In this special episode the CardioScripts crew join Pharmacy to Dose podcast creator and host, Nick Peters, to discuss his Top 3 Trials in cardiology. Listen to the full episode on the Pharmacy to Dose podcast (https://pharmacytodose.com/) where you can also find a full list of references! 

Dr. Sara Ward discusses the SECURE trial with co-host, Dr. Tracy Macaulay

0:00-1:08: Introduction

1:09-3:40: SECURE trial overview

3:41-7:55: History of polypill and overall trial considerations

7:56-11:36: Polypill formulation and titration

11:37-14:04: Antiplatelet therapy in SECURE discussion

14:05-18:06: Polypill use in the US

18:07-19:29: Final thoughts

19:30-20:00: Closing

References: 

SECURE Castellano JM, Pocock SJ, Bhatt DL, et al. Polypill Strategy in Secondary Cardiovascular Prevention. N Engl J Med. 2022;387(11):967-977. doi:10.1056/NEJMoa2208275

Roth GA, Mensah GA, Johnson CO, et al. Global burden of cardiovascular diseases and riskfactors, 1990–2019: update from the GBD 2019 Study. J Am Coll Cardiol 2020; 76: 2982–3021.

Bansilal S, Castellano JM, Garrido E, et al. Assessing the impact of medication adherence onlong-term cardiovascular outcomes. J Am Coll Cardiol 2016;68:789-801.

KolandaiveluK, Leiden BB, O’Gara PT, Bhatt DL. Non-adherence to cardiovascular medications.Eur Heart J 2014; 35:3267-76.

Ferket BS, Hunink MG, Khanji M, et al. Cost-effectiveness of the polypill versus risk assessment forprevention of cardiovascular disease. Heart 2017;103:483-491.

Munoz D, Uzoije P, Reynolds C, et al. Polypill for cardiovascular disease prevention in an underservedpopulation. New Eng J Med 2019;381:1114-23.

Macaulay T, Sheridan E, Ward S. Reconsidering the Polypill for management of cardiovascularrisk factors in underserved patietsion. Curr Cardiol Rep 2021; 23:19.

Yusuf S, Joseph P, Dans A, et al. Polypill with or without aspirin in persons withoutcardiovascular disease. N Engl J Med 2021; 384: 216–28.

Roshandel G, Khoshnia M, Poustchi H, et al. Effectiveness of polypill for primary and secondaryprevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial. Lancet2019; 394:672–83.

Yusuf S, Lonn E, Pais P, et al. Blood-pressure and cholesterol lowering in persons withoutcardiovascular disease. N Engl J Med 2016; 374: 2032–43.

Castellano JM, Sanz G, Peñalvo JL, et al. A polypill strategy to improve adherence: results fromthe FOCUS project. J Am Coll Cardiol 2014;64:2071-82.

Joseph P, Roshandel G, Gao P, et al. Fixed-dose combination therapies with and without aspirin forprimary prevention of cardiovascular disease: an individual participant data meta-analysis.Lancet2021;398:1133-46.

Dr. Noelle Leung discusses the CHAP trial with co-host, Dr. Tracy Macaulay.

0:00-0:55: Introduction

0:56-4:32: CHAP trial overview

4:33-17:40: Overall thoughts and discussion 

17:41-19:55: Collaboration in patient care

19:56-23:38: Use of aspirin 

23:39-24:37: Final thoughts

24:38-25:12: Closing

References:

CHAP

Tita AT, Szychowski JM, Boggess K, et al. Treatment for Mild Chronic Hypertension during Pregnancy. N Engl J Med. 2022;386(19):1781-1792. doi:10.1056/NEJMoa2201295

Dr. Tomasz Jurga discusses the DELIVER trial with co-host, Dr. Liz Wang.

0:00-2:10: Introduction

2:11-6:05: DELIVER trial overview

6:06-12:51: History of HFpEF treatment 

12:52-24:18: DELIVER overall thoughts

24:19-25:18: Timing of initiation

25:19-29:26: SGLT2 inhibitor place in HFpEF therapy 

29:27-32:59: Considerations for adverse effects and monitoring

33:00-35:15: Final thoughts

35:16-35:54: Closing

References:

DELIVER

Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387(12):1089-1098. doi:10.1056/NEJMoa2206286

DAPA HF

McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303

CHARM-Preserved

Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362(9386):777-781. doi:10.1016/S0140-6736(03)14285-7

TOPCAT

Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383-1392. doi:10.1056/NEJMoa1313731

RELAX

Redfield MM, Chen HH, Borlaug BA, et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013;309(12):1268-1277. doi:10.1001/jama.2013.2024

NEAT-HFpEF

Redfield MM, Anstrom KJ, Levine JA, et al. Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2015;373(24):2314-2324. doi:10.1056/NEJMoa1510774

