Efficacy of Ranolazine In Chronic Angina trial

Slides:

Advertisements

Similar presentations

Ranexa™ for Chronic Angina An Unmet Need

Advertisements

METABOLIC MANUPULATION OF ISCHEMIC HEART DISEASE

Valsartan Antihypertensive Long-Term Use Evaluation Results

Purpose To determine whether metoprolol controlled/extended release

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.

Study by: Granger et al. NEJM, September 2011,Vol No. 11 Presented by: Amelia Crawford PA-S2 Apixaban versus Warfarin in Patients with Atrial Fibrillation.

The ERICA Trial Peter H. Stone, MD, FACC, Nikolay A. Gratsiansky, MD, Alexey Blokhin, MD, I-Zu Huang, MD, Lixin Meng, MS, MPH, for the ERICA Investigators.

How do we further reduce angina in patients already treated with a hemodynamic agent? Benefits of adding a metabolic agent to other antianginal drugs (

Corlanor® - Ivabradine

Assessment of Cardiopulmonary Function in Patients With Stable Coronary Artery Disease Receiving Ticagrelor or Clopidogrel in the ONSET/OFFSET Study Robert.

NEUROPATHIC PAIN – OPTIMIZING PATIENT OUTCOME WITH COMBINATION THERAPY.

TRANSCEND: Telmisartan Randomized AssesmeNt Study in aCE iNtolerant Subjects with Cardiovascular Disease ONTARGET / TRANSCEND Investigators Koon K. Teo,

ASTEROID A Study To evaluate the Effect of Rosuvastatin On Intravascular ultrasound- Derived coronary atheroma burden.

COURAGE: Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation Purpose To compare the efficacy of optimal medical therapy (OMT)

Appendix: Clinical Guidelines VBWG. I Intervention is useful and effective III Intervention is not useful or effective and may be harmful A Data derived.

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

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

Effects on outcomes of heart rate reduction by ivabradine in patients with congestive heart failure: is there an influence of beta-blocker dose? Systolic.

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

European guidelines on the management of stable coronary artery disease Key points & new position for Ivabradine and Trimetazidine ESC 2013 Montalescot.

Dr Jayachandran Thejus.  Coronary artery disease-  Block in coronary artery due to plaque or thrombus  Leads to myocardial ischemia manifested as chest.

VBWG CHARISMA Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance trial.

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.

CR-1 1 Ranolazine Benefit/Risk Jeremy N. Ruskin, MD, FACC.

Management of Chronic Stable Angina AIMGP Seminar Series Mirek Otremba 2007.

Redefining Treatment Strategies for Optimal Medical Care in CAD COURAGE and MERLIN-TIMI 36.

Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stan Schwartz MD,FACP.

S ystolic H eart failure treatment with the I f inhibitor ivabradine T rial Main results Swedberg K, et al. Lancet. 2010;376(9744):

Benefits of adding a energetic agent to  -blockers to achieve optimal reduction of angina. Review of the main studies.

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

MERLIN TIMI 36 M ETABOLIC E FFICIENCY WITH R ANOLAZINE FOR L ESS I SCHEMIA IN N STE ACS.

RALES: Randomized Aldactone Evaluation Study Purpose To determine whether the aldosterone antagonist spironolactone reduces mortality in patients with.

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.

AIRE: Acute Infarction Ramipril Efficacy study Purpose To determine whether the ACE inhibitor ramipril reduces mortality in patients with evidence of heart.

TRANSCEND: Telmisartan Randomized AssesmeNt Study in aCE iNtolerant Subjects with Cardiovascular Disease ONTARGET / TRANSCEND Investigators Koon K. Teo,

SPARCL Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial.

Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 2 ARBITER-2 Trial Presented at The American Heart Association Scientific.

VBWG PROactive: Study design Dormandy JA et al. Lancet. 2005;366: Charbonnel B et al. Diabetes Care. 2004;27: Objective: Assess the effects.

HOPE: Heart Outcomes Prevention Evaluation study Purpose To evaluate whether the long-acting ACE inhibitor ramipril and/or vitamin E reduce the incidence.

Clinical Management of Chronic Stable Angina. Anti-ischemic strategies in stable CAD Medical therapyPCICABG Initial therapy Recurrent ischemia TMREECPSCS.

Influence of background treatment with mineralocorticoid receptor antagonists on ivabradine's effects in patients with chronic heart failure Systolic Heart.

Effects of Ranolazine: from Angina to Cardiac Performance Iacopo Olivotto, MD Referral Center for Cardiomyopathies Careggi University Hospital Florence,

Journal of the American Medical Association (JAMA), 2004, 291:

Effects of Ranolazine on Angina and Quality of Life Following PCI with Incomplete Revascularization -- The Ranolazine for Incomplete Vessel Revascularization.

Contemporary Management of Myocardial Ischemia

Relationship of background ACEI dose to benefits of candesartan in the CHARM-Added trial.

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

J.T. is a 62-year-old man with a history of CAD (MI 3 years ago), hypertension, depression, chronic renal insufficiency (baseline SCr is 2.8 mg/dL), peripheral.

VBWG OASIS-6 The Sixth Organization to Assess Strategies in Acute Ischemic Syndromes trial.

Many alternatives for treating ischemia and angina: how to choose?

Long-Term Tolerability of Ticagrelor for Secondary Prevention: Insights from PEGASUS-TIMI 54 Trial Marc P. Bonaca, MD, MPH on behalf of the PEGASUS-TIMI.

Long-Term Tolerability of Ticagrelor for Secondary Prevention: Insights from PEGASUS-TIMI 54 Trial Marc P. Bonaca, MD, MPH on behalf of the PEGASUS-TIMI.

Effects of Ranolazine on Angina and Quality of Life Following PCI with Incomplete Revascularization -- The Ranolazine for Incomplete Vessel Revascularization.

Date of download: 6/18/2016 Copyright © The American College of Cardiology. All rights reserved. From: Efficacy and Safety of Fasudil in Patients With.

Viagra (sildenafil citrate): Extensive Clinical and Post-Marketing Experience Michael Sweeney, MD Senior Medical Director Pfizer Inc.

GASTROENTEROLOGY 2008; 134 :688–695 소화기내과 R4 이 재 연.

Drugs for Angina Pectoris

Ranolazine The mechanism of action of ranolazine has not been determined, but it may be related to reduction in calcium overload in ischemic myocytes.

Adjuvant Ranolazine for Patients With Incomplete Revascularization

Evaluation of Ranolazine in Patients with Type 2 Diabetes Mellitus

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

REVEAL: Randomized placebo-controlled trial of anacetrapib in 30,449 patients with atherosclerotic vascular disease Louise Bowman on behalf of the HPS.

Senior Medical Director, Cardiovascular

SPIRE Program: Studies of PCSK9 Inhibition and the Reduction of Vascular Events Unanticipated attenuation of LDL-c lowering response to humanized PCSK9.

The following slides highlight a report on a presentation at a Late-Breaking Trial Session of the European Society of Cardiology Congress 2004 held in.

Ranolazine in Microvascular Dysfunction

Efficacy and safety of niacin/laropiprant

The American College of Cardiology Presented by Dr. Timothy Henry

SPIRE Program: Studies of PCSK9 Inhibition and the Reduction of Vascular Events Unanticipated attenuation of LDL-c lowering response to humanized PCSK9.

Presentation transcript:

Efficacy of Ranolazine In Chronic Angina trial 4/26/2017 10:00 AM ERICA Efficacy of Ranolazine In Chronic Angina trial

Background and hypothesis 4/26/2017 10:00 AM Incidence of symptomatic angina in stable CAD patients remains high despite the use of conventional agents and/or revascularization Traditional pharmacologic therapies determinants of MVO2 (heart rate, myocardial contractility, wall stress) Combinations of these therapies may provide incremental antianginal efficacy but may also produce side effects Ranolazine is a new antianginal agent with a novel mechanism of action that does not significantly affect HR or wall stress Does ranolazine reduce angina in CAD patients despite treatment with the maximum dose of a conventional antianginal agent (amlodipine)? MVO2 = Myocardial oxygen consumption Stone PH et al. J Am Coll Cardiol. 2006;48:566-75.

ERICA: Study design Evaluation of Ranolazine In Chronic Angina 4/26/2017 10:00 AM Evaluation of Ranolazine In Chronic Angina History of CAD* Stable angina (≥3 angina episodes/week) Amlodipine 10 mg/day N = 565 Ranolazine extended-release 500 mg bid (1 week) then 1000 mg bid n = 281 Placebo n = 284 Randomized Double-blind 7 weeks Primary efficacy variable: Angina frequency (weekly average) *≥60% stenosis, previous MI, and/or stress-induced perfusion defect Stone PH et al. J Am Coll Cardiol. 2006;48:566-75.

ERICA: Concomitant medications 4/26/2017 10:00 AM N = 564 on amlodipine 10 mg/day Placebo n (%) Ranolazine 1000 mg bid n (%) Aspirin 244 (86) 245 (87) ACE inhibitors 144 (51) 152 (54) Long-acting nitrates* 123 (43) 130 (46) Statins 93 (33) 109 (39) Diuretics 77 (27) 89 (32) Antidiabetics (including insulin) 29 (10) 33 (12) *All other antianginals were proscribed Stone PH et al. J Am Coll Cardiol. 2006;48:566-75.

ERICA: Ranolazine reduces angina frequency and nitrate consumption 4/26/2017 10:00 AM N = 564 on amlodipine 10 mg/day 6 5 4 P = 0.028 Mean number per week P = 0.014 3 2 1 Baseline Week 7 Baseline Week 7 Angina episodes Nitroglycerin use Placebo Ranolazine 1000 mg bid Stone PH et al. J Am Coll Cardiol. 2006;48:566-75.

Mean angina episodes per week ERICA: Consistent treatment effect regardless of gender, age, and concomitant long-acting nitrates 4/26/2017 10:00 AM N = 564 on amlodipine 10 mg/day; week 7 4 3.5 3 Mean angina episodes per week 2.5 2 1.5 1 0.5 Women Men <65 years ≥65 years LAN use No LAN Placebo Ranolazine 1000 mg bid LAN = long-acting nitrates Stone PH et al. J Am Coll Cardiol. 2006;48:566-75.

ERICA subgroup analyses: Frequency of angina N = 564 on amlodipine 10 mg/day Angina episodes per week ≤4.5 >4.5 ≤4.5 >4.5 6 P = 0.029 30 5 P = 0.57 P < 0.001 P < 0.001 4 Number/ week 20 3 P = 0.036 SAQ score ( baseline) P = 0.28 2 10 1 Angina frequency NTG use Angina frequency NTG use Seattle Angina Questionnaire (angina frequency domain) Placebo Ranolazine 1000 mg bid Stone PH et al. J Am Coll Cardiol. 2006;48:566-75.

ERICA: No significant effect on heart rate or BP 4/26/2017 10:00 AM N = 564 on amlodipine 10 mg/day; Supine measurement Placebo Ranolazine 1000 mg bid P Heart rate (bpm) ↓1.6 ↓2.0 0.66 Systolic BP (mm Hg) ↓1.7 0.72 Diastolic BP (mm Hg) ↓0.6 ↓1.0 0.61 Stone PH et al. J Am Coll Cardiol. 2006;48:566-75.

ERICA: Safety and tolerability 4/26/2017 10:00 AM N = 564 on amlodipine 10 mg/day Ranolazine 1000 mg bid (%) Placebo (%) Any adverse event 39.9 35.3 Constipation 8.9 1.8 Peripheral edema 5.7 2.8 Dizziness 3.9 2.5 Nausea 0.7 Headache Discontinued 1.1 1.4 Stone PH et al. J Am Coll Cardiol. 2006;48:566-75.

ERICA: Summary 4/26/2017 10:00 AM Added to maximum-dose amlodipine, ranolazine extended-release 1000 mg bid for 6 weeks significantly reduced angina frequency and nitroglycerin use Treatment effect appeared to be greater in patients with >4.5 angina episodes weekly No significant change in HR or BP; no cases of torsades de pointes reported Low withdrawal rate due to adverse events in both groups 1.1% ranolazine 1.4% placebo Stone PH et al. J Am Coll Cardiol. 2006;48:566-75.

Implications 4/26/2017 10:00 AM ERICA efficacy parameters are in agreement with previous studies using antianginal agents SAQ* provides an appealing feature to assess disease-specific measures of quality of life Because ranolazine can prolong QTc, the daily dose should not exceed 1000 mg/day; use should be limited to patients unresponsive to other antianginal agents Ranolazine provides additional, well-tolerated antianginal efficacy in patients who remain symptomatic despite maximal CCB therapy Cairns JA. J Am Coll Cardiol. 2006;48:576-8. Stone PH et al. J Am Coll Cardiol. 2006;48:566-75. *Seattle Angina Questionnaire