Skip to main content

Candesartan (Monograph)

Brand name: Atacand
Drug class: Angiotensin II Receptor Antagonists
VA class: CV805
Chemical name: (±)-1-[[Cyclohexyloxy)carbonyl]oxy]ethyl ester-2-ethoxy-1-[[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid
Molecular formula: C33H34…N6O6
CAS number: 145040-37-5

Medically reviewed by Drugs.com on Oct 26, 2023. Written by ASHP.

Warning

  • May cause fetal and neonatal morbidity and mortality if used during pregnancy.1 2 55 56 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • If pregnancy is detected, discontinue as soon as possible.1 2 56

Introduction

Angiotensin II receptor (AT1) antagonist (i.e., angiotensin II receptor blocker, ARB).1 2 9

Uses for Candesartan

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 16 17 18 19 20 21 58 59 1200

Angiotensin II receptor antagonists are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include ACE inhibitors, calcium-channel blockers, and thiazide diuretics.501 502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 503 504 1200 1213

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Previous hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the current ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient’s BP treatment goal.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to angiotensin II receptor antagonists.501 504 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.1200

Angiotensin II receptor antagonists or ACE inhibitors may be particularly useful in hypertensive patients with diabetes mellitus or CKD; angiotensin II receptor antagonists also may be preferred, as an alternative to ACE inhibitors, in hypertensive patients with heart failure or ischemic heart disease and/or post-MI.501 502 504 523 524 527 534 535 536 543 1200 1214 1215

Heart Failure

Used in the management of heart failure.1 52 53 524 800

Because of their established benefits, ACE inhibitors have been the preferred drugs for inhibition of the renin-angiotensin-aldosterone (RAA) system in patients with heart failure and reduced left ventricular ejection fraction (LVEF); 524 however, some evidence indicates that therapy with an ACE inhibitor (enalapril) may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.702 800

Angiotensin II receptor antagonists may be used as an alternative for those patients in whom use of an ACE inhibitor or ARNI is inappropriate.524 528 800

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced LVEF (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.800

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria [off-label] who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.25 26 27 28 29 30 31 32 36 37 39 40 41 535 536 1232

Candesartan Dosage and Administration

General

BP Monitoring and Treatment Goals

Administration

Oral Administration

Administer orally once or twice daily without regard to meals.1 24 58

May substitute oral suspension in children who cannot swallow tablets.1 58

Reconstitution

Prepare extemporaneous candesartan cilexetil oral suspension in concentration range of 0.1–2 mg/mL (1 mg/mL generally suitable for administering most dosages).1 May use any strength of candesartan tablets.1

To prepare 160 mL of a 1-mg/mL suspension, use equal volumes (80 mL each) of Ora-Plus and Ora-Sweet SF or use 160 mL of Ora-Blend SF.1 Add a small amount of the vehicle to the required number of candesartan cilexetil tablets (i.e., five 32-mg tablets), and grind into a smooth paste using a mortar and pestle.1 Add the paste to a preparation container of suitable size.1

Rinse the mortar and pestle clean using the vehicle and add the resulting vehicle mixture to the container; repeat as necessary.1 Add the remaining vehicle to the container and mix thoroughly.1 Dispense in suitably sized amber polyethylene terephthalate (PET) bottles.1

Label with an expiration date of 100 days and the following instructions: Store at room temperature (below 30°C/86°F), use within 30 days after first opening, do not use after the expiration date stated on the bottle, do not freeze, and shake well before each use.1

Dosage

Available as candesartan cilexetil; dosage expressed in terms of the salt.1

Pediatric Patients

Hypertension
Oral

Some experts state drug should be initiated at the low end of the dosage range; dosage may be increased every 2–4 weeks until BP controlled, maximum dosage reached, or adverse effects occur.1150

Children <1 year of age: Do not use candesartan.1 58 (See Infant Morbidity under Cautions.)

Patients 1 to <6 years of age: Initially, 0.2 mg/kg daily (range: 0.05–0.4 mg/kg daily) as oral suspension.1 58 Safety and efficacy of dosages >0.4 mg/kg daily not established.1 58

Patients 6 to <17 years of age who weigh <50 kg: Initially, 4–8 mg daily (range: 2–16 mg daily).1 24 58 Safety and efficacy of dosages >32 mg daily not established.1 58

Patients 6 to <17 years of age who weigh >50 kg: Initially, 8–16 mg daily (range: 4–32 mg daily).1 58 Safety and efficacy of dosages >32 mg daily not established.1 58

Adjust dosage according to BP response.1 Antihypertensive effect usually present within 2 weeks; full effect generally obtained within 4 weeks.1

