The PARADISE-MI Trial

Dr. Stephanie Dwyer Kaluzna and CardioScripts co-host, Dr. Tracy Macaulay, discuss the PARADISE-MI trial. 

0:00-0:25: Introduction 

0:26-1:19: Introduction of Dr. Stephanie Dwyer Kaluzna

1:20-6:14: PARADISE-MI Overview 

6:15-7:56: Overall Thoughts 

7:57-10:28: Use of ACE-I/ARB in MI

10:30-13:43: Background Therapy Considerations 

13:44-18:08: Applicability and Feasibility of Use

18:09-19:24: Final Thoughts 

19:25-20:02: Closing 

References: 

PARADISE-MI Trial: Design and baseline characteristics: Jering KS, Claggett B, Pfeffer MA, et al. Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI): design and baseline characteristics [published online ahead of print, 2021 Apr 12]. Eur J Heart Fail. 2021;10.1002/ejhf.2191. doi:10.1002/ejhf.2191

AIRE Trial: Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet. 1993;342(8875):821-828.

VALIANT Trial: McMurray J, Solomon S, Pieper K, et al. The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). J Am Coll Cardiol. 2006;47(4):726-733. doi:10.1016/j.jacc.2005.09.055

EPHESUS Trial: Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction [published correction appears in N Engl J Med. 2003 May 29;348(22):2271]. N Engl J Med. 2003;348(14):1309-1321. doi:10.1056/NEJMoa030207

Timing of initiation of eplerenone in EPHESUS: Adamopoulos C, Ahmed A, Fay R, et al. Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial. Eur J Heart Fail. 2009;11(11):1099-1105. doi:10.1093/eurjhf/hfp136

EMPEROR-Reduced: Reign of the SGLT2 Inhibitors

Dr. Ted Berei and CardioScripts co-host, Dr. Tracy Macaulay, discuss the EMPEROR-Reduced trial. 

0:00-0:28: Introduction 

0:29-1:05: Introduction of Dr. Ted Berei 

1:06-3:40: EMPEROR-Reduced Overview 

3:41-5:08: Overall Thoughts 

5:09 -11:18: Secondary Endpoints 

11:19-19:04: Considerations for Initiation of SGLT2 Inhibitors 

19:05-21:21: Final Thoughts 

21:22-22:02: Closing 

References: 

  • McMurray, John JV, et al. “Dapagliflozin in patients with heart failure and reduced ejection fraction.” New England Journal of Medicine 381.21 (2019): 1995-2008. 
  • Packer, Milton, et al. “Cardiovascular and renal outcomes with empagliflozin in heart failure.” New England Journal of Medicine 383.15 (2020): 1413-1424. 
  • Vardeny, Orly, and Muthiah Vaduganathan. “Practical guide to prescribing sodium-glucose cotransporter 2 inhibitors for cardiologists.” JACC: Heart Failure 7.2 (2019): 169-172. 
  • Das, Sandeep R., et al. “2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes: a report of the American College of Cardiology solution set oversight committee.” Journal of the American College of Cardiology 76.9 (2020): 1117-1145. 

POPular TAVI Trial [Cohort A]

Dr. John Lindsley and CardioScripts co-host, Dr. Liz Sulaica, discuss cohort A of the POPular TAVI trial.

0:00-0:28: Introduction

0:29-1:04: Introduction of Dr. John Lindsley

1:05-6:12: Cohort A Overview

6:13-10:18: Overall Thoughts

10:19-12:30: Subclinical Valve Thrombosis

12:31-15:05: Management strategies

15:06-15:52: Final Thoughts

15:53-16:31: Closing

References:

  • POPular TAVI Trial [Cohort A]: Brouwer J, Nijenhuis VJ, Delewi RS, et al. Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. N Engl J Med 2020; 383: 1447-57. DOI: 10.1056/NEJMoa2017815.
  • POPular TAVI Trial [Cohort B]: 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.

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