College Call Girls in Haridwar 9667172968 Short 4000 Night 10000 Best call gi...
A clinical update_in_hypertension
1. A Clinical Update in Hypertension See Important Safety Information, including boxed warning for pregnancy, on slides 25-27 TAK-OEC EDARBI is a trademark of Takeda Pharmaceutical Company Limited registered with the U.S. Patent and Trademark Office and used under license by Takeda Pharmaceuticals America, Inc. Trademarks are the property of their respective owners.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12. summary of phase 3 clinical trials: efficacy TAK-OEC See Important Safety Information, including boxed warning for pregnancy, on slides 25-27
13. Extensively Studied in 3672 Patients Taking EDARBI 1. EDARBI (azilsartan medoxomil). Package Insert. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2011. 2. Data on File; 3. White WB, et al. Hypertension . 2011;57:413-420; 4. Bakris GL, et al. J Clin Hypertens . 2011;13:81-88. See Important Safety Information, including boxed warning for pregnancy, on slides 25-27 Study Length (weeks) Total Studied* 1 EDARBI vs placebo, Diovan, Benicar 6 1291 2 EDARBI vs placebo, Benicar 6 1275 3 EDARBI vs Diovan 24 984 4 EDARBI vs ramipril 24 879 5 EDARBI vs placebo in black subjects 6 410 6 EDARBI + CLD vs CLD alone 6 551 7 EDARBI + AML vs AML alone 6 566
14. Study 1 Design: EDARBI vs Placebo, Diovan, Benicar Randomization N=1291 Forced Titration EDARBI 20 mg QD Placebo QD Benicar 20 mg QD Screening 1 week 2 weeks 2 weeks 4 weeks ABPM EDARBI 40 mg QD EDARBI 80 mg QD Placebo QD Diovan 320 mg QD Benicar 40 mg QD ABPM 1. Data on File. EDARBI 40 mg QD Diovan 160 mg QD Single-blind placebo run-in phase Primary endpoint: 24-hour mean ambulatory SBP See Important Safety Information, including boxed warning for pregnancy, on slides 25-27
15.
16. Sustained Efficacy at Each Hour Over 24 Hours in a 6-Week Study SBP, mm Hg 1. EDARBI (azilsartan medoxomil). Package Insert. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2011; 2. White WB, et al. Hypertension . 2011;57:413-420. Study 1: Mean Ambulatory SBP at Each Hour With EDARBI 80 mg at Week 6 Mean baseline 24-hour mean ambulatory SBP: 144.9 mm Hg Hour Post Dose See Important Safety Information, including boxed warning for pregnancy, on slides 25-27 Treatment Group: EDARBI 80 mg (N=285) Benicar 40 mg (N=290) Diovan 320 mg (N=282) Placebo (N=154)
17.
18.
19.
20. EDARBI Responder Rates Percent Reaching Target Response 1. White WB, et al. Hypertension . 2011;57:413-420; 2. Bakris GL, et al. J Clin Hypertens . 2011;13:81-88; 3. EDARBI (azilsartan medoxomil). Package Insert. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2011. 4. Data on File. Responder Rates With EDARBI 80 mg Across 3 Studies Mean baseline clinic SBP: Study 1=157.4 mm Hg; Study 2=159.0 mm Hg; Study 3=157.2 mm Hg Response to therapy defined as achieving a reduction in clinic SBP ≥20 mm Hg and/or reaching a clinic SBP of <140 mm Hg. See Important Safety Information, including boxed warning for pregnancy, on slides 25-27 49% 58% STUDY 1 At Week 6 P =0.05 STUDY 3 At Week 24 P =0.002 STUDY 1 At Week 6 P =0.05 STUDY 2 At Week 6 P =0.402 47% 59% 49% 58% 53% 57% Diovan 320 mg Benicar 40 mg EDARBI 80 mg
21.
22.
23.
24.
25.
26.
27.
28.
29.
