CSM-1 Patients With and Without Obesity LSM Difference and 95% CI in BP (230, 231 Pooled) † -8-7-6-5-4-3-2012345678 Diastolic BP Overall (N = 1,191) Obese.

Slides:

Advertisements

Similar presentations

CR-1 ATACAND ® (candesartan cilexetil) Cardiovascular and Renal Drugs Advisory Committee Bethesda, Maryland July 18, 2002 C.

Advertisements

Newly diagnosed hypertensive patients with type 2 diabetes (n = 1544) Randomisation Avoid ACE inhibitors/ beta-blockers (n = 390) Tight BP control (n =

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by.

1 SECOND AUSTRALIAN NATIONAL BLOOD PRESSURE STUDY (ANBP-2) Enalapril/ACEI vs. HCTZ, n = 6,083 Randomized, open-label (blinded endpoint review) All CV events.

Basic Design Consideration. Previous Lecture Definition of a clinical trial The drug development process How different aspects of the effects of a drug.

Resistant hypertension increases patients’ cardiovascular risk 30% of all treated patients develop resistant hypertension [1-5]. Resistant hypertension.

TROPHY TRial Of Preventing HYpertension. High-normal BP increases CV risk Vasan RS et al. N Engl J Med. 2001;345: Incidence of CV events in women.

Cholesterol quintile (mg/dL)

©2007 RUSH University Medical Center Hyperuricemia in adolescents with primary hypertension: how and when to intervene? Farahnak Assadi, M.D. Professor.

1 The JNC 7 recommendations for initial or combination drug therapy are based on sound scientific evidence.

CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved Purpose To determine whether the angiotensin.

BEAUTI f UL: morBidity-mortality EvAlUaTion of the I f inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction Purpose.

Results of Monotherapy in ALLHAT: On-treatment Analyses ALLHAT Outcomes for participants who received no step-up drugs.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT study overview Double-blind, randomized trial to determine whether.

Blood Pressure Control By Randomized Drug Group In ALLHAT William C. Cushman, Charles E. Ford, Paula T. Einhorn, Jackson T. Wright, Jr., Richard A. Preston,

Blood Pressure Lability During Cardiac Surgery Is Associated With Adverse Outcomes Solomon Aronson, Edwin G. Avery, Cornelius Dyke, Joseph Varon, Jerrold.

1 The Study of Trandolapril- verapamil And insulin Resistance STAR determined whether glycaemic control was maintained to a greater degree by an RAS inhibitor/non-DHP.

New concept – no traditional combination LODOZ contains Bisoprolol and Hydrochlorothiazide in subtherapeutic dosages: - Bisoprolol 2.5 mg (= half / quarter.

Success and Predictors of Blood Pressure Control in Diverse North American Settings: The Antihypertensive and Lipid- lowering Treatment to Prevent Heart.

0902CZR01NL537SS0901 RENAAL Altering the Course of Renal Disease in Hypertensive Patients with Type 2 Diabetes and Nephropathy with the A II Antagonist.

Scott D. Solomon 1, Evan Appelbaum 2, Warren J. Manning 2, Anil Verma 1, Tommy Berglund 3, Valentina Lukashevich 4, Cheraz Cherif-Papst 5, James Carten.

Is It the Achieved Blood Pressure or Specific Medications that Make a Difference in Outcome, or Is the Question Moot? William C. Cushman, MD Professor,

1 Role of Candesartan. Antagonist: AT 1 receptor interaction Losartan Candesartan Rapid dissociation Slow dissociation Lower affinity High affinity Re-association.

Long-Term Efficacy of Dapagliflozin in T2DM Patients Receiving High-Dose Insulin John P.H. Wilding, DM, FRCP 

The TRial Of Preventing HYpertension (TROPHY) TROPHY.

Avoiding Cardiovascular Events through COMbination Therapy in Patients LIving with Systolic Hypertension The First Outcomes Trial of Initial Therapy With.

