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Hypertension update,ARB

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  • 1. Hypertension: New Concept New Targets 2014 Ko Ko UMMG Mawlamyaing MMA3.1.14
  • 2. Global Mortality 2000: Hypertension is the major risk factor 7.6 million deaths Developing regions Developed regions 0 1 2 3 4 5 6 7 8 Attributable mortality in millions (total: 55 861 000) Adapted from Ezzati et al. Lancet 2002;360:1347-1360.
  • 3. Guidelines: a paradox? Goals of treatment “The primary goal of treatment of the hypertensive patient is to achieve the maximum reduction in the long-term total risk of cardiovascular morbidity and mortality.“ Therapeutic management of hypertension “Antihypertensive treatment translates into significant reductions of cardiovascular morbidity and mortality while having a less significant effect on all cause mortality.” European guidelines for the management of arterial hypertension. J Hypertens. 2007, 25:1105–1187
  • 4. Relationship between BP reduction and cardiovascular outcomes Relative risk of outcome event All-cause mortality Systolic blood pressure difference between randomized groups (mm Hg) BPLTT Collaboration. Lancet. 2003;362:1527-1535.
  • 5. RAAS inhibitors are the cornerstone of the antihypertensive treatment CCB 31% ACEi plain + comb RAAS inhibitors 47% BB 12% DIU 10% ARB plain + comb MS in prescriptions Source: IMS. Medical Universe - MAT in prescriptions, 35 countries, 2009 Canada, Republic, Kingdom, United States, Austria, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, Poland, Australia, Egypt, Indonesia, Japan (includes hospital data), New Zealand, Belgium, Portugal, Slovakia, Spain, Switzerland, Pakistan, Philippines, Saudi Arabia, Czech United South
  • 6. 2009 Reappraisal of 2007 European Guidelines: recommended combinations Diuretics -blockers Angiotensin receptor blockers Calcium channel blockers 1-blockers ACE inhibitors Preferred combinations Other possible combinations J Hypertens. 2007;25:1105–1187.J Hypertens. 2009;27:2121-2158.
  • 7. Reduction in mortality with amlodipine/perindopril in ASCOT Cardiovascular mortality 24%, p=0.001 11%, p=0.0247 % % 10.0 3.5 3.0 atenolol/thiazide atenolol/thiazide (No. of events 820) 8.0 (No. of events 342) 2.5 6.0 2.0 4.0 1.5 1.0 amlodipine/perindopril 0.5 0.0 All-cause mortality (No. of events 263) 0.0 1.0 3.0 2.0 Years 4.0 5.0 2.0 amlodipine/perindopril (No. of events 738) 0.0 0.0 1.0 2.0 3.0 4.0 5.0 Years Dahlof B, et al. Lancet. 2005;366:895-906.
  • 8. Components of antihypertensive efficacy… Prognostic value of blood pressure parameters … have independent predictive value 3.5 Adjusted 5-year risk of CV death (%) Nocturnal BP 3.0 24-hour BP 2.5 Daytime BP 2.0 1.5 Conventional office BP 1.0 N=5292 0.5 90 110 130 150 170 190 210 230 Systolic BP (mm Hg) Dolan E, et al. Hypertension. 2005;46:156-161.
  • 9. 24 hour antihypertensive efficacy: trough-to-peak ratio perindopril Acertil Fosinopril Lisinopril Ramipril Benazepril Enalapril Telmisartan Losartan Valsartan Olmesartan Irbesartan 0 10 20 30 40 50 60 70 80 90 100 T/P ratio (%) 1. Physicians Desk Reference. NJ: Medical Economics Company; 2008. 2. Diamant H and Vincent HH. Lisinopril versus enalapril: evaluation of trough:peak ratio by ambulatory blood pressure monitoring. J Hum Hypertens. 1999;13:405-412. 3. Martell M, Gill B, Marin R, et al. Trough to peak ratio of once-daily lisinoprol and twice-daily captopril in patients with essential hypertension. J Hum Hypertens. 1998;12:69-72. 4. Hermida RC, Calvo C, Ayala DE, et al. Administration time-dependent effects of valsartan on ambulatory blood pressure in hypertensive subjects. Hypertension. 2000;42:282-290.
