ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs)






















Overview
  • ACE inhibitors have been shown to improve outcomes in heart failure
  • Because ARBs have a similar mechanism of action, they have also been evaluated in heart failure
  • Candesartan and valsartan are both FDA-approved to treat heart failure. Two large trials involving these drugs are detailed below.
CHARM-ALT trial - Candesartan vs Placebo in Heart Failure, Lancet (2003) [PubMed abstract]
  • The CHARM-ALT trial enrolled 2028 patients with heart failure who were not taking an ACE inhibitor
Main inclusion criteria
  • NYHA II - IV heart failure
  • EF ≤ 40%
  • Intolerant to ACE inhibitors
Baseline characteristics
  • Average age 66 years
  • Average EF - 30%
  • Average BP - 130/77 mmHg
  • NYHA class: II - 48% | III - 49% | IV - 3.6%
  • Heart failure type: Ischemic - 68% | Idiopathic - 19% | Hypertensive - 6%
  • Baseline meds: Diuretic - 85% | Beta blocker - 55% | Spironolactone - 24%
  • Reason for ACE intolerance: Cough - 72% | Hypotension - 13% | Renal dysfunction - 11% | Other - 10%
Randomized treatment groups
  • Group 1 (1013 patients) - Candesartan with a target dose of 32 mg once daily (average dose at 6 months was 23 mg)
  • Group 2 (1015 patients) - Placebo once daily
  • Candesartan was started at a dose of 4 - 8 mg once daily and doubled at a minimum of every 2 weeks to a target of 32 mg
Primary outcome: Cardiovascular death or unplanned admission to hospital for the management of worsening heart failure
Results

Duration: Median of 33.7 months
Outcome Candesartan Placebo Comparisons
Primary outcome 33% 40% HR 0.77, 95%CI [0.67 - 0.89], p=0.0004
Overall mortality 26.2% 29.2% HR 0.87, 95%CI [0.74 - 1.03], p=0.11
Hospitalization for heart failure 20.9% 28.7% p=0.0001
Drug discontinuation 24% 22% p=0.49
Hypotension causing drug discontinuation 3.7% 0.9% p<0.0001
Increase in creatinine causing drug discontinuation 6.1% 2.7% p<0.0001
Hyperkalemia causing drug discontinuation 1.9% 0.3% p=0.0005
  • At 6 months, blood pressure had decreased by 4.4/3.9 mmHg more in the candesartan group than in the placebo group

Findings: Candesartan was generally well tolerated and reduced cardiovascular mortality and morbidity in patients with symptomatic chronic heart failure and intolerance to ACE inhibitors
VALIANT Trial - Valsartan vs Captopril vs Both in Heart Failure, NEJM (2003) [PubMed abstract]
  • The VALIANT trial enrolled 14,703 patients with acute myocardial infarction that was complicated by heart failure or left ventricular dysfunction
Main inclusion criteria
  • Myocardial infarction within past 0.5 - 10 days
  • Clinical or radiologic signs of heart failure or EF < 35% on ECHO or < 40% on radionuclide ventriculography
Main exclusion criteria
  • SBP < 100
  • Serum creatinine ≥ 2.5 mg/dl
  • Previous intolerance to ACE or ARB
  • Significant heart valve disease
Baseline characteristics
  • Average age 65 years
  • Average BP - 122/72
  • Average EF - 35%
  • History of prior heart failure - 15%
  • Received PCI - 35%
  • Baseline meds: ACE/ARB - 41% | Beta blocker - 70% | Diuretics - 60%
Randomized treatment groups
  • Group 1 (4909 patients) - Valsartan with a target dose of 160 mg twice a day (mean dose achieved 247 mg/day)
  • Group 2 (4885 patients) - Valsartan with a target dose 80 mg twice daily + Captopril with a target dose 50 mg three times a day (mean dose achieved 116 mg/day and 105 mg/day, respectively)
  • Group 3 (4909 patients) - Captopril with a target dose of 50 mg three times a day (mean dose achieved 117 mg/day)
  • Initial valsartan dose was 20 mg and initial captopril dose was 6.25 mg. Study drugs were titrated to target over a 3-month period if possible.
Primary outcome: All-cause mortality
Results