Copyleft Clinical Trial Results. You Must Redistribute Slides HYVET Trial The Hypertension in the Very Elderly Trial (HYVET)

Dick de Zeeuw Department of Clinical Pharmacology University Medical Center Groningen The Netherlands Albuminuria; a tool for measuring non-blood pressure.

CARU The HY pertension in the V ery E lderly T rial – latest data Stephen Jackson Professor of Clinical Gerontology King’s Health Partners.

Aim To determine the effects of a Coversyl- based blood pressure lowering regimen on the risk of recurrent stroke among patients with a history of stroke.

To assess the prognostic value of variability in home-measured blood pressure (BP) and heart rate (HR) in a general population. Objective: Methods: BP.

Monocyte damaged endothelium macrophage foam cell lipid thrombocytes plaque oxidative stress smooth muscle cells 4 5 Gaviraghi et al., 1998 Lacidipine:

7/27/2006 Outcomes in Hypertensive Black and Nonblack Patients Treated with Chlorthalidone, Amlodipine, and Lisinopril* * Wright JT, Dunn JK, Cutler JA.

Efficacy and Comparability of Thiazide-type Diuretics

A Controlled Trial of Renal Denervation for Resistant Hypertension

Change in SBP (mmHg) OmapatrilatEnalapril HCTZ (n = 2476) Change in Systolic BP at Week 24 for Patients Receiving Adjuncts After Week 8 (All Randomized.

Empagliflozin Reduces Blood Pressure in Patients With Type 2 Diabetes and Hypertension Featured Article: Ilkka Tikkanen, Kirsi Narko, Cordula Zeller, Alexandra.

Slide Source: Lipids Online Slide Library Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Design Sever PS et al. J Hypertens 2001;19:1139–1147.

VBWG Growth in heart disease, 2000–2050 Deaths Population Foot DK et al. J Am Coll Cardiol. 2000;35:

1 ALLHAT Antihypertensive Trial Results by Baseline Diabetic Status January 28, 2004.

Long-term Cardiovascular Effects of 4.9 Years of Intensive Blood Pressure Control in Type 2 Diabetes Mellitus: The Action to Control Cardiovascular Risk.

Canagliflozin Cardiovascular Safety. 2 Potential CV protection pathways of SGLT2i Diab Vasc Dis Res Mar;12(2):

Downloaded from Slide 1 Dual Inhibition of Two Sources of Cholesterol: Absorption and Production Results of a Clinical Trial.

Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease (HOPE-3 trial) R4. 박은지 / PF. 정혜문 Salim Yusuf, M.B., B.S., D.Phil.,

Date of download: 5/29/2016 Copyright © The American College of Cardiology. All rights reserved. From: Renal Denervation in Moderate Treatment-Resistant.

Journal Club February 7, 2014 Sadie T. Velásquez, MD.

Results from ASCOT-BPLA: Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm VBWG.

Over Time Additional Risk Factors Can Progress: Effect of Cholesterol and BP on CHD Risk in MRFIT Trial

Cardiovascular Disease and Antihypertensives The RENAAL Trial Reference Brunner BM, and the RENAAL study group. Effects of losartan on renal and cardiovascular.

Update on therapy-resistant hypertension:

Blood Pressure and Age in Controlling Hypertension

Health and Human Services National Heart, Lung, and Blood Institute

Neal B, et al. Diabetes Care 2015;38:403–411

Aliskiren and Valsartan for Antihypertensive Therapy Trial

Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease Martin et al. Am J Nephrol 2017;45: (DOI:

ALLHAT: What Outcomes Would Have Been Expected?

The Hypertension in the Very Elderly Trial (HYVET)

MARFAN SARTAN Trial design: Marfan patients were randomized to losartan (n = 153) vs. placebo (n = 150). The dose of losartan was 50 mg for those

Efficacy and safety of naproxcinod in the treatment of patients with osteoarthritis of the knee: a 13-week prospective, randomized, multicenter study

Time point Difference in systolic BP (mm Hg) p

End point Net change with soy supplements vs control (95% CI) p

Adjusted relative risk for developing end-stage renal disease (ESRD) associated with blood-pressure level BP level (mm Hg) Adjusted relative risk 95%

Reasons patients were excluded from the switch from atorvastatin to simvastatin J. A. Usher-Smith, et al. Int J Clin Pract 2007; 61:15–23.

