Uploaded byueda2015
PDF, PPTX881 views

ueda2012 do we still need high doses-d.mohammed

This document discusses hypertension and the need for high doses of antihypertensive medications. It provides data showing that over half of adults with hypertension still have uncontrolled blood pressure despite improvements. It also summarizes trials showing residual cardiovascular risk even when blood pressure is controlled. The document advocates for early use of combination antihypertensive therapy, especially those targeting the renin-angiotensin-aldosterone system, to improve control and reduce organ damage. It highlights valsartan specifically as a well-studied angiotensin receptor blocker with strong evidence from numerous trials across cardiovascular conditions.

Embed presentation

Download as PDF, PPTX
Do we Still need High Doses? Professor : Mohamed Gamal Abdel Aziz Aswan 8/2/2012
Hypertension goes uncontrolled in more than half of adults with the disease 33% 67% NHANES 1999 - 2002 Controlled Blood Pressure Uncontrolled Blood Pressure 46% 54% NHANES 2005-2008 Controlled Blood Pressure Uncontrolled Blood Pressure Ref.: Centers for Disease Control and Prevention. Vital signs: Prevalence, treatment, and control of hypertension—United States, 1999-2002 and 2005-2008. MMWR Morb Mortal Wkly Rep 2011; 60:1-6. Despite the significant improvement in Blood pressure control, still the problem of Uncontrolled patients remains
Trials in diabetic patients 40 30 20 10 0 Major CV events (% of patients over 5 years) Zanchetti A, 2009 Antihypertensive treatments fail to reduce incidence of major CV events below high-risk threshold of 10% in 5-year period Trials in high-risk patients 50 40 30 20 10 0 Major CV events (% of patients over 5 years) Reduction of risk Residual risk Trials in elderly patients 40 30 20 10 0 Major CV events (% of patients over 5 years) Dashed horizontal line indicates conventional threshold of high risk; x axes show randomized controlled trials of anti-HTN treatments.
Current Guidelines Recommend Initiating Combination Therapy Early in Patients with Stage 2 Hypertension or High Cardiovascular Risk • JNC 7 guidelines state1: ―When BP is more than 20 mmHg above systolic goal or 10 mmHg above diastolic 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 3 range or total cardiovascular risk is high or very high.‖ 1Chobanian et al. Hypertension 2003;42:1206–52 2Mancia et al. J Hypertens 2007:25:110587 ESH = European Society of Hypertension ESC = European Society of Cardiology JNC = Joint National Committee
Low-dose 2-drug combinationLow-dose single agent Not at BP goal Full dose of single agent Switch to different agent at low dose Full dose of 2-drug combination Add a third drug at low dose Not at BP goal 2–3 drug combination at full dose Full doses of 2–3-drug combination ESH–ESC: Algorithm for Treatment of Hypertension Full-dose single agent TOD = target organ damage Marked BP elevation High/very high CV risk Lower BP target Mild BP elevation Low/moderate CV risk Conventional BP target Task Force for ESH–ESC. J Hypertens 2007;25:1105–874
CCB Alpha blockers Beta blockers Diuretics Other RAS blockade The Foundation RAAS Blockade With ARBs Can Be Considered a Foundation of Antihypertensive and CV Preventive Therapy
Pre-diabetes Diabetes – Renal RAAS Blockers Have Been Studied Extensively in Outcomes Trials High Risk Myocardial infarction • LIFE • SCOPE • STOP 2 • VALUE • KYOTO HEART • CAPPP • ALLHAT • ANBP2 • HOPE • ONTARGET • TRANSCEND • JIKEI HEART • KYOTO HEART • OPTIMAAL • VALIANT • CONSENSUS II • ISIS-4 • GISSI-3 • SMILE • SAVE • AIRE • TRACE Heart failure • NAVIGATOR • DREAM • RENAAL • IDNT • ABCD Hypertension Coronary Artery Disease • EUROPA • PEACE • IMAGINE • ELITE II • Val-HeFT • CHARM • CONSENSUS I • SOLVD • V-HeFT II • PEP-CHF
GFR Proteinuria Aldosterone release Glomerular sclerosis AII AT1 Receptor Atherosclerosis* Vasoconstriction Vascular hypertrophy Endothelial dysfunction LV hypertrophy Fibrosis Remodeling Apoptosis Stroke Death *Preclinical data. LV=left ventricular; MI=myocardial infarction; GFR=glomerular filtration rate. Hypertension Heart Failure MI Renal Failure Angiotensin II Plays a Central Role in Organ Damage . Willenheimer R, Dahlof B, Rydberg E, Erhardt L. AT1-receptor blockers in hypertension and heart failure: clinical experience and future directions. Eur Heart J. 1999;20:997–1008. 2. Dahlof B. Effect of angiotensin II blockade on cardiac hypertrophy and remodelling: a review. J Hum Hypertens.1995;9(suppl 5):S37–44. 3. Daugherty A, Manning MW, Cassis LA. Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. J Clin Invest. 2000;105:1605–12.
Effects of RAS blockade on stroke: meta-analysis of ARBs and ACE inhibitors MI Cardiovascular mortality All-cause mortality Stroke Favours ARB Favours ACE inhibitor Reboldi et al. J Hypertension 2008;26:1282–1289 Studies (N=63,409 ): ELITE; ELITE-II; OPTIMAAL; DETAIL; VALIANT; ONTARGET
Elliott and Meyer. Lancet 2007;369:201–7 0.57 (0.46–0.72) p<0.0001 0.67 (0.56–0.80) p<0.0001 0.75 (0.62–0.90) p=0.002 0.77 (0.63–0.94) p=0.009 0.90 (0.75–1.09) p=0.30 Referent ARB ACE inhibitor CCB Placebo β-blocker Diuretic Odds ratio of incident diabetes Incoherence=0.000017 0.50 0.70 0.90 1.26 Effects of Different Antihypertensive Agents on Incidence of Diabetes Network meta-analysis assessing the effects of different antihypertensive agents on incidence of diabetes in 48 randomised groups from 22 clinical trials* (n=143,153) *17 trials enrolled patients with hypertension, three enrolled high-risk patients and one enrolled patients with heart failure (HF) ARB=angiotensin receptor blocker; ACE=angiotensin-converting enzyme; CCB=calcium channel blocker
Conditions favoring use of some antihypertensive drugs versus others:
Are all ARBs the same?
There is no such thing as a simple Class Effect that cover all aspect of different molecules Go with the evidence,do not assume
1. VALUE 2. VALIANT 3. NAVIGATOR 4. Val-HeFT 5. JIKEI HEART 6. KYOTO HEART* 7. VART* 8. VALISH* 27. IDNT 28. ACTIVE-I* 29. NID-2 30. SUPPORT* 31. COLM* 32. OSCAR* 33. ORIENT* 34. MOSES 1. Julius et al. 2004; 2. Pfeffer et al. 2003; 3. Califf et al 2008; 4. Cohn et al. 2001; 5. Mochizuki et al. 2007; 6. http://clinicaltrials.gov (NCT00149227); 7. Nakayama et al. 2008; 8. NCT00151229; 9. ONTARGET Investigators 2008; 10. Yusuf et al 2008; 11. TRANSCEND Investigators 2008; 12. http://clinicaltrials.gov (NCT00283686); 13. Dahlöf et al. 2002; 14. Dickstein et al. 2002; 15. Pitt et al. 2000; 16. Brenner et al. 2001; 17. http://clinicaltrials.gov (NCT00090259); 18. http://clinicaltrials.gov (NCT00555217); 19. Pfeffer et al 2003; 20. Papademetriou et al. 2004; 21. http://clinicaltrials.gov (NCT00120003); 22. Ogihara et al. 2008; 23. http://clinicaltrials.gov (NCT00108706); 24. Laufs et al. 2008; 25. Suzuki et al. 2005; 26. Massie et al 2008; 27. Lewis et al. 2001; 28. http://clinicaltrials.gov (NCT00249795); 29. http://clinicaltrials.gov (NCT00535925); 30. http://clinicaltrials.gov (NCT00417222); 31. http://clinicaltrials.gov (NCT00454662); 32. http://clinicaltrials.gov (NCT00134160); 33. http://clinicaltrials.gov (NCT00141453); 34. Schrader et al. 2005 9. ONTARGET 10. PRoFESS 11. TRANSCEND 12. HALT-PKD* 13. LIFE 14. OPTIMAAL 15. ELITE II 16. RENAAL 17. NCT00090259* *Expected enrolment ‡Ongoing and completed randomized controlled trials with death or hard CV events as or part of the primary endpoint ¶Valid as of January 2009 Mortality & Morbidity Endpoint Trials with ARBs 18. VA NEPHRON-D* 19. CHARM 20. SCOPE 21. SCAST* 22. CASE-J 23. ACCOST 24. HIJ-CREATE 25. E-COST 26. I-PRESERVE 0 10,000 20,000 30,000 40,000 50,000 60,000 Numberofpatients Valsartan Telmisartan Losartan Candesartan Irbesartan Olmesartan Eprosartan 57,781 52,896 24,841 23,940 6,577 1,405 15,693 1 2 5 4 3 7 8 6 9 10 16 11 17 18 15 13 14 22 25 21 19 20 34 31 30 32 33 28 27 26 24
Selectivity on AT1 Receptor Valsartan Candesartan LosartanIrbesartan Telmisartan 10000 20000 30000 30,000 1000 8500 10,000 3,000 Valsartan is 3 times more selective for AT1 receptors than other ARB agents Siragy H. Am J Cardiol. 1999;84:3S-8S.
Valsartan: Extensively Studied Across the Cardiovascular Continuum 1. Julius et al. Lancet 2004; 363:2022–31; 2. Pfeffer et al. N Engl J Med 2003;349:1893–906; 3. Cohn et al. N Engl J Med 2001; 345:1667–75 4. Califf et al. Am Heart J 2008;156:623–32; 5. Mochizuki et al. Lancet 2007;369:1431–9; 6. Viberti et al. Circulation 2002;106:6728 7. Karalliedde et al. Hypertension 2008;51:161723; 8. SMART Group. Diabetes Care 2007;30:1581–3; 9. Hollenberg et al. J Hypertens 2007;25:19216 MARVAL6 MARVAL II7 SMART8 DROP9 Endothelial dysfunction Microalbuminuria Proteinuria End-stage renal disease Risk factors Diabetes Hypertension Atherosclerosis and LVH Myocardial infarction Ventricular Remodelling Ventricular Dilation Heart Failure End-stage Heart Disease Death Includes over 50,000 patients*19 JIKEI HEART 1 2 3 4 ‡5 *Not all patients in these studies received valsartan ‡Independent, investigator-initiated study
19 Titrating Valsartan to full dose optimizes CV/Renal Protection in outcome trial Tareg based therapy 40 - 320 mg out come trials Trial Drug used Dose titration NO. of patient outcome VAL-HEFT Valsartan 40 - 320 mg About 5000 pts Composite Mortality & Morbidity end point reduced by 13.2%, Patients not on ACEi Group reduced By 44% VALLIANT valsartan 40-320 mg About 15,000 25% Mortality risk reduction in Post MI patients DROP valsartan 160 – 320 - 640mg 390 pts 51% reduction in UAER •Maggioni et al. J Am Coll Cardiol 2002;40:1414–21,, •McMurray et al. J Am Coll Cardiol 2006; 47:726–33,, •Hollenberg et al J Hypertens 2007,25:1921-1926
Valsartan* Provides Powerful Systolic BP Reductions Across Hypertension Severities -15.9 -23.5 -27 -32.2 -38.9 -46.4 -12.1 -14.3 -17.4 -23.1 -31.5 -25.9 -50 -45 -40 -35 -30 -25 -20 -15 -10 -5 0 140–149 150–159 Post-hoc analysis C-DITT study Category of baseline MSSBP (mmHg) 160–169 170–179 180–189 ChangeinMSSBP(mmHg) atWeek4(LOCF) 6-week, double-blind, multicentre, forced-titration study in patients with DBP ≥110 mmHg and <120 mmHg and SBP ≥140 mmHg and <200 mmHg. Valsartan 160 mg force-titrated to 320 mg at Week 2. Valsartan/HCTZ 160/12.5 mg force-titrated to 160/25 mg and 320/25 mg at Weeks 2 and 4. BP = blood pressure; DBP = diastolic BP; SBP = systolic BP; MSSBP = mean sitting SBP; LOCF = last observation carried forward; C-DITT = Co-Tareg Initial Therapy Trial 190-199 Calhoun et al. Curr Med Opin Res 2008;24:230311
