Class: Angiotensin-Converting Enzyme Inhibitors
VA Class: CV800
Chemical Name: [2S - [1[R*(R*)],2α,3aβ,6aβ]] - 1 - [2 - [[1 - (Ethoxycarbonyl) - 3 - phenylpropyl]amino] - 1 - oxopropy l]octahydrocylopenta[b]pyrrole-2-carboxylic acid
Molecular Formula: C21H28N2O5
CAS Number: 87333-19-5
Brands: Altace
May cause fetal and neonatal morbidity and mortality if used during pregnancy.1 38 39 40 41 42 43 44 45 46 88 89 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
If pregnancy is detected, discontinue ramipril as soon as possible.1 89
Introduction
Nonsulfhydryl ACE inhibitor.1 2 3
Uses for Ramipril
Hypertension
Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 4 11 38
One of several preferred initial therapies in hypertensive patients with heart failure, postmyocardial infarction, high coronary disease risk, diabetes mellitus, chronic renal failure, and/or cerebrovascular disease.69
Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.69
CHF after AMI
Reduction of the risk of mortality in hemodynamically stable patients who have demonstrated clinical signs of CHF within a few days following AMI.1 2 12 18 21 24 27 28 62 Also may reduce rate of heart failure-associated hospitalization and progression to severe and/or resistant heart failure.1 2 12 18 21 24 27 28 62
Prevention of Cardiovascular Events
Reduction of the risk of cardiovascular death, MI, and stroke in patients ≥55 years of age who are at high risk for cardiovascular events (e.g., those with a history of CAD, stroke, peripheral vascular disease, or diabetes mellitus in addition to ≥1 other cardiovascular risk factor [e.g., hypertension, elevated total cholesterol and/or decreased HDL-cholesterol concentrations, smoking, documented microalbuminuria]) but who are not known to have low ventricular ejection fraction or heart failure.1 47 48
Reduction in the incidence of diabetic complications and in new diagnosis of diabetes also reported.47 48
CHF
Management of symptomatic CHF†, usually in conjunction with cardiac glycosides, diuretics, and β-blockers.62 70 71 72 73 74
Diabetic Nephropathy
A first-line agent in the treatment of diabetic nephropathy† in hypertensive patients with type 2 diabetes mellitus.78 79
Ramipril Dosage and Administration
Administration
Oral Administration
Administer orally once or twice daily.1
Swallow capsules whole.1 Alternatively, open capsules and sprinkle contents on small amount (about 4 oz) of applesauce or mix in 120 mL of water or apple juice.1 Consume entire mixture to ensure that no drug is lost.1 (See Storage under Stability.)
Dosage
Adults
Hypertension
Oral
Initially, 1.25–2.5 mg once daily in patients not receiving diuretic therapy.1 2 3 11 38 Adjust dosage at approximately monthly intervals (more aggressively in high-risk patients) to achieve BP control.1
In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating ramipril.1 May cautiously resume diuretic therapy if BP not controlled adequately with ramipril alone.1 If diuretic cannot be discontinued, increase sodium intake or initiate ramipril at 1.25 mg daily under close medical supervision.1
Usual dosage: 2.5–20 mg daily,69 given in 1 dose or 2 divided doses.1 11 38
If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in 2 divided doses.1 38
CHF after MI
Oral
Initially, 2.5 mg twice daily, beginning as early as 2 days after MI.1 12 If hypotension occurs, reduce dosage to 1.25 mg twice daily.1 After 1 week at initial dosage, adjust dosage as tolerated at 3-week intervals to target dosage of 5 mg twice daily.1 1
Following initial dose, monitor closely for ≥2 hours and until BP has stabilized for at least an additional hour.1 To minimize risk of hypotension, reduce diuretic dosage, if possible.1
Prevention of Cardiovascular Events
Oral
Initially, 2.5 mg once daily for 1 week, followed by 5 mg once daily for 3 weeks; subsequently increase dosage as tolerated to maintenance dosage of 10 mg once daily.1 In patients with hypertension or those with recent MI, may administer total daily dosage in divided doses.1
Special Populations
Renal Impairment
Initial dosage of 1.25 mg once daily recommended in patients with renal artery stenosis.1
In patients with Clcr <40 mL/minute per 1.73 m2, 25% of the usual doses are expected to induce full therapeutic concentrations of ramiprilat.1
Hypertension
Oral
Initially, 1.25 mg once daily in patients with Clcr <40 mL/minute per 1.73 m2.1 Titrate until BP is controlled or to maximum dosage of 5 mg daily.1