Editor's Notes
Read as stated For Internal Use Only LXA-00352
74.5 million adults in the US have hypertension (HTN), which is the most common primary diagnosis in America 1,2 Lifetime risk of developing HTN in adults aged 55 years and over is 90% 2 HTN prevalence has not improved significantly in the past 10 years, regardless of age, sex, or race 3 Additional Information Prevalence An estimated 74.5 million adults ≥20 years of age have high blood pressure (HBP), extrapolated to 2006 with NHANES 2003 to 2006 data Source: NHANES (2003-2006, NCHS) and NHLBI. Percentages for racial/ethnic groups are age-adjusted for Americans ≥20 years of age. Hypertension is defined as systolic blood pressure (SBP) ≥140 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg, taking antihypertensive medication, or being told twice by a physician or other professional that one has HTN. Lifetime Risk For 55-year-old subjects, the risk for developing HTN over 25 years represents their lifetime risk In the Framingham Heart Study, during the 1976-1998 period, 1298 participants (589 men and 709 women) provided 8469 person-years of observation. The residual lifetime risk for developing HTN for study participants was 90%. Lifetime risk for HTN was similar for men and women and did not differ between participants aged 55 and 65 years (hazards ratio [HR] for women vs men aged 55 years, 0.91 [95% confidence interval (CI), 0.80-1.04]. References Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics – 2010 update: a report from the American Heart Association. Circulation. 2010;121:e46-e215. Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42;1206-1252 . Yoon S, Ostchega Y, Louis T. Recent trends in the prevalence of high blood pressure and its treatment and control, 1999-2008. NCHS data brief, no 48. Hyattsville, MD: National Center for Health Statistics. 2010. Vasan RS, Beiser A, Seshadri S, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. JAMA. 2002;287:1003-1010. For Internal Use Only
Despite significant investment in treating HTN, 37 million patients with hypertension do not have their BP under control 2,3 More than two-thirds of hypertensive individuals will require 2 or more antihypertensive drugs to achieve effective BP control 4 Additional Information Source: Egan, 2010 1 Data from NHANES from 2007–2008 was analyzed. Control was defined as a BP <140/90 mm Hg for patients without diabetes and <130/80 mm Hg for patients with diabetes 1 Source: CDC, 2011 3 Data from NHANES from 2005–2008, the most recent nationally representative data available on hypertension, were analyzed. Control was defined as average treated blood pressure <140/90 mm Hg on examination among all persons with hypertension. References Egan BM, Zhao Y, Axon N. US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008. JAMA . 2010;303:2043-2050. Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics–2010 update: a report from the American Heart Association. Circulation. 2010;121:e46-e215. Centers for Disease Control and Prevention (CDC).Vital signs: prevalence, treatment, and control of hypertension --- United States, 1999--2002 and 2005--2008. MMWR Morb Mortal Wkly Rep . 2011 Feb 4;60(4):103-108 Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42;1206-1252. For Internal Use Only
Additional Information Regarding FDA Guidance: Hypertension Indication Previous labeling did not include CV outcomes benefits expected from BP reduction unless supported by clinical trials for a specific drug FDA is now encouraging: All anti-hypertensive agents can include CVD outcome claims in the indication and usage of the prescribing information Citing CVD outcome claims in promotional materials FDA based this decision on: BP control is well established as beneficial in preventing serious CV events Numerous meta-analyses and a few large trials (eg, ALLHAT) have found no consistent differences by class in effects on survival, MI, or stroke for regimens achieving the same BP goals Slides 5-7 speak specifically to these CV outcomes claims Reference US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Guidance for Industry. Hypertension Indication: Drug Labeling for Cardiovascular Outcome Claims. March 2011. For Internal Use Only
Having uncontrolled blood pressure is associated with a considerable increase in cardiovascular risk 1,2 Meta-analysis by Lewington, et al. estimated that the risk of CV death doubles with each 20/10 mm Hg increase in BP 1,3 The relationship between increasing BP and risk of CV death is continuous and log linear starting at 115 mm Hg systolic or 75 mm Hg diastolic, and is present in all age groups from 40 to 89 years 1,3 In addition to cardiovascular mortality, HTN is an independent risk factor for stroke, myocardial infarction, and cardiovascular disease 2 Reducing these morbidities and mortality is the goal of treating hypertension 1 There are no controlled trials demonstrating risk reduction with EDARB I References Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42;1206-1252. Gu Q, Burt VL, Paulose-Ram R, Yoon S, Gillum RF. High blood pressure and cardiovascular disease mortality risk among US adults: the Third National Health and Nutrition Examination Survey Mortality follow-up study. Ann Epidemiol . 2008;18:302-309. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet . 2002;360:1903-1913. For Internal Use Only