0 –5 –10 –15 –20 –25 –30 Blacks Hispanic Elderly# Obese‡ Diabetes n=202 n=51 n=117 n=477 n=69 21.4 21.7 25.5 23.6 19.5 n=190 n=58 n=103 n=493 n=97 *p≤0.01 vs valsartan monotherapy: ¶Valsartan 160 mg or valsartan/HCTZ 160/12.5 mg force-titrated to valsartan 320 mg or valsartan/HCTZ 320/12.5 mg, respectively, at Week 2; §SBP ≥160 mmHg and/or DBP ≥100 mmHg; #≥65 years of age; ‡body mass index ≥30 kg/m2; HCTZ = hydrochlorothiazide Val-MARC = Valsartan-Managing blood pressure Aggressively and evaluating Reductions in hsCRPEverett et al.Clin Ther 2008;30:66172 Meanchangefrombaseline inSBPatWeek6(mmHg) 12.6 16.3 16.9 15.9 16.3 * * * * Valsartan and Valsartan-HCTZ Therapy Provides Effective BP Reductions Across Diverse Patient Populations Valsartan/HCTZ¶ Valsartan¶
Co-Tareg® 320 achieves BP goal in up to 9 out of 10 patients with HTN #BP=Blood pressure; DBP=Diastolic blood pressure; HTN=Hypertension; Ref.: Weir et al. J Clin Hypertens 2007;9:103-112 Results from a pooled analysis of 9 randomized trials# in 4278 patients with HTN§ Patients achieving BP goal <140/90 mmHg (%) Co-Tareg 320/25 mg (n=80) Tareg 320 mg (n=271) Co-Tareg 320/12.5 mg (n=87) 40 60 80 100
Tareg/Co-Tareg: Proportion of Patients Achieving BP Goal <140/90 mmHg Co-Tareg 320/25 mg Co-Tareg 320/12.5 mg Tareg 320 mg Co-Tareg 160/25 mg Co-Tareg 160/12.5 mg Tareg 160 mg Co-Tareg 80/12.5 mg Tareg 80 mg Placebo n 167 168 646 94 261 907 96 782 1157 0 10 20 30 40 50 60 70 80 90 100 Patients achieving goal (%) Weir et al. J Clin Hypertens 2007;9:103–112 Meta-analysis of nine randomised, double-blind, placebo-controlled trials; data for overall population shown
Pooled Analysis of Nine Trials Showed More Patients Achieve JNC-7 Goals* in Less Time with Higher Doses or with Combination Therapy Cumulativeproportionof patientsreaching JNC-7goals*(%) Weir et al. Am J Hypertens 2007;20:811–15 Placebo (n=1,156) Tareg 80 mg (n=781) Co-Tareg 80/12.5 mg (n=96) Tareg 160 mg (n=907) Co-Tareg 160‡ mg (n=355) Tareg 320 mg (n=646) Co-Tareg 320‡ mg (n=335) 90 80 70 60 50 40 30 20 10 0 Pooled analysis of data from nine randomised, double-blind, placebo-controlled trials ‡Tareg at stated dose + HCTZ 12.5 or 25 mg *<140/90 mmHg
Cardiovascular Continuum
Proteinuria Is an Independent Risk Factor for Mortality in Type 2 Diabetes 1.0 0.9 0.8 0.7 0.6 0.5 0 1 2 3 4 5 6 Years Survival (all-causemortality) Normoalbuminuria (n=191) [8%] Microalbuminuria (n=86) [20%] Macroalbuminuria (n=51) [35%] Gall, MA et al. Diabetes 1995;44:1303 P<0.01 normo vs. micro- and macroalbuminuria P<0.05 micro vs. macroalbuminuria
Tareg Reduction of Proteinuria (DROP) Study: Albuminuria response to very high-dose valsartan in type 2 diabetes mellitus Hollenberg et al., Journal of Hypertension 2007, 25:1921-1926
The DROP study: Objectives Purpose: • To assess the ability of high-dose valsartan to reduce proteinuria in subjects with diabetic nephropathy Primary Objective: • To compare responses to valsartan at 160, 320, and 640 mg/day in patients with hypertension, type 2 diabetes mellitus, and albuminuria (30–1,000 mg/d) Hollenberg NK et al, J Hypertens, 2007, 25:1921-1926
Study Design • Design: multicentre, double-blind, randomized, parallel group study • Patient population: subjects with hypertension, proteinuria and T2DM Valsartan 160 mg Valsartan 320 mg Valsartan 640 mg Placebo run-inScreening Valsartan 160 mg Week –6 (Visit 1) Week –3 (Visit 3) Week –2 (Visit 4) Week 0 (Visit 6) (Randomisation) Week 4 (Visit 8) Week 16 (Visit 11) Week 30 (Visit 12) Valsartan 160 mg Valsartan 160 mg Hollenberg NK et al, J Hypertens, 2007, 25:1921-1926
DROP Study: Change From Baseline in UAER at Week 30 (ITT-1 Population)‡ –25† –51* –49* –60 –50 –40 –30 –20 –10 0 Medianchangein UAERatWeek30(%) Tareg 160 mg (n=130) Tareg 320 mg (n=130) Tareg 640 mg (n=131) ‡Overall population *p<0.001 vs baseline Hollenberg NK. Suppl to Circulation abstracts from scientific sessions 2006:114(18); II-61
DROP Study: Proportion of Patients Who Returned to Normalisation of UAER (<20 μg/min) at Week 30‡ 12.4 19.2 0 5 10 15 20 25 30 PatientswithUAER <20g/minatendpoint(%) ‡LOCF cases methodology (ITT-1 population) was used *p=0.02 vs Tareg 160 mg Tareg 160 mg (n=130) Tareg 320 mg (n=130) Hollenberg NK. Suppl to Circulation abstracts from scientific sessions 2006:114(18); II-61 Novartis data on file 24.3* Tareg 640 mg (n=131)
DROP Study: Summary • Tareg produced a significant reduction in UAER of up to 48% in hypertensive patients with diabetes and proteinuria • Up-titration of Tareg to either 320 or 640 mg offered a numerically greater reduction in proteinuria vs 160 mg • Outstanding BP goal rates of up to 74% were achieved with a Tareg-based regimen (64% with the approved doses) • In patients that achieved target BP control of <130/80 mmHg, UAER was reduced by up to 65% • A rapid reduction in proteinuria (17–23%) was observed in all groups during the first 4 weeks • All three doses of Tareg were safe and well tolerated with slightly more frequent dizziness and headache at the 640 mg dose Hollenberg NK. Suppl to Circulation abstracts from scientific sessions 2006:114(18); II-61
Time post-randomization (months) 100 95 90 85 80 75 70 65 0 Tareg (n=2,511) Placebo (n=2,499) 0 3 6 9 12 15 18 21 24 27 13.2% risk reduction‡ Event-freeprobability(%) ‡p=0.009 vs. placebo *Combined primary endpoint: all-cause mortality, cardiac arrest with resuscitation, hospitalization for worsening heart failure, or therapy with intravenous inotropes or vasodilators RR = relative risk; CI = confidence interval; CHF = congestive heart failure; Val-HeFT = Valsartan Heart Failure Trial. Results from a 23-month mean follow-up study in 5,010 patients with CHF on standard therapy (Val-HeFT study) Cohn et al. N Engl J Med 2001;345:1667–75 Tareg Improves CV Outcomes* in Patients with Congestive Heart Failure on Standard Therapy RR=0.87; 97.5% CI=0.770.97
*p<0.001;‡Combined primary endpoint: all-cause mortality, cardiac arrest with resuscitation, hospitalization for worsening heart failure, or therapy with intravenous inotropes or vasodilators 33% relative risk reduction (p=0.017) for all-cause mortality ACEI = angiotensin-converting enzyme inhibitor; CHF = congestive heart failure RR = relative risk; CI = confidence interval; Val-HeFT = Valsartan Heart Failure Trial 0 0.486 0.571 0.657 0.743 0.829 0.914 1.000 Time since randomization (months) Event-freeprobability‡ Tareg (n=185) Placebo (n=181) 44% risk reduction* 0 3 6 9 12 15 18 21 24 27 Maggioni et al. J Am Coll Cardiol 2002;40:1414–21 Results from a 23-month mean follow-up study in 366 patients with CHF not on ACEI background therapy (Val-HeFT study post-hoc subgroup analysis) Tareg Significantly Reduces Morbidity and Mortality in Patients with Congestive Heart Failure not on an ACEI RR=0.56; 95% CI=0.390.81
Captopril 0 0.05 0.1 0.15 0.2 0.25 0.3 0 6 12 18 24 30 36 ProbabilityofEvent Mortality by Treatment Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349 Valsartan 4909 4464 4272 4007 2648 1437 357 Months Valsartan vs. Captopril: HR = 1.00; P = 0.982 Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726 Captopril 4909 4428 4241 4018 2635 1432 364 Valsartan + Cap 4885 4414 4265 3994 2648 1435 382 Valsartan Valsartan + Captopril
Tareg is as effective as Captopril(ACE-I) in reducing cardiovascular mortality & morbidity in post MI patients by 25% Hazard Ratio for Mortality Favors Active Drug Favors Placebo Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349 0.5 1 2 Combined TRACE SAVE AIRE VALIANT (Valsartan Vs Captopril) 25% Mortality Reduction
Tareg Reduce BP Beyond 24 Hours Results from a 8-week study in 256 patients with mild-to-moderate hypertension# #sitting DBP between 95 and 115 mm Hg at baseline, *intervals 2-24, n=21 (15 treated with valsartan 80 mg, 6 with 160 mg) intervals 26-48, n=10 (9 treated with valsartan 80 mg, 1 with 160 mg), hour 25-48 without dose Lasko et al. Blood Press Monit 2001;6(2):91-99 15 5 0 -5 -15 -25 -35 15 5 0 -5 -15 -25 -35 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 MeanChangein SBP(mmHg) MeanChangein DBP(mmHg) Time after dose administration (hours)* Mean BP and 95% CI
Tareg 320 as tolerable as placebo Oparil et al. Lancet 2007;370:221–29 ‡Increases in serum potassium over 5·5 mmol/L (but not ≥6·0 mmol/L) were more common with the combined drugs than with the monotherapies or placebo, although the occurrence of such cases after correction for placebo was low. Most of these increases were transient and returned to normal by Week 8. None were associated with AEs or patient discontinuation Placebo (n=458*) Tareg 320 (n=455) Adverse events Any adverse event 168 (37%) 167 (37%) Any serious adverse event 5 (1%) 6 (1%) Discontinuations due to adverse events 10 (2%) 11 (2%) Laboratory abnormalities Serum potassium <3.5 mmol/L 17 (4%) 20 (4%) >5.5 mmol/L‡ 12 (3%) 7 (2%) 6.0 mmol/L 6 (1%) 5 (1%) Creatinines >176.8 µmol/L 0 2 (0.4%) Blood urea nitrogens >14.3 mmol/L 0 1 (0.2%)
High dose of Valsartan Tareg 320mg for hypertensive high risk patients Superior & complete blockade of the RAS system Significant renal protection in hypertensive patients with diabetes and proteinuria
So when to use the new high dose of Valsartan? - High risk and very high risk hypertensive patients - For Nephroprotection (Diabetics with proteinuria)
Conclusions The recommended doses of AT1 receptor blockers are adequate for blood pressure control. However, they are probably too low to afford an optimal protection of target organs. Thus, there is today a rational for using higher doses of ARBs such as Valsartan 320 mg in high risk patients (ISH severe hypertension, metabolic syndrome, diabetes with proteinuria…)
Thank You