CHF after MI
Oral
Initially, 1.25 mg once daily in patients with Clcr <40 mL/minute per 1.73 m2.1 May increase dosage to 1.25 mg twice daily; subsequently titrate according to clinical response and tolerance up to maximum dosage of 2.5 mg twice daily.1
Volume-and/or Salt-Depleted Patients
Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy at dosage of 1.25 mg once daily.1
Cautions for Ramipril
Contraindications
Warnings/Precautions
Warnings
Hepatic Effects
Clinical syndrome that usually is manifested initially by cholestatic jaundice and may progress to fulminant hepatic necrosis (occasionally fatal) reported rarely with ACE inhibitors.1
If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.1
Hypotension
Possible symptomatic hypotension, particularly in volume- and/or salt depleted patients (e.g., those receiving prolonged diuretic therapy or undergoing dialysis, those with dietary salt restriction, patients with diarrhea or vomiting).1 Risk of excessive hypotension, sometimes associated with oliguria, azotemia, and, rarely, acute renal failure and death in patients with CHF with or without associated renal insufficiency.1
Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.1
To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical circumstances.1 Correct volume and/or salt depletion (e.g., by withholding diuretic therapy, increasing sodium intake) prior to initiation of ramipril or reduce initial dosage.1 (See Dosage and also Special Populations, under Dosage and Administration.)
In patients at risk of excessive hypotension, initiate therapy under close medical supervision; monitor closely for first 2 weeks following initiation of ramipril or any increase in ramipril or diuretic dosage.1
If hypotension occurs, place patient in supine position, and if necessary, administer IV infusion of physiological saline.1 Ramipril therapy usually can be continued following restoration of volume and BP.1
Hematologic Effects
Neutropenia and agranulocytosis reported with captopril; risk appears to depend principally on presence of renal impairment and/or presence of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma);1 also reported in patients receiving immunosuppressive therapy.5 6 Hematologic effects (e.g., agranulocytosis; pancytopenia; bone marrow depression; reductions in hemoglobin content or leukocyte, erythrocyte, or platelet counts) reported rarely with ramipril.1
Consider monitoring leukocytes in patients with collagen vascular disease, especially if renal impairment exists.1
Fetal/Neonatal Morbidity and Mortality
Possible fetal and neonatal morbidity and mortality when used during pregnancy.1 88 89 (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.89
Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.88 89
Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.89 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.44 46
Sensitivity Reactions
Anaphylactoid reactions and/or head and neck angioedema possible; if associated with laryngeal edema, may be fatal.1 Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.1
Intestinal angioedema possible; consider in differential diagnosis of patients who developabdominal pain.1
Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption or following initiation of hemodialysis that utilized high-flux membrane.1
Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.1
Contraindicated in patients with a history of angioedema associated with ACE inhibitors.1 47 Patients with history of angioedema unrelated to ACE inhibitors may be at increased risk of angioedema associated with ACE inhibitor therapy.1
General Precautions
Renal Effects
Transient increases in BUN and Scr possible, especially in patients with preexisting renal impairment or those receiving concomitant diuretic therapy.1 Possible increases in BUN and Scr in patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of ramipril and/or diuretic therapy.1
Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe CHF.1
Closely monitor renal function for the first few weeks of therapy in hypertensive patients with unilateral or bilateral renal-artery stenosis.1 Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic therapy.1
Hyperkalemia
Possible hyperkalemia, especially in patients with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).1 (See Interactions.)