The relative risk estimates of CHD events and stroke in the blood pressure difference trials were similar to the epidemiology cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The estimates from the blood pressure difference trials meta-analysis were 22% (95% confidence interval 17% to 27%) reduction in CHD events and 41% (33% to 48%) reduction in stroke. The cohort study meta-analysis showed a 25% decrease in CHD events and a 36% decrease in stroke. There are no controlled trials demonstrating risk reduction with EDARBI Additional information Blood pressure difference trials 1 108 randomized trials of blood pressure lowering drugs recording CHD events and strokes totaling 248,445 subjects were analyzed. BP reductions across trials were standardized to a BP reduction of 10 mm Hg SBP and 5 mm Hg DBP Mean age on trial entry was 62 years with mean study duration of 3.5 years. Number of disease events recorded was 12,324 coronary heart disease events and 5420 strokes Range of mean pretreatment BP in individual trials was 112-186 mm Hg for SBP and 70-119 mm Hg for DBP Epidemiological cohort studies 1,2 61 prospective observational studies of blood pressure and mortality totaling 958,000 subjects were analyzed During 12.7 million person-years at risk, there were approximately 56,000 vascular deaths (12,000 stroke, 34,000 ischemic heart disease, 10,000 other vascular) BP reductions across trials were standardized to a BP reduction of 10 mm Hg SBP and 5 mm Hg DBP References 1. Law MR, Morris JK, and Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological trials. Brit Med J . 2009;338:b1665 doi: 10.1136/bmj.b1665. 2. Lewington S et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903-13. For Internal Use Only
Additional data reported in the JNC guidelines suggest that a 3 mm Hg reduction in usual SBP would save 18,657 lives a year, based on the most recent population data available 1,2,3 Table values are based on SBP and mortality in 5 large population follow-up studies, as reported in Stamler 1991 2 There are no controlled trials demonstrating risk reduction with EDARBI References Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42;1206-1252. Stamler R. Implications of the INTERSALT study. Hypertension. 1991;17(supp 1):I-16-I-20. US Census Bureau. 116 - Deaths by Age and Specific Causes. The 2010 Statistical Abstract. www.census.gov/compendia/statab/cats/births_deaths_marriages_divorces. html. Accessed 11 Nov 2010. For Internal Use Only
Please read boxed warning for pregnancy as stated EDARBI is an angiotensin II receptor blocker (ARB) indicated for the treatment of hypertension in adults to lower blood pressure Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions It may be used alone or in combination with other antihypertensive agents 1. EDARBI (azilsartan medoxomil). Package Insert. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2011. For Internal Use Only
These are the key points that will be discussed during this presentation: For each of these key topics, specific data will be presented and discussed in the context of the relevant clinical study Volume and/or salt depletion should be corrected prior to administering EDARBI, or treatment should start with 40 mg dose Monitor for worsening renal function in patients with renal impairment: In patients whose renal function may depend on the activity of the renin‐angiotensin system, treatment with ACE inhibitors and ARBs has been associated with oliguria or progressive azotemia and rarely with acute renal failure and death. Similar results may be anticipated in patients treated with EDARBI. In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen have been reported. There has been no long‐term use of EDARBI in these patients but similar results may be expected. Trademarks are the property of their respective owners For Internal Use Only
These are the key points that will be discussed during this presentation: For each of these key topics, specific data will be presented and discussed in the context of the relevant clinical study Correct volume or salt depletion prior to administration of EDARBI: In patients with an activated renin‐angiotensin system, such as volume‐ and/or salt‐depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with EDARBI. Serum Creatinine: Small reversible increases in serum creatinine are seen in patients receiving 80 mg of EDARBI. The increase may be larger when co‐administered with chlorthalidone or hydrochlorothiazide and was more likely in patients who had moderate to severe renal impairment at baseline or age 75 years or older. For Internal Use Only WARNING: AVOID USE IN PREGNANCY When pregnancy is detected, discontinue EDARBI as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS AND PRECAUTIONS in complete Prescribing Information.
