Trandolapril is used alone or in combination with drugs from other classes of antihypertensive agents in the management of hypertension. Trandolapril also is used to reduce the risk of mortality (mainly cardiovascular mortality) as well as to reduce the risk of heart failure-associated hospitalization following myocardial infarction (MI) in hemodynamically stable patients who have evidence of left ventricular systolic dysfunction (identified by wall motion abnormalities) or who demonstrated clinical signs of heart failure within a few days following acute MI.
Because captopril, another angiotensin-converting enzyme (ACE) inhibitor, may cause serious adverse effects (e.g., neutropenia, agranulocytosis), particularly in patients with renal impairment (especially those with collagen vascular disease) or in patients receiving immunosuppressive therapy, the possibility that similar adverse effects may occur with trandolapril should be considered since current evidence is insufficient to rule out such risk.
Trandolapril is used alone or in combination with drugs from other classes of antihypertensive agents in the management of hypertension. ACE inhibitors are considered one of several preferred antihypertensive drugs for the initial management of hypertension; other options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics. While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes. ACE inhibitors may be particularly useful in the management of hypertension in patients with certain coexisting conditions such as heart failure, ischemic heart disease, diabetes mellitus, chronic kidney disease, or cerebrovascular disease or following MI. (See Uses: Hypertension in and in )
In general, black hypertensive patients tend to respond better to monotherapy with thiazide diuretics or calcium-channel blockers than to monotherapy with ACE inhibitors. Although ACE inhibitors have lowered blood pressure in all races studied, monotherapy with these agents has produced a smaller reduction in blood pressure in black hypertensive patients, a population associated with low-renin hypertension; however, this population difference in response does not appear to occur during combined therapy with an ACE inhibitor and a thiazide diuretic or calcium-channel blocker. In addition, ACE inhibitors appear to produce a higher incidence of angioedema in black patients than in other races studied. (See Race under Hypertension: Other Special Considerations for Antihypertensive Therapy, in Uses in and in )
In controlled clinical trials, verapamil in fixed combination with trandolapril (2 or 4 mg trandolapril and 180 or 240 mg verapamil, respectively) administered once daily decreased placebo-corrected seated systolic blood pressure by about 7-12 mm Hg and diastolic blood pressure by about 6-8 mm Hg 24 hours after dosing. Blood pressure reductions were greater with fixed combination of 240 mg of verapamil and 4 mg of trandolapril than with either drug alone. Efficacy was not affected by age or gender, and antihypertensive effects have continued during long-term therapy (i.e., at least 1 year).
For additional information on the role of ACE inhibitors in the management of hypertension, and . For information on overall principles and expert recommendations for treatment of hypertension,
Heart Failure or Left Ventricular Dysfunction After Acute Myocardial Infarction
Trandolapril is used to reduce the risk of mortality (mainly cardiovascular mortality) and reduce the risk of heart failure-associated hospitalization following MI in hemodynamically stable patients who have evidence of left ventricular systolic dysfunction (identified by wall motion abnormalities) or clinical signs of heart failure within the first few days following acute MI. In these patients, when compared with those receiving placebo, trandolapril therapy initiated 3-7 days after acute MI reduced the risk of mortality from any cause by approximately 16% (mainly cardiovascular mortality); the risk of progression of heart failure (defined by heart failure-associated hospitalization, death, or requirement of an ACE inhibitor for the treatment of heart failure) was reduced by 20%. This evidence of efficacy was obtained from a large, multicenter, randomized, double-blind, placebo-controlled, long-term (2-4 years) study (the Trandolapril Cardiac Evaluation; TRACE) in Caucasian patients. Heart failure developed substantially earlier in patients receiving placebo compared with those receiving trandolapril. Trandolapril did not appear to reduce the rates of reinfarction, although there was a trend to fewer such events when compared with placebo. Trandolapril therapy was not associated with substantial effects on subsequent hospitalization, exercise tolerance, ventricular function, ventricular dimensions, or New York Heart Association (NYHA) heart failure status.
