MVIIIHealth The MVIII app
← Back

Research · Medication

ARBs (angiotensin receptor blockers)

Pooled trials found ARBs lowered blood pressure about 8/5 mm Hg, slowed diabetic kidney disease and lowered stroke and heart failure, without fewer heart attacks or deaths. Cough and angioedema were less frequent than on ACE inhibitors. The label carries a boxed warning about harm to the fetus. Olmesartan was linked to a rare severe gut disorder.

Add to Bio HackChecked 2026-11-13
Status
Prescription drugs in the US. Losartan is FDA-approved for high blood pressure, to lower stroke risk in people with high blood pressure and an enlarged left ventricle, and for diabetic kidney disease. Valsartan is approved for high blood pressure, heart failure and after a heart attack. Approved uses differ by drug. The losartan label carries an FDA boxed warning for harm to the fetus.
Also called
losartan, Cozaar, valsartan, Diovan, olmesartan, Benicar, telmisartan, Micardis, candesartan, Atacand, irbesartan, Avapro, azilsartan, Edarbi, angiotensin II receptor blocker, angiotensin receptor antagonist, sartans, ARB
Taken for
high blood pressure, heart failure, kidney protection in diabetes, stroke prevention, recovery after a heart attack, an alternative when ACE inhibitors cause cough, migraine prevention, Marfan syndrome

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help7

Reported risks12

What people take it for, and what was found

Shown to help7

Strong

Lowering blood pressure

Shown to lower blood pressure about 8/5 mm Hg in adults with high blood pressure, with no difference found between drugs in the class.

The numbers and sources
Effect
Across 46 placebo-controlled trials of 9 ARBs, the largest trials put the trough blood pressure effect of the class at about 8 mm Hg systolic and 5 mm Hg diastolic. One eighth to one quarter of the maximum dose gave 60 to 70% of the full effect, half the maximum gave 80%, and doses above the maximum did not lower blood pressure further. No one ARB lowered blood pressure more than another [1]. A separate analysis of 354 trials found thiazides, beta-blockers, ACE inhibitors, ARBs and calcium channel blockers produced similar reductions, on average 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard dose [2].
Population
13,451 adults with primary hypertension and a baseline blood pressure of 156/101 mm Hg [1]; about 40,000 treated and 16,000 placebo participants in 354 trials [2].
Sources
[1], [2]
Caveats
The Cochrane authors found evidence of publication bias and relied on the largest trials for the estimate [1].
Moderate

Kidney disease in type 2 diabetes

Shown to slow kidney disease in type 2 diabetes with protein in the urine, with 16 to 20% fewer people reaching kidney failure, doubled creatinine or death.

The numbers and sources
Effect
Over a mean 3.4 years, losartan lowered the composite of doubled creatinine, end-stage kidney disease or death by 16% against placebo (327 against 359 people). Doubled creatinine fell 25% and end-stage kidney disease 28%, with no effect on death [3]. Over a mean 2.6 years, irbesartan lowered the same composite by 20% against placebo and 23% against amlodipine, and doubled creatinine by 33% against placebo [4]. A Cochrane review of 50 studies found ACE inhibitors and ARBs had similar benefits on kidney outcomes, and ARBs did not lower mortality against placebo (RR 0.99, 95% CI 0.85 to 1.17) [5].
Population
1,513 people with type 2 diabetes and kidney disease [3]; 1,715 people with high blood pressure and kidney disease from type 2 diabetes [4]; 13,215 people with diabetic kidney disease in 50 studies, 5 comparing ARBs with placebo [5].
Sources
[3], [4], [5]
Caveats
The trial evidence is for losartan and irbesartan. Both trials added the ARB to other blood pressure drugs.
Moderate

Heart attack, stroke and death

Shown to lower stroke by about 10% and heart failure by 13% across 37 trials, with no reduction in heart attacks or deaths.

