Top

Published in:

01-02-2011

Rationale for Combining a Direct Renin Inhibitor with other Renin- Angiotensin System Blockers. Focus on Aliskiren and Combinations

Author: Helmy M. Siragy

Published in: Cardiovascular Drugs and Therapy | Issue 1/2011

Abstract

Inhibition of the renin-angiotensin system has been a highly successful therapeutic approach for the prevention of hypertension-related end organ damage. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers lower blood pressure and reduce morbidity and mortality in patients with cardiovascular and kidney disease. However, progression to end-stage disease remains common in these patient populations. A compensatory increase in plasma renin activity occurs with the use of either angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, thus causing increased levels of angiotensin II, which may limit the therapeutic effectiveness of these agents. The direct renin inhibitor, aliskiren, suppresses the renin-angiotensin system by inhibiting its first and rate-limiting step. This early inhibition reduces the production of all downstream components of the system. In this review, recent clinically relevant advances in the understanding of renin-angiotensin system biology are explored as a rationale for combining aliskiren with other blockers of the renin-angiotensin system. These combinations more fully inhibit the renin-angiotensin system, with the goal of providing additional therapeutic benefits in diseases associated with chronic activation of the renin-angiotensin system.

Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics–2010 update: a report from the American Heart Association. Circulation. 2010;121:e46–215.PubMedCrossRef

Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–9.PubMedCrossRef

Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–60.PubMedCrossRef

Fisher ND, Hollenberg NK. Renin inhibition: what are the therapeutic opportunities? J Am Soc Nephrol. 2005;16:592–9.PubMedCrossRef

Paul M, Poyan Mehr A, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev. 2006;86:747–803.PubMedCrossRef

Li J, Doerffel Y, Hocher B, Unger T. Inflammation in the genesis of hypertension and its complications–the role of angiotensin II. Nephrol Dial Transplant. 2007;22:3107–9.PubMedCrossRef

Heymes C, Bendall JK, Ratajczak P, et al. Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol. 2003;41:2164–71.PubMedCrossRef

Kranzhofer R, Schmidt J, Pfeiffer CA, et al. Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1999;19:1623–9.PubMed

Ha H, Lee HB. Reactive oxygen species and matrix remodeling in diabetic kidney. J Am Soc Nephrol. 2003;14:S246–9.PubMedCrossRef

10.

Ruster C, Wolf G. Renin-angiotensin-aldosterone system and progression of renal disease. J Am Soc Nephrol. 2006;17:2985–91.PubMedCrossRef

11.

Endemann DH, Schiffrin EL. Endothelial dysfunction. J Am Soc Nephrol. 2004;15:1983–92.PubMedCrossRef

12.

Weber KT. Extracellular matrix remodeling in heart failure: a role for de novo angiotensin II generation. Circulation. 1997;96:4065–82.PubMed

13.

Hollenberg NK, Fisher ND, Price DA. Pathways for angiotensin II generation in intact human tissue: evidence from comparative pharmacological interruption of the renin system. Hypertension. 1998;32:387–92.PubMed

14.

Carey RM. Cardiovascular and renal regulation by the angiotensin type 2 receptor: the AT2 receptor comes of age. Hypertension. 2005;45:840–4.PubMedCrossRef

15.

Carey RM, Howell NL, Jin XH, Siragy HM. Angiotensin type 2 receptor-mediated hypotension in angiotensin type-1 receptor-blocked rats. Hypertension. 2001;38:1272–7.PubMedCrossRef

16.

Padia SH, Howell NL, Siragy HM, Carey RM. Renal angiotensin type 2 receptors mediate natriuresis via angiotensin III in the angiotensin II type 1 receptor-blocked rat. Hypertension. 2006;47:537–44.PubMedCrossRef

17.

Siragy HM, Xue C, Abadir P, Carey RM. Angiotensin subtype-2 receptors inhibit renin biosynthesis and angiotensin II formation. Hypertension. 2005;45:133–7.PubMed

18.