More Related Content

PDF
Achieving Blood Pressure Goal: From Clinical Trial into Real-World Data
bySuharti Wairagya
 
PPT
Hypertension: New Concepts, Guidelines, and Clinical Management Hypertensio...
byMedicineAndFamily
 
PPTX
Diabetic Kidney Disease (DKD) : 2022 update
byMalsawmkima Chhakchhuak
 
PDF
Non Invasive Biomarkers in NASH (non-alcoholic steatohepatitis) Webinar Slides
byCovance
 
PDF
Comparative effectiveness of acei and arbi
byhttps://aiimsbhubaneswar.nic.in/
 
PDF
Glutathione - Their role in cancer and anticancer therapies
byQuicksilver Scientific
 
PDF
PCSK9 Inhibitors
byTerri Newman
 
PDF
Kỹ năng Huy động nguồn lực cho dự án cộng đồng
bycaominhth199x
 
Achieving Blood Pressure Goal: From Clinical Trial into Real-World Data
bySuharti Wairagya
 
Hypertension: New Concepts, Guidelines, and Clinical Management Hypertensio...
byMedicineAndFamily
 
Diabetic Kidney Disease (DKD) : 2022 update
byMalsawmkima Chhakchhuak
 
Non Invasive Biomarkers in NASH (non-alcoholic steatohepatitis) Webinar Slides
byCovance
 