The numbers and sources
Effect
Across 37 randomized trials against placebo or other drugs, ARBs lowered stroke (RR 0.90, 95% CI 0.84 to 0.98), heart failure (RR 0.87, 95% CI 0.81 to 0.93) and new diabetes (RR 0.85, 95% CI 0.78 to 0.93). They did not change the risk of heart attack (RR 0.99, 95% CI 0.92 to 1.07), death or cardiovascular death [6]. In people who could not take ACE inhibitors, telmisartan did not significantly lower the composite of cardiovascular death, heart attack, stroke or heart failure hospitalization (15.7% against 17.0% on placebo, HR 0.92, 95% CI 0.81 to 1.05) [7]. Across hypertension trials, ARBs were not associated with lower all-cause mortality (HR 0.99, 95% CI 0.94 to 1.04) [8].
Population
147,020 participants in 37 trials with at least 1 year of follow-up [6]; 5,926 high-risk people intolerant to ACE inhibitors, median 56 months [7]; 158,998 people in 20 trials of renin-angiotensin drugs [8].
Sources
[6], [7], [8]
Caveats
The pooled trials mixed placebo and active comparators [6]. The evidence in [7] is for telmisartan.
Limited

Stroke in high blood pressure with an enlarged left ventricle

One trial found losartan lowered stroke by 25% against atenolol in adults with high blood pressure and an enlarged left ventricle, at similar blood pressure.

The numbers and sources
Effect
Over at least 4 years, the composite of death, heart attack or stroke occurred at 23.8 per 1,000 patient-years on losartan and 27.9 on atenolol (RR 0.87, 95% CI 0.77 to 0.98). Stroke occurred in 232 people on losartan and 309 on atenolol (RR 0.75, 95% CI 0.63 to 0.89). Heart attack did not differ (RR 1.07, 95% CI 0.88 to 1.31). Blood pressure fell by 30.2/16.6 mm Hg on losartan and 29.1/16.8 mm Hg on atenolol [9].
Population
9,193 adults aged 55 to 80 with high blood pressure and left ventricular hypertrophy on ECG [9].
Sources
[9]
Caveats
The comparison was atenolol, not placebo. The losartan label states there is evidence this benefit does not apply to Black patients [10].
Why limited
This rests on one trial, of 9,193 people. Strength counts independent studies that agree, so one trial is limited at any size.
Moderate

Preventing type 2 diabetes

Shown to lower new type 2 diabetes by about 14 to 15%, with 33.1% against 36.8% developing it over 5 years in one valsartan trial.

The numbers and sources
Effect
In adults with impaired glucose tolerance, diabetes developed in 33.1% on valsartan and 36.8% on placebo over a median 5 years (HR 0.86, 95% CI 0.80 to 0.92). Valsartan did not lower cardiovascular events (14.5% against 14.8%) [18]. Across randomized trials of ARBs, new diabetes was less frequent than in controls (RR 0.85, 95% CI 0.78 to 0.93) [6].
Population
9,306 adults with impaired glucose tolerance and cardiovascular disease or risk factors [18]; 147,020 participants in 37 trials [6].
Sources
[18], [6]
Caveats
The trial evidence is for valsartan up to 160 mg a day, given alongside lifestyle modification [18].
Moderate

Aortic growth in Marfan syndrome

Shown to about halve the yearly growth of the aortic root in Marfan syndrome against control. Losartan did not differ from atenolol.

The numbers and sources
Effect
In individual data from 4 trials, the annual increase in aortic root Z score was 0.07 on an ARB and 0.13 on control (difference -0.07, 95% CI -0.12 to -0.01) over a median 3 years [19]. In a head-to-head trial, the rate of change in aortic root Z score did not differ significantly between losartan and atenolol (-0.107 against -0.139 standard deviation units a year, P = 0.08) [20].
Population
676 people with Marfan syndrome and no prior aortic surgery in 4 trials of ARB against control, within a 7-trial analysis of 1,442 people [19]; 608 people aged 6 months to 25 years with an aortic root Z score above 3.0 [20].
Sources
[19], [20]
Caveats
The outcome is aortic size, not dissection or death. Not an FDA-approved use [10].
LimitedVery common

Migraine prevention

Small trials found candesartan lowered migraine days against placebo, with about 40% of people having at least half as many.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Over 12 weeks, days with headache were 13.6 on candesartan 16 mg and 18.5 on placebo, and days with migraine 9.0 against 12.6. Migraine days fell by at least half in 23 of 57 people (40.4%) [21]. In a second crossover trial, migraine days per 4 weeks were 2.95 on candesartan, 2.91 on propranolol and 3.53 on placebo. The share with at least a 50% reduction was 43% on candesartan, 40% on propranolol and 23% on placebo [22].
Population
60 adults with 2 to 6 migraine attacks a month, 57 analyzed [21]; 72 adults with episodic or chronic migraine [22].
Sources
[21], [22]
Caveats
Two small crossover trials from the same Norwegian group, both of candesartan. Not an FDA-approved use.