EDARBI is conveniently administered once daily as an 80 mg tablet Greater sensitivity of some older individuals cannot be ruled out Geriatric Patients: Abnormally high serum creatinine values were more likely to be reported for patients age 75 or older. No overall difference in efficacy vs younger patients, but greater sensitivity of some older individuals cannot be ruled out. In patients with an activated renin-angiotensin system, as by volume or salt depletion, renin-angiotensin-aldosterone system (RAAS) blockers such as azilsartan medoxomil can cause excessive hypotension. In susceptible patients, eg, with renal artery stenosis, RAAS blockers can cause renal failure. Has not been studied in patients with severe hepatic impairment For Internal Use Only
Read as stated For Internal Use Only
A total of 5941 patients were studied in 7 double-blind, randomized, placebo- and comparator-controlled studies 3672 were given EDARBI, 801 were given placebo, and 1468 were given comparator Additional Notes Study 1*: EDARBI 40 mg and EDARBI 80 mg vs placebo, Benicar (olmesartan) 40 mg, Diovan (valsartan) 320 mg 5-arm study; placebo-controlled, active-controlled, forced titration Study 2: EDARBI 20 mg, EDARBI 40 mg, and EDARBI 80 mg vs placebo, Benicar 40 mg 5-arm study; placebo-controlled, active-controlled; no forced titration Study 3 † : EDARBI 40 mg and EDARBI 80 mg vs Diovan 320 mg 3-arm study; active -controlled (not placebo -controlled), forced titration Study 4 ‡ : EDARBI 40 mg and EDARBI 80 mg vs ramipril 10 mg EDARBI compared with the ACE inhibitor ramipril to satisfy an EU requirement for an “other-class” comparator study 3-arm study; active -controlled (not placebo -controlled), forced titration; clinic BP not ambulatory BP monitoring (ABPM) was primary endpoint Study 5: EDARBI 40 mg and EDARBI 80 mg vs placebo in black subjects EDARBI monotherapy was studied in black subjects with mild-to-moderate HTN because a large proportion of the black population exhibits low-renin HTN; therefore, black patients are more likely to have an attenuated response to RAAS-blockade 3-arm study, placebo-controlled Study 6: EDARBI 40 mg + CLD 25 mg and EDARBI 80 mg + CLD 25 mg vs placebo + CLD 25 mg Chlorthalidone (CLD) was selected to evaluate the coadministration of EDARBI and thiazide-type diuretics The 25 mg dose of CLD was selected because 25 mg is the lowest commercially available strength 3-arm study, placebo-controlled Study 7: EDARBI 40 mg + AML 5 mg and EDARBI 80 mg + AML 5 mg vs placebo + AML 5 mg Amlodipine (AML) was selected to evaluate for coadministration with EDARBI because its clinical efficacy is well established, The 5 mg dose of AML was selected because it is the most commonly prescribed dose strength and has better tolerability compared with the higher dose; 3-arm study, placebo-controlled *Doses were up-titrated after 2 weeks as follows: EDARBI 20 mg to 40 mg, EDARBI 40 mg to 80 mg, Benicar 20 mg to 40 mg, Diovan 160 mg to 320 mg † Doses were up-titrated after 2 weeks as follows: EDARBI 20 mg to 40 mg, EDARBI 20 mg to 80 mg, Diovan 80 mg to 320 mg ‡ Doses were up-titrated after 2 weeks as follows: EDARBI 20 mg to 40 mg, EDARBI 20 mg to 80 mg, ramipril 2.5 mg to 10 mg For Internal Use Only
Study 1 compared EDARBI to placebo, Diovan, and Benicar simultaneously 3- to 4-week washout period for subjects previously receiving antihypertensive therapy 2-week, single-blind, placebo run-in period Purpose was to reduce the influence of placebo effect on baseline BP measurement Patients who were nonadherent with the single-blind placebo were not randomized All doses were up-titrated after 2 weeks ABPM was performed at baseline and at 6 weeks Additional Notes Inclusion criteria for all monotherapy studies: Mild-to-moderate essential HTN: Baseline clinic SBP ≥150 and ≤180 mm Hg Baseline 24-hour mean SBP ≥130 and ≤170 mm Hg Not required in Study 4, as clinic SBP was primary endpoint Exclusion