Adults

Hypertension
Candesartan Therapy
Oral

Manufacturer recommends initial dosage of 16 mg once daily as monotherapy in adults without intravascular volume depletion.1 2 3

Usual dosage is 8–32 mg daily, given in 1 dose or 2 divided doses;1 2 5 1200 no additional therapeutic benefit with higher dosages.1 2

Candesartan/Hydrochlorothiazide Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.2 5 11

If BP is not adequately controlled by monotherapy with candesartan 32 mg daily, can switch to fixed-combination tablets (candesartan 32 mg and hydrochlorothiazide 12.5 mg; then candesartan 32 mg and hydrochlorothiazide 25 mg).2 24

If BP is not adequately controlled by monotherapy with 25 mg of hydrochlorothiazide or if BP is controlled but hypokalemia is problematic at this dosage, can use fixed-combination tablets containing candesartan 16 mg and hydrochlorothiazide 12.5 mg.2 24

Heart Failure
Oral

Initially, 4 mg once daily recommended by manufacturer;1 some experts recommend initial dosage of 4–8 mg once daily.524 Increase dosage (by doubling the dosage at approximately 2-week intervals) as tolerated to target dosage of 32 mg once daily;1 ACCF/AHA recommend maximum dosage of 32 mg once daily.524

Special Populations

Hepatic Impairment

No initial dosage adjustments necessary in patients with mild hepatic impairment.1

Manufacturer recommends considering initial dosage reduction in patients with moderate hepatic impairment.1

If a lower initial candesartan cilexetil dosage (<8 mg once daily) is selected in patients with moderate hepatic impairment, do not use the commercially available preparation containing candesartan cilexetil in fixed combination with hydrochlorothiazide for initial titration, because the appropriate starting dose of candesartan cilexetil is not available as a fixed-combination preparation.2 Individualize and adjust dosage carefully when using the fixed combination preparation in patients with hepatic impairment .2 Some clinicians recommend initial candesartan cilexetil dosage of 4 or 8 mg daily in patients with severe hepatic impairment.3 10 22 23 24

Renal Impairment

Manufacturer states that no initial candesartan cilexetil dosage adjustments are necessary in adults with renal impairment.1 2 However, some clinicians recommend initial dosage of 4 or 8 mg daily in those with severe impairment.3 10 22 23 24

Do not administer to pediatric patients with GFR <30 mL/minute per 1.73 m2; safety and efficacy not established in this patient population.1 58

Volume- and/or Salt-Depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy under close medical supervision using lower initial dosage.1 2

Cautions for Candesartan

Contraindications

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Possible reduction in fetal renal function and increase in fetal and neonatal morbidity and mortality when used during pregnancy.1 2 56 (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.56

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.55 56 Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death.1 Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.1

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.1 55 56 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.12

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible;1 2 7 13 not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitor or angiotensin II receptor antagonist therapy.14 21

Other Warnings and Precautions

Effects on Potassium

Potential hyperkalemia, especially in patients receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).1 Monitor serum potassium levels periodically.1

Hypotension

Possible symptomatic hypotension, particularly in patients with intravascular volume depletion (e.g., those treated with diuretics).1 2 (See Volume- and/or Salt-Depleted Patients under Dosage and Administration.)

May need temporarily to reduce dosage of candesartan cilexitil and/or of a diuretic in patients with heart failure; monitor BP during dosage escalation and periodically thereafter.1 Initiate candesartan with caution in patients with heart failure.1

Transient hypotension is not a contraindication to additional doses; may reinstate therapy cautiously after BP is stabilized.1 2 24

Infant Morbidity

Patients <1 year of age must not receive candesartan; drugs that act directly on the renin-angiotensin system can affect development of immature kidneys.1

Malignancies

In July 2010, FDA initiated a safety review of angiotensin II receptor antagonists after a published meta-analysis found a modest but statistically significant increase in risk of new cancer occurrence in patients receiving an angiotensin II receptor antagonist compared with control.120 121 123 126 However, subsequent studies, including a larger meta-analysis conducted by FDA, have not shown such risk.126 127 128 129 Based on currently available data, FDA has concluded that angiotensin II receptor antagonists do not increase the risk of cancer.126

Renal Effects

Possible oliguria, progressive azotemia and, rarely, acute renal failure and/or death in patients with severe heart failure.1 2

Increases in BUN and SCr possible in patients with unilateral or bilateral renal artery stenosis.1 2

Use of Fixed Combinations

When candesartan is used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.2

Specific Populations

Pregnancy

Category D.1 2

Can cause fetal and neonatal morbidity and mortality when administered to a pregnant woman.1 Discontinue drug as soon as possible when pregnancy is detected.1 (See Boxed Warning.) Effects on labor and delivery in humans not established.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 2 Discontinue nursing or the drug.1 2