Mixed results1

Moderate

Heart failure

Mixed results: candesartan and valsartan trials found fewer heart failure hospital stays, and a Cochrane review found no significant drop in deaths or total hospital stays.

The numbers and sources
Effect
In people with reduced ejection fraction who could not take ACE inhibitors, cardiovascular death or heart failure admission occurred in 33% on candesartan and 40% on placebo (HR 0.77, 95% CI 0.67 to 0.89) [11]. Valsartan added to usual therapy did not change mortality and lowered a combined endpoint of death and illness (RR 0.87, 97.5% CI 0.77 to 0.97), mainly through fewer heart failure hospitalizations (13.8% against 18.2%) [12]. A Cochrane review of 22 studies in reduced ejection fraction found ARBs did not significantly lower total mortality (RR 0.87, 95% CI 0.76 to 1.00) or total hospitalizations (RR 0.94, 95% CI 0.88 to 1.01) against placebo. In 2 studies of people with ejection fraction above 40%, neither outcome differed from placebo [13].
Population
2,028 people with ejection fraction of 40% or less, median 33.7 months [11]; 5,010 people with heart failure [12]; 17,900 people with ejection fraction of 40% or less and 7,151 with ejection fraction above 40% [13].
Sources
[11], [12], [13]
Caveats
The trial evidence is for candesartan and valsartan. About 93% of people in the valsartan heart failure trials also took an ACE inhibitor [14].

Not shown to help1

Moderate

Compared with ACE inhibitors

Not shown to differ from ACE inhibitors in deaths or cardiovascular events. Fewer people stopped ARBs over side effects, mainly cough.

The numbers and sources
Effect
In 9 head-to-head trials in hypertension, total mortality (RR 0.98, 95% CI 0.88 to 1.10) and total cardiovascular events (RR 1.07, 95% CI 0.96 to 1.19) did not differ, and withdrawals over adverse effects were lower on ARBs (RR 0.83, 95% CI 0.74 to 0.93) [15]. In ONTARGET, the main cardiovascular outcome occurred in 16.7% on telmisartan and 16.5% on ramipril (RR 1.01, 95% CI 0.94 to 1.09) [16]. After a heart attack with heart failure or left ventricular dysfunction, deaths did not differ between valsartan and captopril (979 against 958, HR 1.00, 97.5% CI 0.90 to 1.11) [17]. In heart failure trials, mortality did not differ between ARBs and ACE inhibitors (RR 1.05, 95% CI 0.91 to 1.22), and withdrawals over adverse effects were lower on ARBs (RR 0.63, 95% CI 0.52 to 0.76) [13].
Population
11,007 people in 9 hypertension trials [15]; 17,118 people assigned to telmisartan or ramipril [16]; 9,818 people assigned to valsartan or captopril after a heart attack, median 24.7 months [17]; heart failure trials within a 22-study review [13].
Sources
[15], [16], [17], [13]
Caveats
The evidence in [16] is for telmisartan and in [17] for valsartan.

Doses studied

The losartan label gives a usual starting dose of 50 mg once daily for high blood pressure, up to 100 mg, and 50 to 100 mg once daily for diabetic kidney disease [10]. The kidney trials used losartan 50 to 100 mg a day [3] and irbesartan 300 mg a day [4]. The heart failure trials used candesartan with a target of 32 mg once daily [11] and valsartan 160 mg twice daily [12]. ONTARGET and TRANSCEND used telmisartan 80 mg a day [16][7]. The diabetes prevention trial used valsartan up to 160 mg a day [18], and the migraine trials used candesartan 16 mg a day [21][22].

Across dose-ranging trials, one eighth to one quarter of the maximum labeled dose gave 60 to 70% of the full blood pressure effect [1].