Duration: Median of 24.7 months
Outcome Valsartan Val + Cap Captopril Comparisons
Primary outcome 19.9% 19.3% 19.5% 1 or 2 vs 3 p>0.50
Hospitalization for myocardial infarction or heart failure 18.7% 17.1% 19.3% 1 vs 3 p=0.50 | 2 vs 3 p=0.005
Hypotension causing drug discontinuation 1.4% 1.9% 0.8% 1 or 2 vs 3 p<0.05
Renal dysfunction causing drug discontinuation 1.1% 1.3% 0.8% 1 vs 3 p>0.05 | 2 vs 3 p<0.05
Hyperkalemia causing drug discontinuation 0.1% 0.2% 0.1% 1 or 2 vs 3 p>0.05
Cough causing drug discontinuation 0.6% 2.1% 2.5% 1 vs 3 p<0.05 | 2 vs 3 p>0.05
Drug discontinuation due to any adverse event 5.8% 9% 7.7% 1 or 2 vs 3 p<0.05
Average blood pressure at 1 year 127/75 125/75 127/76 N/A

Findings: Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival.
AHA recommendations
  • The AHA 2017 heart failure guidelines state that ARBs or ACE inhibitors are indicated for patients with chronic HFrEF to reduce morbidity and mortality in conjunction with evidence-based beta blockers and aldosterone antagonists in selected patients
  • Patients who cannot tolerate ACE inhibitors because of cough or angioedema should be tried on an ARB [47]
Summary
  • Like ACE inhibitors, ARBs improve outcomes in patients with heart failure. Combining ARBs with ACE inhibitors (see combination therapy below) does not improve efficacy and increases the risk of side effects.
  • Candesartan and valsartan are FDA-approved for heart failure, but other ARBs including losartan have also been shown to be effective [8]
  • The heart failure drug Entresto® also contains valsartan



Overview
  • Diabetic kidney disease occurs in 20 - 40% of patients with diabetes, and it is the leading cause of end-stage kidney disease in the United States
  • ACE inhibitors have been shown to improve renal outcomes in DKD so ARBs have also been studied
  • Two randomized controlled trials that evaluated the effects of ARBs in DKD are presented below. In the CSG trial, irbesartan was compared to amlodipine and placebo for the treatment of DKD. In the ROADMAP trial, olmesartan was compared to placebo for the prevention of DKD. A meta-analysis that compared the effects of ARBs and ACE inhibitors to other antihypertensive classes in DKD is also presented.
CSG Trial - Irbesartan vs Amlodipine vs Placebo in Diabetic Kidney Disease, NEJM (2001) [PubMed abstract]
  • The CSG trial enrolled 1715 diabetics with hypertension and proteinuria
Main inclusion criteria
  • Age 30 - 70 years
  • Type 2 diabetes
  • Treated hypertension or untreated BP > 135/85
  • Proteinuria ≥ 900 mg/day
  • Serum creatinine 1 - 3 mg/dl in women or 1.2 - 3 mg/dl in men
Baseline characteristics
  • Average age 59 years
  • Average BP - 159/87
  • Average serum creatinine - 1.67 mg/dl
  • Median 24-hour protein - 2.9 grams
  • Average A1C - 8.2%
Randomized treatment groups
  • Group 1 (579 patients) - Irbesartan 75 - 300 mg once daily
  • Group 2 (567 patients) - Amlodipine 2.5 - 10 mg once daily
  • Group 3 (569 patients) - Placebo
  • Patients were treated to a target BP of < 135/85. Non-study ACE inhibitors, ARBs, and calcium channel blockers were not allowed.
Primary outcome: Composite of doubling of the baseline serum creatinine concentration, the development of end-stage renal disease, or death from any cause
Results

Duration: Average of 2.6 years
Outcome Irbesartan Amlodipine Placebo Comparisons
Primary outcome 32.6% 41.1% 39% 1 vs 2 p=0.005 | 1 vs 3 p=0.03
End-stage renal disease 14.2% 18.3% 17.8% 1 vs 2 p=0.06 | 1 vs 3 p=0.19
Doubling of serum creatinine 16.9% 25.4% 23.7% 1 vs 2 p<0.001 | 1 vs 3 p=0.009
Overall mortality 15% 14.6% 16.3% 1 vs 2 p=0.75 | 1 vs 3 p=0.69
Hyperkalemia leading to drug discontinuation 1.9% 0.5% 0.4% 1 vs 2 p=0.01 | 1 vs 3 p=0.01
Average blood pressure during trial 140/77 141/77 144/80 N/A
  • Amlodipine was not significantly better than placebo for any measured outcome