Comparative effectiveness of acei and arbi
byhttps://aiimsbhubaneswar.nic.in/
 
Glutathione - Their role in cancer and anticancer therapies
byQuicksilver Scientific
 
PCSK9 Inhibitors
byTerri Newman
 
Kỹ năng Huy động nguồn lực cho dự án cộng đồng
bycaominhth199x
 

What's hot

PPT
Diagnosis & Management of Resistant Hypertension
byDr.Vinod Sharma
 
PDF
Ueda 2016 diabetes mellitus and heart failure - yahia kishk
byueda2015
 
PPTX
Diabetic Kidney Disease 2022 Update
byChristos Argyropoulos
 
PPTX
Sacubitril valsartan EK
byEdgardo Kaplinsky
 
PPTX
Journal dapagliflozin dapahf trial
byPriyanka Thakur
 
PDF
Icosapent ethyl: evidence and guidelines recommendations
bySociedad Española de Cardiología
 
PDF
Hypertrophic cardiomyopathy state of the art
bydrucsamal
 
PPT
Are+all+sartans+equal
bydhavalshah4424
 
PPTX
KDIGO 2024 guidelines for diabetologists
byد.محمود نجيب
 
PPTX
Management of dyslipidemia
byRajesh Rayidi
 
PPT
Dyslipidemia approach
bychhabilal bastola
 
PPTX
Dapagliflozin in Clinical Trial212.pptx
byAliShahen2
 
PPTX
Hypolipidemic drugs MBBS and PG Dr. Resu Neha Reddy
byDr Resu Neha Reddy
 
PPTX
Bempedoic Acid.pptx
bySubbuPoola1
 
PPTX
Dengue & Cardiac Complications
byMohammad Arifur Rahman
 
PPTX
Vymada - Sacubitril & Valsartan (ARNI) For Heart Failure
byDr Sunny Kumar Gupta
 
ODP
Jardiance (Empagliflozin Tablets)
byClearsky Pharmacy
 
PPTX
Pioneer hf
byHimanshu Rana
 
PPTX
Crs
bySiddharth Pugalendhi
 
PPTX
Arni
bykazi alam nowaz
 
Diagnosis & Management of Resistant Hypertension
byDr.Vinod Sharma
 
Ueda 2016 diabetes mellitus and heart failure - yahia kishk
byueda2015
 
Diabetic Kidney Disease 2022 Update
byChristos Argyropoulos
 
Sacubitril valsartan EK
byEdgardo Kaplinsky
 
Journal dapagliflozin dapahf trial
byPriyanka Thakur
 
Icosapent ethyl: evidence and guidelines recommendations
bySociedad Española de Cardiología
 
Hypertrophic cardiomyopathy state of the art
bydrucsamal
 
Are+all+sartans+equal
bydhavalshah4424
 
KDIGO 2024 guidelines for diabetologists
byد.محمود نجيب
 
Management of dyslipidemia
byRajesh Rayidi
 
Dyslipidemia approach
bychhabilal bastola
 
Dapagliflozin in Clinical Trial212.pptx
byAliShahen2
 
Hypolipidemic drugs MBBS and PG Dr. Resu Neha Reddy
byDr Resu Neha Reddy
 
Bempedoic Acid.pptx
bySubbuPoola1
 
Dengue & Cardiac Complications
byMohammad Arifur Rahman
 
Vymada - Sacubitril & Valsartan (ARNI) For Heart Failure
byDr Sunny Kumar Gupta
 
Jardiance (Empagliflozin Tablets)
byClearsky Pharmacy
 
Pioneer hf
byHimanshu Rana
 
Crs
bySiddharth Pugalendhi
 
Arni
bykazi alam nowaz
 

Viewers also liked

PPTX
Anaemia in heart failure
bydrabhishekbabbu
 
PPTX
Drug therapy for heart failure
byDr Ranjita Santra(Dhali)
 
PDF
Ueda2016 workshop - diabetes in the elderly - mesbah kamel
byueda2015
 
PPT
Hypernatremia(1)
byKhalid Ramadan
 
PPTX
Biologics
bymarwa oraby
 
PPT
ueda2011 hf to mi -d.samer sayed
byueda2015
 
PPTX
Iron therapies
byousama Aklan
 
PPTX
Endothelin ppt
bykunjpatel1408
 
PPTX
Ckd dr. shanjida
byFerdous Rafy
 
PDF
Ueda2016 new horizon in the management of dyslipidemia - diaa ewais
byueda2015
 
PDF
Importance of iron deficiency in asian patients with heart failure
bydrucsamal
 
PPTX
Diabetesforall emad
byueda2015
 
PPTX
NEPHROPROTECTIVE PLANTS
bykonatham teja kumar reddy
 
PPT
The Effects of Obstructive Sleep Apnea and Visceral Fat on Insulin Resistance
byBiomedical Statistical Consulting
 
PDF
Dept activities pharmacology, pescp 3 2-2016
byDr.Shivalinge Gowda KP
 
PDF
NEPHROPROTECTIVE ACTIVITY OF AERIAL PARTS OF BAUHINIA PURPUREA
bypharmaindexing
 
PPT
Hypertension
byAnac09
 
PPT
Blood pressure guide
bysanjeeb mukherjee
 
PDF
Ueda2016 workshop - hypoglycemia1 -lobna el toony
byueda2015
 
PDF
Determination of nephroprotective activity of ethanolic leaf extract of morin...
bypharmaindexing
 
Anaemia in heart failure
bydrabhishekbabbu
 
Drug therapy for heart failure
byDr Ranjita Santra(Dhali)
 
Ueda2016 workshop - diabetes in the elderly - mesbah kamel
byueda2015
 
Hypernatremia(1)
byKhalid Ramadan
 
Biologics
bymarwa oraby
 
ueda2011 hf to mi -d.samer sayed
byueda2015
 
Iron therapies
byousama Aklan
 
Endothelin ppt
bykunjpatel1408
 
Ckd dr. shanjida
byFerdous Rafy
 
Ueda2016 new horizon in the management of dyslipidemia - diaa ewais
byueda2015
 
Importance of iron deficiency in asian patients with heart failure
bydrucsamal
 
Diabetesforall emad
byueda2015
 
NEPHROPROTECTIVE PLANTS
bykonatham teja kumar reddy
 
The Effects of Obstructive Sleep Apnea and Visceral Fat on Insulin Resistance
byBiomedical Statistical Consulting
 
Dept activities pharmacology, pescp 3 2-2016
byDr.Shivalinge Gowda KP
 
NEPHROPROTECTIVE ACTIVITY OF AERIAL PARTS OF BAUHINIA PURPUREA
bypharmaindexing
 
Hypertension
byAnac09
 
Blood pressure guide
bysanjeeb mukherjee
 
Ueda2016 workshop - hypoglycemia1 -lobna el toony
byueda2015
 
Determination of nephroprotective activity of ethanolic leaf extract of morin...
bypharmaindexing
 

Similar to ueda2012 do we still need high doses-d.mohammed

PPTX
Update in hypertension management
byTarek Khalil
 
PPT
ueda2011 hypertensive diabetic patient-d.adel
byueda2015
 
PPTX
Telsarta-A final-01-04-16
byMuhammad Aun
 
PPT
Hypertension
bydhavalshah4424
 
PPT
Hypertension (BLOOD PRESSURE)
byMuhammad Arsal
 
PDF
THE IMPORTANCE OF 24-HOUR BP CONTROL FOR MANAGING CV RISK by dr hendro
bySuharti Wairagya
 
PPT
Hypertension+clinical
bydhavalshah4424
 
PPTX
The Role of Nitroglycerin in Emergency Hypertension update.pptx
byGestana
 
PDF
Hypertension
byPHAM HUU THAI
 
PPT
Nhi teveten
byAmir Mahmoud
 
PPTX
HTN (1).pptx hypertension diseases, chronic follow
byticay68913
 
PPTX
Bugando Hypertension.pptx
byMkindi Mkindi
 
PPTX
ANTIHYPERTENSIVE THERAPY-market review 2013
bypooja sharma
 
PPT
Htn the silent killer25 4-2013
byhospital
 
PPSX
Hypertension lecture prof zak (1)
byProfessor M Zak Khalil, MD, MRCP (UK), FACC, FESC
 