Risks

Reported risks11

ModerateVery common

With an ACE inhibitor or aliskiren

Shown to raise high potassium, low blood pressure and kidney failure when an ARB is combined with an ACE inhibitor or aliskiren, with no fewer deaths.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Across 33 trials, combining two blockers of the renin-angiotensin system did not lower all-cause mortality against one (RR 0.97, 95% CI 0.89 to 1.06) and raised hyperkalemia by 55%, low blood pressure by 66% and kidney failure by 41% [36]. In ONTARGET, telmisartan plus ramipril brought more low blood pressure symptoms (4.8% against 1.7%) and kidney dysfunction (13.5% against 10.2%) than ramipril alone [16]. In people with diabetic kidney disease on losartan, adding lisinopril raised hyperkalemia (6.3 against 2.6 events per 100 person-years) and acute kidney injury (12.2 against 6.7), and the trial was stopped early [37].
Population
68,405 people in 33 trials, mean 52 weeks [36]; 17,078 people assigned to the combination or ramipril alone [16]; 1,448 people with type 2 diabetes and kidney disease [37].
Sources
[36], [16], [37]
Caveats
Hospital admissions for heart failure fell 18% on dual therapy in the pooled analysis [36]. The losartan label carries the same warning [10].
ModerateCommon

Dizziness and low blood pressure

Shown to raise dizziness slightly in high blood pressure, 3% against 2% on placebo, and more in heart failure, 17% against 9%.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In 4 hypertension trials of losartan, dizziness occurred in 3% on losartan and 2% on placebo [10]. In heart failure trials of valsartan, dizziness occurred in 17% against 9% on placebo and low blood pressure in 7% against 2% [14]. In ONTARGET, low blood pressure symptoms were more frequent on telmisartan than on ramipril (2.6% against 1.7%) [16].
Population
More than 1,000 people on losartan and more than 300 on placebo [10]; 3,282 people on valsartan and 2,740 on placebo in heart failure trials, about 93% also on an ACE inhibitor [14]; 17,118 people in ONTARGET [16].
Sources
[10], [14], [16]
Caveats
The band is taken from the hypertension trials. Rates were higher in heart failure, where most people also took an ACE inhibitor [14].
ModerateCommon

High blood potassium

Shown to raise blood potassium, reported as hyperkalemia in 2% on valsartan against 1% on placebo in heart failure trials.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In heart failure trials, hyperkalemia was reported in 2% on valsartan and 1% on placebo, and 0.5% against 0.1% stopped treatment over raised potassium [14]. The losartan label lists hyperkalemia among the events more frequent than placebo in its diabetic kidney disease trial, and warns that other drugs that raise potassium may lead to hyperkalemia [10].
Population
3,282 people on valsartan and 2,740 on placebo in heart failure trials [14]; 1,513 people in the losartan kidney trial [10].
Sources
[14], [10]
Caveats
About 93% of people in the valsartan heart failure trials also took an ACE inhibitor [14].
ModerateCommon

Kidney function changes

Shown to raise creatinine in some people with heart failure, by more than half in 3.9% on valsartan against 0.9% on placebo.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In heart failure trials, creatinine rose by more than 50% in 3.9% on valsartan and 0.9% on placebo. After a heart attack, creatinine doubled in 4.2% on valsartan and 3.4% on captopril [14]. The losartan label warns that acute kidney failure can occur, particularly with renal artery stenosis, chronic kidney disease, severe heart failure or volume depletion [10].
Population
People in valsartan heart failure and heart attack trials [14].
Sources
[14], [10]
Caveats
For the long-term effect on diabetic kidney disease, see the kidney outcome block above.
LimitedUncommon

With trimethoprim-sulfamethoxazole

Linked to hospital admission for high potassium and to sudden death in adults over 65 on an ARB or ACE inhibitor given this antibiotic.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
Among older adults on an ARB or ACE inhibitor, hospital admission with hyperkalemia within 14 days was about 7 times as likely after trimethoprim-sulfamethoxazole as after amoxicillin (adjusted OR 6.7, 95% CI 4.5 to 10.0) [39]. Sudden death within 7 days was also more likely than after amoxicillin (adjusted OR 1.38, 95% CI 1.09 to 1.76), about 3 sudden deaths within 14 days per 1,000 prescriptions [40].
Population
Ontario residents aged 66 or older on an ACE inhibitor or ARB, with 4,148 hyperkalemia admissions over 14 years [39] and 39,879 sudden deaths from 1994 to 2012 [40].
Sources
[39], [40]
Caveats
Observational studies in older adults from one province. Neither abstract separates ARB users from ACE inhibitor users.
LimitedRare

