Table 2.

Meta-analyses comparing the efficacy of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)

Author	Type of comparison	Main objective	Number and type of studies	Type of patients	Number of patients	Treatment duration	Main outcome
Matchar, 2008 [21]	Head-to-head trials	BP lowering	47 RCTs, 1 non-RCT, 12 cohort studies and 1 case control study	Hypertension	16,597	≥ 3 months	ACEIs and ARBs had similar long-term effects on BP [difference in rate of BP control, 1.3 (− 1.0, 3.5)%; p = 0.260] No consistent differential effects were observed for other outcomes (death, CV events, quality of life, rate of single antihypertensive use, lipid levels, progression of diabetes, left ventricular mass or function, kidney disease) ACEIs were associated with a greater risk for cough [OR, 0.32 (0.29, 0.36); p = 0.0001] ARBs were associated with fewer withdrawals due to adverse events and greater persistence to therapy [OR, 0.51 (0.38, 0.70); p < 0.05]
Powers, 2012 [22]	Head-to-head trials	BP lowering	74 RCTs, 4 non-RCTs, 21 cohort studies and 1 case control study	Hypertension	24,350	≥ 3 months	Equivalence in BP control between ACEIs and ARBs is confirmed [difference in rate of BP control, OR, 1.1 (0.9, 1.3)] The superiority of ARBs over ACEIs for short-term adverse events is confirmed [OR for cough ACEIs vs. ARBs, 4.74 (3.56, 6.31)] The strength of evidence for other outcomes (long-term CV outcomes, quality of life, progression of renal disease, medication adherence or persistence, rates of angioedema) remains low or moderate
Li, 2014 [23]	Head-to-head trials	Total mortality CV events	9 RCTs	Hypertension	11,007	≥ 1 years	No difference between ACEIs and ARBs for total mortality [RR, 0.98 (0.88, 1.10)], total CV events [RR, 1.07 (0.96, 1.19)] or CV mortality [RR, 0.98 (0.85, 1.13)] Lower rate of withdrawals due to an adverse event with ARBs [RR, 0.83 (0.74, 0.93)]
Kizilirmak, 2017 [24]	Active drug vs. placebo or active control + head-to-head trials	Fatal and non fatal CV events Total deaths	51 RCTs	Hypertension, myocardial infarction, heart failure, kidney disease	277,609	≥ 2 years	In non-direct comparative studies a marginal but statistically significant (p = 0.034) larger risk reduction of all-cause mortality with ACEIs or ARBs vs. control [RR, 0.97 (0.94, 0.99)] was observed A significant reduction in the risk of all CV events was also observed [RR, 0.93 (0.89, 0.98); p = 0.003] In 8 head-to-head studies ACEIs and ARBs did not differentiate from each other in terms of all-cause mortality and CV morbidity and mortality
Bangalore, 2016 [25]	Active drug vs. placebo or active control + head-to-head trials	Fatal and non fatal CV events Total deaths	106 RCTs	Patients with no heart failure	254,301	≥ 1 year	Compared to placebo ACEIs but not ARBs reduced the risk of all-cause mortality [RR, 0.89 (0.80, 1.00) vs. 1.01 (0.96, 1.06), p = 0.04], CV death [RR, 0.83 (0.70, 0.99) vs. 1.02 (0.92, 1.14), p = 0.05] and AMI [RR, 0.83 (0.78, 0.90) vs. 0.93 (0.85, 1.03), p = 0.06] Head-to-head trials exhibited no difference in outcomes except for a lower risk of drug withdrawal for adverse events with ARBs [RR, 0.72 (0.65, 0.81)]
van Vark, 2012 [26]	Active drug vs. placebo, active control or usual care	Total deaths CV deaths	20 RCTs	Hypertension	158,998	≥ 1 year	ACEIs or ARBs were altogether responsible of a significant reduction in all-cause mortality [HR, 0.95 (0.91, 1.00); p = 0.032], which was larger with ACEIs [HR, 0.90 (0.84, 0.97); p = 0.004] than with ARBs [HR, 0.99 (0.94, 1.04); p = 0.683] Treatment with ACEIs [HR, 0.88 (0.77, 1.00); p = 0.051] but not with ARBs [HR, 0.96 (0.90, 1.01); p = 0.143] resulted in a significant reduction of CV mortality
Savarese, 2013 [27]	Active drug vs. placebo	Fatal and non-fatal CV events Total deaths	26 RCTs	High-risk patients without heart failure	108,212	≥ 2 years	Both ACEIs and ARBs significantly reduced the composite outcomes of CV death, myocardial infarction and stroke [ACEIs: OR, 0.83 (0.74, 0.93), p = 0.001; ARBs: 0.92 (0.87, 0.98), p = 0.005] The risk for all cause of death was significantly reduced by ACEIs [OR, 0.91 (0.85, 0.98), p = 0.008] but not by ARBs [OR, 1.00 (0.94, 1.08; p = 0.866]: this was the case also for CV death Both ACEIs [OR, 0.85 (0.75, 0.97), p < 0.012] and ARBs [OR, 0.86 (0.80, 0.92), p < 0.001] reduced the risk of new-onset diabetes mellitus
Salvador, 2017 [28]	Active drug vs. placebo	Fatal and non-fatal CV events Total deaths	17 RCTs	Hypertension	73,761	≥ 18 months	Both classes similarly prevented major CV outcomes (AMI, stroke and heart failure/hospitalization) compared to control However, ACEIs were more effective in reducing total deaths [OR, 0.85 (0.78, 0.93) vs. 1.02 (0.96, 1.09)] and CV deaths [OR, 0.77 (0.69, 0.87) vs. 0.95 (0.86, 1.06)]

BP blood pressure, RCT randomized controlled trial, CV cardiovascular, OR odds ratio, RR relative risk, AMI acute myocardial infarction, HR hazard ratio