BP and risk of CVD events is continuous, consistentand independent of other risk factors. The higher the BP, the greater is thechance of heart attack, heart failure, stroke, and kidney disease. Most patients with hypertension will require two or more antihypertensiveagents to achieve their BP goals. When BP is more than 20 mm Hg above systolicgoal or 10 mm Hg above diastolic goal, consideration should be given to initiatetherapy with 2 drugs, either as separate prescriptions or in fixed-dosecombinations.NIH P u b l i c a t i o n N o . 0 3 - 5 2 3 3 December 2003
GuidelinesESH-ESC More than one agent is necessary to achieve target BP in the majorityof patientsTreatment can be initiated with monotherapy or a combination of twodrugs at low doses Drug dose or number of drugs may be increased ifnecessary 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 complianceTask Force of ESH/ESC. J Hypertens 2007;25:1105–87
ESH–ESC: Algorithm for Treatment of HypertensionTask Force for ESH–ESC. J Hypertens 2007;25:1105–87
BP Regulation: The Two Key Vasoconstrictor Systems Mutually reinforcing actions combine to regulate BPGrassi. 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
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 complianceTask 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/ValsartanBP lowering efficacy & get to goal rates
Amlodipine/ValsartanEfficacy on Non- responders to Monotherapy
Efficacy of the combination of amlodipine and valsartan inpatients with hypertension uncontrolled with previousmonotherapy: 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 toamlodipine/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 fordiabetics) was achieved in 72.7% of patients receiving amlodipine/valsartan 5/160mg and in 74.8% receiving amlodipine/valsartan 10/160 mg. Incremental reductions from baseline in mean sitting systolic and diastolic BPwere 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 ofprevious monotherapy, hypertension severity, diabetic status, body mass index,and age.
Conclusion: These results provide additional support for the rationale ofcombining antihypertensive drugs with complementary mechanismsof action for the treatment of patients with hypertension. These data add to the literature indicating that combination therapylowers 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 withhypertension not previously controlled by use of a singleantihypertensive agent..
Amlodipine/ValsartanEfficacy across Different Grades of Hypertension
Conclusion: These data gives us more rationale of combination antihypertensivetherapies. 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 ofBP 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
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 combinationversus montherapy.
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 oncomplementary pathways of BP control 1 Each component can potentially neutralize counter-regulatorymechanisms, e.g. Diuretics reduce plasma volume, which in turn stimulates the reninangiotensin system (RAS) and thus increases BP; addition of a RASblocker attenuates this effect 1,2 Multiple-mechanism therapy may result in BP reductions that areadditive 2 1Sica. Drugs 2002;62:443−62 2Quan et al. Am J Cardiovasc Drugs 2006;6:103−13