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Special Alerts
Angiotensin II Receptor Blockers (ARBs) and Cancer Risk
June 2011
The U.S. Food and Drug Administration (FDA) has notified healthcare providers of the results from an ongoing review of ARB use and cancer risk. In June 2010, a published meta-analysis of 5 clinical trials reported a statistically significant increased risk of developing cancer in patients who received treatment with ARBs compared to those who did not. The FDA has completed a meta-analysis of 31 trials to further investigate the association between ARB use and cancer risk. The results of the FDA meta-analysis, along with other available data, have found no evidence for an increased risk of cancer with ARB use.
For additional information, see http://www.fda.gov/Drugs/DrugSafety/ucm257516.htm
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(val SAR tan)
Generic Available (U.S.)
No
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Alone or in combination with other antihypertensive agents in the treatment of essential hypertension; reduction of cardiovascular mortality in patients with left ventricular dysfunction postmyocardial infarction; treatment of heart failure (NYHA Class II-IV)
Pregnancy Risk Factor
D
Pregnancy Considerations
[U.S. Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. The use of drugs which act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. Use is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. The exposed fetus should be monitored for fetal growth, amniotic fluid volume, and organ formation. Infants exposed in utero should be monitored for hyperkalemia, hypotension, and oliguria.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
It is not known if valsartan is found in breast milk; the manufacturer recommends discontinuing the drug or discontinuing nursing based on the importance of the drug to the mother.
Contraindications
There are no contraindications listed in manufacturer's labeling.
Canadian labeling: Hypersensitivity to valsartan or any component of the formulation
Warnings/Precautions
Boxed warnings:
• Pregnancy: See “Special populations” below.
Concerns related to adverse effects:
• Hyperkalemia: May occur; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use with caution with these agents; monitor potassium closely.
• Hypotension: During the initiation of therapy, hypotension may occur, particularly in patients with heart failure or post-MI patients.
• Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function.
Disease-related concerns:
• Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis.
• Heart failure: Use caution when initiating in heart failure; may need to adjust dose, and/or concurrent diuretic therapy, because of valsartan-induced hypotension. Careful monitoring of BUN, serum creatinine, and potassium is necessary especially if preexisting renal disease exists.
• Hepatic impairment: Use caution in patients with significant hepatic impairment since clearance is significantly reduced.
• Hypovolemia: Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first.
• Renal artery stenosis: Use valsartan with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.
• Renal impairment: Use with caution with pre-existing renal insufficiency and severe renal impairment.
Concurrent drug therapy issues:
• Angiotensin-converting enzyme (ACE) inhibitors: Concurrent use of ACE inhibitors may increase the risk of clinically-significant adverse events (eg, renal dysfunction, hyperkalemia).
Special populations:
• Pediatrics: Canadian labeling: Use is not approved in patients <18 years of age.
• Pregnancy: [U.S. Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
Adverse Reactions
>10%:
Central nervous system: Dizziness (heart failure trials 17%)
Renal: BUN increased >50% (heart failure trials 17%)
1% to 10%:
Cardiovascular: Hypotension (heart failure trials 7%; MI trial 1%), postural hypotension (heart failure trials 2%), syncope (up to >1%)
Central nervous system: Dizziness (hypertension trial 2% to 8%), fatigue (heart failure trials 3%; hypertension trial 2%), postural dizziness (heart failure trials 2%), headache (heart failure trials >1%), vertigo (up to >1%)
Endocrine & metabolic: Serum potassium increased by >20% (4% to 10%), hyperkalemia (heart failure trials 2%)
Gastrointestinal: Diarrhea (heart failure trials 5%), abdominal pain (2%), nausea (heart failure trials >1%), upper abdominal pain (heart failure trials >1%)
Hematologic: Neutropenia (2%)
Neuromuscular & skeletal: Arthralgia (heart failure trials 3%), back pain (up to 3%)
