The document discusses hypertension and the benefits of combination therapy using amlodipine and valsartan. It summarizes that: 1) Amlodipine/valsartan provides powerful blood pressure reductions of up to 43 mmHg in systolic blood pressure across different hypertension severities and patient types, including the elderly, those with isolated systolic hypertension, obesity, and diabetes. 2) In patients uncontrolled on monotherapy, amlodipine/valsartan reduces blood pressure by around 21 mmHg on average. 3) Fewer patients experience peripheral edema with amlodipine/valsartan compared to amlodipine monotherapy.

1. HypertensionRole of New Combination TherapyAziz-ur-RehmanServices Institute of Medical SciencesLahore

2. Hypertension is very prevalent

3. Hypertension is one of the easiest condition to diagnosis

4. End-stageRenal DiseaseHeart failureCoronaryHeart DiseasePersistentlyElevated BPStrokeLeft VentricularHypertrophyAtherosclerosisUncontrolled hypertension may be asymptomatic but has lot of CV morbidity & mortality

5. CV Mortality Risk Doubles with Each 20/10 mmHg Increment in BP*Cardiovascular mortality risk88X risk644X risk22X risk1X risk0115/75135/85155/95175/105Systolic BP/Diastolic BP (mmHg)Lewington et al. Lancet 2002;360:1903–13*Individuals aged 40–69 years

7. Treatment of Hypertension reduces CV morbidity & mortality

8. Benefits of Blood Pressure ReductionMeta-analysis of 61 prospective, observational studies1 million adults12.7 years7% reduction in risk of ischemic heart disease mortality2 mmHg decrease in mean SBP10% reduction in risk of stroke mortalityLewington et al. Lancet 2002;360:1903–13

9. Treatment of hypertension is very cost-effective

10. Majority of the patients are either not diagnosed or not treated adequately

11. Law of 50%Pakistan< 3%

12. Hypertension is a multifactorialdisease

15. Limitations of Agents with a Single Mechanism of Action (MoA)Inadequate in 4060% of hypertensive patients1In majority two or more antihypertensive agents are required to achieve the recommended target BP of <130/80 mmHg2Multiple channels are needed to be blocked31Materson et al. N Engl J Med 1993;328:914212Bakris et al. Am J Kidney Dis 2000;36:646613Milani. Am J Manag Care 2005;11:S2207

16. Advantages of Multiple-mechanism Therapy: Safety/TolerabilityComponents of multiple-mechanism therapy can add the desirable effects but not the undesirable ones1,2Neutralize adverse events.1,2Hyperkalaemia of ACEIs & ARBs neutralised by diureticsRAAS blockers may attenuate the oedema that is caused by CCBsMultiple-mechanism therapy may have an improved tolerability profile compared with its single-mechanism components1,21Sica. Drugs 2002;62:443622Quan et al. Am J Cardiovasc Drugs 2006;6:10313

17. Current Guidelines Recommend Combination Therapy JNC 7 guidelines state1:“When BP is more than 20/10 mmHg above goal, consideration should be given to initiate therapy with 2 drugs...”ESH/ESC guidelines state2:“A combination of two drugs at low doses should be preferred as first step treatment when initial BP is in the grade 2 or when CV risk is high.”ESH = European Society of HypertensionESC = European Society of CardiologyJNC = Joint National Committee1Chobanian et al. Hypertension 2003;42:1206–52 2Mancia et al. J Hypertens 2007:25:110587

19. Amlodipine has a Wealth of CV Outcomes Data1Pitt et al. Circulation 2000;102:1503–10; 2Nissen et al. JAMA 2004;292:2217–26; 3Dahlof et al. Lancet 2005;366:895–906 4Williams et al. Circulation 2006;113:1213–25; 5Leenen et al. Hypertension 2006;48:374–84

20. Valsartan has a Wealth of CV Outcomes Data1Julius et al. Lancet 2004;363:2022–31; 2Pfeffer et al. N Engl J Med 2003;349:1893–9063Maggioni et al. Am Heart J 2005;149:548–57; 4Wong et al. J Am Coll Cardiol 2002;40:970–55Cohn et al. N Engl J Med 2001;345:1667–7; 6Mochizuki et al. Lancet 2007;369:1431–9

21. Valsartan also has a Wealth of CV Protection Data1Viberti et al. Circulation 2002;106:672–82Ridker et al. Hypertension 2006;48:73–9

22. CCBs and ARBs compliment each other’s functionsnegative sodium balance reinforces the effects of the ARBNatriuresisVasodilation Arterial +VenousArterialCCB (Aml)↑ SNS  ↑RAS

23. Arteriodilation

24. Effective in low-renin patients

25. No renal or congestive heart failure benefits

26. Peripheral edema

27. Reduces cardiac ischemiaARB (Val)↓ RAS  ↓SNS

28. Arterio- and venodilation

29. Effective in high-renin patients

30. Congestive heart failure and renal benefits

31. Attenuates peripheral edema

32. No effect on cardiac ischemiaSNS = sympathetic nervous system; RAS = renin-angiotensin system

33. Amlodipine/Valsartan Provides Powerful BP ReductionsModerate HTN1‡Mild HTN1¶Baseline SBP≥180 mmHg20–10–20–30–40–50n=69n=15n=140Mean change in MSSBPfrom baseline (mmHg)–20–3010/160 (aml+val)–43¶DBP 9099 mmHg, SBP 140159 mmHg‡DBP ≥100 mmHg, SBP ≥160 mmHgBP = blood pressure; DBP = diastolic BP; SBP = systolic BP; MSSBP = mean sitting SBP1Smith et al. J Clin Hypertens 2007;9:355–64 (Dose 10/160 mg)2Poldermans et al. Clin Ther 2007;29:279–89 (Dose 5–10/160 mg)