Prof .Aziz-ur-Rehman


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Prof .Aziz-ur-Rehman

  1. 1. HypertensionRole of New Combination Therapy<br />Aziz-ur-Rehman<br />Services Institute of Medical Sciences<br />Lahore<br />
  2. 2. Hypertension is very prevalent<br />
  3. 3. Hypertension is one of the easiest condition to diagnosis<br />
  4. 4. End-stageRenal Disease<br />Heart failure<br />CoronaryHeart Disease<br />PersistentlyElevated BP<br />Stroke<br />Left Ventricular<br />Hypertrophy<br />Atherosclerosis<br />Uncontrolled hypertension may be asymptomatic but has lot of CV morbidity & mortality<br />
  5. 5. CV Mortality Risk Doubles with Each 20/10 mmHg Increment in BP*<br />Cardiovascular mortality risk<br />8<br />8X risk<br />6<br />4<br />4X risk<br />2<br />2X risk<br />1X risk<br />0<br />115/75<br />135/85<br />155/95<br />175/105<br />Systolic BP/Diastolic BP (mmHg)<br />Lewington et al. Lancet 2002;360:1903–13<br />*Individuals aged 40–69 years<br />
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  7. 7. Treatment of Hypertension reduces CV morbidity & mortality<br />
  8. 8. Benefits of Blood Pressure Reduction<br />Meta-analysis of 61 prospective, observational studies<br />1 million adults<br />12.7 years<br />7% reduction in risk of ischemic heart disease mortality<br />2 mmHg decrease in mean SBP<br />10% reduction in risk of stroke mortality<br />Lewington et al. Lancet 2002;360:1903–13<br />
  9. 9. Treatment of hypertension is very cost-effective<br />
  10. 10. Majority of the patients are either not diagnosed or not treated adequately<br />
  11. 11. Law of 50%<br />Pakistan< 3%<br />
  12. 12. Hypertension is a multifactorialdisease<br />
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  15. 15. Limitations of Agents with a Single Mechanism of Action (MoA)<br />Inadequate in 4060% of hypertensive patients1<br />In majority two or more antihypertensive agents are required to achieve the recommended target BP of <130/80 mmHg2<br />Multiple channels are needed to be blocked3<br />1Materson et al. N Engl J Med 1993;328:91421<br />2Bakris et al. Am J Kidney Dis 2000;36:64661<br />3Milani. Am J Manag Care 2005;11:S2207<br />
  16. 16. Advantages of Multiple-mechanism Therapy: Safety/Tolerability<br />Components of multiple-mechanism therapy can add the desirable effects but not the undesirable ones1,2<br />Neutralize adverse events.1,2<br />Hyperkalaemia of ACEIs & ARBs neutralised by diuretics<br />RAAS blockers may attenuate the oedema that is caused by CCBs<br />Multiple-mechanism therapy may have an improved tolerability profile compared with its single-mechanism components1,2<br />1Sica. Drugs 2002;62:44362<br />2Quan et al. Am J Cardiovasc Drugs 2006;6:10313<br />
  17. 17. Current Guidelines Recommend Combination Therapy <br />JNC 7 guidelines state1:<br />“When BP is more than 20/10 mmHg above goal, consideration should be given to initiate therapy with 2 drugs...”<br />ESH/ESC guidelines state2:<br />“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.”<br />ESH = European Society of Hypertension<br />ESC = European Society of CardiologyJNC = Joint National Committee<br />1Chobanian et al. Hypertension 2003;42:1206–52 2Mancia et al. J Hypertens 2007:25:110587<br />
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  19. 19. Amlodipine has a Wealth of CV Outcomes Data<br />1Pitt 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<br />
  20. 20. Valsartan has a Wealth of CV Outcomes Data<br />1Julius 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<br />
  21. 21. Valsartan also has a Wealth of CV Protection Data<br />1Viberti et al. Circulation 2002;106:672–8<br />2Ridker et al. Hypertension 2006;48:73–9<br />
  22. 22. CCBs and ARBs compliment each other’s functions<br />negative sodium balance reinforces the effects of the ARB<br />Natriuresis<br />Vasodilation <br />Arterial +<br />Venous<br />Arterial<br />CCB (Aml)<br /><ul><li>↑ SNS  ↑RAS
  23. 23. Arteriodilation
  24. 24. Effective in low-renin patients
  25. 25. No renal or congestive heart failure benefits
  26. 26. Peripheral edema
  27. 27. Reduces cardiac ischemia</li></ul>ARB (Val)<br /><ul><li>↓ RAS  ↓SNS
  28. 28. Arterio- and venodilation
  29. 29. Effective in high-renin patients
  30. 30. Congestive heart failure and renal benefits
  31. 31. Attenuates peripheral edema
  32. 32. No effect on cardiac ischemia</li></ul>SNS = sympathetic nervous system; RAS = renin-angiotensin system<br />