PARAGON-HF

Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019;381(17):1609-1620. doi:10.1056/NEJMoa1908655

VITALITY-HFpEF

Armstrong PW, Lam CSP, Anstrom KJ, et al. Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial [published correction appears in JAMA. 2021 Feb 2;325(5):494]. JAMA. 2020;324(15):1512-1521. doi:10.1001/jama.2020.15922

EMPEROR-Preserved 

Anker SD, Butler J, Filippatos G, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385(16):1451-1461. doi:10.1056/NEJMoa2107038

EMPULSE

Biegus J, Voors AA, Collins SP, et al. Impact of empagliflozin on decongestion in acute heart failure: the EMPULSE trial [published online ahead of print, 2022 Oct 18]. Eur Heart J. 2022;ehac530. doi:10.1093/eurheartj/ehac530

EMPAG HF 

Schulze PC, Bogoviku J, Westphal J, et al. Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF). Circulation. 2022;146(4):289-298. doi:10.1161/CIRCULATIONAHA.122.059038

Vaduganathan M, Docherty KF, Claggett BL, et al. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet. 2022;400(10354):757-767. doi:10.1016/S0140-6736(22)01429-5

Dr. Zac Cox discusses the ADVOR trial with co-host, Dr. Tracy Macaulay.

0:00-0:55: Introduction

0:56-4:58: ADVOR trial overview

4:59-06:51: Overall thoughts

06:52-09:39: The exclusion of SGLT2 inhibitor use

09:40-10:57: Baseline medical therapy

10:58-16:00: Congestion score

16:01-28:45: Sample size and other considerations for application

28:46-31:13: Final thoughts and Acetazolamide Trivia! 

31:14-31:55: Closing

References:

ADVOR

Mullens W, Dauw J, Martens P, et al. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022;387(13):1185-1195. doi:10.1056/NEJMoa2203094

DOSE

Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364(9):797-805. doi:10.1056/NEJMoa1005419

CARESS HF

Bart BA, Goldsmith SR, Lee KL, et al. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012;367(24):2296-2304. doi:10.1056/NEJMoa1210357

ROSE AHF

Chen HH, Anstrom KJ, Givertz MM, et al. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA. 2013;310(23):2533-2543. doi:10.1001/jama.2013.282190

The 3T Trial

Cox ZL, Hung R, Lenihan DJ, Testani JM. Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure: The 3T Trial. JACC Heart Fail. 2020;8(3):157-168. doi:10.1016/j.jchf.2019.09.012

Dr. Paul Dobesh discusses the MICHELLE trial with co-host, Dr. Tracy Macaulay.

0:00-1:00: Introduction

1:01-4:14: MICHELLE trial overview

4:15-11:10: Risk stratification and current recommendations for thromboprophylaxis

11:11-19:43: Thoughts on the MICHELLE trial and application to current practice

19:44-23:00: Future directions

23:01-24:03: Closing

References:

MICHELLE

Ramacciotti E, Barile Agati L, Calderaro D, et al. Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. Lancet. 2022;399(10319):50-59. doi:10.1016/S0140-6736(21)02392-8

ADOPT

Goldhaber SZ, Leizorovicz A, Kakkar AK, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. 2011;365(23):2167-2177. doi:10.1056/NEJMoa1110899

MAGELLAN

Cohen AT, Spiro TE, Büller HR, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013;368(6):513-523. doi:10.1056/NEJMoa1111096

APEX

Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med. 2016;375(6):534-544. doi:10.1056/NEJMoa1601747

ACTION

Lopes RD, de Barros E Silva PGM, Furtado RHM, et al. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet. 2021;397(10291):2253-2263. doi:10.1016/S0140-6736(21)01203-4

ACTIV-4B

Connors JM, Brooks MM, Sciurba FC, et al. Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial. JAMA.2021;326(17):1703–1712. doi:10.1001/jama.2021.17272

Dobesh PP, Trujillo TC. Coagulopathy, Venous Thromboembolism, and Anticoagulation in Patients with COVID-19. Pharmacotherapy. 2020;40(11):1130-1151. doi:10.1002/phar.2465

Dr. Mary Blanton Covell discusses the cardiovascular benefits of exercise and physical activity with co-host, Dr. Tracy Macaulay.

0:00-1:07: Introduction

1:08-5:05: Background

5:06-15:45: Patient Education and Cardiopulmonary Rehabilitation Programs 

15:46-22:30: What type of exercise is best?