Severe gut disorder with olmesartan

FDA states olmesartan can cause sprue-like enteropathy, with severe chronic diarrhea and weight loss months to years after starting. A French cohort linked it to malabsorption admissions.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
In a series of 22 people on olmesartan with unexplained chronic diarrhea, median weight loss was 18 kg, 14 were hospitalized, celiac disease was ruled out, and all improved after stopping the drug [26]. In a French national cohort, hospitalization for intestinal malabsorption was more frequent on olmesartan than on ACE inhibitors (adjusted rate ratio 2.49, 95% CI 1.73 to 3.57), rising to 10.65 beyond 2 years of use, with no difference in the first year [27]. FDA approved label changes in 2013 and stated that the disorder had not been detected with other ARBs [28]. The olmesartan label carries the warning [29].
Population
22 people seen at one US clinic [26]; 4,546,680 adults starting an ARB or ACE inhibitor, with 218 malabsorption admissions over 9,010,303 person-years [27].
Sources
[26], [27], [28], [29]
Caveats
A case series and one observational cohort. The evidence is for olmesartan only.
LimitedRare

With NSAIDs

Linked to more acute kidney injury when an NSAID is taken with both a diuretic and an ARB or ACE inhibitor, about 31% higher in one cohort.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
Among users of blood pressure drugs, current use of an NSAID with both a diuretic and an ARB or ACE inhibitor was associated with a higher rate of acute kidney injury (rate ratio 1.31, 95% CI 1.12 to 1.53), highest in the first 30 days (1.82, 95% CI 1.35 to 2.46). An NSAID with only one of those drugs was not associated with a higher rate. Acute kidney injury occurred at 7 per 10,000 person-years in the cohort [38]. The losartan label states that NSAIDs taken with ARBs may worsen kidney function in people who are elderly, volume-depleted or have impaired kidneys, and may weaken the blood pressure effect [10].
Population
487,372 users of blood pressure drugs in UK general practice, mean follow-up 5.9 years [38].
Sources
[38], [10]
Caveats
Observational. The rate is for the whole cohort, not only people on the three-drug combination [38].
LimitedHow often is not known

Boxed warning: harm to the fetus

FDA states that drugs acting on the renin-angiotensin system can cause injury and death to the developing fetus.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The losartan label states that use of drugs acting on the renin-angiotensin system in the second and third trimesters reduces fetal kidney function and raises fetal and newborn illness and death, with low amniotic fluid, underdeveloped lungs, skull underdevelopment and kidney failure among the effects described [10]. In a review of published case reports, 13% of 68 newborns exposed to ARBs before birth had no complications, against 52% of those exposed to ACE inhibitors. Complications included kidney failure, low amniotic fluid, death, low blood pressure and growth restriction [23].
Population
68 published cases of exposure to ARBs before birth, in 35 reports [23].
Sources
[10], [23]
Caveats
Case reports favor poor outcomes and give no rate [23].
LimitedHow often is not known

Nitrosamine contamination of some lots

FDA reported nitrosamine impurities in some generic valsartan, losartan and irbesartan lots from 2018. Two cohorts found no rise in cancer overall.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
FDA reported from 2018 that some generic valsartan, losartan and irbesartan products contained nitrosamine impurities, including NDMA and NDEA, which it classes as probable human carcinogens, and that the affected lots were recalled. Not all products or lots were affected [33]. In a Danish cohort, exposure to NDMA-contaminated valsartan was not associated with cancer overall (HR 1.09, 95% CI 0.85 to 1.41) and showed no dose-response [34]. A German cohort found no association with cancer overall and an association with liver cancer (HR 1.16, 95% CI 1.03 to 1.31) [35].
Population
5,150 Danish valsartan users followed a median 4.6 years [34]; 780,871 people in Germany who filled a valsartan prescription from 2012 to 2017 [35].
Sources
[33], [34], [35]
Caveats
Follow-up was short for cancer. The finding concerns a manufacturing impurity in specific lots, not the drugs themselves.
LimitedHow often is not known

With potassium supplements and potassium-sparing diuretics

The label warns that potassium-sparing diuretics, potassium supplements, potassium salt substitutes and heparin may raise blood potassium further on an ARB.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The valsartan label states that taking it with potassium-sparing diuretics, naming spironolactone, triamterene and amiloride, with potassium supplements, with salt substitutes containing potassium, or with other drugs that may raise potassium, naming heparin, may lead to increases in serum potassium, and in heart failure to increases in creatinine [14]. The losartan label carries a similar warning [10].
Population
People taking valsartan or losartan, as described in the labels [14][10].
Sources
[14], [10]
Caveats
The labels give no rate for the combinations.
LimitedHow often is not known

With lithium

The label warns that raised lithium levels and lithium toxicity have been reported when lithium is taken with an ARB. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The losartan label states that increases in serum lithium concentrations and lithium toxicity have been reported during use of lithium with angiotensin II receptor antagonists [10].
Population
People taking lithium with an ARB, as described in the label [10].
Sources
[10]
Caveats
Based on reports, with no rate or comparison group.