PPT
C:\Cema\HipertensióN Arterial Curso 2008 2
bygueste2c1102
 
PPTX
arterial health in hypertension
byKyaw Win
 
PPTX
lipid effects of antihypertensive medications
bySoM
 
PPTX
Management of hypertension to prevent CV events
byFaris Basalamah, MD FIHA
 
PPTX
Hipertension arterial en tiempos de crisis
byMartin Velarde
 
Update in hypertension management
byTarek Khalil
 
ueda2011 hypertensive diabetic patient-d.adel
byueda2015
 
Telsarta-A final-01-04-16
byMuhammad Aun
 
Hypertension
bydhavalshah4424
 
Hypertension (BLOOD PRESSURE)
byMuhammad Arsal
 
THE IMPORTANCE OF 24-HOUR BP CONTROL FOR MANAGING CV RISK by dr hendro
bySuharti Wairagya
 
Hypertension+clinical
bydhavalshah4424
 
The Role of Nitroglycerin in Emergency Hypertension update.pptx
byGestana
 
Hypertension
byPHAM HUU THAI
 
Nhi teveten
byAmir Mahmoud
 
HTN (1).pptx hypertension diseases, chronic follow
byticay68913
 
Bugando Hypertension.pptx
byMkindi Mkindi
 
ANTIHYPERTENSIVE THERAPY-market review 2013
bypooja sharma
 
Htn the silent killer25 4-2013
byhospital
 
Hypertension lecture prof zak (1)
byProfessor M Zak Khalil, MD, MRCP (UK), FACC, FESC
 
C:\Cema\HipertensióN Arterial Curso 2008 2
bygueste2c1102
 
arterial health in hypertension
byKyaw Win
 
lipid effects of antihypertensive medications
bySoM
 
Management of hypertension to prevent CV events
byFaris Basalamah, MD FIHA
 
Hipertension arterial en tiempos de crisis
byMartin Velarde
 

More from ueda2015

PDF
Ueda2016 woman’s health &amp; diabetes - lobna el toony
byueda2015
 
PDF
Ueda2016 recommendations for management of diabetes during ramadan - update 2...
byueda2015
 
PDF
Ueda2016 hyperparathyroidism - mohamed mashahit
byueda2015
 
PDF
Ueda2016 wark shop - insulin therapy - mohamed mashahit
byueda2015
 
PDF
Ueda2016 thyroid nodule in practice - khaled el hadidy
byueda2015
 
PDF
Ueda2016 metabolic syndrome in different population,which one is appropriate ...
byueda2015
 
PDF
قنديل ام هاشم يحيى حقى
byueda2015
 
PDF
Ueda2016 type 1 diabetes guidelines - hesham el hefnawy
byueda2015
 
PDF
Ueda2016 wark shop - insulin pens - precise injection technique - khaled el...
byueda2015
 
PPTX
Diabetesforall emad
byueda2015
 
PDF
Diabetesforall emad
byueda2015
 
PDF
Ueda2016 the role of gut microbiota in the pathogenesis of obesity &amp; tdm2...
byueda2015
 
PDF
Ueda2016 prevention of diabetes,the role of patients’ associations -mominaat ...
byueda2015
 
PDF
Ueda2016 do we know what is type 2 -assem zeyada
byueda2015
 
PDF
Ueda2016 the agenda for ncd prevention and control - samer jabbour
byueda2015
 
PDF
Ueda2016 non pharmacological diabetes management - emad hamed
byueda2015
 
PDF
Ueda2016 nc ds alliances - adel el sayed
byueda2015
 
PDF
Ueda2016 idf in the coming years,what are the global priorities- nam cho
byueda2015
 
PDF
Ueda2016 tobacco and nc ds - wael safwat
byueda2015
 
PDF
Ueda2016 pitfalls in df - hanan gawish
byueda2015
 
Ueda2016 woman’s health &amp; diabetes - lobna el toony
byueda2015
 
Ueda2016 recommendations for management of diabetes during ramadan - update 2...
byueda2015
 
Ueda2016 hyperparathyroidism - mohamed mashahit
byueda2015
 
Ueda2016 wark shop - insulin therapy - mohamed mashahit
byueda2015
 
Ueda2016 thyroid nodule in practice - khaled el hadidy
byueda2015
 
Ueda2016 metabolic syndrome in different population,which one is appropriate ...
byueda2015
 
قنديل ام هاشم يحيى حقى
byueda2015
 
Ueda2016 type 1 diabetes guidelines - hesham el hefnawy
byueda2015
 
Ueda2016 wark shop - insulin pens - precise injection technique - khaled el...
byueda2015
 
Diabetesforall emad
byueda2015
 
Diabetesforall emad
byueda2015
 
Ueda2016 the role of gut microbiota in the pathogenesis of obesity &amp; tdm2...
byueda2015
 
Ueda2016 prevention of diabetes,the role of patients’ associations -mominaat ...
byueda2015
 
Ueda2016 do we know what is type 2 -assem zeyada
byueda2015
 
Ueda2016 the agenda for ncd prevention and control - samer jabbour
byueda2015
 
Ueda2016 non pharmacological diabetes management - emad hamed
byueda2015
 
Ueda2016 nc ds alliances - adel el sayed
byueda2015
 
Ueda2016 idf in the coming years,what are the global priorities- nam cho
byueda2015
 
Ueda2016 tobacco and nc ds - wael safwat
byueda2015
 
Ueda2016 pitfalls in df - hanan gawish
byueda2015
 

Recently uploaded

PDF
Scholar.postdoc - Anaesthesia: Dalamagka, Maria
bycatlist1
 
PPTX
BILIARY TREE RADIOLOGY ADVANCE IMAGING (USG, CT SCAN, MRI AND ERCP) OF ITS AN...
byjuryshira
 
PDF
Key Steps to Success With CDK4/6 Inhibition in Early Through Metastatic Breas...
byPVI, PeerView Institute for Medical Education
 
PPTX
Biostatistics- Data types and presentation
byAnkitMittal145
 
PPTX
Drug use evaluation and WHO drug use Indicators.pptx
byLok Raj Pant
 
PDF
Advanced Prostate Cancer: Symptoms, Progression & Treatment Options
byLetsMeds
 
PPTX
Lumbar Facet Joint Pain – A Pain Generator Based Diagnostic & Treatment Approach
byDaradia: The Pain Clinic
 
PDF
Echocardiography Oct. 15 2023 by Ichilov Hospital
byHaim R. Branisteanu
 
PPTX
Biotransformation and Excretion
byBadrinathSelvakumar
 
PDF
Breast Imaging Breast Imaginorting schem
byNitesh274271
 
PPTX
metabolic syndrome and fasting ( Dr Mohammed bamashmos , sana'a University) ....
byAimanAlkhadher1
 
PPTX
Vitamin Deficiency- Vitamin A, C, D (MBBS)
byReenaz Shaik
 
PDF
General Anesthetics. Dalamagka, Maria. Anaesthetist- physician
bycatlist1
 
PPTX
Human Excretory System (RIT): Kidney Functions & Urine Formation Made Easy
byBALAJI SOMA
 
PDF
KNEE JOINT -Prof.Dr.N.Mugunthan, KMMC Medical College & Hospitals.pdf
byKanyakumari Medical Mission Research Center, Muttom
 
PPTX
MEDIATORS OF INFLAMMATION - MBBS
byReenaz Shaik
 
PDF
PEDIATRIC CATARACT & IT'S MANAGEMENT BY SAMIKSHA RAI
bySamikshaRai22
 
PDF
Retinoscopy & It's Principle - static vs dynamic retinoscopy in detail
bySamikshaRai22
 
PPTX
Easy Peasy Gut: Complete Digestive Support
byEthniq
 
PPTX
Basic Anatomy of the Structure of the Cerebellum.pptx
byLucaDonovan
 
Scholar.postdoc - Anaesthesia: Dalamagka, Maria
bycatlist1
 
BILIARY TREE RADIOLOGY ADVANCE IMAGING (USG, CT SCAN, MRI AND ERCP) OF ITS AN...
byjuryshira
 
Key Steps to Success With CDK4/6 Inhibition in Early Through Metastatic Breas...
byPVI, PeerView Institute for Medical Education
 
Biostatistics- Data types and presentation
byAnkitMittal145
 
Drug use evaluation and WHO drug use Indicators.pptx
byLok Raj Pant
 
Advanced Prostate Cancer: Symptoms, Progression & Treatment Options
byLetsMeds
 
Lumbar Facet Joint Pain – A Pain Generator Based Diagnostic & Treatment Approach
byDaradia: The Pain Clinic
 