22:31-24:20: Overall Thoughts

24:21-25:05: Closing

References:

Netherlands Cardiac Rehab Trial:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2768711

Eijsvogels TMH, Maessen MFH, Bakker EA, et al. Association of Cardiac Rehabilitation With All-Cause Mortality Among Patients With Cardiovascular Disease in the Netherlands. JAMA Netw Open. 2020;3(7):e2011686. doi:10.1001/jamanetworkopen.2020.11686

Iowa State Pilot Study:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322789/

Schroeder EC, Franke WD, Sharp RL, Lee DC. Comparative effectiveness of aerobic, resistance, and combined training on cardiovascular disease risk factors: A randomized controlled trial. PLoS One. 2019;14(1):e0210292. Published 2019 Jan 7. doi:10.1371/journal.pone.0210292

CardioRACE methods paper: 

https://pubmed.ncbi.nlm.nih.gov/31520895/

Brellenthin AG, Lanningham-Foster LM, Kohut ML, Li Y, Church TS, Blair SN, Lee DC. Comparison of the Cardiovascular Benefits of Resistance, Aerobic, and Combined Exercise (CardioRACE): Rationale, design, and methods. Am Heart J. 2019 Nov;217:101-111. doi: 10.1016/j.ahj.2019.08.008. Epub 2019 Aug 15. PMID: 31520895; PMCID: PMC6861681.

WHO Sedentary Guidelines: 

https://www.who.int/publications/i/item/9789240015128

WHO Guidelines on Physical Activity and Sedentary Behaviour. Geneva: World Health Organization; 2020. PMID: 33369898.

ESC Exercise in Patients with Cardiac Disease Guidelines: 

https://academic.oup.com/eurheartj/article/42/1/17/5898937

ESC Scientific Document Group, 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease: The Task Force on sports cardiology and exercise in patients with cardiovascular disease of the European Society of Cardiology (ESC), European Heart Journal, Volume 42, Issue 1, 1 January 2021, Pages 17–96, https://doi.org/10.1093/eurheartj/ehaa605.

ACC Primary Prevention Guidelines: 

https://academic.oup.com/eurheartj/article/42/1/17/5898937

2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

Morris JN, Chave SP, Adam C, Sirey C, Epstein L, Sheehan DJ. Vigorous exercise in leisure-time and the incidence of coronary heart-disease. Lancet. 1973;1(7799):333-339. doi:10.1016/s0140-6736(73)90128-1

Sattelmair J, Pertman J, Ding EL, Kohl HW 3rd, Haskell W, Lee IM. Dose response between physical activity and risk of coronary heart disease: a meta-analysis. Circulation. 2011;124(7):789-795. doi:10.1161/CIRCULATIONAHA.110.010710

Carlsson S, Andersson T, Lichtenstein P, Michaëlsson K, Ahlbom A. Physical activity and mortality: is the association explained by genetic selection?. Am J Epidemiol. 2007;166(3):255-259. doi:10.1093/aje/kwm132

Taylor RS, Brown A, Ebrahim S, et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med. 2004;116(10):682-692. doi:10.1016/j.amjmed.2004.01.009

Paffenbarger RS Jr, Hyde RT, Wing AL, Hsieh CC. Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med. 1986;314(10):605-613. doi:10.1056/NEJM198603063141003

Lee DC, Pate RR, Lavie CJ, Sui X, Church TS, Blair SN. Leisure-time running reduces all-cause and cardiovascular mortality risk [published correction appears in J Am Coll Cardiol. 2014 Oct 7;64(14):1537]. J Am Coll Cardiol. 2014;64(5):472-481. doi:10.1016/j.jacc.2014.04.058

Mons U, Hahmann H, Brenner H. A reverse J-shaped association of leisure time physical activity with prognosis in patients with stable coronary heart disease: evidence from a large cohort with repeated measurements. Heart. 2014;100(13):1043-1049. doi:10.1136/heartjnl-2013-305242

O’Keefe JH, Patil HR, Lavie CJ, Magalski A, Vogel RA, McCullough PA. Potential adverse cardiovascular effects from excessive endurance exercise [published correction appears in Mayo Clin Proc. 2012 Jul;87(7):704]. Mayo Clin Proc. 2012;87(6):587-595. doi:10.1016/j.mayocp.2012.04.005

Grøntved A, Koivula RW, Johansson I, et al. Bicycling to Work and Primordial Prevention of Cardiovascular Risk: A Cohort Study Among Swedish Men and Women. J Am Heart Assoc. 2016;5(11):e004413. Published 2016 Oct 31. doi:10.1161/JAHA.116.004413

Ellingsen Ø, Halle M, Conraads V, et al. High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction. Circulation. 2017;135(9):839-849. doi:10.1161/CIRCULATIONAHA.116.022924

Authors/Task Force Members, Piepoli MF, Hoes AW, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur J Prev Cardiol. 2016;23(11):NP1-NP96. doi:10.1177/2047487316653709

Dr. Mary Blanton Covell discusses the SSaSS Trial with co-host, Dr. Tracy Macaulay.