Mixed results1

ModerateCommon

Cancer

Mixed results: one pooled analysis found 8% more new cancers on ARBs, and two larger analyses of randomized trials found no rise.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
A 2010 meta-analysis of 5 trials found new cancer in 7.2% on ARBs and 6.0% of controls (RR 1.08, 95% CI 1.01 to 1.15). Telmisartan was the drug in 85.7% of the ARB patients [30]. An analysis of 15 trials found cancer in 6.16% on ARBs and 6.31% of controls (OR 1.00, 95% CI 0.95 to 1.04), overall and for each ARB [31]. A network meta-analysis of 70 trials found no difference in cancer between ARBs and placebo (OR 1.01, 95% CI 0.93 to 1.09). An ACE inhibitor plus an ARB showed a higher rate in one model (OR 1.14, 95% CI 1.02 to 1.28) and not in another [32].
Population
61,590 people with new-cancer data in 5 trials [30]; 138,769 people in 15 trials followed 23 to 60 months [31]; 324,168 participants in 70 trials [32].
Sources
[30], [31], [32]
Caveats
Follow-up was 5 years or less, and cancer was not the planned outcome of most trials.

Checked, no increase found2

Moderate

Cough

Not shown to raise cough above placebo. Cough was reported by 1.1% on telmisartan against 4.2% on ramipril in one large trial.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In two trials of people who had coughed on an ACE inhibitor, cough returned in 17% on losartan, 25% on hydrochlorothiazide and 69% on lisinopril in the first, and in 29% on losartan, 35% on placebo and 62% on lisinopril in the second [10]. In ONTARGET, cough was reported by 1.1% on telmisartan and 4.2% on ramipril [16]. Across randomized trials, cough was 3.2 times as frequent on ACE inhibitors as on ARBs (95% CI 2.91 to 3.51) [24].
Population
People with prior ACE inhibitor cough in two losartan trials [10]; 17,118 people in ONTARGET [16]; 135 randomized trials [24].
Sources
[10], [16], [24]
Caveats
The losartan label notes that cough, including on rechallenge, has been reported after marketing [10].
Moderate

Angioedema

Not shown to raise angioedema above placebo in trials, 0.11% against 0.07%. Cases have been reported, some in people who had it on an ACE inhibitor.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
Across 19 trials, the weighted incidence of angioedema was 0.11% on ARBs (95% CI 0.09 to 0.13) and 0.07% on placebo, a difference that was not significant, against 0.30% on ACE inhibitors [25]. The losartan label lists angioedema, including swelling of the larynx and glottis with airway obstruction, among reactions reported after marketing, and notes that some of these people had angioedema before on other drugs including ACE inhibitors [10].
Population
35,479 people on ARBs in 19 trials with 122,293 person-years of follow-up [25].
Sources
[25], [10]
Caveats
Post-marketing reports give no rate [10].

Claims tested and not found

  1. That ARBs raise the risk of heart attack. Across 37 randomized trials with 147,020 participants, heart attack did not differ between ARBs and controls (RR 0.99, 95% CI 0.92 to 1.07) [6].
  2. That ARBs and ACE inhibitors worsen COVID-19. In 659 people hospitalized with mild to moderate COVID-19, days alive and out of hospital did not differ between stopping and continuing these drugs (21.9 against 22.9 days) [41]. Across 14 randomized trials, all-cause mortality did not differ (7.2% against 7.5%, RR 0.95, 95% CI 0.69 to 1.30) [42].
  3. That adding an ARB to an ACE inhibitor lowers heart attacks and strokes further. In ONTARGET the combination did not differ from ramipril alone (16.3% against 16.5%, RR 0.99, 95% CI 0.92 to 1.07) [16], and in diabetic kidney disease it did not lower deaths or cardiovascular events [37].
  4. That losartan slows aortic growth more than atenolol in Marfan syndrome. In 608 children and young adults, the rate of aortic root enlargement did not differ significantly between the two over 3 years [20].
  5. That stopping an ARB or ACE inhibitor in advanced kidney disease preserves kidney function. In 411 people with an eGFR below 30, eGFR at 3 years was 12.6 after stopping and 13.3 after continuing (difference -0.7, 95% CI -2.5 to 1.0) [43].