Cough
Persistent and nonproductive cough; resolves after drug discontinuance.1
Specific Populations
Pregnancy
Category C (1st trimester); Category D (2nd and 3rd trimesters).1 (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)
Lactation
Undetectable in human milk following single oral dose; not known whether distributed into milk following multiple doses.1 Use not recommended.1
Pediatric Use
Safety and efficacy not established in children <18 years of age.1
Geriatric Use
No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1
Hepatic Impairment
Use with caution in patients with cirrhosis and/or ascites, due to possible increased activity of renin-angiotensin-aldosterone system.1
Possible marked increase in plasma ramipril concentrations; peak plasma ramiprilat concentrations not appreciably altered. (See Absorption: Special Populations, under Pharmacokinetics.)1
Renal Impairment
Systemic exposure to ramiprilat may be increased.1 (See Pharmacokinetics.) Initial dosage adjustment may be necessary depending on degree of renal impairment.1 (See Renal Impairment under Dosage and Administration.)
Deterioration of renal function may occur.1 (See Renal Effects under Cautions.)
Blacks
BP reduction may be smaller in black patients compared with nonblack patients;1 14 15 67 68 however, no apparent population difference during combined therapy with ACE inhibitor and thiazide diuretic.11 14 16 17 38 Use in combination with a diuretic.11 14 16 17 38
Higher incidence of angioedema reported with ACE inhibitors in blacks compared with other races.1 68 69
Common Adverse Effects
Patients with hypertension: Headache, dizziness, fatigue.1
Patients with CHF: Dizziness, cough, nausea, vomiting, angina pectoris, syncope, postural hypotension, vertigo, hypotension.1
Interactions for Ramipril
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
Antacid
|
Pharmacokinetic interaction unlikely1
|
|
Antidiabetic agents (insulin, oral agents)
|
Possible hypoglycemia in diabetic patients1
|
Monitor closely for symptoms of hypoglycemia following initiation or dosage adjustment of ramipril; adjust dosage of antidiabetic agent as necessary1
|
Cimetidine
|
Pharmacokinetic interaction unlikely1
|
|
Digoxin
|
Pharmacokinetic interaction unlikely1
|
|
Diuretics
|
Increased hypotensive effect1
|
If possible, discontinue diuretic before initiating ramipril1 (see Dosage and also Special Populations, under Dosage and Administration)
|
Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)
|
Enhanced hyperkalemic effect1
|
Use with caution; monitor serum potassium concentrations frequently1
|
Lithium
|
Increased serum lithium concentrations; possible toxicity1
|
Use with caution; monitor serum lithium concentrations frequently1
|
NSAIAs
|
Potential for reduction of renal function and increase in serum potassium1
No interaction observed with indomethacin1
|
|
Potassium supplements or potassium-containing salt substitutes
|
Enhanced hyperkalemic effect1
|
Use with caution; monitor serum potassium concentrations frequently1
|
Simvastatin
|
Pharmacokinetic interaction unlikely1
|
|
Warfarin
|
Pharmacologic interaction unlikely1
|
|
Ramipril Pharmacokinetics
Absorption
Bioavailability
Following oral administration, peak plasma concentrations of ramipril usually attained within 1 hour.1 Peak plasma concentrations of ramiprilat attained within 2–4 hours after oral dose.1 About ≥50–60% of an oral dose is absorbed.1
Onset
Following multiple oral doses (≥2 mg), >90% inhibition of plasma ACE activity achieved 4 hours after dosing.1
Duration
Following multiple oral doses (≥2 mg), inhibition of >80% of plasma ACE activity persists for about 24 hours.1
Food
Food decreases rate but not extent of absorption.1 Opening the capsules and sprinkling the contents on applesauce or mixing the contents in apple juice does not alter serum concentrations of ramiprilat.1 (See Oral Administration under Dosage and Administration.)