Echocardiography Oct. 15 2023 by Ichilov Hospital
byHaim R. Branisteanu
 
Biotransformation and Excretion
byBadrinathSelvakumar
 
Breast Imaging Breast Imaginorting schem
byNitesh274271
 
metabolic syndrome and fasting ( Dr Mohammed bamashmos , sana'a University) ....
byAimanAlkhadher1
 
Vitamin Deficiency- Vitamin A, C, D (MBBS)
byReenaz Shaik
 
General Anesthetics. Dalamagka, Maria. Anaesthetist- physician
bycatlist1
 
Human Excretory System (RIT): Kidney Functions & Urine Formation Made Easy
byBALAJI SOMA
 
KNEE JOINT -Prof.Dr.N.Mugunthan, KMMC Medical College & Hospitals.pdf
byKanyakumari Medical Mission Research Center, Muttom
 
MEDIATORS OF INFLAMMATION - MBBS
byReenaz Shaik
 
PEDIATRIC CATARACT & IT'S MANAGEMENT BY SAMIKSHA RAI
bySamikshaRai22
 
Retinoscopy & It's Principle - static vs dynamic retinoscopy in detail
bySamikshaRai22
 
Easy Peasy Gut: Complete Digestive Support
byEthniq
 
Basic Anatomy of the Structure of the Cerebellum.pptx
byLucaDonovan
 

ueda2012 do we still need high doses-d.mohammed

  • 1.
    Do we Stillneed High Doses? Professor : Mohamed Gamal Abdel Aziz Aswan 8/2/2012
  • 2.
    Hypertension goes uncontrolledin more than half of adults with the disease 33% 67% NHANES 1999 - 2002 Controlled Blood Pressure Uncontrolled Blood Pressure 46% 54% NHANES 2005-2008 Controlled Blood Pressure Uncontrolled Blood Pressure Ref.: Centers for Disease Control and Prevention. Vital signs: Prevalence, treatment, and control of hypertension—United States, 1999-2002 and 2005-2008. MMWR Morb Mortal Wkly Rep 2011; 60:1-6. Despite the significant improvement in Blood pressure control, still the problem of Uncontrolled patients remains
  • 3.
    Trials in diabeticpatients 40 30 20 10 0 Major CV events (% of patients over 5 years) Zanchetti A, 2009 Antihypertensive treatments fail to reduce incidence of major CV events below high-risk threshold of 10% in 5-year period Trials in high-risk patients 50 40 30 20 10 0 Major CV events (% of patients over 5 years) Reduction of risk Residual risk Trials in elderly patients 40 30 20 10 0 Major CV events (% of patients over 5 years) Dashed horizontal line indicates conventional threshold of high risk; x axes show randomized controlled trials of anti-HTN treatments.
  • 4.
    Current Guidelines RecommendInitiating Combination Therapy Early in Patients with Stage 2 Hypertension or High Cardiovascular Risk • JNC 7 guidelines state1: ―When BP is more than 20 mmHg above systolic goal or 10 mmHg above diastolic 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 3 range or total cardiovascular risk is high or very high.‖ 1Chobanian et al. Hypertension 2003;42:1206–52 2Mancia et al. J Hypertens 2007:25:110587 ESH = European Society of Hypertension ESC = European Society of Cardiology JNC = Joint National Committee
  • 5.
    Low-dose 2-drug combinationLow-dosesingle agent Not at BP goal Full dose of single agent Switch to different agent at low dose Full dose of 2-drug combination Add a third drug at low dose Not at BP goal 2–3 drug combination at full dose Full doses of 2–3-drug combination ESH–ESC: Algorithm for Treatment of Hypertension Full-dose single agent TOD = target organ damage Marked BP elevation High/very high CV risk Lower BP target Mild BP elevation Low/moderate CV risk Conventional BP target Task Force for ESH–ESC. J Hypertens 2007;25:1105–874
  • 6.
    CCB Alpha blockers Beta blockers Diuretics Other RAS blockade TheFoundation RAAS Blockade With ARBs Can Be Considered a Foundation of Antihypertensive and CV Preventive Therapy
  • 7.
    Pre-diabetes Diabetes – Renal RAASBlockers Have Been Studied Extensively in Outcomes Trials High Risk Myocardial infarction • LIFE • SCOPE • STOP 2 • VALUE • KYOTO HEART • CAPPP • ALLHAT • ANBP2 • HOPE • ONTARGET • TRANSCEND • JIKEI HEART • KYOTO HEART • OPTIMAAL • VALIANT • CONSENSUS II • ISIS-4 • GISSI-3 • SMILE • SAVE • AIRE • TRACE Heart failure • NAVIGATOR • DREAM • RENAAL • IDNT • ABCD Hypertension Coronary Artery Disease • EUROPA • PEACE • IMAGINE • ELITE II • Val-HeFT • CHARM • CONSENSUS I • SOLVD • V-HeFT II • PEP-CHF
  • 8.
    GFR Proteinuria Aldosterone release Glomerular sclerosis AIIAT1 Receptor Atherosclerosis* Vasoconstriction Vascular hypertrophy Endothelial dysfunction LV hypertrophy Fibrosis Remodeling Apoptosis Stroke Death *Preclinical data. LV=left ventricular; MI=myocardial infarction; GFR=glomerular filtration rate. Hypertension Heart Failure MI Renal Failure Angiotensin II Plays a Central Role in Organ Damage . Willenheimer R, Dahlof B, Rydberg E, Erhardt L. AT1-receptor blockers in hypertension and heart failure: clinical experience and future directions. Eur Heart J. 1999;20:997–1008. 2. Dahlof B. Effect of angiotensin II blockade on cardiac hypertrophy and remodelling: a review. J Hum Hypertens.1995;9(suppl 5):S37–44. 3. Daugherty A, Manning MW, Cassis LA. Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. J Clin Invest. 2000;105:1605–12.
  • 10.
    Effects of RASblockade on stroke: meta-analysis of ARBs and ACE inhibitors MI Cardiovascular mortality All-cause mortality Stroke Favours ARB Favours ACE inhibitor Reboldi et al. J Hypertension 2008;26:1282–1289 Studies (N=63,409 ): ELITE; ELITE-II; OPTIMAAL; DETAIL; VALIANT; ONTARGET
  • 11.
    Elliott and Meyer.Lancet 2007;369:201–7 0.57 (0.46–0.72) p<0.0001 0.67 (0.56–0.80) p<0.0001 0.75 (0.62–0.90) p=0.002 0.77 (0.63–0.94) p=0.009 0.90 (0.75–1.09) p=0.30 Referent ARB ACE inhibitor CCB Placebo β-blocker Diuretic Odds ratio of incident diabetes Incoherence=0.000017 0.50 0.70 0.90 1.26 Effects of Different Antihypertensive Agents on Incidence of Diabetes Network meta-analysis assessing the effects of different antihypertensive agents on incidence of diabetes in 48 randomised groups from 22 clinical trials* (n=143,153) *17 trials enrolled patients with hypertension, three enrolled high-risk patients and one enrolled patients with heart failure (HF) ARB=angiotensin receptor blocker; ACE=angiotensin-converting enzyme; CCB=calcium channel blocker
  • 12.
    Conditions favoring useof some antihypertensive drugs versus others:
  • 13.
  • 15.
    There is nosuch thing as a simple Class Effect that cover all aspect of different molecules Go with the evidence,do not assume
  • 16.