Pediatric Use

If oliguria or hypotension occurs in neonates with a history of in utero exposure to candesartan, support BP and renal function; exchange transfusions or dialysis may be required.1 58 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Geriatric Use

No substantial differences in safety or efficacy for the treatment of hypertension relative to younger adults, but increased sensitivity cannot be ruled out.1 2 3

Increased incidence of adverse effects (e.g., abnormal renal function, hypotension, hyperkalemia) and consequent discontinuance of candesartan in patients with heart failure who were ≥75 years of age when compared with younger patients.1

Hepatic Impairment

Systemic exposure to candesartan may be increased.1 (See Absorption: Special Populations, under Pharmacokinetics.) Dosage adjustments may be necessary based on degree of hepatic impairment.1 3 10 22 23 24 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Systemic exposure to candesartan may be increased.1 (See Absorption: Special Populations, under Pharmacokinetics.) Some clinicians recommend initial dosage adjustment in patients with severe renal impairment.3 10 22 23 24 (See Renal Impairment under Dosage and Administration.)

Use of candesartan in fixed combination with hydrochlorothiazide is not recommended in patients with Clcr <30 mL/minute.2

Deterioration of renal function may occur in susceptible patients.1 30 (See Renal Effects under Cautions.)

Black Patients

BP reduction may be smaller in black patients than in patients of other races.1 (See Hypertension under Uses.)

Common Adverse Effects

Back pain, dizziness, upper respiratory tract infection, pharyngitis, rhinitis.1 3

Drug Interactions

Not substantially metabolized by CYP isoenzymes; has no effect on CYP isoenzymes at therapeutic concentrations.1

Specific Drugs

Drug

Interaction

Comment

ACE inhibitors

Increased risk of renal impairment, hyperkalemia, and hypotension1

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly1

Aliskiren

Increased risk of renal impairment, hyperkalemia, and hypotension1 550

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly1 550

Concomitant use contraindicated in patients with diabetes mellitus1 550

Avoid concomitant use in patients with GFR <60 mL/minute1 550

Angiotensin II receptor antagonists

Increased risk of renal impairment, hyperkalemia, and hypotension1

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly1

Cardiac drugs (e.g., digoxin, nifedipine)

Pharmacologic interactions unlikely1 2 3

Contraceptives, oral

Pharmacokinetic interaction unlikely1 2 3

Diuretics, potassium-sparing

Possible hyperkalemia1

Monitor serum potassium concentrations1

Glyburide

Pharmacologic interaction unlikely1 2

Lithium

Increased serum lithium concentrations; possible toxicity1

Closely monitor serum lithium concentrations1

NSAIAs (including COX-2 inhibitors)

Geriatric, volume-depleted, or renally impaired patients: Possible deterioration in renal function, including renal failure;1 effects usually reversible1

Monitor renal function periodically 1

Salt substitutes, potassium-containing

Possible hyperkalemia1

Monitor serum potassium concentrations1

Warfarin

Pharmacologic interaction unlikely1 2 3

Candesartan Pharmacokinetics

Absorption

Bioavailability

Candesartan cilexetil (prodrug) is rapidly and completely hydrolyzed to candesartan during absorption in the GI tract.1 2 3

Absolute bioavailability of candesartan is about 15%.1

Onset

Antihypertensive effect evident within 2 weeks, with maximum BP reduction after 4–6 weeks.1

Food

Food with high-fat content does not affect bioavailability.1

Special Populations

In patients with mild hepatic impairment (Child-Pugh class A), peak plasma concentration and AUC are increased by 56 and 30%, respectively,1 2 while in those with moderate hepatic insufficiency (Child-Pugh class B), peak plasma concentration and AUC are increased by 73 and 145%, respectively.1 2 Pharmacokinetics not studied in patients with severe hepatic impairment.1 2

In patients with severe renal impairment (Clcr <30 mL/min/1.73 m2), AUC and peak plasma concentration after repeated dosing are approximately double the values in patients with normal renal function.1

Distribution

Extent

Crosses the placenta and is distributed in the fetus in animals.

Crosses the blood-brain barrier poorly, if at all, in animals.1

Distributed into milk in rats; not known whether distributed into human milk.1 2

Plasma Protein Binding

>99%.1

Elimination

Metabolism

Undergoes minor hepatic metabolism by O-deethylation to an inactive metabolite.1

Elimination Route

Eliminated mainly as unchanged drug in urine and feces (via bile).1 2

Half-life

Approximately 9 hours.1

Special Populations

Not removed by hemodialysis.1 Pharmacokinetics in hypertensive patients undergoing hemodialysis are similar to those in hypertensive patients with severe renal impairment.1 (See Absorption: Special Populations, under Pharmacokinetics.)

