TERMINATINGTHE TERMINATOR
DR. ABDUL RAB SHAIKH
MD CARDIOLOGY (UK)
DIP CARD (UK)
Consultant Interventional Cardiologist
Red...
Nikolai Korotkov
<40 40-49 50-59 60-69 70-79 80+
Age (y)
17% 16% 16% 20% 20% 11%
Distribution of Hypertension Subtype in the untreated
Hype...
Peripheral vascular
disease
 Morbidity
 Disability
Renal disease
CAD
CHF
LVHStroke
Hypertension
National High Blood Pres...
Treating and Managing blood pressure
ESH–ESC: Algorithm for Treatment of Hypertension
Task Force for ESH–ESC. J Hypertens 2007;25:1105–87
Bakris et al. Am J Kidney Dis. 2000;36:646-661; Bakris et al. Arch Intern Med. 2003;163:1555-1565; Lewis et al. N Engl J M...
Are All ARB’s the same??
Olmesarta
n
Losarta
n
Candesarta
n
Irbesarta
n
Telmisarta
n
Eprosarta
n
Valsarta
n
Prodrug Yes Yes Yes No No No No
Recepto...
ARB’s and half-life
Belz GG et al. Clin Pharmacol Ther 1999;66:367-373
Single administration 6 days administration
Better Blockade of Ang II R...
Irbesartan Blood Pressure Efficacy is
Superior to Losartan
Kassler-Taub K et al. Am J Hypertens 1998;11:44–53.
MeanChangeF...
BP/Baseline(mmHg)
irbesartan 150 mg valsartan 80 mg
Self Measurement
(Morning values)
ABPM
(Trough)
Office Measurement
(T...
Power to Achieve BP Goals in Uncontrolled Hypertensive Patients
Irbesrartan/HCTZ and JNCVII goal BP
Why Irbesartan is Unique?
• Irbesartan’s specific targeting of the AT1 receptor completely blocking of
the renin-angiotens...
ICE: Persistence with initial antihypertensive
monotherapy after 12 months
0
10
20
30
40
50
60
70
Diuretics ACEIs CCBs Los...
UNSURPASSED ECONOMY VS BRANDED ARBs
51.67
39
26
0
10
20
30
40
50
60
50mg 80mg 150mg
Cozaar Diovan Aprovel
Price(Rupees)
Pr...
80
57.14
39
0
10
20
30
40
50
60
70
80
90
100 mg 160mg 300mg
Cozaar Diovan Aprovel
Price(PKR)
Products
Daily Cost of Therap...
We can conclude that APROVEL
• has superior AT 1 receptor blockade activity as compared to
Losartan and Valsartan
• Even A...
We can conclude that
APROVEL (Cont.)
• Controls 8 out of 10 patients who were
uncontrolled on any monotherapy achieved
the...
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  • Nikolai SergeyevichKorotkov (also romanized Korotkoff; Russian: Николай Сергеевич Коротков) (26 February [O.S. 14 February]1874 – 14 March 1920) was a Russian surgeon, a pioneer of 20th century vascular surgery, and the inventor of auscultatory technique for blood pressure measurement.Korotkoff method is a non-invasive auscultatory technique for determining both systolic and diastolic blood pressure levels. The method requires а sphygmomanometer and а stethoscope. Due to ease and accuracy, it is considered a &quot;gold standard&quot; for blood pressure measurementKorotkoff sounds are pulse-synchronous circulatory sounds heard through the stethoscope in auscultation of blood pressure using Riva-Rocci&apos;s sphygmomanometer.Korotkoff test or Korotkoff sign is a collateral circulation test: in aneurysm, if the blood pressure in the peripheral circulation remains fairly high while the artery above the aneurysm is compressed, the collateral circulation is good.The cuff of Riva-Rocci is placed on the middle third of the upper arm; the pressure within the cuff is quickly raised up to complete cessation of circulation below the cuff. Then, letting the mercury of the manometer fall one listens to the artery just below the cuff with a children&apos;s stethoscope. At first no sounds are heard. With the falling of the mercury in the manometer down to a certain height, the first short tones appear; their appearance indicates the passage of part of the pulse wave under the cuff. It follows that the manometric figure at which the first tone appears corresponds to the maximal pressure. With the further fall of the mercury in the manometer one hears the systolic compression murmurs, which pass again into tones (second). Finally, all sounds disappear. The time of the cessation of sounds indicates the free passage of the pulse wave; in other words at the moment of the disappearance of the sounds the minimal blood pressure within the artery predominates over the pressure in the cuff. It follows that the manometric figures at this time correspond to the minimal blood pressure.