    1. VALUE 2. VALIANT 3.NAVIGATOR 4. Val-HeFT 5. JIKEI HEART 6. KYOTO HEART* 7. VART* 8. VALISH* 27. IDNT 28. ACTIVE-I* 29. NID-2 30. SUPPORT* 31. COLM* 32. OSCAR* 33. ORIENT* 34. MOSES 1. Julius et al. 2004; 2. Pfeffer et al. 2003; 3. Califf et al 2008; 4. Cohn et al. 2001; 5. Mochizuki et al. 2007; 6. http://clinicaltrials.gov (NCT00149227); 7. Nakayama et al. 2008; 8. NCT00151229; 9. ONTARGET Investigators 2008; 10. Yusuf et al 2008; 11. TRANSCEND Investigators 2008; 12. http://clinicaltrials.gov (NCT00283686); 13. Dahlöf et al. 2002; 14. Dickstein et al. 2002; 15. Pitt et al. 2000; 16. Brenner et al. 2001; 17. http://clinicaltrials.gov (NCT00090259); 18. http://clinicaltrials.gov (NCT00555217); 19. Pfeffer et al 2003; 20. Papademetriou et al. 2004; 21. http://clinicaltrials.gov (NCT00120003); 22. Ogihara et al. 2008; 23. http://clinicaltrials.gov (NCT00108706); 24. Laufs et al. 2008; 25. Suzuki et al. 2005; 26. Massie et al 2008; 27. Lewis et al. 2001; 28. http://clinicaltrials.gov (NCT00249795); 29. http://clinicaltrials.gov (NCT00535925); 30. http://clinicaltrials.gov (NCT00417222); 31. http://clinicaltrials.gov (NCT00454662); 32. http://clinicaltrials.gov (NCT00134160); 33. http://clinicaltrials.gov (NCT00141453); 34. Schrader et al. 2005 9. ONTARGET 10. PRoFESS 11. TRANSCEND 12. HALT-PKD* 13. LIFE 14. OPTIMAAL 15. ELITE II 16. RENAAL 17. NCT00090259* *Expected enrolment ‡Ongoing and completed randomized controlled trials with death or hard CV events as or part of the primary endpoint ¶Valid as of January 2009 Mortality & Morbidity Endpoint Trials with ARBs 18. VA NEPHRON-D* 19. CHARM 20. SCOPE 21. SCAST* 22. CASE-J 23. ACCOST 24. HIJ-CREATE 25. E-COST 26. I-PRESERVE 0 10,000 20,000 30,000 40,000 50,000 60,000 Numberofpatients Valsartan Telmisartan Losartan Candesartan Irbesartan Olmesartan Eprosartan 57,781 52,896 24,841 23,940 6,577 1,405 15,693 1 2 5 4 3 7 8 6 9 10 16 11 17 18 15 13 14 22 25 21 19 20 34 31 30 32 33 28 27 26 24
  • 17.
    Selectivity on AT1Receptor Valsartan Candesartan LosartanIrbesartan Telmisartan 10000 20000 30000 30,000 1000 8500 10,000 3,000 Valsartan is 3 times more selective for AT1 receptors than other ARB agents Siragy H. Am J Cardiol. 1999;84:3S-8S.
  • 18.
    Valsartan: Extensively StudiedAcross the Cardiovascular Continuum 1. Julius et al. Lancet 2004; 363:2022–31; 2. Pfeffer et al. N Engl J Med 2003;349:1893–906; 3. Cohn et al. N Engl J Med 2001; 345:1667–75 4. Califf et al. Am Heart J 2008;156:623–32; 5. Mochizuki et al. Lancet 2007;369:1431–9; 6. Viberti et al. Circulation 2002;106:6728 7. Karalliedde et al. Hypertension 2008;51:161723; 8. SMART Group. Diabetes Care 2007;30:1581–3; 9. Hollenberg et al. J Hypertens 2007;25:19216 MARVAL6 MARVAL II7 SMART8 DROP9 Endothelial dysfunction Microalbuminuria Proteinuria End-stage renal disease Risk factors Diabetes Hypertension Atherosclerosis and LVH Myocardial infarction Ventricular Remodelling Ventricular Dilation Heart Failure End-stage Heart Disease Death Includes over 50,000 patients*19 JIKEI HEART 1 2 3 4 ‡5 *Not all patients in these studies received valsartan ‡Independent, investigator-initiated study
  • 19.
    19 Titrating Valsartan tofull dose optimizes CV/Renal Protection in outcome trial Tareg based therapy 40 - 320 mg out come trials Trial Drug used Dose titration NO. of patient outcome VAL-HEFT Valsartan 40 - 320 mg About 5000 pts Composite Mortality & Morbidity end point reduced by 13.2%, Patients not on ACEi Group reduced By 44% VALLIANT valsartan 40-320 mg About 15,000 25% Mortality risk reduction in Post MI patients DROP valsartan 160 – 320 - 640mg 390 pts 51% reduction in UAER •Maggioni et al. J Am Coll Cardiol 2002;40:1414–21,, •McMurray et al. J Am Coll Cardiol 2006; 47:726–33,, •Hollenberg et al J Hypertens 2007,25:1921-1926
  • 20.
    Valsartan* Provides PowerfulSystolic BP Reductions Across Hypertension Severities -15.9 -23.5 -27 -32.2 -38.9 -46.4 -12.1 -14.3 -17.4 -23.1 -31.5 -25.9 -50 -45 -40 -35 -30 -25 -20 -15 -10 -5 0 140–149 150–159 Post-hoc analysis C-DITT study Category of baseline MSSBP (mmHg) 160–169 170–179 180–189 ChangeinMSSBP(mmHg) atWeek4(LOCF) 6-week, double-blind, multicentre, forced-titration study in patients with DBP ≥110 mmHg and <120 mmHg and SBP ≥140 mmHg and <200 mmHg. Valsartan 160 mg force-titrated to 320 mg at Week 2. Valsartan/HCTZ 160/12.5 mg force-titrated to 160/25 mg and 320/25 mg at Weeks 2 and 4. BP = blood pressure; DBP = diastolic BP; SBP = systolic BP; MSSBP = mean sitting SBP; LOCF = last observation carried forward; C-DITT = Co-Tareg Initial Therapy Trial 190-199 Calhoun et al. Curr Med Opin Res 2008;24:230311
  • 21.
    0 –5 –10 –15 –20 –25 –30 Blacks Hispanic Elderly#Obese‡ Diabetes n=202 n=51 n=117 n=477 n=69 21.4 21.7 25.5 23.6 19.5 n=190 n=58 n=103 n=493 n=97 *p≤0.01 vs valsartan monotherapy: ¶Valsartan 160 mg or valsartan/HCTZ 160/12.5 mg force-titrated to valsartan 320 mg or valsartan/HCTZ 320/12.5 mg, respectively, at Week 2; §SBP ≥160 mmHg and/or DBP ≥100 mmHg; #≥65 years of age; ‡body mass index ≥30 kg/m2; HCTZ = hydrochlorothiazide Val-MARC = Valsartan-Managing blood pressure Aggressively and evaluating Reductions in hsCRPEverett et al.Clin Ther 2008;30:66172 Meanchangefrombaseline inSBPatWeek6(mmHg) 12.6 16.3 16.9 15.9 16.3 * * * * Valsartan and Valsartan-HCTZ Therapy Provides Effective BP Reductions Across Diverse Patient Populations Valsartan/HCTZ¶ Valsartan¶
  • 22.
    Co-Tareg® 320 achievesBP goal in up to 9 out of 10 patients with HTN #BP=Blood pressure; DBP=Diastolic blood pressure; HTN=Hypertension; Ref.: Weir et al. J Clin Hypertens 2007;9:103-112 Results from a pooled analysis of 9 randomized trials# in 4278 patients with HTN§ Patients achieving BP goal <140/90 mmHg (%) Co-Tareg 320/25 mg (n=80) Tareg 320 mg (n=271) Co-Tareg 320/12.5 mg (n=87) 40 60 80 100
  • 23.
    Tareg/Co-Tareg: Proportion ofPatients Achieving BP Goal <140/90 mmHg Co-Tareg 320/25 mg Co-Tareg 320/12.5 mg Tareg 320 mg Co-Tareg 160/25 mg Co-Tareg 160/12.5 mg Tareg 160 mg Co-Tareg 80/12.5 mg Tareg 80 mg Placebo n 167 168 646 94 261 907 96 782 1157 0 10 20 30 40 50 60 70 80 90 100 Patients achieving goal (%) Weir et al. J Clin Hypertens 2007;9:103–112 Meta-analysis of nine randomised, double-blind, placebo-controlled trials; data for overall population shown
  • 24.
    Pooled Analysis ofNine Trials Showed More Patients Achieve JNC-7 Goals* in Less Time with Higher Doses or with Combination Therapy Cumulativeproportionof patientsreaching JNC-7goals*(%) Weir et al. Am J Hypertens 2007;20:811–15 Placebo (n=1,156) Tareg 80 mg (n=781) Co-Tareg 80/12.5 mg (n=96) Tareg 160 mg (n=907) Co-Tareg 160‡ mg (n=355) Tareg 320 mg (n=646) Co-Tareg 320‡ mg (n=335) 90 80 70 60 50 40 30 20 10 0 Pooled analysis of data from nine randomised, double-blind, placebo-controlled trials ‡Tareg at stated dose + HCTZ 12.5 or 25 mg *<140/90 mmHg
  • 25.
  • 27.
    Proteinuria Is anIndependent Risk Factor for Mortality in Type 2 Diabetes 1.0 0.9 0.8 0.7 0.6 0.5 0 1 2 3 4 5 6 Years Survival (all-causemortality) Normoalbuminuria (n=191) [8%] Microalbuminuria (n=86) [20%] Macroalbuminuria (n=51) [35%] Gall, MA et al. Diabetes 1995;44:1303 P<0.01 normo vs. micro- and macroalbuminuria P<0.05 micro vs. macroalbuminuria
  • 28.
    Tareg Reduction ofProteinuria (DROP) Study: Albuminuria response to very high-dose valsartan in type 2 diabetes mellitus Hollenberg et al., Journal of Hypertension 2007, 25:1921-1926
  • 29.