criteria for all monotherapy studies: Secondary HTN Baseline clinic DBP >114 mm Hg Baseline 24-hour ABPM of insufficient quality Noncompliance during the placebo run-in period Arm circumference not consistent with available cuff sizes Works nightshift History of myocardial infarction, unstable angina, heart failure, coronary intervention, hypertensive encephalopathy, cardiovascular accident, or transient ischemic attack In coadministration studies and active-controlled monotherapy studies without a placebo control (Studies 3, 4, 6, and 7), subjects with a history of cardiovascular event may have been enrolled at the investigator’s discretion if the event was >6 months prior History of severe renal disease (eGFR <30 mL/min/1.73 m 2 ) Based on creatinine clearance in Study 4 Suspected unilateral or bilateral renal artery stenosis Hyperkalemia Use of other medication classes known to have BP altering effects (other antihypertensives, insulin, thiazolidinediones, tricyclic antidepressants, MAO inhibitors, atypical antipsychotics, diet medications, amphetamines, systemic corticosterioids, chronic use of cold medications, and NSAIDs) For Internal Use Only
For Internal Use Only EDARBI 80 mg was statistically superior to the highest doses of Diovan and Benicar in Study 1 as measured by 24-hour ABPM FDA-approved PI includes statistical superiority in 24-hour mean ambulatory SBP with EDARBI 80 mg compared with Diovan 320 mg and Benicar 40 mg These data are from Study 1 of 3 studies investigating EDARBI superiority over Diovan and Benicar Patient numbers in each study arm: Diovan (n=282); Benicar (n=290); EDARBI 80 mg (n=285)
The efficacy of EDARBI 80 mg was sustained over 24 hours Data shown here are from Study 1. Study 1 design was previously reviewed. Studies 2 and 3 showed similar 24-hour ambulatory blood pressure profiles. For Internal Use Only
EDARBI 80 mg was superior to the highest doses of Diovan and Benicar in Studies 1, 2, and 3, as measured by 24-hour ABPM EDARBI 80 mg lowered SBP 4.3 mm Hg and 4.0 mm Hg further than the highest dose of Diovan and 2.6 mm Hg and 2.0 mm Hg further than the highest dose of Benicar FDA-approved PI includes statistical superiority in 24-hour mean ambulatory SBP with EDARBI 80 mg compared with Diovan 320 mg and Benicar 40 mg Patient numbers in each study arm: Study 1: Diovan (n=282); Benicar (n=290); EDARBI 80 mg (n=285) Study 2: Benicar (n=282); EDARBI 80 mg (n=285) Study 3: Diovan (n=326); EDARBI 80 mg (n=329) EDARBI was effective in reducing BP regardless of age, gender, or race EDARBI was effective in reducing BP regardless of the age, gender, or race of patients, but the effect as monotherapy was smaller (approximately half), in black patients, who tend to have low renin levels This has been generally true for other angiotensin II antagonists and ACE inhibitors Geriatric Patients: Abnormally high serum creatinine values were more likely to be reported for patients age 75 or older. No overall difference in efficacy versus younger patients, but greater sensitivity of some older individuals cannot be ruled out For Internal Use Only
EDARBI 80 mg was superior to the highest dose of Diovan in Study 1 and Study 3 in reducing clinic SBP EDARBI 80 mg lowered clinic SBP 5.4 mm Hg and 5.3 mm Hg further than the highest dose of Diovan as measured by the mean change from baseline to Week 6 (Study 1) or Week 24 (Study 3) This difference was statistically significant in both Study 1 and Study 3 Patient numbers in each study arm: Study 1: Diovan (n=278); EDARBI (n=283) Study 3: Diovan (n=326); EDARBI (n=329) Serum Creatinine: Small reversible increases in serum creatinine are seen in patients receiving 80 mg of EDARBI. The increase may be larger when co‐administered with chlorthalidone or hydrochlorothiazide and was more likely in patients who had moderate to severe renal impairment at baseline or age 75 years or older. In volume- and/or salt-depleted patients, symptomatic hypotension may occur after initiation of treatment with EDARBI. Correct volume or salt depletion prior to administration of EDARBI, or start treatment at 40 mg For Internal Use Only
