1 / 25

Change in Systolic BP at Week 24 for Patients Receiving Adjuncts After Week 8 (All Randomized Patients)

Enalapril. Omapatrilat. Change in Systolic BP at Week 24 for Patients Receiving Adjuncts After Week 8 (All Randomized Patients). Other Diuretics (n = 690). Other CCB (n = 735). Beta Blockers (n = 890). HCTZ (n = 2476). Amlodipine (n = 695). ARB (n = 274). Change in SBP (mmHg).

niveditha
Télécharger la présentation

Change in Systolic BP at Week 24 for Patients Receiving Adjuncts After Week 8 (All Randomized Patients)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Enalapril Omapatrilat Change in Systolic BP at Week 24 for Patients Receiving Adjuncts After Week 8 (All Randomized Patients) Other Diuretics(n = 690) Other CCB(n = 735) Beta Blockers(n = 890) HCTZ(n = 2476) Amlodipine(n = 695) ARB(n = 274) Change in SBP (mmHg) OCTAVE (CV137-120)

  2. Omapatrilat (n = 65) Enalapril (n = 70) OCTAVE Group 3: Effectiveness of Omapatrilatin Patients Treated with HCTZ and Amlodipineat Randomization at Week 24 SBP DBP BP Change (mmHg) OCTAVE (CV137-120)

  3. Enalapril Comparison in Severe Hypertension(CV137-049) B1 B8 B15 B29 B71 20 40 40 80 Forced titrationto 40, elective to 80 Omapatrilat C1 Adjunct Level I Level II Level III SeDBP 115-130mmHg Forced titration to 20, elective to 40 Enalapril 10 20 20 40 A7 B1 B71 C1 Period A Single-Blind Placebo Lead-In Period B Double-Blind Randomized Period C Long-Term Open-Label

  4. Primary Efficacy ResultsMean Changed from Baseline in Trough SeDBP,and SeSBP and SePP at Week 10 CV137-049

  5. Most Common Adverse Events* * Excluding Angioedema OCTAVE (CV137-120)

  6. Definition of Hospitalization for Heart Failure • OVERTURE Trial • Included all hospitalizations attributable to heart failure as adjudicated by Endpoint Committee which required IV treatmentand had a duration > 24 hours • SOLVD Treatment Trial • Included all hospitalizations attributable to heart failure by the investigator regardless of treatment or duration OVERTURE (CV137-068)

  7. Study Design (CV137-071) Single blind Double blind Placebo Omapatrilat 10 mg 40 mg 80 mg +CAD +Exertional angina R wk 1 wk 2 wk 4 ETT ETT Placebo ETT ETT 3 Wk (max) Period A 4 Wk Period B Day 28 Day 29 BMS data on file

  8. Omapatrilat Placebo Primary Efficacy Results:Change in Peak Exercise Parameters vs Baseline ETT p < 0.001 p < 0.001 p < 0.001 Increased Time (sec) Maximal Exercise Duration Time to Onset of Angina Time to ST Depression BMS data on file CV137-071

  9. Type II diabetics with microalbuminuria (30-300 mg/gram creatinine) or overt nephropathy (> 300 mg/gram creatinine) omapatrilat 20 mg 40 mg 80 mg amlodipine DBP 85-110 mmHg or SeSBP 130-180 mmHg 2.5 mg 5 mg 10 mg wk 4 wk 8 Elective titration Randomization 12 week Double-blind 2 week placebo lead-in Diabetic Patients (CV137-046)

  10. Omapatrilat Amlodipine Summary of Primary Efficacy Results Adjusted Geometric Mean % Change from Baseline for Albumin Excretion Rate Adjusted GM% Change from Baseline Study Week CV137-046

  11. Losartan Comparison in LVH (CV137-038) omapatrilat 20 mg 40 mg 80 mg + HCTZ 80 mg + HCTZ/AML Baseline EchoLVH losartan HypertensionDBP 95-115 mmHgand / orSBP 160-200 mmHg 50 mg 100 mg 100 mg + HCTZ 100 mg + HCTZ/AML Wk 8 Wk 16 Wk 24(Echo) Wk 52(Echo) Force Titration Open-label adjuncts added to Level III

  12. Summary of Primary Efficacy Results Mean Changes from Baseline inEchocardiographic Measures at Week 24 CV137-038

  13. BP Changes From Baseline Per Study Week 0 -5 -10 -15 -20 -25 -30 -35 Losartan Omapatrilat DBP Change in BP (mmHg) SBP 0 24 30 36 44 52 Week Adjunctive therapy % Omapatrilat 6.3 22.2 32.7 32.5 34.4 Losartan 16.5 50.0 54.8 59.3 60.0 CV137-038

  14. CHOIRS Background(Conduit Hemodynamics ofOmapatrilat International Research Study) • Elevated pulse pressure, an indirect measure of increased vascular stiffness, associated with: • Myocardial infarction, stroke • Development and progression of heart failure • Increased mortality • Current epidemic of uncontrolled systolic hypertension due to a lack of treatments thatreduce arterial stiffness • Natriuretic peptides have a favorable effect on largearteries in basic studies although their effects in humans have not been elevated