Ocular: Blurred vision (heart failure trials >1%)
Renal: Creatinine doubled (MI trial 4%), creatinine increased >50% (heart failure trials 4%), renal dysfunction (up to >1%)
Respiratory: Cough (1% to 3%)
Miscellaneous: Viral infection (3%)
All indications: <1%, postmarketing, and/or case reports: Allergic reactions, alopecia, anaphylaxis, anemia, angioedema, anorexia, anxiety, chest pain, constipation, dyspepsia, dyspnea, flatulence, hematocrit/hemoglobin decreased, hepatitis, impotence, insomnia, liver function tests increased, microcytic anemia, muscle cramps, myalgia, palpitation, paresthesia, photosensitivity, pruritus, rash, rhabdomyolysis, somnolence, taste disorder, thrombocytopenia, vasculitis, vomiting, weakness, xerostomia
Metabolism/Transport Effects
Substrate of SLCO1B1; Inhibits CYP2C9 (weak)
Drug Interactions
ACE Inhibitors: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Management: According to eltrombopag prescribing information, consideration of a preventative dose reduction may be warranted. Risk D: Consider therapy modification
Eplerenone: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hydrochlorothiazide: May enhance the hypotensive effect of Valsartan. Valsartan may increase the serum concentration of Hydrochlorothiazide. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Lithium: Angiotensin II Receptor Blockers may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an angiotensin II receptor antagonist. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Potassium-Sparing Diuretics: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Sodium Phosphates: Angiotensin II Receptor Blockers may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ARBs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Trimethoprim: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Decreases the peak plasma concentration and extent of absorption by 50% and 40%, respectively. Potassium supplements and/or potassium-containing salts may cause or worsen hyperkalemia. Management: Take consistently with regard to food. Consult prescriber before consuming a potassium-rich diet, potassium supplements, or salt substitutes.
Herb/Nutraceutical: Some herbal medications may worsen hypertension (eg, licorice); others may increase the antihypertensive effect of valsartan (eg, shepherd's purse). Management: Avoid bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (American), kola, licorice, and yohimbe. Avoid black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, and shepherd's purse.
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.
Mechanism of Action
Valsartan produces direct antagonism of the angiotensin II (AT2) receptors, unlike the ACE inhibitors. It displaces angiotensin II from the AT1 receptor and produces its blood pressure-lowering effects by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses. This action results in more efficient blockade of the cardiovascular effects of angiotensin II and fewer side effects than the ACE inhibitors.
Pharmacodynamics/Kinetics
Onset of action: ~2 hours
Duration: 24 hours
Distribution: Vd: 17 L (adults)
Protein binding: 95%, primarily albumin
Metabolism: To inactive metabolite
Bioavailability: Tablet: 25% (range: 10% to 35%); suspension: ~40% (~1.6 times more than tablet)
Half-life elimination: ~6 hours
Time to peak, serum: 2-4 hours
Excretion: Feces (83%) and urine (13%) as unchanged drug
Dosage
Oral:
Hypertension:
Children 6-16 years: Initial: 1.3 mg/kg once daily (maximum: 40 mg/day); dose may be increased to achieve desired effect; doses >2.7 mg/kg (maximum: 160 mg) have not been studied
Adults: Initial: 80 mg or 160 mg once daily (in patients who are not volume depleted); dose may be increased to achieve desired effect; maximum recommended dose: 320 mg/day
Heart failure: Adults: Initial: 40 mg twice daily; titrate dose to 80-160 mg twice daily, as tolerated; maximum daily dose: 320 mg
Left ventricular dysfunction after MI: Adults: Initial: 20 mg twice daily; titrate dose to target of 160 mg twice daily as tolerated; may initiate ≥12 hours following MI
Dosing adjustment in renal impairment:
Children: Use is not recommended if Clcr <30 mL/minute.
Adults: No dosage adjustment necessary if Clcr >10 mL/minute.
Dialysis: Not significantly removed
Dosing adjustment in hepatic impairment In mild-to-moderate liver disease no adjustment is needed. Use caution in patients with liver disease. Patients with mild-to-moderate chronic disease have twice the exposure as healthy volunteers.
Administration: Oral
Administer with or without food.