Savoia C, Touyz RM, Volpe M, Schiffrin EL. Angiotensin type 2 receptor in resistance arteries of type 2 diabetic hypertensive patients. Hypertension. 2007;49:341–6.PubMedCrossRef

19.

Widdop RE, Jones ES, Hannan RE, Gaspari TA. Angiotensin AT2 receptors: cardiovascular hope or hype? Br J Pharmacol. 2003;140:809–24.PubMedCrossRef

20.

Ferrario CM. Angiotensin-converting enzyme 2 and angiotensin-(1-7): an evolving story in cardiovascular regulation. Hypertension. 2006;47:515–21.PubMedCrossRef

21.

Tipnis SR, Hooper NM, Hyde R, et al. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000;275:33238–43.PubMedCrossRef

22.

Santos RA, Simoes e Silva AC, Maric C, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci USA. 2003;100:8258–63.PubMedCrossRef

23.

Chai SY, Fernando R, Peck G, et al. The angiotensin IV/AT4 receptor. Cell Mol Life Sci. 2004;61:2728–37.PubMedCrossRef

24.

Albiston AL, McDowall SG, Matsacos D, et al. Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. J Biol Chem. 2001;276:48623–6.PubMedCrossRef

25.

Nguyen G, Delarue F, Burckle C, et al. Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest. 2002;109:1417–27.PubMed

26.

Danser AH, Deinum J. Renin, prorenin and the putative (pro)renin receptor. Hypertension. 2005;46:1069–76.PubMedCrossRef

27.

Stankovic AR, Fisher ND, Hollenberg NK. Prorenin and angiotensin-dependent renal vasoconstriction in type 1 and type 2 diabetes. J Am Soc Nephrol. 2006;17:3293–9.PubMedCrossRef

28.

Deinum J, Ronn B, Mathiesen E, et al. Increase in serum prorenin precedes onset of microalbuminuria in patients with insulin-dependent diabetes mellitus. Diabetologia. 1999;42:1006–10.PubMedCrossRef

29.

Siragy HM, Huang J. Renal (pro)renin receptor upregulation in diabetic rats through enhanced angiotensin AT1 receptor and NADPH oxidase activity. Exp Physiol. 2008;93:709–14.PubMedCrossRef

30.

Singh VP, Le B, Khode R, Baker KM, Kumar R. Intracellular angiotensin II production in diabetic rats is correlated with cardiomyocyte apoptosis, oxidative stress, and cardiac fibrosis. Diabetes. 2008;57:3297–306.PubMedCrossRef

31.

Singh VP, Le B, Bhat VB, Baker KM, Kumar R. High-glucose-induced regulation of intracellular ANG II synthesis and nuclear redistribution in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2007;293:H939–48.PubMedCrossRef

32.

Huang Y, Wongamorntham S, Kasting J, et al. Renin increases mesangial cell transforming growth factor-beta1 and matrix proteins through receptor-mediated, angiotensin II-independent mechanisms. Kidney Int. 2006;69:105–13.PubMedCrossRef

33.

Huang Y, Noble NA, Zhang J, Xu C, Border WA. Renin-stimulated TGF-beta1 expression is regulated by a mitogen-activated protein kinase in mesangial cells. Kidney Int. 2007;72:45–52.PubMedCrossRef

34.

Schefe JH, Menk M, Reinemund J, et al. A novel signal transduction cascade involving direct physical interaction of the renin/prorenin receptor with the transcription factor promyelocytic zinc finger protein. Circ Res. 2006;99:1355–66.PubMedCrossRef

35.

Campbell DJ. Critical review of prorenin and (pro)renin receptor research. Hypertension. 2008;51:1259–64.PubMedCrossRef

36.

Reudelhuber TL. Prorenin, renin, and their receptor. Moving targets. Hypertension 2010.