  15. CHOIRS: Study Design Baseline hemodynamic study (n = 213)SBP  160 mmHg Randomize: Force-titrationWks 0, 2, 4 Enalapril 10 / 20 / 40 mg daily (n = 109) Omapatrilat 10 / 40 / 80 mg daily (n = 104) Withdrawn (n = 22) Withdrawn (n = 24) 8 Wks at maximal dose Trough (24 Hr)Hemodynamic Study (n = 87) Trough (24 Hr)Hemodynamic Study (n = 80)

  16. Central Pulse Pressure (80 ± 20 mmHg) Brachial Pulse Pressure (78.6 ± 16.6 mmHg) 0 -5 -10 -15 -20 0 -5 -10 -15 -20 † * † Enalapril Omapatrilat Central and Peripheral Pulse Pressure * = < 0.005 † = < 0.05 Mitchell, et al., Circulation 2002; 105:2955

  17. Omapatrilat Target Population • Patients with: • A high risk of major cardiovascular events* • Cardiovascular disease (e.g., MI, CHF) • Target organ damage (e.g., LVH, proteinuria) • 3 or more cardiovascular risk factors • Diabetes or renal disease and • Hypertension that is difficult to controlwith existing medications Use with special caution in black patientsand current smokers *Based on WHO-ISH guidelines

  18. Subgroups at Increased CV Risk:Change in Systolic BP at Week 24 Adjusted SBP Changeat Week 24 (mmHg) Omapatrilat Enalapril Difference(oma / ena) Severe Hypertension (n = 7197) Group 1 (n = 983) -18.7 -36.6 -15.9 -32.0 -2.7-4.6 Diabetes Mellitus (n = 3275) -17.6 -13.4 -4.2 Atherosclerotic Disease* (n = 2283) -20.7 -18.0 -2.7 ISH (n = 1332) -22.2 -17.7 -4.5 Renal Disease (n = 582) -17.0 -13.4 -3.6 Heart Failure (n = 233) -20.9 -16.4 -4.5 *Includes chronic stable angina, unstable angina, myocardial infarction, and stroke / TIA OCTAVE (CV137-120)

  19. Omapatrilat Enalapril (n = 2849) (n = 2840) Age (Mean) 62 62 Age, n (%) < 65 years 1654 (58%) 1652 (59%) 65 - 74 years 793 (28%) 802 (28%) ³ 75 years 402 (14%) 385 (14%) Gender, n (%) Male 1602 (56%) 1566 (55%) Female 1247 (44%) 1273 (45%) Race, n (%) White Black 2490 (87%) 314 (11%) 2488 (88%) 309 (11%) Target Population – Baseline Demographics(Diabetes, Renal Disease, Athero Disease, HF) OCTAVE (CV137-120)

  20. Omapatrilat Enalapril OCTAVE: Efficacy in Target Population at Week 24 (Diabetes, Renal Disease, Athero Disease, HF) Use of NewAdjunctive Therapy Change in Systolic BP % of Patients SBP Change (mmHg) ** -3.6** ** p< 0.001 vs enalapril

  21. Target Population – Severity of Angioedema Events, Week 24(Diabetes, Renal Disease, Athero Disease, HF) Number (%) of Patients Omapatrilat (n = 2842) Enalapril (n = 2807) Severity 28 (0.99%) 14 (0.50%) I. No Treatment Administered or Antihistamines Only 15 (0.53%) 2 (0.07%) II. Treated with Catecholamines or Steroids 2 (0.07%) 1 (0.04%) III. Hospitalized but no Mechanical Airway Protection IIIa. No Airway Compromise 2 1 0 0 IIIb. With Airway Compromise 0 (0%) 0 (0%) IV. Mechanical Airway Protection or Death from Airway Compromise 45 (1.58%) 17 (0.61%) Total OCTAVE (CV137-120)

  22. Omapatrilat 80 mg Lisinopril 40 mg Change in 24-Hour Average AmbulatorySystolic BP in Patients Uncontrolledwith ACE-Inhibitor Regimens at Baseline ACE-I Monotherapy(n = 171) ACE-ICombination(n = 75) ASBP Change (mmHg) -11.5** -7.6** Week 4 Maintenance * *p < 0.001 vs. lisinopril CV137-073

  23. Difficult to Control Patients Difficult to Control Patients • Omapatrilat provides consistent benefit in BP reduction over enalapril in each of these difficultto control populations. Untreated patients with severe hypertension Patients uncontrolled witha regimen not including an ACE-I Patients uncontrolled witha regimen including an ACE-I

  24. BP Control in Uncontrolled Patients at Sites with Highest Adjunct Use (64.0% - 100%) at Week 24 Change in SBP (mmHg) BP Control n / N (%) Difference Omapatrilat (n = 967) Enalapril (n = 966) 544 / 907 (60.0%) 466 / 903 (51.6%) -19.1 -15.7 -3.4 OCTAVE (CV137-120)

  25. Retail Pharmacist Validation of Counseling and Delivery of Patient Education Medication Dispensed in Unit-of-Use Packaging Message with PPI Omapatrilat Educational Program Counseling PharmacistEducation MD Education Initial MD-Patient ConsultationPatient BrochureRx Given Mandatory Counseling Service Retail PharmacistEducation Follow-up MD Patient ConsultationRx Given

More Related