  • 10. ASCOT: night-time SBP and DBP Night-time SBP 145 140 135 Night-time DBP Mean atenolol/thiazide = 125.2 mm Hg Mean amlodipine/perindopril = 123.0 mm Hg Mean difference (95% CI) = 2.2 (-3.4, -0.9) mm Hg P=0.0008 SBP = –2.2 mm Hg 90 85 Mean atenolol/thiazide = 68.6 mm Hg Mean amlodipine/perindopril = 69.4 mm Hg Mean difference (95% CI) = 0.8 (0.0-1.6) mm Hg P=0.0523 DBP = 0.8 mm Hg 80 130 75 125 70 120 65 1 2 3 4 Time (years) 5 1 2 3 4 Time (years) 5 PP = –1.4 mm Hg amlodipine/perindopril atenolol/thiazide Dolan E, et al. J Hypertens 2009.
  • 11. BP variability predicts cardiovascular events better than does mean brachial systolic BP Stroke CHD By decile of mean SBP By decile of standard deviation (SD) in SBP amlodipine/perindopril atenolol/thiazide Rothwell PM, et al. Lancet. 2010;375:895-905.
  • 12. ASCOT: amlodipine/perindopril lowers BP variability vs atenolol/thiazide All patients Mean within-visit CV SBP 4.5 atenolol/bendroflumethiazide 4.3 4.1 3.9 amlodipine/perindopril 3.7 3.5 Follow-up (years) Baseline 6 W 3 Mths 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 Rothwell PM, et al. Lancet Neurol. 2010;9:469-480.
  • 13. Reduction of central pressure Brachial systolic pressure Central systolic pressure mm Hg mm Hg 0 Athenolol/thiazide 130 5 125 -10 -15 120 -20 115 -25 -30 Amalodipine/perindopril 110 NS P<0.2 Amlodipine/perindopril 1 Atenolol/thiazide 2 3 4 Time (years) 5 6 Central pressure difference: - 4.3 mm Hg (P<0.0001) Williams B, et al. Circulation. 2006;113:1213-1225.
  • 14. Conclusion • Hypertension is a major risk factor for mortality worldwide • Reduction in the mortality risk is the ultimate goal of the antihypertensive treatment • According to our analysis, regimens based on ACE inhibition, in particular with perindopril, significantly improve survival in hypertensive patients • Benefits of perindopril in monotherapy or in combination with amlodipine or indapamide are strongly supported by evidence from large morbidity-mortality trials (EUROPA, PROGRESS, ADVANCE, HYVET, ASCOT) • This benefits might not be necessarily shared by other available antihypertensive drugs and their combinations
  • 15. ASH(American Society of Hypertension) and ISH(International Society of Hypertension  Age 80 or more-------- >150/90  CKD and DM----------- <140/90  Age<60-------------------ACEI or ARB(non black)  Age >60------------------CCB or Thiazide(non black) AHA/ACC/CDC Stage 1 H/T--------systolic (140-159 or diastolic(90-99) Stage 2 H/T--------systolic (>160 or diastolic >100 Recommended----combination of thiazide diuretic and ACEI,ARB or CCB Goal not achieved---increase the dose and or add drug from different class
  • 16. New European Hypertension Guidelines Released: Goal Is Less Than 140 mm Hg for All(ESH and ESC) High-normal------systolic (130 to 139 diastolic (85 to 89) Grade 1 H/T--------systolic (140-159 or diastolic(90-99) Grade 2 H/T--------systolic (160-179 or diastolic 100-109) Grade 3 H/T---------systolic (>180 or diastolic >110) Life style-----salt <5 to 6 gram/day) BMI-------------25 Target organ damage/disease CVD risk Target <140 mmHg systolic in age <80 <150 mmHg systolic in age >80 DM diastolic <85 mmHg
  • 17. JNC 8
  • 18. New Targets  Treat hypertension >150/90 or higher in Target---Below this level age>60 or older  Treat hypertension >140/90 or higher in CKD or DM regardless of age age<60 ----30 or patients with Initial choice of treatment • For non black including DM-----ACEI/ARB/CCB/Thiazide diuretic-------first line therapy • For black including DM------------CCB and Thiazide (first line) • CKD regardless of DM------------ACEI or ARB initial or add on therapy to improve renal outcome
  • 19. From: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) JAMA. 2013;():. doi:10.1001/jama.2013.284427 Figure Legend: Comparison of Current Recommendations With JNC 7 Guidelines Date of download: 12/20/2013 Copyright © 2012 American Medical Association. All rights reserved.