37.

Muller DN, Hilgers KF, Mathews S, et al. Effects of human prorenin in rats transgenic for human angiotensinogen. Hypertension. 1999;33:312–7.PubMed

38.

Veniant M, Menard J, Bruneval P, et al. Vascular damage without hypertension in transgenic rats expressing prorenin exclusively in the liver. J Clin Invest. 1996;98:1966–70.PubMedCrossRef

39.

Mercure C, Prescott G, Lacombe MJ, Silversides DW, Reudelhuber TL. Chronic increases in circulating prorenin are not associated with renal or cardiac pathologies. Hypertension. 2009;53:1062–9.PubMedCrossRef

40.

Alderman MH, Ooi WL, Cohen H, et al. Plasma renin activity: a risk factor for myocardial infarction in hypertensive patients. Am J Hypertens. 1997;10:1–8.PubMedCrossRef

41.

Verma S, Gupta M, Holmes D, et al. Plasma renin activity is associated with increased cardiovascular events and mortality in the HOPE study. Circulation. 2009;120:S453.

42.

Bair TL, May HT, Prescott MF, et al. Association between baseline levels of plasma renin activity and risk of cardiovascular events. Presented at: American College of Cardiology Annual Meeting; March 29–31, 2009; Orlando, FL.

43.

Parikh NI, Gona P, Larson MG, et al. Plasma renin and risk of cardiovascular disease and mortality: the Framingham Heart Study. Eur Heart J. 2007;28:2644–52.PubMedCrossRef

44.

Adiyaman A, Staessen JA. Renin turning full circle as cardiovascular risk factor. Eur Heart J. 2007;28:2557–8.PubMedCrossRef

45.

Laragh JH. Abstract, closing summary, and table of contents for Laragh’s 25 lessons in pathophysiology and 12 clinical pearls for treating hypertension. Am J Hypertens. 2001;14:1173–7.PubMedCrossRef

46.

Furberg CD. Renin-guided treatment of hypertension: time for action. Am J Hypertens. 2010;23:929–30.PubMedCrossRef

47.

Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group. N Engl J Med. 1987; 316:1429–35.

48.

Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med. 1991; 325:293–302.

49.

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. The SAVE Investigators. N Engl J Med. 1992;327:669–77.PubMedCrossRef

50.

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; 342:821–8.

51.

Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329:1456–62.PubMedCrossRef

52.

Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The angiotensin-converting-enzyme inhibition in progressive renal insufficiency study group. N Engl J Med. 1996;334:939–45.PubMedCrossRef

53.

Biollaz J, Brunner HR, Gavras I, Waeber B, Gavras H. Antihypertensive therapy with MK 421: angiotensin II–renin relationships to evaluate efficacy of converting enzyme blockade. J Cardiovasc Pharmacol. 1982;4:966–72.PubMedCrossRef

54.

Roig E, Perez-Villa F, Morales M, et al. Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Eur Heart J. 2000;21:53–7.PubMedCrossRef

55.

Huang XR, Chen WY, Truong LD, Lan HY. Chymase is upregulated in diabetic nephropathy: implications for an alternative pathway of angiotensin II-mediated diabetic renal and vascular disease. J Am Soc Nephrol. 2003;14:1738–47.PubMedCrossRef

56.

Wei CC, Hase N, Inoue Y, et al. Mast cell chymase limits the cardiac efficacy of Ang I-converting enzyme inhibitor therapy in rodents. J Clin Invest. 2010;120:1229–39.PubMedCrossRef

57.

Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet. 2000;355:637–45.PubMedCrossRef

58.

Maggioni AP, Anand I, Gottlieb SO, et al. Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors. J Am Coll Cardiol. 2002;40:1414–21.PubMedCrossRef

59.

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;362:772–6.PubMedCrossRef

60.

Turnbull F, Neal B, Pfeffer M, et al. Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system. J Hypertens. 2007;25:951–8.PubMedCrossRef

61.

Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119:e391–479.PubMedCrossRef

62.

KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis. 2007; 49:S12-154.

63.

Brown MJ. Aliskiren. Circulation. 2008;118:773–84.PubMedCrossRef

64.

Weir MR, Bush C, Anderson DR, et al. Antihypertensive efficacy, safety, and tolerability of the oral direct renin inhibitor aliskiren in patients with hypertension: a pooled analysis. J Am Soc Hypertens. 2007;1:264–77.PubMedCrossRef

65.

Doulton TW, He FJ, MacGregor GA. Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension. Hypertension. 2005;45:880–6.PubMedCrossRef

66.

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. Lancet. 2003;362:767–71.PubMedCrossRef

67.

Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–75.PubMedCrossRef

68.

Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349:1893–906.PubMedCrossRef

69.

Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547–59.PubMedCrossRef

70.

Jong P, Demers C, McKelvie RS, Liu PP. Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2002;39:463–70.PubMedCrossRef

71.

Lee VC, Rhew DC, Dylan M, et al. Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med. 2004;141:693–704.PubMed

72.

Lakhdar R, Al-Mallah MH, Lanfear DE. Safety and tolerability of angiotensin-converting enzyme inhibitor versus the combination of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in patients with left ventricular dysfunction: a systematic review and meta-analysis of randomized controlled trials. J Card Fail. 2008;14:181–8.PubMedCrossRef

73.

Phillips CO, Kashani A, Ko DK, Francis G, Krumholz HM. Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials. Arch Intern Med. 2007;167:1930–6.PubMedCrossRef

74.

Fried LF, Duckworth W, Zhang JH, et al. Design of combination angiotensin receptor blocker and angiotensin-converting enzyme inhibitor for treatment of diabetic nephropathy (VA NEPHRON-D). Clin J Am Soc Nephrol. 2009;4:361–8.PubMedCrossRef

75.

Latini R, Masson S, Anand I, et al. The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT. Eur Heart J. 2004;25:292–9.PubMedCrossRef

76.

Uresin Y, Taylor AA, Kilo C, et al. Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension. J Renin Angiotensin Aldosterone Syst. 2007;8:190–8.PubMedCrossRef

77.

Oparil S, Yarows SA, Patel S, et al. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet. 2007;370:221–9.PubMedCrossRef

78.

McMurray JJ, Pitt B, Latini R, et al. Effect of the oral direct renin inhibitor aliskiren in patients with symptomatic heart failure. Circ Heart Fail. 2008;1:17–24.PubMedCrossRef

79.

Mancia G, Seravalle G, Grassi G. Tolerability and treatment compliance with angiotensin II receptor antagonists. Am J Hypertens. 2003;16:1066–73.PubMedCrossRef

80.

Berlowitz MS, Latif F, Hankins SR, et al. Dose-dependent blockade of the angiotensin II type 1 receptor with losartan in normal volunteers. J Cardiovasc Pharmacol. 2001;37:692–6.PubMedCrossRef

81.

Diovan® (valsartan). Full Prescribing Information, Novartis Pharmacueticals, 2010.

82.

Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP. Clinical pharmacokinetics and pharmacodynamics of aliskiren. Clin Pharmacokinet. 2008;47:515–31.PubMedCrossRef

83.

Oh BH, Mitchell J, Herron JR, et al. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J Am Coll Cardiol. 2007;49:1157–63.PubMedCrossRef

84.

Andersen K, Weinberger MH, Egan B, et al. Comparative efficacy and safety of aliskiren, an oral direct renin inhibitor, and ramipril in hypertension: a 6-month, randomized, double-blind trial. J Hypertens. 2008;26:589–99.PubMedCrossRef

85.

Feldman DL, Jin L, Xuan H, et al. Effects of aliskiren on blood pressure, albuminuria, and (pro)renin receptor expression in diabetic TG(mRen-2)27 rats. Hypertension. 2008;52:130–6.PubMedCrossRef

86.