  • terminating the terminator

    1. 1. TERMINATINGTHE TERMINATOR DR. ABDUL RAB SHAIKH MD CARDIOLOGY (UK) DIP CARD (UK) Consultant Interventional Cardiologist Red Crescent Institute Of Cardiology
    2. 2. Nikolai Korotkov
    3. 3. <40 40-49 50-59 60-69 70-79 80+ Age (y) 17% 16% 16% 20% 20% 11% Distribution of Hypertension Subtype in the untreated Hypertensive Population in NHANES III by Age ISH (SBP 140 mm Hg and DBP <90 mm Hg) SDH (SBP 140 mm Hg and DBP 90 mm Hg) IDH (SBP <140 mm Hg and DBP 90 mm Hg) 0 20 40 60 80 100 Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age. Franklin et al. Hypertension 2001;37: 869-874. Frequency of hypertension subtypes in all untreated hypertensives (%)
    4. 4. Peripheral vascular disease  Morbidity  Disability Renal disease CAD CHF LVHStroke Hypertension National High Blood Pressure Education Program Working Group. Arch Intern Med. 1993;153:186- 208. Hypertension: A Significant CV and Renal Disease Risk Factor
    5. 5. Treating and Managing blood pressure
    6. 6. ESH–ESC: Algorithm for Treatment of Hypertension Task Force for ESH–ESC. J Hypertens 2007;25:1105–87
    7. 7. Bakris et al. Am J Kidney Dis. 2000;36:646-661; Bakris et al. Arch Intern Med. 2003;163:1555-1565; Lewis et al. N Engl J Med. 2001;345:851-860. Number of BP Medications Antihypertensive Therapy: Number of Agents Required to Achieve BP Goal UKPDS (<85 mm Hg, diastolic) 4321 MDRD (<92 mm Hg, MAP) HOT (<80 mm Hg, diastolic) AASK (<92 mm Hg, MAP) RENAAL (<140/90 mm Hg) IDNT (135/85 mm Hg)
    8. 8. Are All ARB’s the same??
    9. 9. Olmesarta n Losarta n Candesarta n Irbesarta n Telmisarta n Eprosarta n Valsarta n Prodrug Yes Yes Yes No No No No Receptor antagonism Non- competitive Competitiv e (active metabolite is non- competitiv e Non- competitive Non- competitive Non- competitive Competitiv e Non- competitiv e AT1:AT2 affinity 12,500 1,000 >10,000 8,500 >3,000 1,000 20,000 t1/2 (hours) 10-15 6-9 9 11-15 >20 5-9 9 Tmax (hours) 1-2 3-4 3-4 1.5-2 0.5-1 1-2 2-4 Vd (L) 16-29 34 0.1 L/kg 53-93 500 ~13 ~23 Bioavailability (%) 25.6 ~33 14 60-80 50 13 23
    10. 10. ARB’s and half-life
    11. 11. Belz GG et al. Clin Pharmacol Ther 1999;66:367-373 Single administration 6 days administration Better Blockade of Ang II Receptor by irbesartan than valsartan, losartan IRBESARTAN SHOWED SUPERIOR ANTAGONISTIC ACTIVITY AS COMPARE TO VALSARTAN AND LOSARTAN
    12. 12. Irbesartan Blood Pressure Efficacy is Superior to Losartan Kassler-Taub K et al. Am J Hypertens 1998;11:44–53. MeanChangeFromBaseline atWeek8(mmHg) 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 -20 Irbesartan 300 mg (n=134) Diastolic blood pressure -9.7 Irbesartan 150 mg (n=129) -8.7 Losartan 100 mg (n=131) -4.9 placebo (n=138) -11.7 (p<0.01) Irbesartan 300 mg (n=134) Systolic blood pressure -16.4 -12.1 Irbesartan 150 mg (n=129) -11.3 Losartan 100 mg (n=131) -3.7 placebo (n=138) (p<0.01) At Maximum QD Doses Both drugs were well tolerated 8-week, randomized, double blind mild-moderate HTN (95-110 mmHg) Δ 5.1 mm Hg Δ 3.0 mm Hg