Special Populations
In patients with hepatic impairment, plasma concentrations of ramipril are increased; peak plasma ramiprilat concentrations are similar to those in individuals with normal hepatic function.1
In patients with renal impairment (Clcr <40 mL/minute per 1.73m2), plasma concentrations and AUC of ramiprilat are increased, and time to peak plasma ramiprilat concentrations is slightly prolonged.1
Distribution
Extent
Distributes into a large peripheral compartment.1 Crosses the placenta.1 Undetectable in human milk following single oral dose; not known whether distributed into milk following multiple doses.1
Plasma Protein Binding
Ramipril: About 73%.1
Ramiprilat: About 56%.1
Elimination
Metabolism
Metabolized mainly in the liver, principally to an active metabolite, ramiprilat.1
Elimination Route
Excreted in urine (60%) as unchanged drug and ramiprilat and in feces (approximately 40%).1
Half-life
Triphasic; apparent elimination half-life of ramiprilat: Approximately 13–17 hours.1
Special Populations
In patients with Clcr <40 mL/minute per 1.73m2, urinary excretion of ramipril, ramiprilat, and their metabolites is decreased.1
Stability
Storage
Oral
Capsules
15–30 ºC.1
Mixtures of ramipril with applesauce, water, or apple juice (see Oral Administration under Dosage and Administration) are stable for 24 hours at room temperature and 48 hours when refrigerated.1
ActionsActions
Advice to Patients
Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions.1 47 Importance of reporting sensitivity reactions (e.g., edema of face, eyes, lips, tongue, larynx, or extremities; hoarseness; swallowing or breathing with difficulty) immediately to clinician and of discontinuing the drug.1
Importance of reporting signs of infection (e.g., sore throat, fever).1
Risk of hypotension.1 Importance of informing clinicians promptly if lightheadedness or fainting occurs.1
Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.1
Risks of use during pregnancy.1 88 89 (See Boxed Warning.)
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of advising patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Ramipril
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Oral
|
Capsules
|
1.25 mg*
|
Altace
|
Monarch
|
|
|
|
Ramipril Capsules
|
Cobalt
|
|
|
2.5 mg*
|
Altace
|
Monarch
|
|
|
|
Ramipril Capsules
|
Cobalt
|
|
|
5 mg*
|
Altace
|
Monarch
|
|
|
|
Ramipril Capsules
|
Cobalt
|
|
|
10 mg*
|
Altace
|
Monarch
|
|
|
|
Ramipril Capsules
|
Cobalt
|
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Altace 1.25MG Capsules (MONARCH PHARMACEUTICALS): 30/$67.99 or 90/$185.97
Altace 10MG Capsules (MONARCH PHARMACEUTICALS): 30/$85.99 or 90/$239.95
Altace 2.5MG Capsules (MONARCH PHARMACEUTICALS): 30/$76.99 or 90/$211.97
Altace 5MG Capsules (MONARCH PHARMACEUTICALS): 30/$75.99 or 90/$209.97
Ramipril 10MG Capsules (WATSON LABS): 30/$65.99 or 90/$179.97
Ramipril 2.5MG Capsules (WATSON LABS): 30/$49.99 or 90/$139.97
Ramipril 5MG Capsules (WATSON LABS): 30/$55.99 or 90/$149.99
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
1. Monarch. Altace (ramipril) capsules prescribing information. Kansas City, MO; 2005 Sep.
2. Frampton JE, Peters DH. Ramipril: an updated review of its therapeutic use in essential hypertension and heart failure. Drugs. 1995;49:440-466.