Monitoring Parameters
Baseline and periodic electrolyte panels, renal function, BP; in CHF, serum potassium during dose escalation and periodically thereafter
Dietary Considerations
Avoid salt substitutes which contain potassium. May be taken with or without food.
Patient Education
This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. May cause dizziness, lightheadedness, postural hypotension, or diarrhea. Report changes in urinary pattern, swelling of extremities, unusual back ache, chest pain or palpitations, unrelenting headache, or unusual cough.
Geriatric Considerations
No dosage adjustment is necessary when initiating angiotensin II receptor antagonists in the elderly. In clinical studies, no differences between younger adults and elderly were demonstrated. Many elderly may be volume depleted due to diuretic use and/or blunted thirst reflex resulting in inadequate fluid intake.
Additional Information
Valsartan may have an advantage over losartan due to minimal metabolism requirements and consequent use in mild-to-moderate hepatic impairment.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: In patients on chronic angiotensin receptor blocker (ARB) therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; however, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent. Episodes of intraoperative hypotension may be managed by fluid administration and/or modest doses of alpha-adrenergic agents. If discontinued preoperatively, reinstitute when patient is hemodynamically stable. Patients who have undergone coronary artery bypass graft (CABG) surgery should have therapy reinstituted once the patient is stable or initiated in those who were not receiving ACE inhibition prior to CABG surgery; continue indefinitely (Hillis, 2011).
Cardiovascular Considerations
Heart Failure: Currently, the use of angiotensin II receptor blockers (ARBs) should not supersede angiotensin converting enzyme inhibitors (ACEIs) in the treatment of heart failure. One may be considered, however, when an ACEI cannot be tolerated. Because they are angiotensin II blockers rather than inhibitors of ACE, ARBs do not cause increases in bradykinin levels. ELITE II (Pitt, 2000) compared losartan (50 mg/day) with captopril (150 mg/day) in a heart failure population (mean EF 31%). There were 280 deaths in the losartan group and 250 in the captopril group. Mortality was insignificantly higher for losartan (17.7% vs 16% for captopril). The secondary endpoint (sudden cardiac death or resuscitated cardiac arrest) favored captopril, but the improvement did not achieve statistical significance. The discontinuation rate for adverse events was significantly lower for losartan. In the doses used, losartan appears to be less effective or as effective as captopril.
CHARM-Alternative is a prospective, randomized trial (Granger, 2003) in ACE inhibitor intolerant patients with HF. Patients were randomized to candesartan (target dose: 32 mg/day; mean dose at 6 months: 23 mg/day) or placebo. Baseline characteristics included NYHA Class II or III (97% of patients), and mean LVEF 30%. Therapy included beta-blocker (55%), diuretic (86%), spironolactone (24%), and digitalis (46%). During a 33-month follow up, the combined primary endpoint (CV death or heart failure hospitalizations) was significantly reduced in the candesartan group mainly because of reduced hospitalization. Death due to cardiovascular disease was not significantly different. There were significantly more MIs (75) in the candesartan group than in the placebo group (48). Candesartan was discontinued because of hypotension, renal dysfunction, and hyperkalemia.
Heart Failure: Concomitant ACE-I Therapy: The Val-HeFT study (Cohn, 2001) randomized HF patients maintained on standard therapy to valsartan (320 mg/day; mean dose 254 mg/day) or placebo. The primary outcome was mortality and a combined endpoint of morbidity and mortality (cardiac arrest, hospitalization for HF, need for intravenous inotrope or vasodilator). Patients (5010 in number) with predominately NYHA class II or III heart failure (85% on diuretic; 67% on digoxin; 35% on beta-blocker; ~93% on ACEI; 5% on spironolactone) were randomized to valsartan or placebo. The mean duration of follow-up was 23 months. Overall mortality was similar in both groups. The incidence of combined endpoints was lower with valsartan than placebo (p=.009) primarily because of decreased heart failure hospitalizations in the valsartan group. In a post hoc analysis of the endpoints in subgroups defined by baseline treatments (ACEI or beta-blockers), valsartan had a positive effect on patients receiving neither or one of these drugs. A higher incidence of mortality was seen in patients receiving valsartan in combination with an ACEI and a beta-blocker.
