Introduction
Angiotensin Receptor Blockers and Angiotensin Converting Enzyme Inhibitors in the Treatment of Hypertension
ACEIs | ARBs | |
---|---|---|
Preferable conditions | LVH Microalbuminuria Renal dysfunction Previous stroke Previous MI Heart failure Prevention of atrial fibrillation ESRD or proteinuria Metabolic syndrome Diabetes mellitus Asymptomatic atherosclerosis Peripheral artery disease | LVH Microalbuminuria Renal dysfunction Previous stroke Previous MI Heart failure Prevention of atrial fibrillation ESRD or proteinuria Metabolic syndrome Diabetes mellitus |
Compelling contraindications | Pregnancy Previous angioneurotic oedema Hyperkalaemia (potassium > 5.5 mmol/L) Bilateral renal stenosis | Pregnancy Hyperkalaemia (potassium > 5.5 mmol/L) Bilateral renal stenosis |
Possible contraindications | Women with child-bearing potential without reliable contraception | Women with child-bearing potential without reliable contraception |
Are Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Equally Effective?
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)] |
Head-to-Head Comparative Studies of Olmesartan and Angiotensin Converting Enzyme Agents
Safety of Angiotensin Receptor Blockers and Angiotensin Converting Enzyme Inhibitors
Author | Type of comparison | Main objective | Number and type of studies | Type of patients | Number of patients | Treatment duration | Main outcome |
---|---|---|---|---|---|---|---|
Schneider, 2010 [17] | Active drug vs. placebo, active control | AF prophylaxis | 14 RCTs | Hypertension or heart failure or at high risk for CV disease | 92,817 | ≥ 1 year | ARBs showed a stronger effect in the reduction of onset AF [RR, 0.78 (0.66, 0.92), p = 0.009] than ACEIs [0.79 (0.62, 1.00), p = 0.05] |
Chaugai, 2016 [51] | Active drug vs. placebo, active control | AF prophylaxis | 26 RCTs | Hypertension or heart failure or ischemic heart disease | 165,387 | ≥ 1 year | Both ACEIs and ARBs effectively reduced the risk of new-onset [OR, 0.81 (0.67, 1.00), p = 0.037] and recurrent AF [OR, 0.46 (0.33, 0.62), p = 0.0001] in hypertensive patients The benefit was greater than that obtained with beta-blockers, calcium channel blockers and diuretics ARBs were marginally superior to ACEIs in both primary and secondary prevention of AF |
Li, 2017 [15] | Active drug vs. placebo or active control | New-onset diabetes | 38 RCTs | Hypertension | 224,140 | ≥ 1 year | Both ACEIs [OR, 0.77 (0.61, 0.97)] and ARBs [0.86 (0.81, 0.91)] were associated with a lower risk of developing diabetes compared to placebo There was no difference in the risk of new cases of diabetes between ACEIs and ARBS [OR, 1.07 (0.82, 1.39)] |
Al-Mallah, 2010 [52] | Active drug vs. placebo or active control | New-onset diabetes | 18 RCTs | Hypertension | 100,848 | ≥ 1 year | Treatment with ACEIs and ARBs was associated with a decrease in new onset diabetes mellitus [RR, 0.78 (0.70, 0.88), p = 0.003 for ACEIs and 0.80 (0.75, 0.86), p < 0.0001 for ARBs] |
Kunutsor, 2017 [53] | Active drug vs. control | Bone fractures | 11 cohort studies | Adults | 3,526,319 | ≥ 1 year | The risk for composite fractures was not significantly increased in ACEIs- [HR, 1.09 (0.89, 1.33)] or ARBs-treated patients [0.87 (0.76, 1.01)] compared to patients not treated with these drugs A benefit was observed on hip fracture risk [ACEIs: HR, 0.91 (0.86, 0.95); ARBs: 0.80 (0.75, 0.85)] |
Elderly hypertensive patients [40] | Olmesartan 10–40 mg (n = 712) | Ramipril 2.5–10 mg (n = 714) | p value |
---|---|---|---|
Any AE | 105 (14.7) | 96 (13.4) | 0.480 |
Drug-related AE | 21 (2.9) | 23 (3.2) | 0.767 |
Discontinuation due to AE | 21 (2.9) | 16 (2.2) | 0.400 |
Adult hypertensive patients [41] | Olmesartan 40 mg + amlodipine 10 mg (n = 244) | Perindopril 8 mg + amlodipine 10 mg (n = 241) | p value |
---|---|---|---|
Any AE | 125 (51.2) | 114 (47.3) | 0.387 |
Drug-related AE | 61 (25.0) | 62 (25.7) | 0.854 |
Discontinuation due to AE | 18 (7.4) | 19 (7.9) | 0.834 |
Hypertensive patients with type 2 diabetes mellitus [44] | Olmesartan 20–40 mg + amlodipine 5–10 mg (n = 128) | Perindopril 4-8 mg + amlodipine 5–10 mg (n = 132) | p value |
---|---|---|---|
Any AE | 32 (25.0) | 37 (28.0) | 0.580 |
Drug-related AE | 10 (7.8) | 13 (9.8) | 0.563 |
Discontinuation due to AE | 4 (3.1) | 2 (1.5) | 0.387 |