3. Anon. Three new ACE inhibitors for hypertension. Med Lett Drugs Ther. 1991; 33:83-4. [PubMed 1831531]
4. McAreavey D, Robertson JI. Angiotensin converting enzyme inhibitors and moderate hypertension. Drugs. 1990; 40:326-45. [PubMed 2226219]
5. Squibb. Capoten (captopril) tablets prescribing information. In: Physician’s desk reference. 47th ed. Montvale, NJ: Medical Economics Company Inc; 1993:2356-62.
6. Reviewers’ comments on Enalaprilat/Enalapril 24:32.04 (personal observations).
7. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Ann Intern Med. 1984; 144:1045-57.
8. Anon. Drugs for hypertension. Med Lett Drugs Ther. 1984; 26:107-12. [PubMed 6150424]
9. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988; 148:1023-38. [IDIS 242588] [PubMed 3365073]
10. US Food and Drug Administration. Dangers of ACE inhibitors during second and third trimesters of pregnancy. FDA Med Bull. 1992; 22:2.
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. [IDIS 309043] [PubMed 8422206]
12. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 1993; 342:821-8. [IDIS 320478] [PubMed 8104270]
13. 1988 Joint National Committee. The 1988 report of the Joint National Committee on detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988; 148:1023-38. [IDIS 242588] [PubMed 3365073]
14. Saunders E. Tailoring treatment to minority patients. Am J Med. 1990; 88(Suppl 3B):21-23S. [PubMed 2294761]
15. Chrysant SG, Danisa K, Kem DC et al. Racial differances in pressure, volume and renin interrelationships in essential hypertension. Hypertension. 1979; 1:136-41. [PubMed 399939]
16. Holland OB, Kuhnert L, Campbell WB et al. Synergistic effect of captopril with hydrochlorothiazide for the treatment of low-renin hypertensive black patients. Hypertension. 1983; 5:235-9. [PubMed 6337951]
17. Ferguson RK, Vlasses PH, Rotmesch HH. Clinical applications of angiotensin-enzyme inhibitors. Am J Med. 1984; 77:690-8. [IDIS 191617] [PubMed 6091446]
18. LeJemtel TH, Hochman JS, Sonnenblick EH. Indications for immedicate angiotensin-converting enzyme inhibition in patients with acute myocardial infarction. J Am Coll Cardiol. 1995; 25(Suppl):47-51S. [PubMed 7798525]
19. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate single and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet. 1994; 343:1115-22. [IDIS 329049] [PubMed 7910229]
20. Ambrosioni E, Borghi C, Magnani B for the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators. The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. N Engl J Med. 1995; 332:80-5. [IDIS 340649] [PubMed 7990904]
21. Ball SG, Hall AS, Murray GD. Angiotensin-converting enzyme inhibitors after myocardial infarction: indications and timing. J Am Coll Cardiol. 1995; 25(Suppl):42-6S.
22. ISIS-4 Collaborative Group. Fourth international study of infarct survival: protocol for a large simple study of the effects of oral mononitrate, of oral captopril, and of intravenous magnesium. Am J Cardiol. 1991; 68:87-100D.
23. Simoons ML. Myocardial infarction: ACE inhibitors for all? for ever? Lancet. 1994; 344:279-81. Editorial.
24. Anon. An ACE inhibitor after a myocardial infarction. Med Lett Drugs Ther. 1994; 36:69-70. [PubMed 8035753]
25. Ertl G, Jugdutt B. ACE inhibition after myocardial infarction: can megatrials provide answers? Lancet. 1994; 344:1068-9.
26. Ertl G. Angiotensin converting enzyme inhibitors in angina and myocardial infarction: what role will they play in the 1990s? Drugs. 1993; 46:209-18.
