Comparison between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of myocardial infarction, stroke and death: a meta-analysis

Objectives To compare the effects of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors on the risk of myocardial infarction, stroke, cardiovascular mortality and total mortality. Methods We conducted a meta-analysis of randomized comparative trials between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors. Inclusion criteria were publication in peer-reviewed journals indexed in Medline, randomized comparison of angiotensin II receptor blockers vs. angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers + angiotensin-converting enzyme inhibitors vs. angiotensin-converting enzyme inhibitors, report of major complications including myocardial infarction, stroke, cardiovascular mortality or all-cause mortality; average follow-up of at least 1 year in at least 200 patients. Results Six trials fulfilled the inclusion criteria, for a total of 49 924 patients. In the pooled estimate, there were no significant differences between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors on the risk of myocardial infarction (odds ratio 1.01; 95% confidence interval 0.95–1.07; P = 0.75), cardiovascular mortality (odds ratio 1.03; 95% confidence interval 0.98–1.08; P = 0.23) and total mortality (odds ratio 1.03; 95% confidence interval 0.97–1.10; P = 0.20). This was the case also when the analysis involved only the comparison between angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Overall, the risk of stroke was slightly lower with angiotensin II receptor blockers than angiotensin-converting enzyme inhibitors (odds ratio 0.92; 95% confidence interval 0.85–0.99; P = 0.037), the direct angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers comparison showing a nonsignificant trend in a similar direction. Statistical heterogeneity among trials was not significant, with a low to null inconsistency statistic, for stroke (P = 0.67), myocardial infarction (P = 0.86), cardiovascular mortality (P = 0.14) and total mortality (P = 0.12). Conclusion This overview suggests that angiotensin II receptor blockers are as effective as angiotensin-converting enzyme inhibitors on the risk of myocardial infarction, cardiovascular mortality and total mortality. Angiotensin II receptor blockers may be slightly more protective than angiotensin-converting enzyme inhibitors on the risk of stroke.

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

[2]  A. Villringer,et al.  Candesartan but not ramipril pretreatment improves outcome after stroke and stimulates neurotrophin BNDF/TrkB system in rats , 2008, Journal of hypertension.

[3]  R. Collins,et al.  Body Mass Index, Blood Pressure, and Mortality From Stroke: A Nationally Representative Prospective Study of 212 000 Chinese Men , 2008, Stroke.

[4]  A. Dominiczak,et al.  2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. , 2007, Journal of hypertension.

[5]  T. Unger,et al.  Rationale for double renin-angiotensin-aldosterone system blockade. , 2007, The American journal of cardiology.

[6]  F. Messerli,et al.  Does a change in angiotensin II formation caused by antihypertensive drugs affect the risk of stroke?: A meta-analysis of trials according to treatment with potentially different effects on angiotensin II , 2007, Journal of hypertension.

[7]  J. Rouleau,et al.  Angiotensin receptor blockers vs. angiotensin converting enzyme inhibitors and acute coronary syndrome outcomes in elderly patients: a population-based cohort study (UMPIRE study results). , 2007, Journal of the American Society of Hypertension : JASH.

[8]  G. Oster,et al.  Valsartan versus lisinopril or extended-release metoprolol in preventing cardiovascular and renal events in patients with hypertension. , 2007, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[9]  A. Dominiczak,et al.  2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) , 2007, European heart journal.

[10]  M. Pfeffer,et al.  Blood pressure-dependent and independent effects of agents that inhibit the renin–angiotensin system , 2007, Journal of hypertension.

[11]  R. Tsuyuki,et al.  Response to Tsuyuki and McDonald , 2006 .

[12]  A. Hall,et al.  Angiotensin Receptor Blockers May Increase Risk of Myocardial Infarction: Unraveling the ARB-MI Paradox , 2006, Circulation.

[13]  J. Staessen,et al.  Blood Pressure Lowering for Primary and Secondary Prevention of Stroke , 2006, Hypertension.

[14]  S. Solomon,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). , 2006, Journal of the American College of Cardiology.

[15]  R. Tsuyuki,et al.  Angiotensin receptor blockers do not increase risk of myocardial infarction. , 2006, Circulation.

[16]  G. Mancia,et al.  Angiotensin II receptor blockers and myocardial infarction: deeds and misdeeds , 2005, Journal of hypertension.

[17]  G. Reboldi,et al.  Do angiotensin II receptor blockers increase the risk of myocardial infarction? , 2005, European heart journal.

[18]  J. Staessen,et al.  Angiotensin-Converting Enzyme Inhibitors and Calcium Channel Blockers for Coronary Heart Disease and Stroke Prevention , 2005, Hypertension.

[19]  H. Diener,et al.  Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention: Principal Results of a Prospective Randomized Controlled Study (MOSES) , 2005, Stroke.

[20]  U. Dirnagl,et al.  Angiotensin AT2 receptor protects against cerebral ischemia‐induced neuronal injury , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[21]  S. Verma,et al.  Angiotensin receptor blockers and myocardial infarction , 2004, BMJ : British Medical Journal.

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

[23]  R. Chen,et al.  Possible Inhibition of Focal Cerebral Ischemia by Angiotensin II Type 2 Receptor Stimulation , 2004, Circulation.

[24]  F. Messerli,et al.  Is the angiotensin ii type 2 receptor cerebroprotective? , 2004, Current hypertension reports.

[25]  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.

[26]  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.

[27]  F. Turnbull Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials , 2003, The Lancet.

[28]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[29]  J. Staessen,et al.  Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003 , 2003, Journal of hypertension.

[30]  A. Whitehead Estimating the Treatment Difference in an Individual Trial , 2003 .

[31]  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.

[32]  Daniel F McCaffrey,et al.  Occurrence of Secondary Ischemic Events Among Persons With Atherosclerotic Vascular Disease , 2002, Stroke.

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

[34]  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.

[35]  JurajCulman,et al.  Blockade of Central Angiotensin AT1 Receptors Improves Neurological Outcome and Reduces Expression of AP-1 Transcription Factors After Focal Brain Ischemia in Rats , 1999 .

[36]  T. Herdegen,et al.  Blockade of central angiotensin AT(1) receptors improves neurological outcome and reduces expression of AP-1 transcription factors after focal brain ischemia in rats. , 1999, Stroke.

[37]  E. Schiffrin,et al.  In vivo study of AT(1) and AT(2) angiotensin receptors in apoptosis in rat blood vessels. , 1999, Hypertension.

[38]  M. Bennett,et al.  Cooperative interactions between RB and p53 regulate cell proliferation, cell senescence, and apoptosis in human vascular smooth muscle cells from atherosclerotic plaques. , 1998, Circulation research.

[39]  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.

[40]  A R Jadad,et al.  Assessing the quality of reports of randomized clinical trials: is blinding necessary? , 1996, Controlled clinical trials.

[41]  R. Brian Haynes,et al.  Developing optimal search strategies for detecting clinically sound studies in MEDLINE. , 1994, Journal of the American Medical Informatics Association : JAMIA.

[42]  F. Fyhrquist [The clinical use of angiotensin converting enzyme inhibitors]. , 1986, Duodecim; laaketieteellinen aikakauskirja.