Findings: The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of the reduction in blood pressure it causes.
ROADMAP Trial - Olmesartan vs Placebo for the Prevention of Diabetic Kidney Disease, NEJM (2011) [PubMed abstract]
  • The ROADMAP trial enrolled 4447 diabetics without proteinuria
Main inclusion criteria
  • Type 2 diabetes
  • Normoalbuminuria (UACR [mg/g]: ≤ 35 for females, ≤ 25 for males)
  • At least one of the following - dyslipidemia, hypertension, obesity, smoker, or high waist circumference
Main exclusion criteria
  • CrCl < 30 ml/min
  • SBP > 200, DBP > 110
  • Treatment with ARB or ACE inhibitor within last 6 months
  • Cardiovascular event within 6 months
  • Renal-vascular disease
Baseline characteristics
  • Average age 58 years
  • Average A1C - 7.7%
  • Average BP 136/81
  • Average GFR 85 ml/min
  • Average duration of diabetes - 6.1 years
Randomized treatment groups
  • Group 1 (2232 patients) - Olmesartan 40 mg once daily
  • Group 2 (2215 patients) - Placebo
  • ACE inhibitors and non-study ARBs were not allowed in either group. Other classes of BP meds were allowed.
  • Patients were treated to a target BP of 130/80
Primary outcome: Development of microalbuminuria
Results

Duration: Median of 3.2 years
Outcome Olmesartan Placebo Comparisons
Primary outcome 8.2% 9.8% HR 0.77, 95%CI [0.63 - 0.94], p=0.01
Doubling of serum creatinine 1% 1% p>0.05
Overall mortality 1.2% 0.7% HR 1.70, 95%CI [0.90 - 3.22], p=0.10
Hypotension 2.6% 0.3% p<0.001
Hyperkalemia 0.5% 0.4% p=0.50
  • Group 1 had a lower average blood pressure during the study - SBP lower by 3.3 mmHg and DBP lower by 1.3 mmHg
  • When the results were adjusted for the lower blood pressure achieved in the olmesartan group, the statistical significance became borderline nonsignificant (p=.08 for SBP, p=0.06 for DBP)

Findings: Olmesartan was associated with a delayed onset of microalbuminuria, even though blood-pressure control in both groups was excellent according to current standards. The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern.
ACE Inhibitors and ARBs compared to other antihypertensives for DKD outcomes, BMJ meta-analysis (2016) [PubMed abstract]
  • A meta-analysis published in the BMJ in 2016 compared outcomes in diabetics who were prescribed ACE inhibitors or ARBS to those who were prescribed other blood pressure medications
  • The analysis included 19 randomized controlled trials (25,414 patients) totaling 95,910 patient-years of follow-up. The average follow-up of the trials was 3.8 years.
  • ACE inhibitors were used in 14 trials, and ARBs were used in 6. The comparison drug was a calcium channel blocker in 15 trials, a thiazide diuretic in 3 trials, and a beta blocker in 2 trials.
  • The majority of the trials (n=17) enrolled patients with hypertension
  • The following results were seen:
    • End-stage renal disease (ACE/ARB vs all other): RR 0.99, 95% CI [0.78 - 1.28]
    • Overall mortality (ACE/ARB vs all other): RR 0.99, 95% CI [0.93 - 1.05]
    • Heart attack (ACE/ARB vs all other): RR 0.87, 95% CI [0.64 - 1.18]
    • Heart failure (ACE/ARB vs all other): RR 0.90, 95% CI [0.76 - 1.07]
    • In meta-regression analysis, the presence of nephropathy at baseline had no significant effect on results
  • Findings: In people with diabetes, RAS blockers are not superior to other antihypertensive drug classes such as thiazides, calcium channel blockers, and beta blockers at reducing the risk of hard cardiovascular and renal endpoints.
Professional recommendations
Summary
  • When compared to other blood pressure medications, ACE inhibitors and ARBs are superior for treating and preventing proteinuria
  • When it comes to improving hard renal outcomes like end-stage renal disease, there is no evidence that ACE inhibitors or ARBs are superior to other classes of blood pressure medications
  • Patients with diabetic kidney disease should focus on blood sugar and blood pressure control to help prevent progression of their disease