Stability

Storage

Oral

Tablets

Tightly closed container at 25°C (may be exposed to 15–30°C).1 2

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Candesartan Cilexetil

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

4 mg

Atacand

AstraZeneca

8 mg

Atacand

AstraZeneca

16 mg

Atacand

AstraZeneca

32 mg

Atacand

AstraZeneca

Candesartan Cilexetil Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

16 mg with Hydrochlorothiazide 12.5 mg

Atacand HCT

AstraZeneca

32 mg with Hydrochlorothiazide 12.5 mg

Atacand HCT

AstraZeneca

AHFS DI Essentials™. © Copyright 2024, Selected Revisions November 5, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

1. AstraZeneca. Atacand (candesartan cilexetil) tablets prescribing information. Wilmington, DE; 2016 Jul.

2. AstraZeneca. Atacand HCT (candesartan cilexetil-hydrochlorothiazide) tablets prescribing information. Wilmington, DE; 2016 Jul.

3. McClellan KJ, Goa KL. Candesartan cilexetil: a review of its use in essential hypertension. Drugs. 1998; 56:847-69. http://www.ncbi.nlm.nih.gov/pubmed/9829158?dopt=AbstractPlus

5. Anon. Drugs for hypertension. Med Lett Drugs Ther. 2001; 43:17-22. http://www.ncbi.nlm.nih.gov/pubmed/11242494?dopt=AbstractPlus

6. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure. Am J Cardiol. 1999; 83:9-38A.

7. Warner KK, Visconti JA, Tschampel MM. Angiotensin II receptor blockers in patients with ACE inhibitor-induced angioedema. Ann Pharmacother. 2000; 34:526-8. http://www.ncbi.nlm.nih.gov/pubmed/10772441?dopt=AbstractPlus

8. Zuschke CA, Keys I, Munger MA et al. (Candesartan Cilexetil Study Investigators.) Candesartan cilexetil: comparison of once-daily versus twice-daily administration for systemic hypertension. Candesartan Cilexetil Study Investigators. Clin Ther. 1999; 21:464-74. http://www.ncbi.nlm.nih.gov/pubmed/10321416?dopt=AbstractPlus

9. Unger T. Significance of angiotensin type 1 receptor blockade: why are angiotensin II receptor blockers different? Am J Cardiol. 1999; 84:9-15S.

10. Martineau P, Goulet J. New competition in the realm of renin-angiotensin axis inhibition; the angiotensin II receptor antagonists in congestive heart failure. Ann Pharmacother. 2001; 35:71-84. http://www.ncbi.nlm.nih.gov/pubmed/11197588?dopt=AbstractPlus

11. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993; 153:154-83. http://www.ncbi.nlm.nih.gov/pubmed/8422206?dopt=AbstractPlus

12. US Food and Drug Administration. Dangers of ACE inhibitors during second and third trimesters of pregnancy. FDA Med Bull. 1992; 22:2.

13. Mazzolai L, Burnier M. Comparative safety and tolerability of angiotensin II receptor antagonists. Drug Safety. 1999; 21:23-33. http://www.ncbi.nlm.nih.gov/pubmed/10433351?dopt=AbstractPlus

14. Kirk JK. Therapy with angiotensin II receptor antagonists. Clin Geriatrics. From the MultiMedia Health Care website:. http://www.mmhc.com

15. Velasquez MT. Angiotensin II receptor blockers: a new class of hypertensive drugs. Arch Fam Med. 1996; 5:351-356. http://www.ncbi.nlm.nih.gov/pubmed/8640326?dopt=AbstractPlus

16. Sever P, Holzgreve H. Long-term efficacy and tolerability of candesartan cilexetil in patients with mild to moderate hypertension. J Hum Hypertens. 1997; 11(Suppl 2):S69-73. http://www.ncbi.nlm.nih.gov/pubmed/9331014?dopt=AbstractPlus

17. Zanchetti A, Omboni S, for the Italian Candesartan Study Group. Comparison of candesartan versus enalapril in essential hypertension. Am J Hypertens. 2001; 14:129-34. http://www.ncbi.nlm.nih.gov/pubmed/11243303?dopt=AbstractPlus

18. Franke H. Antihypertensive effects of candesartan cilexetil, enalapril and placebo. J Hum Hypertens. 1997; 11(Suppl 2):S61-2. http://www.ncbi.nlm.nih.gov/pubmed/9331010?dopt=AbstractPlus

19. Zanchetti A, Omboni S, Di Biagio C. Candesartan cilexetil and enalapril are of equivalent efficacy in patients with mild to moderate hypertension. J Hum Hypertens. 1997; 11(Suppl 2):S57-9. http://www.ncbi.nlm.nih.gov/pubmed/9331009?dopt=AbstractPlus

20. Reif M, White WB, Fagan T et al. Effects of candesartan cilexetil in patients with systemic hypertension. Am J Cardiol. 1998; 82:961-5. http://www.ncbi.nlm.nih.gov/pubmed/9794352?dopt=AbstractPlus

21. Papademetriou V, Reif M, Henry D et al. Combination therapy with candesartan cilexetil and hydrochlorothiazide in patients with systemic hypertension. J Clin Hypertens. 2000; 2:372-8.

22. Buter H, Navis GY, Woittiez AJJ et al. Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function. Eur J Clin Pharmacol. 1999; 54:953-8. http://www.ncbi.nlm.nih.gov/pubmed/10192757?dopt=AbstractPlus

23. de Zeeuw D, Remuzzi G, Kirch W. Pharmacokinetics of candesartan cilexetil in patients with renal or hepatic impairment. J Hum Hypertens. 1997; 11(Suppl 2):S37-42. http://www.ncbi.nlm.nih.gov/pubmed/9331004?dopt=AbstractPlus

24. AstraZeneca, Wayne, PA: Personal communication.

25. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2002; 25:134-47. http://www.ncbi.nlm.nih.gov/pubmed/11772914?dopt=AbstractPlus

26. 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. N Engl J Med. 2001; 345:861-9. http://www.ncbi.nlm.nih.gov/pubmed/11565518?dopt=AbstractPlus

27. Lewis EJ, Hunsicker LG, Claarke WR et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001; 345:851-60. http://www.ncbi.nlm.nih.gov/pubmed/11565517?dopt=AbstractPlus

28. Sica DA, Bakris GL. Type 2 diabetes: RENAAL and IDNT—the emergence of new treatment options. J Clin Hypertens (Greenwich). 2002; 4:52-7. http://www.ncbi.nlm.nih.gov/pubmed/11821641?dopt=AbstractPlus

29. Parving HH, Brenner BM, Cooper ME et al. [Effect of losartan on renal and cardiovascular complications of patients with type 2 diabetes and nephropathy.] (Danish; with English abstract.) Ugeskr Laeger. 2001; 163:5514-9.

30. Weekers L, Krzesinski JM. [Clinical study of the month. Nephroprotective role of angiotensin II receptor antagonists in typre 2 diabetes: results of IDNT and RENAAL trials.] (French; with English abstract.) Rev Med Liege. 2001; 56:723-6.

31. Parving HH, Lehnert H, Brochner-Mortensen J et al and the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001; 345:870-8. http://www.ncbi.nlm.nih.gov/pubmed/11565519?dopt=AbstractPlus

32. Walser M. Angiotensin-receptor blockers, type 2 diabetes, and renoprotection. N Engl J Med. 2002; 346:706.

35. Hunt SA, Baker DW, Chin MH et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). 2001. Available from website. Accessed July 25, 2002. http://www.cardiosource.org/Science-And-Quality/Practice-Guidelines-and-Quality-Standards.aspx

36. Fournier A. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1994; 330:937. http://www.ncbi.nlm.nih.gov/pubmed/8114873?dopt=AbstractPlus

37. Viberti G, Mogensen CE, Groop LC et al. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. JAMA. 1994; 271:275-9. http://www.ncbi.nlm.nih.gov/pubmed/8295285?dopt=AbstractPlus

39. Lewis EJ, Hunsicker LG, Bain RP et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993; 329:1456-62. http://www.ncbi.nlm.nih.gov/pubmed/8413456?dopt=AbstractPlus

40. Remuzzi G. Slowing the progression of diabetic nephropathy. N Engl J Med. 1993; 329:1496-7. http://www.ncbi.nlm.nih.gov/pubmed/8413463?dopt=AbstractPlus

41. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. http://www.ncbi.nlm.nih.gov/pubmed/8622249?dopt=AbstractPlus

44. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60. http://www.ncbi.nlm.nih.gov/pubmed/12479770?dopt=AbstractPlus

45. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. http://www.ncbi.nlm.nih.gov/pubmed/12479763?dopt=AbstractPlus

47. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. http://www.ncbi.nlm.nih.gov/pubmed/10818056?dopt=AbstractPlus

48. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. http://www.ncbi.nlm.nih.gov/pubmed/10818055?dopt=AbstractPlus

49. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. http://www.ncbi.nlm.nih.gov/pubmed/10977801?dopt=AbstractPlus

52. 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. Lancet. 2003; 362:772-6. http://www.ncbi.nlm.nih.gov/pubmed/13678870?dopt=AbstractPlus

53. McMurray JJ, Ostergren J, Swedberg K et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet. 2003; 362:767-71. http://www.ncbi.nlm.nih.gov/pubmed/13678869?dopt=AbstractPlus

54. Cohn JN, Tognoni G, for the Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001; 345:1667-75. http://www.ncbi.nlm.nih.gov/pubmed/11759645?dopt=AbstractPlus

55. Cooper WO, Hernandez-Diaz S, Arbogast PG et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006; 354:2443-51. http://www.ncbi.nlm.nih.gov/pubmed/16760444?dopt=AbstractPlus

56. Food and Drug Administration. FDA public health advisory: angiotensin-converting enzyme inhibitor (ACE inhibitor) drugs and pregnancy. From FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm053113.htm

58. Food and Drug Administration. AstraZeneca NDA 20-838 S031: Atacand (candesartan cilexetil) clinical pharmacology review pediatric supplement. Wilmington, DE. Available from FDA website. Accessed 2017 Nov 5. https://www.fda.gov/downloads/drugs/developmentapprovalprocess/developmentresources/ucm189128.pdf

59. Trachtman H, Hainer JW, Sugg J et al. Efficacy, safety, and pharmacokinetics of candesartan cilexetil in hypertensive children aged 6 to 17 years. J Clin Hypertens. 2008; 10:743-50.

120. Food and Drug Administration. FDA drug safety communication: ongoing safety review of the angiotensin receptor blockers and cancer. Rockville, MD; 2010 Jul 15. From FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm218845.htm

121. Sipahi I, Debanne SM, Rowland DY et al. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010; 11:627-36. http://www.ncbi.nlm.nih.gov/pubmed/20542468?dopt=AbstractPlus

122. Nissen SE. Angiotensin-receptor blockers and cancer: urgent regulatory review needed. Lancet Oncol. 2010; 11:605-6. http://www.ncbi.nlm.nih.gov/pubmed/20542469?dopt=AbstractPlus

123. Sica DA. Angiotensin receptor blockers and the risk of malignancy: a note of caution. Drug Saf. 2010; 33:709-12. http://www.ncbi.nlm.nih.gov/pubmed/20701404?dopt=AbstractPlus

126. Food and Drug Administration. FDA drug safety communication: No increase in risk of cancer with certain blood pressure drugs-angiotensin receptor blockers (ARBs). Rockville, MD; 2011 Jun 2. Available from FDA website. Accessed 2011 Jun 15. http://www.fda.gov/Drugs/DrugSafety/ucm257516.htm

127. 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. Lancet Oncol. 2011; 12:65-82. http://www.ncbi.nlm.nih.gov/pubmed/21123111?dopt=AbstractPlus

128. ARB Trialists Collaboration. Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals. J Hypertens. 2011; 29:623-35. http://www.ncbi.nlm.nih.gov/pubmed/21358417?dopt=AbstractPlus

129. Pasternak B, Svanström H, Callréus T et al. Use of angiotensin receptor blockers and the risk of cancer. Circulation. 2011; 123:1729-36. http://www.ncbi.nlm.nih.gov/pubmed/21482967?dopt=AbstractPlus

130. Volpe M, Morganti A. 2010 Position Paper of the Italian Society of Hypertension (SIIA): Angiotensin Receptor Blockers and Risk of Cancer. High Blood Press Cardiovasc Prev. 2011; 18:37-40. http://www.ncbi.nlm.nih.gov/pubmed/21612311?dopt=AbstractPlus

131. Siragy HM. A current evaluation of the safety of angiotensin receptor blockers and direct renin inhibitors. Vasc Health Risk Manag. 2011; 7:297-313. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3104607&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/21633727?dopt=AbstractPlus

501. James PA, Oparil S, Carter BL et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311:507-20. http://www.ncbi.nlm.nih.gov/pubmed/24352797?dopt=AbstractPlus

502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC 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). J Hypertens. 2013; 31:1281-357. http://www.ncbi.nlm.nih.gov/pubmed/23817082?dopt=AbstractPlus

503. Go AS, Bauman MA, Coleman King SM et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014; 63:878-85. http://www.ncbi.nlm.nih.gov/pubmed/24243703?dopt=AbstractPlus

504. Weber MA, Schiffrin EL, White WB et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014; 16:14-26. http://www.ncbi.nlm.nih.gov/pubmed/24341872?dopt=AbstractPlus

505. Wright JT, Fine LJ, Lackland DT et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014; 160:499-503. http://www.ncbi.nlm.nih.gov/pubmed/24424788?dopt=AbstractPlus

506. Mitka M. Groups spar over new hypertension guidelines. JAMA. 2014; 311:663-4. http://www.ncbi.nlm.nih.gov/pubmed/24549531?dopt=AbstractPlus

507. Peterson ED, Gaziano JM, Greenland P. Recommendations for treating hypertension: what are the right goals and purposes?. JAMA. 2014; 311:474-6. http://www.ncbi.nlm.nih.gov/pubmed/24352710?dopt=AbstractPlus

508. Bauchner H, Fontanarosa PB, Golub RM. Updated guidelines for management of high blood pressure: recommendations, review, and responsibility. JAMA. 2014; 311:477-8. http://www.ncbi.nlm.nih.gov/pubmed/24352759?dopt=AbstractPlus

511. JATOS Study Group. Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res. 2008; 31:2115-27. http://www.ncbi.nlm.nih.gov/pubmed/19139601?dopt=AbstractPlus

515. Thomas G, Shishehbor M, Brill D et al. New hypertension guidelines: one size fits most?. Cleve Clin J Med. 2014; 81:178-88. http://www.ncbi.nlm.nih.gov/pubmed/24591473?dopt=AbstractPlus

523. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471. http://www.ncbi.nlm.nih.gov/pubmed/23166211?dopt=AbstractPlus

524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240-327. http://www.ncbi.nlm.nih.gov/pubmed/23741058?dopt=AbstractPlus

525. Smith SC, Benjamin EJ, Bonow RO et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011; 124:2458-73. http://www.ncbi.nlm.nih.gov/pubmed/22052934?dopt=AbstractPlus

526. Kernan WN, Ovbiagele B, Black HR et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014; :. http://www.ncbi.nlm.nih.gov/pubmed/24788967?dopt=AbstractPlus

527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 127:e362-425. http://www.ncbi.nlm.nih.gov/pubmed/23247304?dopt=AbstractPlus

528. Pfeffer MA, Swedberg K, Granger CB et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003; 362:759-66. http://www.ncbi.nlm.nih.gov/pubmed/13678868?dopt=AbstractPlus

530. Myers MG, Tobe SW. A Canadian perspective on the Eighth Joint National Committee (JNC 8) hypertension guidelines. J Clin Hypertens (Greenwich). 2014; 16:246-8. http://www.ncbi.nlm.nih.gov/pubmed/24641124?dopt=AbstractPlus

534. Qaseem A, Hopkins RH, Sweet DE et al. Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013; 159:835-47. http://www.ncbi.nlm.nih.gov/pubmed/24145991?dopt=AbstractPlus

535. Taler SJ, Agarwal R, Bakris GL et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis. 2013; 62:201-13. http://www.ncbi.nlm.nih.gov/pubmed/23684145?dopt=AbstractPlus

536. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012: 2: 337-414.

541. Perk J, De Backer G, Gohlke H et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012; 33:1635-701. http://www.ncbi.nlm.nih.gov/pubmed/22555213?dopt=AbstractPlus

543. National Kidney Foundation Kidney Disease Outcomes Quality Initiative. K/DOQI Clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease (2002). From National Kidney Foundation website. http://www.kidney.org/professionals/kdoqi/guidelines_commentaries.cfm

550. US Food and Drug Administration. FDA Drug Safety Communication: new warning and contraindication for blood pressure medicines containing aliskiren (Tekturna). Rockville, MD; 2012 April 20. From FDA website. http://www.fda.gov/Drugs/DrugSafety/ucm300889.htm

701. Ponikowski P, Voors AA, Anker SD et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016; 37:2129-200. http://www.ncbi.nlm.nih.gov/pubmed/27206819?dopt=AbstractPlus

702. McMurray JJ, Packer M, Desai AS et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014; 371:993-1004. http://www.ncbi.nlm.nih.gov/pubmed/25176015?dopt=AbstractPlus

703. Ansara AJ, Kolanczyk DM, Koehler JM. Neprilysin inhibition with sacubitril/valsartan in the treatment of heart failure: mortality bang for your buck. J Clin Pharm Ther. 2016; 41:119-27. http://www.ncbi.nlm.nih.gov/pubmed/26992459?dopt=AbstractPlus

800. Yancy CW, Jessup M, Bozkurt B et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2016; 134:e282-93. http://www.ncbi.nlm.nih.gov/pubmed/27208050?dopt=AbstractPlus

1150. Flynn JT, Kaelber DC, Baker-Smith CM et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017; 140 http://www.ncbi.nlm.nih.gov/pubmed/28827377?dopt=AbstractPlus

1200. Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018; 71:el13-e115. http://www.ncbi.nlm.nih.gov/pubmed/29133356?dopt=AbstractPlus

1201. Bakris G, Sorrentino M. Redefining hypertension - assessing the new blood-pressure guidelines. N Engl J Med. 2018; 378:497-499. http://www.ncbi.nlm.nih.gov/pubmed/29341841?dopt=AbstractPlus

1202. Carey RM, Whelton PK, 2017 ACC/AHA Hypertension Guideline Writing Committee. Prevention, detection, evaluation, and management of high blood pressure in adults: synopsis of the 2017 American College of Cardiology/American Heart Association hypertension guideline. Ann Intern Med. 2018; 168:351-358. http://www.ncbi.nlm.nih.gov/pubmed/29357392?dopt=AbstractPlus

1207. Burnier M, Oparil S, Narkiewicz K et al. New 2017 American Heart Association and American College of Cardiology guideline for hypertension in the adults: major paradigm shifts, but will they help to fight against the hypertension disease burden?. Blood Press. 2018; 27:62-65. http://www.ncbi.nlm.nih.gov/pubmed/29447001?dopt=AbstractPlus

1209. Qaseem A, Wilt TJ, Rich R et al. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017; 166:430-437. http://www.ncbi.nlm.nih.gov/pubmed/28135725?dopt=AbstractPlus

1210. SPRINT Research Group, Wright JT, Williamson JD et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015; 373:2103-16. http://www.ncbi.nlm.nih.gov/pubmed/26551272?dopt=AbstractPlus

1213. Reboussin DM, Allen NB, Griswold ME et al. Systematic review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018; 71:2176-2198. http://www.ncbi.nlm.nih.gov/pubmed/29146534?dopt=AbstractPlus

1214. American Diabetes Association. 9. Cardiovascular disease and risk management: standards of medical care in diabetes 2018. Diabetes Care. 2018; 41:S86-S104. http://www.ncbi.nlm.nih.gov/pubmed/29222380?dopt=AbstractPlus

1215. de Boer IH, Bangalore S, Benetos A et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care. 2017; 40:1273-1284. http://www.ncbi.nlm.nih.gov/pubmed/28830958?dopt=AbstractPlus

1216. Taler SJ. Initial treatment of hypertension. N Engl J Med. 2018; 378:636-644. http://www.ncbi.nlm.nih.gov/pubmed/29443671?dopt=AbstractPlus

1218. Messerli FH, Bangalore S, Bavishi C et al. Angiotensin-converting enzyme inhibitors in hypertension: to use or not to use?. J Am Coll Cardiol. 2018; 71:1474-1482. http://www.ncbi.nlm.nih.gov/pubmed/29598869?dopt=AbstractPlus

1219. Karmali KN, Lloyd-Jones DM. Global risk assessment to guide blood pressure management in cardiovascular disease prevention. Hypertension. 2017; 69:e2-e9. http://www.ncbi.nlm.nih.gov/pubmed/28115516?dopt=AbstractPlus

1220. Cifu AS, Davis AM. Prevention, detection, evaluation, and management of high blood pressure in adults. JAMA. 2017; 318:2132-2134. http://www.ncbi.nlm.nih.gov/pubmed/29159416?dopt=AbstractPlus

1222. Bell KJL, Doust J, Glasziou P. Incremental benefits and harms of the 2017 American College of Cardiology/American Heart Association high blood pressure guideline. JAMA Intern Med. 2018; 178:755-7. http://www.ncbi.nlm.nih.gov/pubmed/29710197?dopt=AbstractPlus

1223. LeFevre M. ACC/AHA hypertension guideline: What is new? What do we do?. Am Fam Physician. 2018; 97(6):372-3. http://www.ncbi.nlm.nih.gov/pubmed/29671534?dopt=AbstractPlus

1224. Brett AS. New hypertension guideline is released. From NEJM Journal Watch website. Accessed 2018 Jun 18. https://www.jwatch.org/na45778/2017/12/28/nejm-journal-watch-general-medicine-year-review-2017

1229. Ioannidis JPA. Diagnosis and treatment of hypertension in the 2017 ACC/AHA guidelines and in the real world. JAMA. 2018; 319(2):115-6. http://www.ncbi.nlm.nih.gov/pubmed/29242891?dopt=AbstractPlus

1232. American Diabetes Association. 10. Microvascular complications and foot care: standards of medical care in diabetes 2018. Diabetes Care. 2018; 41:S105-S118. http://www.ncbi.nlm.nih.gov/pubmed/29222381?dopt=AbstractPlus