    13. 13. BP/Baseline(mmHg) irbesartan 150 mg valsartan 80 mg Self Measurement (Morning values) ABPM (Trough) Office Measurement (Trough) ADBP ASBP (P<0.01) (P<0.01) (P<0.01) (P<0.01) -12 -8 -4 0 (P=0.035) (P<0.01) DBP SBP SBPDBP -16 -12 -8 -4 0 Mancia G, et al. Blood Press Monit 2002 ;7: 135–142 Δ2.5(66%) Δ3.2(46%) Δ3.2(44%) Δ6.2(62%) -10.5 -16.2 -7.3 -10.0 -6.3 -10.2 -3.8 -7.0 -4.8 -7.5 -6.7 -11.6 Δ1.9(40%) Δ4.1(55%) -6.7 3-week washout, 8-week follow-up, randomized, double blind, mild-moderate HTN (95-110 mmHg) Greater BP Reduction Observed in Monotherapy with irbesartan 150mg than valsartan 80mg
    14. 14. Power to Achieve BP Goals in Uncontrolled Hypertensive Patients
    15. 15. Irbesrartan/HCTZ and JNCVII goal BP
    16. 16. Why Irbesartan is Unique? • Irbesartan’s specific targeting of the AT1 receptor completely blocking of the renin-angiotensin system than that offered by angiotensin-converting enzyme inhibitors.(1) • Irbesartan is well absorbed, does not require biotransformation to an active metabolite . • Irbesartan is associated with a strong and consistent dose-response and has been demonstrated to provide a level of angiotensin II antagonism that is statistically superior to that offered by some other ARBs.(1) • Shows better compliance than ACE Inhibitors 1. Adams MA, Trudeau L. Can J Clin Pharmacol. 2000 Spring;7(1):22-31. Irbesartan: review of pharmacology and comparative properties.
    17. 17. ICE: Persistence with initial antihypertensive monotherapy after 12 months 0 10 20 30 40 50 60 70 Diuretics ACEIs CCBs Losartan Beta- blockers AIIRAs‡ Irbesartan 34.4 42.0 43.6 44.7 49.7 51.3 60.8 * * * * * † Univariate analysis * p < 0.05; † p = 0.009 vs. irbesartan ‡ Excluding irbesartan Proportion of patients persistent with initial monotherapy (%) Hasford J et al. J Human Hypertension 2002;16:569–75.
    18. 18. UNSURPASSED ECONOMY VS BRANDED ARBs 51.67 39 26 0 10 20 30 40 50 60 50mg 80mg 150mg Cozaar Diovan Aprovel Price(Rupees) Product Price Comparison Cozaar 50mg Diovan 80mg Aprovel 150mg Saving in comparison with COZAAR 50 mg PKR 26 per day Saving in comparison with DIOVAN 80 mg PKR 13 per day
    19. 19. 80 57.14 39 0 10 20 30 40 50 60 70 80 90 100 mg 160mg 300mg Cozaar Diovan Aprovel Price(PKR) Products Daily Cost of Therapy (Higher doses) Cozaar 100 mg Diovan 160mg Aprovel 300mg Saving in comparison with COZAAR 100 mg PKR 41 per day Saving in comparison with DIOVAN 160 mg PKR 19 approx. per day UNSURPASSED ECONOMY VS BRANDED ARBs
    20. 20. We can conclude that APROVEL • has superior AT 1 receptor blockade activity as compared to Losartan and Valsartan • Even Aprovel initial prescribing dose (150mg) is superior in Blood Pressure lowering efficacy when compared with maximum dose of Losartan (100mg) • Aprovel is superior to Valsartan in Blood Pressure lowering efficacy in monotherapy as well as in combination with HCTZ
    21. 21. We can conclude that APROVEL (Cont.) • Controls 8 out of 10 patients who were uncontrolled on any monotherapy achieved their Blood Pressure goal with CoAprovel • Patients were remained controlled on Aprovel even after 02 years of therapy demonstratrating PERSISTENCE • Along with efficacy, Aprovel is most economical branded ARB available in Pakistan

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