Overview
  • ARBs and ACE inhibitors block the Renin-Angiotensin-Aldosterone System (RAAS) at different steps (see RAAS illustration). Since both drugs have been proven to be beneficial in heart failure, there has been interest in using them together.
  • The VALIANT trial compared the combination of valsartan and captopril (combination therapy) to each drug alone in patients with recent myocardial infarction and heart failure (see VALIANT trial above). For the primary outcome, combination therapy was not superior to each drug alone. Combination therapy was superior to captopril alone for a composite outcome of hospitalization for myocardial infarction or heart failure. Combination therapy had significantly more side effects than individual therapy. [12]
  • The CHARM-ADDED trial detailed below compared combination therapy with candesartan and an ACE inhibitor to an ACE inhibitor alone. A meta-analysis that combined the results of 4 trials is also reviewed.
CHARM-ADDED Trial - Candesartan + ACE Inhibitor vs ACE Inhibitor in Heart Failure, Lancet (2003) [PubMed abstract]
  • The CHARM-Added trial enrolled 2548 patients with NYHA class II-IV heart failure who were being treated with an ACE inhibitor
Main inclusion criteria
  • EF ≤ 40%
  • NYHA class II - IV heart failure (if NYHA class II had to have had hospitalization for cardiac reasons within 6 months)
  • Treatment with ACE inhibitor
Baseline characteristics
  • Average age 64 years
  • Average EF - 28%
  • NYHA class: II - 24% | III - 73% | IV - 3%
  • Heart failure type: Ischemic - 63% | Idiopathic - 27% | Hypertensive - 6.5%
  • Baseline meds: ACE inhibitor - 100% | Diuretic - 90% | Beta blocker - 56% | Spironolactone - 17%
Randomized treatment groups
  • Group 1 (1276 patients) - Candesartan target dose of 32 mg once daily (mean dose at 6 months was 24 mg)
  • Group 2 (1272 patients) - Placebo once daily
  • Candesartan was started at 4 - 8 mg once daily and doubled every 2 weeks to a target of 32 mg if tolerated
Primary outcome: Composite of cardiovascular death or hospitalization for heart failure
Results

Duration: Median of 41 months
Outcome Candesartan Placebo Comparisons
Primary outcome 37.9% 42.3% HR 0.85, 95%CI [0.75 - 0.96], p=0.011
Hospitalization for heart failure 25.3% 30% p=0.002
Overall mortality 30% 32% HR 0.89, 95%CI [0.77 - 1.02], p=0.086
Drug discontinuation for adverse event 24% 18% p=0.0003
Hypotension leading to drug discontinuation 4.5% 3.1% p=0.079
Increase in creatinine leading to drug discontinuation 7.8% 4.1% p=0.0001
Hyperkalemia leading to drug discontinuation 3.4% 0.7% p<0.0001
  • At 6 months, SBP and DBP were reduced more from baseline in the candesartan group than in the placebo group (difference in reduction 4.6/3 mmHg)

Findings: The addition of candesartan to ACE inhibitor and other treatment leads to a further clinically important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction
Adverse effects of combining ACE Inhibitors and ARBs for left ventricular dysfunction, Archives of IM meta-analysis (2007) [PubMed abstract]
  • A meta-analysis in the Archives of Internal Medicine compared the adverse effects of ACE inhibitor + ARB therapy to ACE inhibitor therapy in patients with heart failure and left ventricular dysfunction
  • The analysis included four studies that encompassed 17,337 patients with an average follow-up of 25 months
  • The following effects were seen when ACE + ARB therapy was compared to ACE inhibitor alone:
    • Worsening kidney function (Combo vs ACE): RR 2.17, 95% CI [1.59 - 2.97]
    • Hyperkalemia (Combo vs ACE): RR 4.87, 95% CI [2.39 - 9.94]
    • Symptomatic hypotension (Combo vs ACE): RR 1.50, 95% CI [1.09 - 2.07]
    • Drug discontinuation due to adverse effects (Combo vs ACE): RR 1.38, 95% CI [1.22 - 1.55] [34]
  • Findings: Combination ARB plus ACE inhibitor therapy in subjects with symptomatic left ventricular dysfunction was accompanied by marked increases in adverse effects
AHA recommendations
  • The AHA/ACC 2017 heart failure guidelines do not recommend combining an ACE inhibitor and an ARB [47]
StraightHealthcare analysis
  • Combination therapy with an ACE inhibitor and an ARB showed a modest benefit in the CHARM-ADDED study. Combination therapy is associated with a greater risk of potentially serious side effects. Patients who require additional therapy while taking an ACE inhibitor or ARB should be considered for Entresto.