    The DROP study:Objectives Purpose: • To assess the ability of high-dose valsartan to reduce proteinuria in subjects with diabetic nephropathy Primary Objective: • To compare responses to valsartan at 160, 320, and 640 mg/day in patients with hypertension, type 2 diabetes mellitus, and albuminuria (30–1,000 mg/d) Hollenberg NK et al, J Hypertens, 2007, 25:1921-1926
  • 30.
    Study Design • Design:multicentre, double-blind, randomized, parallel group study • Patient population: subjects with hypertension, proteinuria and T2DM Valsartan 160 mg Valsartan 320 mg Valsartan 640 mg Placebo run-inScreening Valsartan 160 mg Week –6 (Visit 1) Week –3 (Visit 3) Week –2 (Visit 4) Week 0 (Visit 6) (Randomisation) Week 4 (Visit 8) Week 16 (Visit 11) Week 30 (Visit 12) Valsartan 160 mg Valsartan 160 mg Hollenberg NK et al, J Hypertens, 2007, 25:1921-1926
  • 31.
    DROP Study: ChangeFrom Baseline in UAER at Week 30 (ITT-1 Population)‡ –25† –51* –49* –60 –50 –40 –30 –20 –10 0 Medianchangein UAERatWeek30(%) Tareg 160 mg (n=130) Tareg 320 mg (n=130) Tareg 640 mg (n=131) ‡Overall population *p<0.001 vs baseline Hollenberg NK. Suppl to Circulation abstracts from scientific sessions 2006:114(18); II-61
  • 32.
    DROP Study: Proportionof Patients Who Returned to Normalisation of UAER (<20 μg/min) at Week 30‡ 12.4 19.2 0 5 10 15 20 25 30 PatientswithUAER <20g/minatendpoint(%) ‡LOCF cases methodology (ITT-1 population) was used *p=0.02 vs Tareg 160 mg Tareg 160 mg (n=130) Tareg 320 mg (n=130) Hollenberg NK. Suppl to Circulation abstracts from scientific sessions 2006:114(18); II-61 Novartis data on file 24.3* Tareg 640 mg (n=131)
  • 33.
    DROP Study: Summary •Tareg produced a significant reduction in UAER of up to 48% in hypertensive patients with diabetes and proteinuria • Up-titration of Tareg to either 320 or 640 mg offered a numerically greater reduction in proteinuria vs 160 mg • Outstanding BP goal rates of up to 74% were achieved with a Tareg-based regimen (64% with the approved doses) • In patients that achieved target BP control of <130/80 mmHg, UAER was reduced by up to 65% • A rapid reduction in proteinuria (17–23%) was observed in all groups during the first 4 weeks • All three doses of Tareg were safe and well tolerated with slightly more frequent dizziness and headache at the 640 mg dose Hollenberg NK. Suppl to Circulation abstracts from scientific sessions 2006:114(18); II-61
  • 34.
    Time post-randomization (months) 100 95 90 85 80 75 70 65 0 Tareg(n=2,511) Placebo (n=2,499) 0 3 6 9 12 15 18 21 24 27 13.2% risk reduction‡ Event-freeprobability(%) ‡p=0.009 vs. placebo *Combined primary endpoint: all-cause mortality, cardiac arrest with resuscitation, hospitalization for worsening heart failure, or therapy with intravenous inotropes or vasodilators RR = relative risk; CI = confidence interval; CHF = congestive heart failure; Val-HeFT = Valsartan Heart Failure Trial. Results from a 23-month mean follow-up study in 5,010 patients with CHF on standard therapy (Val-HeFT study) Cohn et al. N Engl J Med 2001;345:1667–75 Tareg Improves CV Outcomes* in Patients with Congestive Heart Failure on Standard Therapy RR=0.87; 97.5% CI=0.770.97
  • 35.
    *p<0.001;‡Combined primary endpoint:all-cause mortality, cardiac arrest with resuscitation, hospitalization for worsening heart failure, or therapy with intravenous inotropes or vasodilators 33% relative risk reduction (p=0.017) for all-cause mortality ACEI = angiotensin-converting enzyme inhibitor; CHF = congestive heart failure RR = relative risk; CI = confidence interval; Val-HeFT = Valsartan Heart Failure Trial 0 0.486 0.571 0.657 0.743 0.829 0.914 1.000 Time since randomization (months) Event-freeprobability‡ Tareg (n=185) Placebo (n=181) 44% risk reduction* 0 3 6 9 12 15 18 21 24 27 Maggioni et al. J Am Coll Cardiol 2002;40:1414–21 Results from a 23-month mean follow-up study in 366 patients with CHF not on ACEI background therapy (Val-HeFT study post-hoc subgroup analysis) Tareg Significantly Reduces Morbidity and Mortality in Patients with Congestive Heart Failure not on an ACEI RR=0.56; 95% CI=0.390.81
  • 36.
    Captopril 0 0.05 0.1 0.15 0.2 0.25 0.3 0 6 1218 24 30 36 ProbabilityofEvent Mortality by Treatment Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349 Valsartan 4909 4464 4272 4007 2648 1437 357 Months Valsartan vs. Captopril: HR = 1.00; P = 0.982 Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726 Captopril 4909 4428 4241 4018 2635 1432 364 Valsartan + Cap 4885 4414 4265 3994 2648 1435 382 Valsartan Valsartan + Captopril
  • 37.
    Tareg is aseffective as Captopril(ACE-I) in reducing cardiovascular mortality & morbidity in post MI patients by 25% Hazard Ratio for Mortality Favors Active Drug Favors Placebo Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349 0.5 1 2 Combined TRACE SAVE AIRE VALIANT (Valsartan Vs Captopril) 25% Mortality Reduction
  • 38.
    Tareg Reduce BPBeyond 24 Hours Results from a 8-week study in 256 patients with mild-to-moderate hypertension# #sitting DBP between 95 and 115 mm Hg at baseline, *intervals 2-24, n=21 (15 treated with valsartan 80 mg, 6 with 160 mg) intervals 26-48, n=10 (9 treated with valsartan 80 mg, 1 with 160 mg), hour 25-48 without dose Lasko et al. Blood Press Monit 2001;6(2):91-99 15 5 0 -5 -15 -25 -35 15 5 0 -5 -15 -25 -35 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 MeanChangein SBP(mmHg) MeanChangein DBP(mmHg) Time after dose administration (hours)* Mean BP and 95% CI
  • 39.
    Tareg 320 astolerable as placebo Oparil et al. Lancet 2007;370:221–29 ‡Increases in serum potassium over 5·5 mmol/L (but not ≥6·0 mmol/L) were more common with the combined drugs than with the monotherapies or placebo, although the occurrence of such cases after correction for placebo was low. Most of these increases were transient and returned to normal by Week 8. None were associated with AEs or patient discontinuation Placebo (n=458*) Tareg 320 (n=455) Adverse events Any adverse event 168 (37%) 167 (37%) Any serious adverse event 5 (1%) 6 (1%) Discontinuations due to adverse events 10 (2%) 11 (2%) Laboratory abnormalities Serum potassium <3.5 mmol/L 17 (4%) 20 (4%) >5.5 mmol/L‡ 12 (3%) 7 (2%) 6.0 mmol/L 6 (1%) 5 (1%) Creatinines >176.8 µmol/L 0 2 (0.4%) Blood urea nitrogens >14.3 mmol/L 0 1 (0.2%)
  • 40.
    High dose ofValsartan Tareg 320mg for hypertensive high risk patients Superior & complete blockade of the RAS system Significant renal protection in hypertensive patients with diabetes and proteinuria
  • 41.
    So when touse the new high dose of Valsartan? - High risk and very high risk hypertensive patients - For Nephroprotection (Diabetics with proteinuria)
  • 42.
    Conclusions The recommended dosesof AT1 receptor blockers are adequate for blood pressure control. However, they are probably too low to afford an optimal protection of target organs. Thus, there is today a rational for using higher doses of ARBs such as Valsartan 320 mg in high risk patients (ISH severe hypertension, metabolic syndrome, diabetes with proteinuria…)
  • 43.