0:00-0:27: Intro

0:28-1:04: Welcome back and Introduction of Dr. Dunn

1:05-6:18 Foundation of antiplatelet therapy with aspirin in ISIS-2 trail and VA Cooperative Study.  What is up with that subgroup analysis?

6:19-10:39: Percutaneous intervention joins conversation develops and STARS trial compares Aspirin alone, aspirin + warfarin, aspirin + ticagrelor in the setting of stenting.

10:40-13:57: The twelve-month duration and DAPT is established as standard of care in ACS with CURE and PCI-CURE.

13:58-23:37: More potent P2Y12 inhibitors evolve DAPT approach with TRITON (prasugrel), PLATO (ticagrelor).  But what are their niches (TRILOGY-ACS).

23:38-24:24: Episode 1 closing

References:

• ISIS-2 Collaborative Group. Randomized Trial of Intravenous Streptokinase, Oral Aspirin, Both, or Neither among 17187 Cases of Suspected Acute Myocardial Infarction. The Lancet 1988;332:349-360.
• Lewis HD, et al. Protective Effects of Aspirin against Acute Myocardial Infarction and Death in Men with Unstable Angina — Results of a Veterans Administration Cooperative Study. N Engl J Med 1983;309:396-403.
• Leon MB, et al. A Clinical Trial Comparing Three Antithrombotic-Drug Regimens after Coronary Artery Stenting (STARS). N Engl J Med 1998; 339:1665-1671.
• Yusuf S, et al. Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment Elevation (CURE). N Engl J Med 2001;345(7):494-502

• Mehta SR, Yusuf S, Peter RJG, Bertrand ME, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001;358:527-533.
• Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001-2015.
• Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057.
• Roe MT, et al. Prasugrel versus Clopidogrel for Acute Coronary Syndromes without Revascularization (TRILOGY-ACS). N Engl J Med 2012; 367:1297-1309

0:00-0:42: Intro

0:43-1:53: Introduction of Dr. Kazuhiko Kido

1:54-6:02: Trial Overview

6:03-9:09: Previous Data for LV Thrombus Management

9:10-10:10: Overall Thoughts

10:11-12:44: Trial Limitations

12:45-15:01: Background Medications and LV Thrombus secondary to ischemic cardiomyopathy vs. non-ischemic cardiomyopathy

15:02-19:08: LV thrombus anticoagulation management in patients

19:09-19:54: Closing

References:

• Robinson AA, Trankle CR, Eubanks G, et al. Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi. JAMA Cardiol 2020;5(6):685-692.
• Vaitkus PT, Barnathan ES. Embolic potential prevention and management of mural thrombus complicating anterior myocardial infarction: a meta-analysis. J Am Coll Cardiol 1993;22(4):1004-1009. doi:10.1016/0735-1097(93)90409-T.
• Robinson A, Ruth B, Dent J. Direct oral anticoagulants compared to warfarin for left ventricular thrombi: a single center experience. J Am Coll Cardiol 2018;71(11)(suppl):A981. doi:10.1016/S0735-1097(18)31522-5
• Cochran JM, Jai X, Hamzeh I, and Birnbaum Y. Direct oral anticoagulant use for left ventricular thrombus: a single center experience. Circulation 2018;138(suppl_1)A16411.
• McCarthy CP, Murphy S, Venkateswaran RV, et al. Left ventricular thrombus: contemporary etiologies, treatment strategies, and outcomes. J Am Coll Cardiol 2019;73(15):2007-2009. doi:10.1016/j.jacc.2019.01.031.
• Fleddermann AM, Hayes CH, Magalski A, and Main ML. Efficacy of direct acting oral anticoagulants in treatment of left ventricular thrombus. Am J Cardiol 2019;124(3):367-372. doi:10.1016/j.amjcard.2019.05.009.

