CardioScipts Classic – Vasodilators in HFrEF [Part 1]

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! 


  • 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.

To be[ta-block], or not to be[ta-block]? How long is long the question.

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


  • 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.

VOYAGER PAD: Live Long and Rivaroxaban

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


  • 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.

The Caravaggio Trial: Painting DOACs into the Picture

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


  • 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.

Popular, I know about POPular TAVI

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


  • 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.

GUIDE-IT Guidance with Dr. Groo

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


  • 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 M1Wojdyla DKitzman 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 GM1Ahmad T2Anstrom 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


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


  • 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.

The Cold Truth of COLCOT

Dr. Toby Trujillo discusses the COLCOT trial.

Episode Breakdown:

0:00-0:40: Intro

0:41-1:30: Introduction of Dr. Toby Trujillo

1:31-3:56: COLCOT overview

3:57-4:50: Toby’s initial thoughts

4:51-6:08: Anti-inflammatory agents

6:09-7:09: Pneumonia?

7:10-8:29: Baseline Management of Patients

8:30-10:15: Who is the niche colchicine patient?

10:16-12:05: Drug burden and cost

12:06-13:03: Follow-up period

13:04-13:59: Final thoughts

14:00-14:44: Closing


  • COLCOT Trial: Tardif J, Kouz S, Water DD, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med 2019;381:2497-505.
  • CANTOS Trial: Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119-31.
  • CIRT Trial: Ridker PM, Everett BM, Pradhan A, et al. Low-dose methotrexate for the prevention of atherosclerotic events. N Engl J Med 2019;380:752-62.
  • LoDoCo Trial: Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol 2013;61:404-10.

Return of the Lytics with Dr. Danielle Blais

Tune in as Dr. Danielle Blais discusses everything lytics.


  • Welt FGP, Shah PB, Aronow HD, et al. Catheterization Laboratory Considerations During the Coronavirus (COVID-19) Pandemic: From American College of Cardiology’s (ACC) Interventional Council and the Society of Cardiovascular Angiography and Intervention (SCAI).  J Am Coll Cardiol  2020; DOI: 10.1016/j.jacc.2020.03.021
  • ISIS-2 Collaborative Group. Randomised Trial of Intravenous Streptokinase, Oral Aspirin, Both, or Neither among 17187 Cases of Suspected Acute Myocardial Infarction. The Lancet. 1988; 332(8607):349-360.
  • O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force of Practice Guidelines. J Am Coll Cardiol 2013; 61(4): DOI: 10.1016/j.jacc.2012.11.019
  • Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018; 39(2):119-177.
  • Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-Segment Elevation (CLARITY). N Engl J Med 2005; 352:1179-1189
  • Chen ZMJiang LXChen YP, et al  Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial (COMMIT). Lancet. 2005 Nov 5;366(9497):1607-21.
  • Berwanger O, Lopes RD, Moia DF, et al. Ticagrelor Versus Clopidogrel in Patients with STEMI Treated with Fibrinolytic Therapy: TREAT Trial. J Am Coll Cardiol 2019;73:2819-28.
  • Wiviott ST, et al. Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes (TRITON). The N Engl J Med. 2007; 357(20):2001-2015. 
  • Antman EM, Morrow DA, McCabe CH, Murphy SA, Ruda M, Sadowski Z, Budaj A, López-Sendón JL, Guneri S, Jiang F, White HD, Fox KAA, Braunwald E, for the ExTRACT-TIMI 25 Investigators. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med 2006;354(15):1477-1488
  • Guillermin A, Yan DJ, Perrier A, et al.  Safety and efficacy of tenecteplase versus alteplase in acute coronary syndrome: a systematic review and meta analysis of randomized trials. Arch Med Sci 2016;12:1181-1187.

Chlorthalidone vs. Hydrochlorothiazide: The Debate That Never Ends

Dr. Karen McConnell discusses a recent trial comparing chlorthalidone vs. hydrochlorothiazide for the treatment of hypertension.

0:00-0:40: Intro
0:41-1:51: Introduction of Dr. Karen McConnell
1:52-6:19: Trial overview
6:20-9:15: Karen’s Overall Thoughts
9:16-10:13: Trial Design 
10:14-10:54: Side Effect Differences
10:55-12:36: Choosing Between Chlorthalidone and HCTZ
12:37-14:03: Final Thoughts
14:04-14:49: Closing


  • Hripcsak G, Suchard MA, Shea S, et al. Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension. JAMA Intern Med 2020. doi: 0.1001/jamainternmed.2019.7454.
  • Lederle FA, Cushman WC, Ferguson RE, Brophy MT, Fiore LD. Chlorthalidone Versus hydrochlorothiazide: a new kind of Veterans Affairs cooperative study. Ann Intern Med 2016;165(9):663-4. doi: 10.7326/M16-1208.
  • Veterans Affairs Diuretic Comparison Project:
  • ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor of calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Tretment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288(23):2981-97.