Studies with various ACE inhibitors have shown that these drugs reduce fatal and nonfatal cardiovascular events in patients with recent MI. The magnitude of benefit appears to be greatest in certain high-risk patients (e.g., those with an anterior infarct, ejection fraction of 40% or less, heart failure, prior infarction, or tachycardia). In addition to their effects on mortality, ACE inhibitors also are used to minimize or prevent the development of left ventricular dilatation and dysfunction (ventricular ''remodeling'') following acute MI. Evidence regarding the efficacy of such therapy has been somewhat conflicting, particularly when parenteral therapy was initiated early (within 24-48 hours) and included patients with no evidence of baseline dysfunction.) However, the preponderance of evidence has shown a benefit of early oral therapy with ACE inhibitors, even in patients with no baseline dysfunction.
Current expert guidelines recommend the use of an oral ACE inhibitor within the first 24 hours of acute MI in patients with an anterior infarction, heart failure, or ejection fraction of 40% or less who do not have any contraindications (e.g., hypotension, shock, renal dysfunction). While early treatment within the first 24 hours of MI has been shown to be beneficial, ACE inhibitors should be used with caution (and with gradual upward titration) during the initial postinfarction period because of the possibility of hypotension or renal dysfunction. ACE inhibitor therapy generally should be continued indefinitely in all patients with left ventricular dysfunction or other compelling indications for use (e.g., hypertension, diabetes mellitus, chronic kidney disease). The benefits of long-term ACE inhibitor therapy are less certain in low-risk patients who have undergone revascularization and are receiving aggressive antilipemic therapy.
ACE inhibitors have been used in the management of heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).
Current guidelines for the management of heart failure in adults generally recommend a combination of drug therapies to reduce morbidity and mortality, including neurohormonal antagonists (e.g., ACE inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors [ARNIs], β-blockers, aldosterone receptor antagonists) that inhibit the detrimental compensatory mechanisms in heart failure. Additional agents (e.g., cardiac glycosides, diuretics, sinoatrial modulators [i.e., ivabradine]) added to a heart failure treatment regimen in selected patients have been associated with symptomatic improvement and/or reduction in heart failure-related hospitalizations. Experts recommend that all asymptomatic patients with reduced left ventricular ejection fraction (LVEF) (American College of Cardiology Foundation [ACCF]/American Heart Association [AHA] stage B heart failure) receive therapy with an ACE inhibitor and β-blocker to prevent symptomatic heart failure and to reduce morbidity and mortality. In patients with prior or current symptoms of chronic heart failure and reduced LVEF (ACCF/AHA stage C heart failure), ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend inhibition of the renin-angiotensin-aldosterone (RAA) system with an ACE inhibitor, angiotensin II receptor antagonist, or ARNI in conjunction with a β-blocker, and an aldosterone antagonist in selected patients, to reduce morbidity and mortality. While ACE inhibitors have been the preferred drugs for inhibition of the RAA system because of their established benefits in patients with heart failure and reduced ejection fraction, some evidence indicates that therapy with sacubitril/valsartan, an ARNI, may be more effective than ACE inhibitor therapy (enalapril) in reducing cardiovascular death and heart failure-related hospitalization. ACCF, AHA, and 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. However, in patients in whom an ARNI is not appropriate, continued use of an ACE inhibitor for all classes of heart failure with reduced ejection fraction remains strongly advised. In patients in whom an ARNI or ACE inhibitor is not appropriate, an angiotensin II receptor antagonist may be used. In patients in whom an ARNI or ACE inhibitor is not appropriate, an angiotensin II receptor antagonist may be used. For additional information on the use of ACE inhibitors in the management of heart failure, and in
Both ACE inhibitors and angiotensin II receptor antagonists have been shown to slow the rate of progression of renal disease in patients with diabetes mellitus and persistent albuminuria, and use of a drug from either class is recommended in such patients with modestly elevated (30-300 mg/24 hours) or higher (exceeding 300 mg/24 hours) levels of urinary albumin excretion. The usual precautions of ACE inhibitor or angiotensin II receptor antagonist therapy in patients with substantial renal impairment should be observed. For additional information on the use of ACE inhibitors in the treatment of diabetic nephropathy, see