EDARBI 80 mg was superior to the highest dose of Benicar in Study 1 and Study 2 in reducing clinic SBP EDARBI 80 mg lowered clinic SBP 3.5 mm Hg and 2.7 mm Hg further than the highest dose of Benicar as measured by the mean change from baseline to Week 6 (mm Hg) Patient numbers in each study arm: Study 1: Benicar (n=290); EDARBI 80 mg (n=285) Study 2: Benicar (n=282); EDARBI 80 mg (n=285) Serum Creatinine: Small reversible increases in serum creatinine are seen in patients receiving 80 mg of EDARBI. The increase may be larger when co‐administered with chlorthalidone or hydrochlorothiazide and was more likely in patients who had moderate to severe renal impairment at baseline or age 75 years or older. In volume- and/or salt-depleted patients, symptomatic hypotension may occur after initiation of treatment with EDARBI. Correct volume or salt depletion prior to administration of EDARBI, or start treatment at 40 mg For Internal Use Only
This slide shows the proportion of patients who had a reduction in clinic SBP to <140 mm Hg and⁄or a reduction of 20 mm Hg with EDARBI 80 mg across 3 studies Study 1 was a 6-week, randomized, double-blind, placebo-controlled, forced-titration study in patients (N=1291) with clinic SBP ≥150 mm Hg and ≤180 mm Hg and 24-hour mean SBP ≥130 mm Hg and ≤170 mm Hg. The primary endpoint was change in 24-hour mean ambulatory SBP. Study 2 was a 6-week, randomized, double-blind, placebo-controlled study in patients (N=1275) with clinic SBP ≥150 mm Hg and ≤180 mm Hg and 24-hour mean SBP ≥130 mm Hg and ≤170 mm Hg. The primary endpoint was change in 24-hour mean ambulatory SBP. Study 3 was a 24-week, randomized, double-blind, forced-titration study in patients (N=984) with clinic SBP ≥150 mm Hg and ≤180 mm Hg and 24-hour mean SBP ≥130 mm Hg and ≤170 mm Hg. The primary endpoint was change in 24-hour mean ambulatory SBP. For Internal Use Only
EDARBI has its usual BP-lowering effect size when added to a thiazide-type diuretic (chlorthalidone) EDARBI 80 mg co-administered with CLD 25 mg provided an additional 15.5 mm Hg reduction in 24-hour mean ambulatory SBP vs CLD 25 mg alone EDARBI 40 mg co-administered with CLD 25 mg provided an additional 14.4 mm Hg reduction in clinic SBP vs CLD 25 mg alone (36.2 mm Hg reduction vs 21.8 mm Hg reduction, respectively) Serum Creatinine: Small reversible increases in serum creatinine are seen in patients receiving 80 mg of EDARBI. The increase may be larger when co‐administered with chlorthalidone or hydrochlorothiazide and was more likely in patients who had moderate to severe renal impairment at baseline or age 75 years or older. Volume and/or salt depletion should be corrected prior to administering EDARBI, or start treatment at 40 mg dose Additional Notes Inclusion and exclusion criteria for co-administration studies were similar to those for monotherapy studies, with the following exceptions: Inclusion criteria: Moderate to severe essential HTN (instead of mild-to-moderate essential HTN): Baseline clinic SBP ≥160 and ≤190 mm Hg Baseline 24-hour mean SBP ≥140 and ≤180 mm Hg Exclusion criteria: Baseline clinic DBP >117 mm Hg (instead of >114 mm Hg) Hypokalemia, in addition to hyperkalemia (Study 6 only) For Internal Use Only
EDARBI has its usual BP-lowering effect size when added to a calcium channel blocker (amlodipine) EDARBI 80 mg co-administered with AML 5 mg provided an additional 10.9 mm Hg reduction in 24-hour mean ambulatory SBP vs AML 5 mg alone EDARBI 40 mg co-administered with AML 5 mg provided an additional 11.2 mm Hg reduction in clinic SBP vs AML 5 mg alone (27.0 mm Hg reduction vs 15.9 mm Hg reduction, respectively) Volume and/or salt depletion should be corrected prior to administering EDARBI, or treatment should start under close medical supervision Additional Notes Inclusion and exclusion criteria for co-administration studies were similar to those for monotherapy studies, with the following exceptions: Inclusion criteria: Moderate to severe essential HTN (instead of mild-to-moderate essential HTN): Baseline clinic SBP ≥160 and ≤190 mm Hg Baseline 24-hour mean SBP ≥140 and ≤180 mm Hg Exclusion criteria: Baseline clinic DBP >117 mm Hg (instead of >114 mm Hg) Hypokalemia, in addition to hyperkalemia (Study 6 only) For Internal Use Only