Sources

  1. Heran BS, Wong MM, Heran IK, Wright JM. Blood pressure lowering efficacy of angiotensin receptor blockers for primary hypertension. Cochrane Database of Systematic Reviews. 2008. https://doi.org/10.1002/14651858.CD003822.pub2
  2. Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003. https://doi.org/10.1136/bmj.326.7404.1427
  3. 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. New England Journal of Medicine. 2001. https://doi.org/10.1056/NEJMoa011161
  4. 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. New England Journal of Medicine. 2001. https://doi.org/10.1056/NEJMoa011303
  5. Strippoli GF, Bonifati C, Craig M, Navaneethan SD, Craig JC. Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease. Cochrane Database of Systematic Reviews. 2006. https://doi.org/10.1002/14651858.CD006257
  6. Bangalore S, Kumar S, Wetterslev J, Messerli FH. Angiotensin receptor blockers and risk of myocardial infarction: meta-analyses and trial sequential analyses of 147 020 patients from randomised trials. BMJ. 2011. https://doi.org/10.1136/bmj.d2234
  7. TRANSCEND Investigators, Yusuf S, Teo K, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. The Lancet. 2008. https://doi.org/10.1016/S0140-6736(08)61242-8
  8. van Vark LC, Bertrand M, Akkerhuis KM, 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. European Heart Journal. 2012. https://doi.org/10.1093/eurheartj/ehs075
  9. Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. The Lancet. 2002. https://doi.org/10.1016/S0140-6736(02)08089-3
  10. Cozaar (losartan potassium) tablets, prescribing information. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9949448f-c3b9-44ee-94ed-c1aca8c90f39
  11. 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. The Lancet. 2003. https://doi.org/10.1016/S0140-6736(03)14284-5
  12. Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. New England Journal of Medicine. 2001. https://doi.org/10.1056/NEJMoa010713
  13. Heran BS, Musini VM, Bassett K, Taylor RS, Wright JM. Angiotensin receptor blockers for heart failure. Cochrane Database of Systematic Reviews. 2012. https://doi.org/10.1002/14651858.CD003040.pub2
  14. Diovan (valsartan) tablets, prescribing information. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ddba454-f3e6-43c2-a7a6-58365d297213
  15. Li EC, Heran BS, Wright JM. Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database of Systematic Reviews. 2014. https://doi.org/10.1002/14651858.CD009096.pub2
  16. ONTARGET Investigators, Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. New England Journal of Medicine. 2008. https://doi.org/10.1056/NEJMoa0801317
  17. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. New England Journal of Medicine. 2003. https://doi.org/10.1056/NEJMoa032292
  18. NAVIGATOR Study Group, McMurray JJ, Holman RR, et al. Effect of valsartan on the incidence of diabetes and cardiovascular events. New England Journal of Medicine. 2010. https://doi.org/10.1056/NEJMoa1001121
  19. Pitcher A, Spata E, Emberson J, et al. Angiotensin receptor blockers and β blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials. The Lancet. 2022. https://doi.org/10.1016/S0140-6736(22)01534-3
  20. Lacro RV, Dietz HC, Sleeper LA, et al. Atenolol versus losartan in children and young adults with Marfan's syndrome. New England Journal of Medicine. 2014. https://doi.org/10.1056/NEJMoa1404731
  21. Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003. https://doi.org/10.1001/jama.289.1.65
  22. Stovner LJ, Linde M, Gravdahl GB, et al. A comparative study of candesartan versus propranolol for migraine prophylaxis: A randomised, triple-blind, placebo-controlled, double cross-over study. Cephalalgia. 2014. https://doi.org/10.1177/0333102413515348
  23. Bullo M, Tschumi S, Bucher BS, Bianchetti MG, Simonetti GD. Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists: a systematic review. Hypertension. 2012. https://doi.org/10.1161/HYPERTENSIONAHA.112.196352