27. Purcell H, Coats A, Fox K et al. Improving outcome after acute myocardial infarction: what is the role of ACE inhibitors? Br J Clin Pract. 1995; 49:195-9. (IDIS 349780)
28. Ball SG, Hass AS. What to expect from ACE inhibitors after myocardial infarction. Br Heart J. 1994; 72(Suppl):S70-4.
29. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assesssing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction. Lancet. 1995; 345:669-85. [PubMed 7661937]
30. Chinese Cardiac Study Collaborative Group. Oral captopril versus placebo among 13 634 patients with suspected acute myocardial infarction: interim report from the Chinese Cardiac Study (CCS-1). Lancet. 1995; 345:686-7. [IDIS 344925] [PubMed 7885123]
31. Cohn JN. The prevention of heart failure—a new agenda. N Engl J Med. 1992; 327:725-7. [IDIS 301135] [PubMed 1495526]
32. Pfeffer MA, Braunwald E, Moyé LA et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1992; 327:669-77. [IDIS 301129] [PubMed 1386652]
33. Swedberg K, Held P, Kjekshus J et al. Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction: results of the Cooperative New Scandinavian enalapril survival study II (Consensus II). N Engl J Med. 1992; 327:678-84. [IDIS 301130] [PubMed 1495520]
34. Sharpe N, Smith H, Murphy J et al. Early prevention of left ventricular dysfunction after myocardial infarction with angiotensin-converting-enzyme inhibition. Lancet. 1991; 337:872-6. [IDIS 279768] [PubMed 1672967]
35. Oldroyd KG, Pye MP, Ray SG et al. Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction. Am J Cardiol. 1991; 68:713-8. [IDIS 288996] [PubMed 1892076]
36. Sharpe N, Murphy J, Smith H et al. Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Lancet. 1988; 1:255-9. [IDIS 238337] [PubMed 2893080]
37. Pfeffer MA, Lamas GA, Vaughan DE et al. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med. 1988; 319:80-6. [IDIS 243316] [PubMed 2967917]
38. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)
39. Rey E, LeLorier J, Burgess E et al. Report of the Canadian Hypertension Society consensus conference: 3. pharmacologic treatment of hypertensive disorders in pregnancy. CMAJ. 1997; 157:1245-54. [IDIS 396283] [PubMed 9361646]
40. American College of Obstetricians and Gynecologists. ACOG technical bulletin No. 219: hypertension in pregnancy. 1996 Jan.
41. Hanssens M, Keirse MJ, Van Assche FA. Fetal and neonatal effects of treatment with angiotensin-converting enzyme inhibitors in pregnancy. Obstet Gynecol. 1991; 78:128-35. [IDIS 284531] [PubMed 2047053]
42. Brent RL, Beckman D. Angiotensin-converting enzyme inhibitors, an embryopathic class of drugs with unique properties: information for clinical teratology counselors. Teratology. 1991; 43:543-6. [PubMed 1882342]
43. Piper JM, Ray WA, Rosa FW. Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors. Obstet Gynecol. 1992; 80:429-32. [IDIS 300973] [PubMed 1495700]
44. Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med. 1996; 335:257-65. [IDIS 369138] [PubMed 8657243]
45. Barr M, Cohen MM. ACE inhibitor fetopathy and hypocalvaria: the kidney-skull connection. Teratology. 1991; 44:485-95. [PubMed 1771591]
46. US Food and Drug Administration. Dangers of ACE inhibitors during pregnancy. FDA Med Bull. 1992; 22:2.
47. Yusuf S, Sleight P, Pogue J et al for the Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on death from cardiovascular causes, myocardial infarction, and stroke in high-risk patients. N Engl J Med. (in press)
48. Kleinert S. HOPE cardiovascular disease prevention with ACE inhibitor ramipril. Lancet. 1999; 354:841. [PubMed 10485736]
49. Hansson L, Lindholm LH, Niskanen L et al. Effects of angiotensin-converting enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet. 1999; 353:611-616. [IDIS 421531] [PubMed 10030325]
50. Lonn EM, Yusuf S, Jha P et al. Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection. Circulation. 1994; 90:2056-69. [IDIS 336978] [PubMed 7923694]
51. American Diabetes Association. Clinical Practice Recommendations 1999. Position Statement. Diabetic nephropathy. Diabetes Care. 1999; 22(Suppl 1):S66-9.