The CHARM-Added trial is a prospective, randomized trial (McMurray, 2003) evaluating the addition of candesartan therapy (target dose: 32 mg/day; mean dose at 6 months: 24 mg/day) to HF patients maintained on an ACEI. Baseline characteristics: NYHA class II (24%), class III (73%), and mean LVEF 28%. Baseline therapy was similar to CHARM-Alternative except all patients were maintained on an ACEI and ~55% were on a beta-blocker. The median duration of follow-up was 41 months. The combined primary endpoint (CV death or heart failure hospitalizations) was significantly reduced in the candesartan group.
Hypertension: According to the 2003 JNC 7 guidelines for the treatment of hypertension, most patients with hypertension will require treatment with at least 2 antihypertensives. First-line therapy for hypertension is a diuretic (eg, hydrochlorothiazide or chlorthalidone). When a diuretic cannot be used or when a compelling indication exists for another drug, other types of antihypertensives may be used (eg, ACEIs, ARBs, beta-blockers, CCBs). Angiotensin II receptor blockers are among the multiple choices of agents that have shown benefit in a number of different patient subtypes. Compelling indications for an ARB include patients with heart failure, diabetes, or chronic kidney disease. The LIFE trial (Dahlof, 2002) confirmed that ARB (losartan 50-100 mg daily) was better tolerated than a beta-blocker (atenolol), and resulted in significant reduction in mortality, angina, or HF hospitalization (primary endpoint). Stroke and new-onset diabetes were significantly reduced in the losartan treatment group.
Treatment should be targeted to a goal blood pressure of <140/90 mm Hg. If diabetes or renal disease coexists, the blood pressure goal should be <130/80 mm Hg.
Myocardial Infarction: The 2004 ACC/AHA STEMI guidelines suggest an angiotensin receptor blocker should be administered to STEMI patients who are intolerant of ACE inhibitors and who have either clinical or radiological signs of heart failure or LVEF <0.4. The OPTIMAAL trial evaluated whether losartan (50 mg/day) would be superior or noninferior to captopril (150 mg/day) in post-MI patients. They were randomized to one of two treatments and followed up for 2.7 years. There was no difference between the two treatment groups (499 deaths in losartan group; 447 deaths in the captopril-treated group). The VALIANT trial compared the effects of valsartan, captopril, and the combination in patients who had suffered a recent MI (0.5 to 10 days prior) complicated by left ventricular systolic dysfunction (Pfeffer, 2003). The primary endpoint was mortality from any cause. Mortality in the valsartan group and the valsartan-captopril group was similar to the captopril group alone. Valsartan was found to be noninferior to captopril in this patient population. Combining valsartan with captopril increased the rate of adverse events without improving survival. Hypotension and renal dysfunction were more common in the valsartan group. Cough, rash, and taste disturbances were more common in the captopril group.
Cautions: ARB therapy may elicit an increase in potassium and creatinine, especially when used in patients with bilateral renal artery stenosis. Severe hypotension may occur in patients who are sodium- and/or volume-depleted; initiate lower doses and monitor closely when starting therapy in these patients. Concomitant NSAID therapy may attenuate blood pressure control; use of NSAIDs should be avoided or limited, with monitoring of blood pressure control. In the setting of heart failure, NSAID use may be associated with an increased risk for fluid accumulation and edema. Because of the lack of effect on the response to bradykinin, angiotensin receptor blockers are less likely to be associated with nonrenin-angiotensin effects such as cough and angioedema. The angiotensin II antagonists do not cause increases in levels of bradykinin as the ACEIs do.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness or drowsiness
Mental Health: Effects on Psychiatric Treatment
May rarely cause neutropenia; use caution with clozapine and carbamazepine; barbiturates and carbamazepine may increase the metabolism of valsartan. May also decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels.