0:00-0:43: Intro

0:44-1:04: Welcome back of Dr. Robert Page and Recap of Part 1

1:05-3:09: Discussion of ARB trials in HFrEF from highlighting ELITE I and II

3:10-7:42: What we learned from Val-HeFT and CHARM-ADDED

7:43-11:13: Angioedema approach, lessons from CHARM-ALTERNATIVE and HTN trials

11:14-14:10: PARADIGM-HF a shift in vasodilator therapy for HFrEF

14:11-16:48: Dose discussion: low vs. high-dose afterload reduction… Holding on to your money!

16:49-19:04: Final Thoughts from Dr. Page – Read CONSENSUS, SOLVD PREVENTION, SOLVD Treatment, SAVE, ATLAS

19:05-19:50: Renal function and safety thoughts

19:51-21:01: Closing

References:

• Pitt B, Segal R, Martinez FA, et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet. 1997; 349:747-752.
• Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial – the Losartan Heart Failure Survival Study ELITE II. Lancet. 2000;355:1582-1587.
• Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators, et al. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure (Val-HeFT). New Engl J Med. 2001;345(23):1667-75.
• McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: The CHARM-Added trial. The Lancet. 2003; 362(9386):767-771.
• Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. New Engl J Med. 1999;341(10):709-717.
• Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003;362(9386):772-6.
• Beavers CJ, Dunn SP, Macaulay TE.  The role of angiotensin receptor blockers in patients with angiotensin-converting enzyme inhibitor-induced angioedema.  Ann Pharmacother. 2011;45:520-524.
• Granger CB, McMurray JJV, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. The Lancet. 2003. 362(9386):772-776.
• McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. New Engl J Med. 2014; 371(11):993-1004.
• Vardeny O, Claggett B, Packer M, et al.  Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fractions: the PARADIGM-HF trial. European J of Heart Failure. 2016;18:1228-1234.
• Packer M, Poole-Wilson PA, Armstrong PW, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor lisinopril on morbidity and mortality in chronic heart failure. Circulation. 1999;100:2312-2318.
• Konstam MA, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure. The Lancet 2009. 374(9704):1840-1848.
• CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure, results of the cooperative north Scandinavian enalapril survival study. New Engl J Med. 1987;316(23):1429-35.
• Das SR, Drazner MH, Yancy CW, et al.  Effect of diabetes mellitus and ischemic heart disease on the progression from asymptomatic left ventricular dysfunction to symptomatic heart failure: a retrospective analysis from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention trial. Am Heart J. 2004 Nov;148(5):883-8.
• Glick H, Cook J, Kinosian B, et al.  Costs and effects of enalapril therapy in patients with symptomatic heart failure: an economic analysis of the studies of left ventricular dysfunction (SOLVD) treatment trial.  J Card Fail. 1995;1:371-80.
• Pfeffer MA, Braunwald E, Moye LA, et al. Effect of Captopril on Mortality and Morbidity in Patients with Left Ventricular Dysfunction after Myocardial Infarction — Results of the Survival and Ventricular Enlargement Trial. New Engl J Med. 1992; 327:669-677.
• Schoolwerth AC, Sica DA, Ballermann BJ, et al.  Renal considerations in angiotensin converting enzyme inhibitor therapy: A statement for healthcare professionals from the council on the kidney in cardiovascular disease and the council high blood pressure research of the american heart association. Circulation. 2001;104:1985-1991.

Dr. Robert Page and CardioScripts co-host, Dr. Tracy Macaulay, take a deep dive into classic literature pertaining to use of vasodilators in HFrEF.

0:00-0:47: Intro

0:41-1:23: Introduction of Dr. Robert Page

1:23-2:16: Intro of the Classic Episode Format

2:17-6:48: Foundation of HFrEF pharmacotherapy prior to 1986 and discussion of the V-HeFT I trial

6:48-9:12: CONSENSUS Trial and introduction of ACE-I as gold standard afterload reducer in HFrEF

9:12-12:34: V-HeFT II trial discussion.  A comparison of Hydralazine/Nitrate to Enalapril, solidification of ACE-I role.

12:34-13:46: Using other forms of nitrate in combination with hydralazine for HFrEF

13:47-20:28: Role of hydralazine/nitrate for African American patients with HFrEF withh discussion of A-HeFT trial

20:29-21:08: We ran out of time to cover ALL our conversation, so join us next time for Episode 2 with Dr. Page discussing vasodilators in HFrEF! 

References:

• V-HEFT: Cohn JN, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. The New England Journal of Medicine. 1986. 314(24):1547-52.
• ALLHAT: Wright JT, et al. Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs. Diuretic. Journal of the American Medical Association. 2002. 288(23):2981-2997.
• CONSENSUS Trial Study Group. “Effects of enalapril on mortality in severe congestive heart failure, results of the cooperative north Scandinavian enalapril survival study”. The New England Journal of Medicine. 1987. 316(23):1429-35.
• V-HEFT-II: Cohn JN, et al. “A Comparison of Enalapril with Hydralazine–Isosorbide Dinitrate in the Treatment of Chronic Congestive Heart Failure”. The New England Journal of Medicine. 1991. 325(5):303-310.
• SAVE: Pfeffer MA, et al. “Effect of Captopril on Mortality and Morbidity in Patients with Left Ventricular Dysfunction after Myocardial Infarction — Results of the Survival and Ventricular Enlargement Trial”. The New England Journal of Medicine. 1992. 327(10):669-677.
• Carson P, Ziesche S, Johnson G, Cohn JN, for the Vasodilator-Heart Failure Trial Study Group. Racial differences in response to therapy for heart failure: analysis of the Vasodilator-Heart Failure Trials. J Cardiac Failure. 1999. 5:178–187.
• A-HeFT: Taylor AL, et al. Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure. The New England Journal of Medicine. 2004. 351(20):2049-2057.
• SOLVD: Yusuf S, et al. Effect of Enalapril on Survival in Patients with Reduced Left Ventricular Ejection Fractions and Congestive Heart Failure. The New England Journal of Medicine. 1991. 325(5):293-302.
• Tam SW, Worcel M, Sabolinski ML, Packer M, Cohn JN.  Lack of bioequivalence between different formulations of isosorbide dinitrate and hydralazine and the fixed-dose combination of isosorbide dinitrate/hydralazine. The V-HeFT paradox. Clin Pharmacokinet  2007. 46:885–895.

Dr. Kristin Watson discusses the use of beta-blockers post-MI in patients without heart failure.

0:00-0:40: Intro

0:41-1:18: Introduction of Dr. Kristin Watson

1:19-6:40: Trial overview

6:41-10:46: Background of beta-blocker use post-MI

10:47-12:36: Kristin’s overall thoughts

12:37-14:49: Types of beta-blockers used

14:50-16:06: Final thoughts

16:07-16:49: Closing

References:

• Kim J, Kang D, Park H, et al. Long-term β-blocker therapy and clinical outcomes after acute myocardial infarction in patients without heart failure: nationwide cohort study. Eur Heart J. 2020; doi: 10.1093/eurheartj/ehaa376.
• Kukin A, Noel Z, and Watson K. Through the Decades: β-blocker Use and Outcomes in Acute Coronary Syndromes. Cardiol Rev. 2018;26(3):157-166. doi: 10.1097/CRD.0000000000000197.
• Snow PJ. Effect of propranolol in myocardial infarction. Lancet. 1965;2:551-3.
• Snow PJ. Treatment of acute myocardial infarction with propranolol. Am J Cardiol. 1966;18:458-62.
• Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001;357:1385-90. doi: 10.1016/s0140-6736(00)04560-8.
• Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366:1622-32. doi: 10.1016/S0140-6736(05)67661-1.

Dr. Jessica Carey discusses the VOYAGER PAD trial and antithrombotic management in PAD patients post-revascularization.

0:00-0:40: Intro

0:41-1:46: Introduction of Dr. Jessica Carey

1:47-5:52: VOYAGER PAD Overview

5:53-9:10: Previous management of PAD

9:11-11:18: PAD Interventions

11:19-13:49: Overall thoughts about VOYAGER PAD

13:50-15:19: Antithrombotic management of PAD

15:19-16:01: Closing

References:

• VOYAGER PAD: Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in Peripheral Artery Disease after Revascularization. N Engl J Med 2020;382:1994-2004.
• COMPASS: Anand SS, Bosch J, Eikelboom JW, et al. Rivaroxaban with or without aspirin I patients with stable peripheral or carotid artery disease: an international, randomized, double-blind placebo-controlled trial. Lancet 2018;391(10117):219-229.
• CASPER: Bellch JJF, Dormandy J, et al. Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial. J Vasc Surg 2010;52:825-33.
• Dutch BOA: Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral Anticoagulants or Aspirin Study): a randomized trial. Lancet 2000;355:346-51.
• ATLAS-TIMI 51: Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in Patients with a Recent Acute Coronary Syndrome. N Engl J Med 2012;366:9-19.

Guest Dr. Paul Dobesh discusses the Caravaggio trial and DOAC use for VTE management in patients with cancer.

0:00-0:40: Intro
0:41-1:35: Introduction of Dr. Paul Dobesh
1:36-4:02: Caravaggio trial overview
4:03-7:08: Background of VTE antithrombotic management in cancer 7:09-9:09: Overall thoughts and where apixaban fits
9:10-10:42: ADAM-VTE Trial
10:43-13:36: Bleeding
13:37-14:37: PROBE trial design
14:38-15:47: Approach the VTE antithrombotic management in cancer patients
15:47-16:34: Closing

References:

• Caravaggio trial: Agnelli G, et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer.  N Engl J Med 2020;382:1599-1607. 
• CLOT trial: Lee AY, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349(2):146-53.
• ADAM VTE trial: McBane RD, et al. Apixaban, dalteparin, in Active Cancer Associated Venous Thromboembolism, the ADAM VTE Trial. Blood 2018;132(1):421. 
• Hokusai VTE trial: Raskob GE, et al. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med 2018;378(7):615-624. 
• SELECT-D trial:  Young AM, et al. Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). J Clin Oncol 2018;36(20):2017-2023.

0:00-0:40: Intro

0:41-1:25: Introduction of Dr. John Lindsley

1:26-5:57: POPular TAVI trial overview

5:58-8:35: Background of TAVI antithrombotic management

8:36-10-43: Intial thoughts about POPular TAVI

10:44-14:53: Study design

14:54- 17:22: Antithrombotic management

17:23-18:06: Closing

References

• POPular TAVI Trial: Nijenhuis VJ, Brouwer J, Delewi R, et al.  Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. N Engl J Med 2020; 382:1696-1707. DOI: 10.1056/NEJMoa1915152
• ARTE Trial: Rodes-Cabau J, Masson J, Welsh RC, et al. Aspirin Versus Aspirin Plus Clopidogrel as Antithrombotic Treatment Following Transcatheter Aortic Valve Replacement With a Balloon-Expandable Valve: The ARTE (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation) Randomized Clinical Trial. JACC Cardiovasc Interv. 2017 Jul 10;10(13):1357-1365.
• GALILEO Trial: Dangas G, Tijssen JG, Wöhrle J, et al. A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.
• PARTNER Trial: Leon MB, Smith CR, Mack M, et al. Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery. N Engl J Med 2010; 363:1597-1607.
• Otto CM, Kumbhani DJ, Alexander KP, et al. 2017 ACC Expert Consensus Decision Pathway for Transcatheter Aortic Valve Replacement in the Management of Adults With Aortic Stenosis: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2017;69(10):1313-46.