Cough (lack of)

High potassium (hyperkalemia)
Overview
  • Like ACE inhibitors, ARBs can raise potassium levels
  • In clinical trials, hyperkalemia has occurred in anywhere from 0.6 - 19% of patients depending on the trial and the patient population [10,16,23-26]
  • The risk depends greatly on a patient's concurrent medical conditions
  • For patients with hypertension and no other medical problems, the risk is minimal. For patients with kidney disease, heart failure, and other comorbidities, the risk is higher.
  • Patients on ARBs should have their potassium checked periodically. High-risk patients should have their potassium checked more frequently.
Factors associated with an increased risk of hyperkalemia:
  • Kidney disease
  • Advanced age
  • Diabetes
  • Heart failure
  • Patients taking certain medications (see drug interactions below)
AHA recommendations
  • The AHA recommends that renal function and potassium be checked within 1-2 weeks of starting an ACE inhibitor or ARB [15]

Angioedema (swelling of mouth, lips, and tongue)
Overview
  • Angioedema is an allergic reaction that causes swelling of the lips, mouth, face, throat, and tongue. Angioedema may be mild or life-threatening.
  • ACE inhibitors are known to cause angioedema. ARBs can also cause angioedema, but to a lesser degree.
  • The question then arises as to whether ARBs are safe to use in patients who have experienced angioedema on ACE inhibitors. Only a handful of small studies have looked at the issue.
Studies
  • In the CHARM-ALTERNATIVE trial, 39 patients in the candesartan group had experienced previous ACE inhibitor-induced angioedema. Of these 39, three patients given candesartan experienced angioedema. [10]
  • A small meta-analysis found that the incidence of angioedema in patients with a history of prior ACE inhibitor-induced angioedema who were subsequently given ARBs was 2 - 17% [30]
Summary
  • Significant angioedema can be a terrifying experience for patients, and the risk of a recurrence may be too much for some patients to accept
  • If ARBs are to be prescribed in patients with a prior history of ACE inhibitor-induced angioedema, the risk needs to be understood and proper precautions taken

Increase in serum creatinine
Overview
  • Serum creatinine is a measure of kidney function. ARBs may cause an increase in serum creatinine levels.
  • The risk and significance of serum creatinine increases on ARBs depends on a person's concurrent medical problems
  • For healthy patients taking ARBs for hypertension, the risk is minimal. For patients with kidney disease, heart failure, and other comorbidities, the risk is greater.
  • Patients on ARBs should have their kidney function assessed periodically. High-risk patients should have their kidney function checked more frequently.
Factors associated with a rise in creatinine levels on ARB therapy:
  • Kidney disease
  • Advanced age
  • Diabetes
  • Heart failure
  • Patients taking certain medications (ex. diuretics)
  • Renal artery stenosis
AHA recommendations
  • The AHA recommends that renal function and potassium be checked within 1-2 weeks of starting an ACE inhibitor or ARB [15]

Enteropathy (olmesartan only)






Kidney disease
Overview
  • While ARBs are often beneficial in kidney disease, their inhibitory effects on the RAAS system may be detrimental when kidneys are severely compensated
  • Elevations in potassium, serum creatinine, and BUN may occur in patients with significant kidney disease
  • ARBs should be started at their lowest doses in patients with significant kidney disease, and frequent monitoring of kidney function and electrolytes (particularly potassium) should be performed
Azilsartan (Edarbi®)
  • No dose adjustment necessary
Candesartan (Atacand®)
  • Use caution
  • Manufacturer makes no specific dosage recommendation
Eprosartan (Teveten®)
  • Moderate-to-severe kidney disease (CrCl < 60 ml/min): Max dose 600 mg a day
Irbesartan (Avapro®)
  • No dose adjustment necessary
Losartan (Cozaar®)
  • No dose adjustment necessary
Olmesartan (Benicar®)
  • No dose adjustment necessary
Telmisartan (Micardis®)
  • No dose adjustment necessary
Valsartan (Diovan®)
  • In mild-to-moderate kidney disease, no dose adjustment necessary
  • Use caution in severe kidney disease

Liver disease
Azilsartan (Edarbi®)
  • In mild-to-moderate liver disease, no dose adjustment necessary
  • Has not been studied in severe liver disease
Candesartan (Atacand®)
  • In mild liver disease, no dose adjustment necessary
  • In moderate liver disease, starting dose should be 8 mg when treating hypertension
  • Has not been studies in severe liver disease
Eprosartan (Teveten®)
  • No dose adjustment necessary in patients with liver disease
Irbesartan (Avapro®)
  • No dose adjustment necessary in patients with liver disease
Losartan (Cozaar®)
  • Starting dose should be 25 mg in patients with liver disease
Olmesartan (Benicar®)
  • No dose adjustment necessary for patients with moderate to marked liver disease
Telmisartan (Micardis®)
  • Telmisartan should be started at low doses and titrated slowly in patients with liver disease and/or biliary disorders
Valsartan (Diovan®)
  • In mild-to-moderate liver disease, no dose adjustment necessary
  • Care should be used when using in severe liver disease

Renal artery stenosis

Black patients
Overview
  • ARBs appear to be less effective at lowering blood pressure in black patients when compared to other classes of blood pressure medications
STUDY
Systematic review: antihypertensive drug therapy in black patients, Annals of Internal Medicine (2004) [PubMed abstract]
  • A meta-analysis compared the effects of ARBs to other classes of antihypertensives in black patients
    • The analysis found the following:
      • ARBs lowered systolic blood pressure (SBP) an average of 3.63 mmHg when compared to placebo
      • ARBs lowered diastolic blood pressure (DBP) an average of 2.09 mmHg when compared to placebo
    • Compare to:
      • Diuretics - average SBP reduction of 11.81 mmHg / DBP reduction of 8.06 mmHg
      • Calcium channel blockers - average SBP reduction 12.10 mmHg / DBP 9.40 mmHg [39]
  • Findings: Drugs differ in their efficacy for reducing blood pressure in black patients, but there is no solid evidence that efficacy for reducing morbidity and mortality outcomes differs once patients achieve the blood pressure goal
Professional recommendations
Summary
  • Other classes of blood pressure medications tend to be more effective in lowering blood pressure in black patients, but ARBs still improve clinical outcomes in these patients, and therefore, should still be used when indicated (e.g. heart failure, kidney disease).

Pregnant or nursing



All ARBs

  • ACE inhibitors - see combining ARBs and ACE inhibitors
  • Aliskiren (Tekturna®) - Aliskiren should not be prescribed with ARBs in patients with diabetes or decreased kidney function (GFR<60ml/min)
  • Lithium - ARBs can increase lithium levels. This combination should be avoided, or lithium levels should be checked frequently if they are taken together.
  • Medications that can raise potassium levels - ARBs have the potential to raise potassium levels. When taken with other medications that raise potassium, the risk may be compounded. While it is often appropriate to prescribe ARBs with these medications, patients and providers should be aware of the potential risks (see elevated potassium above)
  • NSAIDS (Advil®, Aleve®, etc.) - NSAIDS can attenuate the effect of ARBs. This is more of a concern if NSAIDS are taken on a chronic basis. Reports of decreased kidney function have been reported when NSAIDS were taken with ARBs. The risk appears to be greater with advanced age, dehydration, and underlying kidney disease.
  • Potassium supplements (K-Dur®, etc.) - ARBs can elevate potassium levels. Potassium levels should be monitored frequently in patients taking potassium supplements and ARBs.
  • Salt substitutes (No-Salt®, etc.) - Salt substitutes typically contain a high amount of potassium. Since ARBs can raise potassium levels, caution should be used when consuming salt substitutes.

Telmisartan (Micardis®)

  • Digoxin - telmisartan has been shown to increase digoxin levels. When taken together, digoxin levels should be monitored.
  • Ramipril (Altace®) - Ramipril, an ACE inhibitor, should not be taken with telmisartan. Telmisartan has been shown to significantly increase ramipril levels.

Metabolism and clearance
Azilsartan (Edarbi®)
Candesartan (Atacand®)
  • No significant liver metabolism
Eprosartan (Teveten®)
  • No significant liver metabolism
Irbesartan (Avapro®)
Losartan (Cozaar®)
Olmesartan (Benicar®)
Telmisartan (Micardis®)
Valsartan (Diovan®)