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions with other pharmacological agents and herbal products (eg, concurrent use of potassium supplements, ACE inhibitors, potassium-sparing diuretics may increase risk of hyperkalemia). Monitor for changes in renal function, dizziness, cough, headache, nausea, hypotension, and hyperkalemia.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral:
Diovan®: 40 mg [scored]
Diovan®: 80 mg, 160 mg, 320 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Diovan)
40 mg (30): $89.99
80 mg (30): $100.99
160 mg (30): $106.99
320 mg (30): $131.99
Extemporaneously Prepared
A 4 mg/mL oral suspension may be made from tablets, Ora-Plus®, and Ora-Sweet® SF. Add 80 mL of Ora-Plus® to an 8-ounce amber glass bottle containing eight valsartan 80 mg tablets. Shake well for ≥2 minutes. Allow the suspension to stand for a minimum of 1 hour, then shake for ≥1 minute. Add 80 mL of Ora-Sweet SF® to the bottle and shake for ≥10 seconds. Store in amber glass prescription bottles; label "shake well". Stable for 30 days at room temperature or 75 days refrigerated.
Diovan® prescribing information, Novartis Pharmaceuticals Corp, East Hanover, NJ, 2007.
References
American Diabetes Association, “Standards of Medical Care in Diabetes Mellitus -- 2012,” Diabetes Care, 2012, 35(Suppl ):11-63.
Anderson JL, Adams CD, Antman EM, et al, “ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration With the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine,” J Am Coll Cardiol, 2007, 50(7):e1-e157.
Antman EM, Anbe SC, Alpert JS, et al, “ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction),” Circulation, 2004, 110(5):588-636.
Antman EM, Hand M, Armstrong PW, et al, “2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines,” J Am Coll Cardiol, 2008, 51(2):210-49.
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Cohn JN and Tognoni G, “Valsartan Heart Failure Trial Investigators. A Randomized Trial of the Angiotensin-Receptor Blocker Valsartan in Chronic Heart Failure,” N Engl J Med, 2001, 345(23):1667-75.
Conlin P, Moore T, Swartz S, et al, “Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients,” Hypertension, 2000, 36(3):461-5.
Dahlof 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,” Lancet, 2002, 359(9311):995-1003.
Dickstein K and Kjekshus J, “Effects of Losartan and Captopril on Mortality and Morbidity in High-Risk Patients After Acute Myocardial Infarction: The OPTIMAAL Randomised Trial. Optimal Trial in Myocardial Infarction With Angiotensin II Antagonist Losartan,” Lancet, 2002, 360(9335):752-60.
Epstein BJ and Gums JG, “Angiotensin Receptor Blockers Versus ACE Inhibitors: Prevention of Death and Myocardial Infarction in High-Risk Populations,” Ann Pharmacother, 2005, 39(3):470-80.
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(9386):772-6.
Hillis LD, Smith PK, Anderson JL, et al, “2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines,” Circulation, 2011, 124(23):2610-42.
Hunt SA, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-e90.
“K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Kidney Disease Outcome Quality Initiative,” Am J Kidney Dis, 2002, 39(2 Suppl 2):1-246. Available at http://www.kidney.org/professionals/KDOQI/guidelines_ckd/toc.htm
Lindenfeld J, Albert NM, Boehmer JP, et al, “HFSA 2010 Comprehensive Heart Failure Practice Guideline,” J Card Fail, 2010, 16(6):e1-194.
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(9386):767-71.
Pfeffer MA, McMurray JJ, Velazquez EJ, et al, “Valsartan, Captopril, or Both in Myocardial Infarction Complicated by Heart Failure, Left Ventricular Dysfunction, or Both,” N Engl J Med, 2003, 349(20):1893-1906.
Pitt B, Poole-Wilson PA, Segal R, et al, “Effect of Losartan Compared With Captopril on Mortality in Patients With Symptomatic Heart Failure: Randomised Trial - The Losartan Heart Failure Survival Study ELITE II,” Lancet, 2000, 355(9215):1582-7.
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(7):627-36.
Smith SC Jr, 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(22):2458-73.
International Brand Names
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Last full review/revision March 2012
Content last modified March 2012
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