Fisher ND, Jan Danser AH, Nussberger J, Dole WP, Hollenberg NK. Renal and hormonal responses to direct renin inhibition with aliskiren in healthy humans. Circulation. 2008;117:3199–205.PubMedCrossRef

87.

Mezzano S, Droguett A, Burgos ME, et al. Renin-angiotensin system activation and interstitial inflammation in human diabetic nephropathy. Kidney Int Suppl. 2003;86:S64–70.PubMedCrossRef

88.

Hodroj W, Legedz L, Foudi N, et al. Increased insulin-stimulated expression of arterial angiotensinogen and angiotensin type 1 receptor in patients with type 2 diabetes mellitus and atheroma. Arterioscler Thromb Vasc Biol. 2007;27:525–31.PubMedCrossRef

89.

Azizi M, Menard J, Bissery A, et al. Pharmacologic demonstration of the synergistic effects of a combination of the renin inhibitor aliskiren and the AT1 receptor antagonist valsartan on the angiotensin II-renin feedback interruption. J Am Soc Nephrol. 2004;15:3126–33.PubMedCrossRef

90.

Solomon SD, Appelbaum E, Manning WJ, et al. Effect of the direct renin inhibitor aliskiren, the angiotensin receptor blocker losartan, or both on left ventricular mass in patients with hypertension and left ventricular hypertrophy. Circulation. 2009;119:530–7.PubMedCrossRef

91.

Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008;358:2433–46.PubMedCrossRef

92.

Yarows SA. Aliskiren/valsartan combination for the treatment of cardiovascular and renal diseases. Expert Rev Cardiovasc Ther. 2010;8:19–33.PubMedCrossRef

93.

Brown NJ. Aldosterone and vascular inflammation. Hypertension. 2008;51:161–7.PubMedCrossRef

94.

Vasan RS, Evans JC, Larson MG, et al. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med. 2004;351:33–41.PubMedCrossRef

95.

Sowers JR, Whaley-Connell A, Epstein M. Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension. Ann Intern Med. 2009;150:776–83.PubMed

96.

Parving HH, Brenner BM, McMurray JJ, et al. Aliskiren trial in type 2 diabetes using cardio-renal endpoints (ALTITUDE): rationale and study design. Nephrol Dial Transplant. 2009;24:1663–71.PubMedCrossRef

97.

Chrysant SG, Murray AV, Hoppe UC, et al. Long-term safety, tolerability and efficacy of aliskiren in combination with valsartan in patients with hypertension: a 6-month interim analysis. Curr Med Res Opin. 2008;24:1039–47.PubMedCrossRef

Title: Rationale for Combining a Direct Renin Inhibitor with other Renin- Angiotensin System Blockers. Focus on Aliskiren and Combinations
Author: Helmy M. Siragy
Publication date: 01-02-2011
Publisher: Springer US
Published in: Cardiovascular Drugs and Therapy / Issue 1/2011
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-010-6278-0

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The STEP trials

Springer Medicine

Rationale for Combining a Direct Renin Inhibitor with other Renin- Angiotensin System Blockers. Focus on Aliskiren and Combinations

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2011

Achievement of Lipid Targets with the Combination of Rosuvastatin and Fenofibric Acid in Patients with Type 2 Diabetes Mellitus

Clinical Trials Update AHA Congress 2010

Statins in Heart Failure—Where Do We Stand?

The Role of β-adrenergic Receptors in the Cardioprotective Effects of Beta-Preconditioning (βPC)

Pre-treatment with a DPP-4 Inhibitor is Infarct Sparing in Hearts from Obese, Pre-diabetic Rats

Long-Term Efficacy of Adding Fenofibric Acid to Moderate-Dose Statin Therapy in Patients with Persistent Elevated Triglycerides

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page