0:00-1:24: Introduction

1:25-5:00: SSaSS Trial Overview

5:01-8:50: Thoughts on the SSaSS Trial

8:51-9:55: Application to Clinical Practice

9:56-11:46: Recent FDA Guidance on Industry Sodium Content

11:47-22:15: Other Dietary Recommendations

22:16 – 23:21: Closing

References:

SSaSS Trial: Neal B, Tian M, Li N, et al. Rationale, design, and baseline characteristics of the Salt Substitute and Stroke Study (SSaSS)-A large-scale cluster randomized controlled trial. Am Heart J. 2017;188:109-117. doi:10.1016/j.ahj.2017.02.033

Guidance for Industry: Voluntary Sodium Reduction Goals: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-voluntary-sodium-reduction-goals

Estruch R, Ros E, Salas-Salvadó J, et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. 2018;378(25):e34. doi:10.1056/NEJMoa1800389

Kim H, Caulfield LE, Garcia-Larsen V, Steffen LM, Coresh J, Rebholz CM. Plant-Based Diets Are Associated With a Lower Risk of Incident Cardiovascular Disease, Cardiovascular Disease Mortality, and All-Cause Mortality in a General Population of Middle-Aged Adults. J Am Heart Assoc. 2019;8(16):e012865. doi:10.1161/JAHA.119.012865

Victor RG, Lynch K, Li N, et al. A Choi Y, Larson N, Steffen LM, et al. Plant-Centered Diet and Risk of Incident Cardiovascular Disease During Young to Middle Adulthood. J Am Heart Assoc. 2021;10(16):e020718. doi:10.1161/JAHA.120.020718

Kaiser J, van Daalen KR, Thayyil A, Cocco MTARR, Caputo D, Oliver-Williams C. A Systematic Review of the Association Between Vegan Diets and Risk of Cardiovascular Disease. J Nutr. 2021;151(6):1539-1552. doi:10.1093/jn/nxab037v

Drouin-Chartier JP, Chen S, Li Y, et al. Egg consumption and risk of cardiovascular disease: three large prospective US cohort studies, systematic review, and updated meta-analysis. BMJ. 2020;368:m513. Published 2020 Mar 4. doi:10.1136/bmj.m513

Part 2 of the CardioScripts Classics episode on hypertension with Drs. Tracy Macaulay and Liz Wang.

0:00-1:07: Introduction

1:08-5:23: SPRINT Trial

5:23-9:14: Elderly patients with hypertension

9:15-17:50: Hypertension management in Black patients

17:51-21:57: Hypertension nuances

21:58-23:30: Closing

References:

SPRINT Trial: The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015;373(22):2103-16.

European Hypertension Guidelines: Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018;39(33):3021-3104.

Sulaica EM, Wollen JT, Kotter J, Macaulay TE. A Review of Hypertension Management in Black Male Patients. Mayo Clin Proc 2020;95(9):1955-1963.

Victor RG, Ravenell JE, Freeman Anne, et al. Effectiveness of a barber-based intervention for improving hypertension control in black men: the BARBER-1 study: a cluster randomized trial. Arch Intern Med 2011;171(4):342-50.

Victor RG, Lynch K, Li N, et al. A Cluster-Randomized Trial of Blood-Pressure Reduction in Black Barbershops. N Engl J Med 2018;378(14):1291-1301.

Drs. Tracy Macaulay and Liz Sulaica discuss hypertension.

0:00-0:45: Introduction

0:46-2:14: Intro of Dr. Liz Sulaica

2:15-4:19: SHEP Trial

4:20-6:19: Syst-Eur Trial

6:20-11:17: ALLHAT Trial

11:18-15:59: ACCOMPLISH Trial

16:00-18:53: HCTZ vs. Chlorthalidone

18:54-22:03: JNC 8

22:04-22:35: Closing

References:

SHEP Trial: SHEP Cooperative Research Group. Prevention of Stroke by Antihypertensive Drug Treatment in Older Persons With Isolated Systolic Hypertension. JAMA 1991;265:3255-3264.

Syst-Eur Trial: Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older persons with isolated systolic hypertension. Lancet 1997;350:757-64.

ALLHAT Trial: ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. JAMA 2002;288(23):2981-97.

ACCOMPLISH Trial: Jamerson KJ, Weber MA, Bakris GL, et al. Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk Patients. N Engl J Med 2008; 359:2417-28.

Chlorthalidone vs HCTZ: Hripcsak G, Suchard MA, Shea S, et al. Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs. Hydrochlorothiazide to Treat Hypertension. JAMA Int Med 2020;80(4):542-51.

JNC 8: James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311(5):507-520.

2017 ACC/AHA Hypertension Guideline: Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018;71(19):e127-e248.

Ripley TL, Brenner M, Finks S, et al. Key articles and guidelines in the management of hypertension. J Pharm Pract 2015;28(2):146-61.

Wright JT, Fine LJ, Lackland DT, et al. Evidence supporting a systolic BP goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann Intern Med 2014;160(7):499-503.