HOPE-3 Trial design: Patients without known cardiovascular disease, and with an intermediate risk of cardiovascular events, were randomized in a 2 x 2.

DENERHTN Trial design: Patients with resistant hypertension were randomized to renal denervation plus standardized stepped-care antihypertensive treatment.

Entry, Randomization, and Follow-up of Patients in the Hypertension in the Very Elderly Trial Of the 461 patients who did not meet the protocol criteria,

VK2809 in NAFLD: a phase 2 study

End point Valsartan Valsartan+HCTZ p

Effects of placebo or carvedilol CR on 24-hour mean systolic blood pressure and diastolic blood pressure obtained by ambulatory monitoring in hypertensive.

Role of - Azilsartan - Azilsartan/chlorthalidone

Presentation transcript:

CSM-1 Patients With and Without Obesity LSM Difference and 95% CI in BP (230, 231 Pooled) † Diastolic BP Overall (N = 1,191) Obese (n = 650) Not obese (n = 537) Systolic BP Overall (N = 1,191) Obese (n = 650) Not obese (n = 537) Trough change from baseline at Wk 8, ITT Favors CCFavors losartan 14 CC = Candesartan cilexetil. Obese = BMI ≥ 30 kg/m 2. †Post hoc. ITT population.

CSM-2 Dose Related BP Reduction Mean Change in BP From Baseline at 8 Weeks Measured 24 hr postdose CC = Candesartan cilexetil. *p < vs placebo (per protocol population). Note: p < for dose response over the dose range studied, 2 mg to 32 mg, for DBP and SBP. Adapted from Reif M, et al. Am J Cardiol. 1998;82: * * * * * * 14

CSM-3 Comparison of Antihypertensive Efficacy of Candesartan Cilexetil and Losartan Study Design (175) 1 Gradman AH, et al. Heart Disease. 1999;1: CSR 175 Fig mg 50 mg Placebo run-in 32 mg 16 mg 04 weeks8 weeks Losartan Candesartan cilexetil RAN RRAANNDODOMMIIZZEEDDRRAANNDODOMMIIZZEEDDMIZED Randomized, double-blind, multicenter, titration-to-effect, parallel-group design

CSM-4 Least Squares Mean Change From Baseline to Week 8: Once-daily vs Twice-daily Candesartan Cilexetil (116) (n = 90)(n = 93)(n = 91) *p < versus placebo for each treatment. Zuschke C et al. Clin Ther. 1999; 21: * * * * p = NS 15

CSM-5 Mean Change in Trough Diastolic Blood Pressure from Baseline to Week 4 (Weber) Placebo (n = 30) Losartan 50 mg QD (n = 29) Losartan 100 mg QD (n = 28) Losartan 50 mg BID (n = 30) *p < 0.05 vs placebo ** p < 0.01 vs placebo Baseline DBP, mm Hg Weber MA, et al. Arch Intern Med. 1995;155: * ** mm Hg

CSM-6 Patients With and Without Diabetes LSM Difference and 95% CI in BP (230, 231 Pooled) † Diastolic BP Overall (N = 1,191) Diabetes (n = 107) No diabetes (n = 1,084) Systolic BP Overall (N = 1,191) Diabetes (n = 107) No diabetes (n = 1,084) Trough change from baseline at Wk 8, ITT Favors CCFavors losartan 14 †Post hoc. ITT population. CC = Candesartan cilexetil.

CSM-7 Subpopulations Trough Diastolic Blood Pressure (230, 231) PopulationN  N  N  N  Overall284(–10.4)280(–9.0)321(–11.0)306(–8.9) Black57(–6.4) 52(–7.7)57(–8.2) 47(–6.6) Non-Black227(–11.4)228(–9.3)264(–11.6)259(–9.4) Age ≥ 65 yr58(–8.7) 50(–8.7) 52(–11.1) 47(–8.1) Age < 65 yr226(–10.9)230(–9.1)269(–11.0)259(–9.1) Female118(–11.1)121(–9.8)137(–11.3)127(–9.9) Male166(–9.9)159(–8.4)184(–10.9)179(–8.3) CC = Candesartan cilexetil. ITT population. CSR 230, 231 Table 26 C mm Hg Study 230Study 231 CCLosartanCCLosartan

CSM-8 Mean Change From Baseline to Week 8 in Diastolic Ambulatory Blood Pressure (CHAMP) Lacourcière Y & Asmar R for the Candesartan/Losartan Study Investigators. Am J Hypertens. 1999;12: –2 –4 –6 –8 –10 – Time after dose, hr 2 Candesartan cilexetil 16 mg (n = 106) Losartan 100 mg (n = 100) Mean Change in DBP, mm Hg

CSM-9 Mean Change From Baseline to Week 8 in Systolic Ambulatory Blood Pressure (CHAMP ) Lacourcière Y & Asmar R for the Candesartan/Losartan Study Investigators. Am J Hypertens. 1999;12: –2 –4 –6 –8 –10 –12 –14 –16 – Candesartan cilexetil 16 mg (n = 106) Losartan 100 mg (n = 100) Time after dose, hr Mean Change in SBP, mm Hg 2

CSM-10 Change From Baseline for Serum Chemistry and Hematology Parameters in Randomized Patients Study 230 Study 231 ParameterCCLosartan CC Losartan ALAT, U/L Alkaline phos, U/L ASAT, U/L 1.1–0.7– Bilirubin total, mg/dL Creatinine, mg/dL Potassium, mEq/L Urea nitrogen, mg/dL Uric acid, mg/dL–0.1– –0.5 HCT, %–0.5–0.3–0.2–0.2 Hb, g/dL–0.2–0.1–0.1–0.1 WBC, 10 3 /µL – CSR 230, 231 Table 32 CC = Candesartan cilexetil. Safety population.

CSM-11 Patient Compliance † (230) Compliant, n (%) Treatment< 90%≥ 90%Total, N Candesartan cilexetil 28 (9)279 (91)307 (100) Losartan17 (6)287 (94)304 (100) Total45 (7)566 (93) 611 (100) 7 †Based on tablet counts.

CSM-12 BP Determination Methods (230, 231) Patients: sitting for 5 minutes Sphygmomanometer: Hg column, appropriate cuff size at heart level, right arm Readings:Systolic = Korotkoff I Diastolic = Korotkoff V Determination Mean of 3 sequential readings ≥ 2 minutes apart with ≤ 5 mm Hg highest to lowest value Qualifying blood pressure: diastolic 95 to 114 mm Hg at Wk 3 and 4 (or 4 and 5) of placebo run-in period

CSM-13 Controlled Patients and Responders at Week 8 (Pooled) N = 639N = 625N = 639N = 625N = 639N = 625N = 639N = 625 Control DBP: DBP < 90 mm Hg; Control: SBP < 140 mm Hg; Control DBP and SBP: DBP < 90 mm Hg and SBP < 140 mm Hg; Responder: DBP < 90 mm Hg or DBP ≥ 10 mm Hg decrease. 19

CSM-14 Regulatory Precedent ZESTRIL ® /Prinivil ® Comparative Studies Lisinopril vs HCTZ vs lisinopril + HCTZ Multicenter, randomized, parallel, double-blind, titration-to-effect, 24 wk with extension 390 patients with mild to moderate HTN (DBP 90 to 120 mm Hg) Lisinopril 20 to 80 mg, HCTZ 12.5 to 50 mg or lisinopril 20 mg + HCTZ 12.5 to 80 mg + 50 mg Primary endpoint: mean reduction in diastolic BP Significant reductions in systolic and diastolic BP at Wk 12 and 24: HCTZ + lisinopril (–18.2 mm Hg) > lisinopril (–12.5 mm Hg) > HCTZ (–6.8 mm Hg) (p  0.01)