The LoDoCo2 Trial

Dr. Toby Trujillo and CardioScripts co-host, Dr. Tracy Macaulay, discuss the LoDoCo2 trial.

0:00-027: Intro

0:28-1:03: Introduction of Dr. Toby Trujillo

1:04-4:10: LoDoCo2 Trial Overview

4:11-8:10: Overall Thoughts

8:11-9:49: Run-in period and tolerability

9:50-10:28: Monitoring and Infection

10:29-14:00: Fun New Game – Guess That Trial!! (hint – CURE and parallels to LoDoCo2)

14:01-14:59: Polypharmacy and When Colchicine??

15:00-15:35: Final Thoughts

15:36-16:09: Closing

References:

LoDoCo2 Trial: Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med 2020; 383: 1838-47.

COLCOT Trial: Tardif J, Kouz S, Waters 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.

CLEAR SYNERGY Trial: NCT03048825. https://clinicaltrials.gov/ct2/show/NCT03048825

CURE Trial: Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345(7): 494-502.

The EVAPORATE Trial

Dr. Dave Dixon and CardioScripts co-host, Dr. Liz Sulaica, discuss the EVAPORATE trial and where icosapent ethyl fits.

0:00-0:27: Intro

0:28-1:09: Introduction of Dr. Dave Dixon

1:10-4:38: EVAPORATE Overview

4:39-6:12: Overall thoughts about EVAPORATE

6:13-9:23: Trial limitations

9:24-11:55: Isocapent ethyl in practice – involve the patient in decision-making!

11:56-14:31: How has practice changed since REDUCE-IT?

14:32-15:31: Final thoughts

15:32-16:09: Closing

References

  • Budoff MJ, Bhatt DL, Kinninger A, et al. Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial. Eur Heart J 2020; doi: 10.1093/eurheartj/ehaa652.
  • Bhatt DL, Steg PG, Miller M , et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019; 380:11-22.
  • Budoff MJ, Muhlestein JB, Bhatt DL, et al. Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results. Cadiovasc Res 2020; doi: 10.1093/cvr/cvaa184.

Digging into Dig[oxin]

Dr. Robert DiDomenico and CardioScripts co-host, Dr. Tracy Macaulay, discuss the RATE AF trial and all things digoxin: its past role, therapeutic levels, and current and future state!

0:00-0:32 Intro

0:28-1:02: Welcome back and Introduction of Dr. DiDomenico

1:03-4:33: Overview of the RATE-AF trial as presented at ESC 2020 and based on published trial rationale.

4:34-6:40: How did RATE AF confirm or add to our understanding of digoxin use in Atrial Fibrillation

6:41-9:36:  If we use digoxin, what levels are you targeting and what goals are you setting?

9:37-11:50: Digoxin in HFpEF patients

11:51-16:26: Digoxin and Mortality

16:27-17:28: Final thoughts

17:29-18:04: Closing

References:

  • Rate Control Therapy Evaluation in Permanent Atrial Fibrillation.  Results presented by Dr. Dipak Kotecha at the European Society of Cardiology Virtual Congress, August 29, 2020.
  • Kotecha D, Calvert M, Deeks JJ, et al.  A review of rate control in atrial fibrillation, and the rationale and protocol for RATE-AF trial.  BMJ Open 2017;7:e015099.
  • Ahmed A, Rich MW, Fleg JL et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation 2006;11397-403.
  • Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525–533. 11.
  • Ahmed A, Rich MW, Love TE, Lloyd-Jones DM, Aban IB, Colucci WS, Adams KF, Gheorghiade M. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J. 2006;27:178–186. 12.
  • Massie BM, Abdalla I. Heart failure in patients with preserved left ventricular systolic function: do digitalis glycosides have a role? Prog Cardiovasc Dis. 1998;40:357–369.
  • Adams KF Jr, Patterson JH, Gattis WA, et al. Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: a retrospective analysis.  J Am Coll Cardiol. 2005 Aug 2;46(3):497-504. 
  • Vamos M, Erath JW, Benz AP, et al. Meta-analysis of effects of digoxin on survival in patients with atrial fibrillation or heart failure: An update. Am J Cardiolo 2019;123:69-74.
  • DiDomenico RJ, Bress AP, NA-Thalang K, et al. Use of a simplified nomogram to individualize digoxin dosing versus standard dosing practice in patients with heart failure. Pharmacotherapy 2014; 34:1121-31.
  • Bauman JL, DiDomenico RJ, Viana M, Fitch M. A method of determining the dose of digoxin for heart failure in the modern era.  Arch Intern Med. 2006 Dec 11-25;166(22):2539-45. 
  • Singh S, Moore H, Karasik PE, et al. Digoxin initiation and outcomes in patients with heart failure (HFrEF and HFpEF) and atrial fibrillation. Am J Med 2002:S0002-9343(20)30528-3.

HOCM POCM and Magical Mavacamten

Dr. Ashley Schenk discusses mavacamten and obstructive hypertrophic cardiomyopathy.

0:00-0:28: Intro

0:29-1:09: Introduction of Dr. Ashley Schenk

1:10-5:55: Trial overview

5:56-8:36: Overview of obstructive hypertrophic cardiomyopathy

8:37-10:23: Pharmacological therapy used in patients with obstructive hypertrophic cardiomyopathy and why mavacamten is different

10:24-11:14: Initial thoughts about the trial

11:15-13:30: Beta-blocker subgroup analysis and disopyramide exclusion

13:31-15:05: Adverse effect profile

15:06-16:09: Where do we anticipate mavacamten to fit in this patient population?

16:10-16:49: Final thoughts

16:50-17:26: Closing

References:

Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2020; 396: 759-69.

CardioScripts Classic – Antiplatelets in ACS [Part 2]

0:00-0:58: Intro

0:59-4:47: 1-year after ISAR-REACT 5, does prasugrel reign supreme?

4:48-7:32: Dr. Dunn and Dr. Macaulay dive into the confusing world of DAPT duration.  Who should get shorter and who get longer, based on DAPT trial, PEGASUS, TWILIGHT, TICO, and more. 

7:33-10:46: When de-escalation is indicated, should it be aspirin or P2Y12 inhibitor that goes away?  Remember CAPRIE?

10:47-13:56: ESC meeting and presentation of 2020 Guidelines for NSTE ACS recommend prasugrel, 12-months for most (but lots of wiggle room), and no upfront treatment with P2Y12. 

13:57-15:41: Pre-treatment with P2Y12 inhibitors or not?  Where is the data for what has become widespread practice.

15:42-20:08: A review of switching between P2Y12 inhibitors.  And defining a role for improved pharmacy continuity between inpatient, ambulatory and community pharmacists.

20:09-20:52: Closing 

References:

  • Schupke S, et al. Ticagrelor or prasugrel in patients with acute coronary syndromes (ISAR-REACT 5). N Engl J Med 2019. (epub doi 10.1056/NEJMoa1908973):1-11.
  • Mauri L, et al. Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents (DAPT Study). N Engl J Med 2014; 371:2155-2166.
  • Bonaca MP, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015;372:1791-1800.
  • Costa F, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trial. Lancet 2017;389:1025-1034.
  • Mehran R, et al. Ticagrelor with or without Aspirin in High-Risk Patients after PCI (TWILIGHT). N Engl J Med 2019; 381:2032-2042.

CardioScripts Classic – Antiplatelets in ACS [Part 1]

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

DOACs and LV Thrombus Management

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.

CardioScripts Classics – Vasodilators in HFrEF [Part 2]

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.

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! 

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.

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

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.