Dr. Vicki Groo discusses the GUIDE-IT trial and medication titration in the heart failure with reduced ejection fraction (HFrEF) population.

0:00-0:40: Intro

0:40-1:27: Introduction of Dr. Vicki Groo

1:28-4:55: Introduction of GUIDE-IT trial and secondary analysis

4:56-7:56: Vicki’s Overall Thoughts

7:57-9:07: Approach to medication titration

9:08-10:31: What about newer HFrEF therapies?

10:32-12:09: Patient Education

12:10-14:07: Thoughts about reasoning for not uptitrating/adding HFrEF medications

14:08-14:37: HFrEF and Pharmacy Services

14:38-14:56: Final Thoughts

14:57-15:33: Closing

References:

• Fiuzat M, Ezekowitz J, Alemayehu W, et al. Assessment of Limitations to Optimization of Guideline-Directed Medical Therapy in Heart Failure From the GUIDE-IT Trial A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. Published online April 22, 2020. doi:10.1001/jamacardio.2020.0640
• Greene SJ, Butler J, Albert NM, et al.  Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry. J Am Coll Cardiol. 2018 Jul 24;72(4):351-366. doi: 10.1016/j.jacc.2018.04.070.
• Crespo-Leiro MG, Anker SD, Maggioni AP, et al. European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions. Eur J Heart Fail. 2016 Jun;18(6):613-25
• Lombardi CM, Ferreira JP, Carubelli V, et al. Geographical differences in heart failure characteristics and treatment across Europe: results from the BIOSTAT-CHF study. Clin Res Cardiol. 2020 Jan 29. doi: 10.1007/s00392-019-01588-7.
• Felker GM, Anstrom KJ, Adams KF, et al. Effect of Natriuretic Peptide–Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction A Randomized Clinical Trial. 2017;318(8):713-720. doi:10.1001/jama.2017.10565
• Fiuzat M¹, Wojdyla D, Kitzman D, et al. Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: results from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial. J Am Coll Cardiol. 2012 Jul 17;60(3):208-15. doi: 10.1016/j.jacc.2012.03.023. Epub 2012 May 2.
• Felker GM¹, Ahmad T², Anstrom KJ³, et al. Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.  JACC Heart Fail. 2014 Oct;2(5):457-65. doi: 10.1016/j.jchf.2014.05.007. Epub 2014 Sep 3.
• Samsky MD, Lin L, Greene SJ, et al. Patient Perceptions and Familiarity With Medical Therapy for Heart Failure. JAMA Cardiol. 2020;5(3):292-299. doi:10.1001/jamacardio.2019.4987
• Bhat S, Kansal M, Kondos GT and Groo V. Outcomes of a Pharmacist-Managed Heart Failure Medication Titration Assistance Clinic. Ann Pharmacother. 2018;52(8):724-732.

Dr. Kristen Pogue discusses the VICTORIA trial.

Episode Breakdown:

0:00-0:40: Intro

0:41-1:36: Introduction of Dr. Kristen Pogue

1:37-5:42: VICTORIA trial overview

5:43-8:18: Kristen’s initial thoughts

8:19-9:44: VICTORIA and PARADIGM-HF

9:45-12:17: How does this fit with DAPA-HF results?

12:18-14:14: Vericiguat in the Black population

14:15-15:45: Final thoughts

15:46-16:32: Closing

References:

• VICTORIA Trial: Armstrong PW, Pieske B, Anstrom KJ, et al. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 2020. DOI: 10.1056/NEJMoa1915928.
• PARADIGM-HF Trial: McMurray JJ, Packer M, Desai AS, et al. Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure. N Engl J Med 2014;371:993-1004.
• DAPA-HF Trial: McMurray JJ, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 2019;381:1995-2008.
• A-HeFT Trial: Taylor AL, Ziesche S, Yancy C, et al. Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure. N Engl J Med 2004;351:2049-2057.