  33. 33. Amlodipine/Valsartan Provides Powerful BP Reductions<br />Moderate HTN1‡<br />Mild HTN1¶<br />Baseline SBP≥180 mmHg2<br />0<br />–10<br />–20<br />–30<br />–40<br />–50<br />n=69<br />n=15<br />n=140<br />Mean change in MSSBPfrom baseline (mmHg)<br />–20<br />–30<br />10/160 (aml+val)<br />–43<br />¶DBP 9099 mmHg, SBP 140159 mmHg‡DBP ≥100 mmHg, SBP ≥160 mmHg<br />BP = blood pressure; DBP = diastolic BP; SBP = systolic BP; MSSBP = mean sitting SBP<br />1Smith et al. J Clin Hypertens 2007;9:355–64 (Dose 10/160 mg)<br />2Poldermans et al. Clin Ther 2007;29:279–89 (Dose 5–10/160 mg)<br />
  34. 34. Amlodipine/Valsartan vs. Amlodipine <br />EX-EFFeCTS1Patients with Stage 2 Hypertension<br />EX-STAND2Black Patients with Stage 2 Hypertension<br />Amlodipine/Valsartan10/160–320 mg<br />Amlodipine10 mg<br />Amlodipine/Valsartan10/160 mg<br />Amlodipine10 mg<br />0<br />0<br />N=55<br />N=42<br />N=46<br />N=38<br />−10<br />−10<br />−20<br />−20<br />−30<br />−30<br />−31.7<br />−40<br />−37.2<br />−40<br />–40.1<br />–43.5<br />p=0.0018<br />−50<br />p=0.1 <br />LSM Change in MSSBP from baseline (mmHg)<br />LSM Change in MSSBP from baseline (mmHg) <br />1.Destro et al. J Am Soc Hypertens 2008;2:294–3022.Flack et al. J Hum Hypertens 2009 (E-pub ahead of print).<br />LSM=least square meanMSSBP=mean sitting systolic blood pressure<br />
  35. 35. Amlodipine/Valsartan: Superior BP Across Diverse Patient Populations (EX-EFFECTS)<br />Elderly<br />(65 yrs)<br />Severe<br />(180 mmHg)<br />ISH†<br />Obese‡<br />Diabetes<br />–5<br />134<br />145<br />34<br />36<br />78<br />98<br />46<br />55<br />86<br />89<br />–10<br />–15<br />–20<br />Mean change in MSSBP at Week 4 (mmHg)<br />–22.0<br />–21.7<br />–22.7<br />–22.9<br />–25<br />–27.2<br />–30<br />–29.5<br />*<br />–30.2<br />–29.7<br />–31.7<br />*<br />*<br />*<br />–35<br />–40<br />–40.1<br />Amlodipine/valsartan 10/160 mg<br />*<br />–45<br />Amlodipine 10 mg<br />*p<0.05 amlodipine/valsartan vs. amlodipine monotherapy<br />MSSBP = mean sitting systolic BP†ISH = isolated systolic hypertension (140 and <90 mmHg)<br />‡Obese defined as body mass index 30 kg/m2<br />Destro et al. J Am Soc Hypertens 2008;2:294–302<br />
  36. 36. Amlodipine/Valsartan Reduces Albuminuria Versus Amlodipine in Black Patients with Stage 2 Hypertension (EX-STAND)<br />Amlodipine<br />5+5 mg<br />Amlodipine/Valsartan<br />5+160 mg<br />15<br />10<br />5<br />0<br />–5<br />–10<br />–15<br />–20<br />–25<br />–30<br />–35<br />10<br />n=160<br />n=157<br />Change from baseline in UACR (%)<br />–30<br />Post-hoc analysis (Week 12 data)UACR = urinary albumin-to-creatinine ratio<br />Flack et al. J Hum Hypertens 2009 (E-pub ahead of print)<br />
  37. 37. Complementary Effects of a CCB/ARB Reduction of CCB-associated Edema<br />I.<br />Arterial hypertension<br /><ul><li>Constricted blood vessels, high resistance</li></ul>CCBs<br /><ul><li>BP reduction due to arterial vasodilation
  38. 38. Tendency towards edema due to absent venodilation
  39. 39. BP reduction stimulates RAAS & causes venoconstriction</li></ul>Edema<br />II.<br />Edema<br />III.<br />CCBs + RAS inhibitors*<br /><ul><li>Blockade of RAAS inhibits effects of angiotensin II, giving rise to additional BP reduction
  40. 40. Additional venodilation by RAS inhibitors reduces edema</li></ul>Messerli. Am J Hypertens 2001;14:978–9<br />*Angiotensin receptor blockers or angiotensin-converting enzyme inhibitors<br />
  41. 41. Amlodipine/Valsartan: Fewer Patients Experience Peripheral Oedema*<br />40<br />30<br />20<br />10<br />0<br />p<0.001<br />31%<br />Proportion of patients experiencing peripheral edema (%)<br />7%<br />n=184/591<br />n=39/592<br />Amlodipine/Valsartan 5/160 mg<br />Amlodipine10 mg<br />Schrader et al. J Int Clin Pract 2009;63:217225<br />*Week 8 data <br />
  42. 42. SUMMARY- CCB/ARB COMBO<br />Amlodipine/Valsartan provides powerful BP reductions<br />across hypertension severities<br />Up to 43 mmHg systolic BP (SBP) drop<br />in diverse patient types<br />Elderly (≥65 years), ISH, obese and diabetics<br />in patients uncontrolled with monotherapy<br />~21 mmHg SBP drops<br />with fewer patients experience peripheral edema<br />
  43. 43. Single-pill combinations of Amlodipine and Valsartan approved as first-line treatments for HTN<br />Approvals consistent with current treatment guidelines<br />Up to 80% of patients may need multiple medications<br />Single-pill combinations offer effective, convenient medications<br />Single pill combination improves compliance<br />
  44. 44. Amlodipine + Valsartan Combo<br />
  45. 45. Make use of this powerful tool to control the menace of hypertension<br />
  46. 46. Combination is Better<br />Thank you<br />Aziz-ur-Rehman<br />