EDARBI was evaluated for safety in 4814 patients Safety data were pooled from all 7 Phase 3, double-blind clinical trials plus 2 additional open-label, long-term safety studies Data were collected for all patients exposed to EDARBI for ≥1 day Withdrawal rates were pooled from placebo-controlled monotherapy and combination therapy trials The most common adverse event leading to discontinuation, hypotension/orthostatic hypotension, was reported by 0.4% (8/2146) patients randomized to EDARBI 40 mg or 80 mg compared to 0% (0/801) patients randomized to placebo For Internal Use Only
For Internal Use Only
Please read the Important Safety Information for EDARBI outlined on this slide. For Internal Use Only
Please read the Important Safety Information for EDARBI outlined on this slide. For Internal Use Only
Please read the Important Safety Information for EDARBI outlined on this slide. For Internal Use Only
These are the key points that will be discussed during this presentation: For each of these key topics, specific data will be presented and discussed in the context of the relevant clinical study Volume and/or salt depletion should be corrected prior to administering EDARBI, or treatment should start with 40 mg dose Monitor for worsening renal function in patients with renal impairment: In patients whose renal function may depend on the activity of the renin‐angiotensin system, treatment with ACE inhibitors and ARBs has been associated with oliguria or progressive azotemia and rarely with acute renal failure and death. Similar results may be anticipated in patients treated with EDARBI. In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen have been reported. There has been no long‐term use of EDARBI in these patients but similar results may be expected. Trademarks are the property of their respective owners For Internal Use Only
These are the key points that will be discussed during this presentation: For each of these key topics, specific data will be presented and discussed in the context of the relevant clinical study Correct volume or salt depletion prior to administration of EDARBI: In patients with an activated renin‐angiotensin system, such as volume‐ and/or salt‐depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with EDARBI. Serum Creatinine: Small reversible increases in serum creatinine are seen in patients receiving 80 mg of EDARBI. The increase may be larger when co‐administered with chlorthalidone or hydrochlorothiazide and was more likely in patients who had moderate to severe renal impairment at baseline or age 75 years or older. For Internal Use Only WARNING: AVOID USE IN PREGNANCY When pregnancy is detected, discontinue EDARBI as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS AND PRECAUTIONS in complete Prescribing Information. LXA-00352
![Hypertension Affects Over 50% of Americans Over Age 55 ,[object Object],[object Object],Percent of Population Prevalence of Hypertension in Adults ≥20 Years of Age (by age and sex) 1. Adapted from Lloyd-Jones D, et al. Circulation . 2010;121:e46-e215. 2. Chobanian AV, et al. Hypertension . 2003;42:1206-1252. 3. Vasan RS, et al. JAMA . 2002;287:1003-1010. See Important Safety Information, including boxed warning for pregnancy, on slides 25-27 70 90 80 60 50 40 30 20 10 0 20-34 35-44 45-54 55-64 65-74 75+ Men Women 12 7 24 16 39 38 53 54 65 71 65 77 Age (years)](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)