52. Genuth S. United Kingdom prospective diabetes study results are in. J Farm Pract. 1998; 47(Suppl 5):S27.
53. Watkins PJ. UKPDS: a message of hope and a need for change. Diabetic Med. 1998; 15:895-6. [PubMed 9827842]
54. UK Prospective Diatetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998; 317:703-13. [IDIS 412064] [PubMed 9732337]
55. Bretzel RG, Voit K, Schatz H et al. The United Kingdom Prospective Diabetes Study (UKPDS): implications for the pharmacotherapy of type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1998; 106:369-72. [PubMed 9831300]
56. American Diabetes Association. Clinical Practice Recommendations 1999. Position statement. Implications of the United Kingdom Prospective Diabetes Study. Diabetes Care. 1999; 22(Supl 1):
57. Tatti P, Pahor M, Byington RP et al. Outcome results of the fosinopril versus amlodipine cardiovascular events randomized trial (FACET) in patients with hypertension and NIDDM. Diabetes Care. 1998; 21:597-603. [IDIS 403787] [PubMed 9571349]
58. American Diabetes Association. The United Kingdom Prospective Diabetes Study (UKPDS) for type 2 diabetes: what you need to know about the results of a long-term study. Washington, DC; 1998 Sep 15 from American Diabetes Association web site.
59. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998; 317:713-20. [IDIS 412065] [PubMed 9732338]
60. Davis TM. United Kingdom Prospective Diabetes Study: the end of the beginning? Med J Aust. 1998; 169:511-2.
61. American Diabetes Association. Clinical Practice Recommendations 1999. Position Statement. Standard of medical care for patients with diabetes mellitus. Diabetes Care. 1999; (Suppl 1):S32-41.
62. 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: approaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9-38A.
63. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]
64. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]
65. 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. [IDIS 452007] [PubMed 10977801]
66. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site.
67. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60. [IDIS 490723] [PubMed 12479770]
68. 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. [IDIS 490721] [PubMed 12479763]
69. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Express. Bethesda, MD: May 14 2003. From NIH website. (Also published in JAMA. 2003; 289.
70. Merck & Co. Vasotec tablets (enalapril maleate) prescribing information. Whitehouse Station, NJ; 2002 Jan.
71. Bristol-Myers Squibb. Monopril (fosinopril sodium) tablets prescribing information. Princeton, NJ; 2002 Feb.
72. Merck. Prinivil (lisinopril) tablets prescribing information. Whitehouse Station, NJ; 2002 Jan.
73. AstraZeneca. Zestril (lisinopril) tablets prescribing information. Wilmington, DE: 2002 Jan.
74. Parke Davis. Accupril (quinapril hydrochloride) tablets prescribing information. Morris Plains, NJ; 2001 Mar.
75. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003; 26(Suppl 1):S80-2.
76. Guidelines Committee. 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension. 2003; 21:1011-53.
77. Novartis. Diovan (valsartan) tablets prescribing information. East Hanover, NJ; 2002 Aug.
78. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2002; 25:134-47. [IDIS 479088] [PubMed 11772914]
79. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2002; 25(Suppl 1):S33-43.
80. American Diabetes Association. Clinical Practice Recommendations 2002. Position Statement. Diabetic nephropathy. Diabetes Care. 2002; 25(Suppl 1):S85-9.
81. 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. [IDIS 321612] [PubMed 8413456]
82. Remuzzi G. Slowing the progression of diabetic nephropathy. N Engl J Med. 1993; 329:1496-7. [PubMed 8413463]
83. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. [IDIS 365188] [PubMed 8622249]
84. Viberti G, Mogensen CE, Groop LC et al. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes