Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in high vascular risk

Objective ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely prescribed in patients with high cardiovascular (CV) risk. However, whether both classes have equivalent effectiveness to prevent CV events remains unclear. The aim of this study was to compare the incidence of major CV events between ACEI and ARB users. Methods The Reduction of Atherothrombosis for Continued Health registry is an observational study who enrolled 69 055 individuals with high CV risk. Among them, 40 625 patients (ACEIs 67.9% and ARBs 32.1%) were included. Main outcome was rates of CV mortality, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for CV disease at 4 years. Results In a propensity score-adjusted cohort, the incidence of the primary outcome was lower in patients on ARBs compared with ACEIs (29.2% vs 33.4%; adjusted HR 0.90; 95% CI 0.86 to 0.95; p<0.001). Similar results were observed for CV (6.9% vs 8.2%; HR 0.83; 95% CI 0.75 to 0.93; p=0.001) and all-cause mortality (11.6% vs 12.6%; HR 0.89; 95% CI 0.82 to 0.97; p=0.005). Analyses using propensity score matching yielded similar results. History of diabetes or estimated glomerular filtration rate did not affect the results. ARB use was associated with lower rates of all-cause mortality in secondary prevention but not in primary prevention patients (p-value for interaction=0.03). Conclusion ARB use appears to be associated with 10% lower rates of CV events compared with ACEIs, especially in patients with established CV disease. Our results suggest that ARBs may provide superior protection against CV events than ACEIs in high-risk patients in real-world practice.

[1]  Deepak L. Bhatt,et al.  International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. , 2006, JAMA.

[2]  S. Yusuf,et al.  Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[3]  Deepak L. Bhatt,et al.  Advancing the care of cardiac patients using registry data: going where randomized clinical trials dare not. , 2010, JAMA.

[4]  E. Boersma,et al.  Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin–angiotensin–aldosterone system inhibitors involving 158 998 patients , 2012, European heart journal.

[5]  Bertram Pitt,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 , 2000, The Lancet.

[6]  Jeroen J. Bax,et al.  2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. , 2013, European heart journal.

[7]  Deepak L. Bhatt,et al.  Renin-angiotensin system antagonists and clinical outcomes in stable coronary artery disease without heart failure. , 2014, European heart journal.

[8]  M. Seguí Díaz,et al.  [Effect of angiotensin-converting enzyme inhibitors and angiotensin ii receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus. A meta-analysis]. , 2014, Semergen.

[9]  Bertram Pitt,et al.  Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE) , 1997, The Lancet.

[10]  K. Dickstein,et al.  Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial , 2002, The Lancet.

[11]  A. Hartz,et al.  A comparison of observational studies and randomized, controlled trials. , 2000, The New England journal of medicine.

[12]  B. Lévy Can Angiotensin II Type 2 Receptors Have Deleterious Effects in Cardiovascular Disease?: Implications for Therapeutic Blockade of the Renin–Angiotensin System , 2003, Circulation.

[13]  S. Bangalore,et al.  Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Patients Without Heart Failure? Insights From 254,301 Patients From Randomized Trials. , 2016, Mayo Clinic proceedings.

[14]  K. Fox,et al.  Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study) , 2003, The Lancet.

[15]  M. Nieminen,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[16]  S. Yusuf,et al.  Telmisartan to prevent recurrent stroke and cardiovascular events. , 2008, The New England journal of medicine.

[17]  Volkmar Falk,et al.  2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure , 2016, Revista espanola de cardiologia.

[18]  J. Ménard,et al.  Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study) , 2004, BMJ : British Medical Journal.

[19]  B. Gersh,et al.  ESC guidelines on the management of stable coronary artery disease — addenda The Task Force on the management of stable coronary artery disease of the European Society of Cardiology , 2013 .

[20]  B. Gersh Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events , 2009 .

[21]  Deepak L. Bhatt,et al.  β-Blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. , 2012, JAMA.

[22]  P. Ponikowski,et al.  [2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure]. , 2016, Kardiologia polska.

[23]  J. Mustonen,et al.  Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. , 2004, The New England journal of medicine.

[24]  Sankey V. Williams,et al.  2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Ass , 2012, Journal of the American College of Cardiology.

[25]  P. Rothwell,et al.  External validity of randomised controlled trials: “To whom do the results of this trial apply?” , 2005, The Lancet.

[26]  Deepak L. Bhatt,et al.  Effect of irbesartan and enalapril in non-ST elevation acute coronary syndrome: results of the randomized, double-blind ARCHIPELAGO study. , 2009, European heart journal.

[27]  M. Pfeffer,et al.  Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both , 2004 .

[28]  K. Dickstein,et al.  Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial , 2009, The Lancet.

[29]  P A Poole-Wilson,et al.  Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. , 1999, Circulation.

[30]  M. Tonelli,et al.  Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis , 2015, The Lancet.

[31]  S. Yusuf,et al.  Telmisartan, ramipril, or both in patients at high risk for vascular events. , 2008, The New England journal of medicine.

[32]  K. Rahimi,et al.  Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. , 2015, JAMA.

[33]  A. Hartz,et al.  A comparison of observational studies and randomized, controlled trials , 2000, American journal of ophthalmology.

[34]  Karl Swedberg,et al.  Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. , 2003, The New England journal of medicine.