  24. Hu Y, Liang L, Liu S, et al. Angiotensin-converting enzyme inhibitor induced cough compared with placebo, and other antihypertensives: A systematic review, and network meta-analysis. The Journal of Clinical Hypertension. 2023. https://doi.org/10.1111/jch.14695
  25. Makani H, Messerli FH, Romero J, et al. Meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors. The American Journal of Cardiology. 2012. https://doi.org/10.1016/j.amjcard.2012.03.034
  26. Rubio-Tapia A, Herman ML, Ludvigsson JF, et al. Severe spruelike enteropathy associated with olmesartan. Mayo Clinic Proceedings. 2012. https://doi.org/10.1016/j.mayocp.2012.06.003
  27. Basson M, Mezzarobba M, Weill A, et al. Severe intestinal malabsorption associated with olmesartan: a French nationwide observational cohort study. Gut. 2016. https://doi.org/10.1136/gutjnl-2015-309690
  28. US Food and Drug Administration. FDA Drug Safety Communication: FDA approves label changes to include intestinal problems (sprue-like enteropathy) linked to blood pressure medicine olmesartan medoxomil. 2013. https://www.fda.gov/files/drugs/published/FDA-Drug-Safety-Communication--FDA--approves-label-changes-to-include-intestinal-problems-(sprue-like-enteropathy)-linked-to-blood-pressure-medicine-olmesartan-medoxomil.pdf
  29. Benicar (olmesartan medoxomil) tablets, prescribing information. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dc3f1fd4-5578-4c5d-be7b-12e3f8f3e7df
  30. Sipahi I, Debanne SM, Rowland DY, Simon DI, Fang JC. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. The Lancet Oncology. 2010. https://doi.org/10.1016/S1470-2045(10)70106-6
  31. ARB Trialists Collaboration. Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals. Journal of Hypertension. 2011. https://doi.org/10.1097/HJH.0b013e328344a7de
  32. Bangalore S, Kumar S, Kjeldsen SE, et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. The Lancet Oncology. 2011. https://doi.org/10.1016/S1470-2045(10)70260-6
  33. US Food and Drug Administration. Recalls of Angiotensin II Receptor Blockers (ARBs) including Valsartan, Losartan and Irbesartan. Content current as of 2021. https://www.fda.gov/drugs/drug-safety-and-availability/recalls-angiotensin-ii-receptor-blockers-arbs-including-valsartan-losartan-and-irbesartan
  34. Pottegård A, Kristensen KB, Ernst MT, et al. Use of N-nitrosodimethylamine (NDMA) contaminated valsartan products and risk of cancer: Danish nationwide cohort study. BMJ. 2018. https://doi.org/10.1136/bmj.k3851
  35. Gomm W, Röthlein C, Schüssel K, et al. N-Nitrosodimethylamine-Contaminated Valsartan and the Risk of Cancer: A Longitudinal Cohort Study Based on German Health Insurance Data. Deutsches Ärzteblatt International. 2021. https://doi.org/10.3238/arztebl.m2021.0129
  36. Makani H, Bangalore S, Desouza KA, Shah A, Messerli FH. Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials. BMJ. 2013. https://doi.org/10.1136/bmj.f360
  37. Fried LF, Emanuele N, Zhang JH, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. New England Journal of Medicine. 2013. https://doi.org/10.1056/NEJMoa1303154
  38. Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study. BMJ. 2013. https://doi.org/10.1136/bmj.e8525
  39. Antoniou T, Gomes T, Juurlink DN, et al. Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. Archives of Internal Medicine. 2010. https://doi.org/10.1001/archinternmed.2010.142
  40. Fralick M, Macdonald EM, Gomes T, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ. 2014. https://doi.org/10.1136/bmj.g6196
  41. Lopes RD, Macedo AVS, de Barros E Silva PGM, et al. Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial. JAMA. 2021. https://doi.org/10.1001/jama.2020.25864
  42. Gnanenthiran SR, Borghi C, Burger D, et al. Renin-Angiotensin System Inhibitors in Patients With COVID-19: A Meta-Analysis of Randomized Controlled Trials Led by the International Society of Hypertension. Journal of the American Heart Association. 2022. https://doi.org/10.1161/JAHA.122.026143
  43. Bhandari S, Mehta S, Khwaja A, et al. Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. New England Journal of Medicine. 2022. https://doi.org/10.1056/NEJMoa2210639

Everything in the library