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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The TRAndolapril Cardiac Evaluation (TRACE) study is evaluating the effect of angiotensin-converting enzyme inhibition with trandolapril on mortality (overall and cardiovascular) and cardiovascular morbidity in patients surviving myocardial infarction (MI) with reduced left ventricular (LV) function. TRACE is a randomized, double-blind, placebo-controlled study conducted in 27 centers in Denmark. Eligible patients had a MI verified by elevated cardiac enzymes, electrocardiographic changes, and/or chest pain as well as reduced LV function, as shown by echocardiographic evaluation of wall motion index < or = 1.2. (A wall motion index < or = 1.2 approximates to a left ventricular ejection fraction < or = 35%). Patients with residual ischemia and/or heart failure were not excluded. Trandolapril or placebo was added to conventional therapy 3-7 days after MI. Between May 1990 and June 1992, 6,674 patients (7,010 infarctions) were screened. A total of 2,614 patients had a wall motion index < or = 1.2; of these, 1,749 were included. Overall 1-year mortality of the patients entered into the study was 24%. Treatment will be continued for 2-4 years (mean, 3 years), ending in mid 1994. The design and organization of the study, the outcome of screening, and demographic features of the screened population are described.
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PMID:The TRAndolapril Cardiac Evaluation (TRACE) study: rationale, design, and baseline characteristics of the screened population. The Trace Study Group. 816 55

To study the importance of giving an angiotensin-converting enzyme (ACE) inhibitor to patients with reduced systolic function after an infarction, the Trandodolapril Cardiac Evaluation study was designed to include the majority of patients with echocardiographic signs of left ventricular dysfunction among consecutively screened patients with infarctions. A total of 2606 consecutive patients with left ventricular systolic dysfunction corresponding to an ejection fraction < or = 35% were identified. Of these patients, 1749 (67%) were randomly assigned to receive oral trandolapril or placebo beginning on day 3 to 7 after the infarction. The follow-up period was 2 to 4 years. Trandolapril reduced all-cause mortality, with a relative risk reduction associated with trandolapril treatment of 0.78 (p = 0.0013). Benefit was seen within 1 month of treatment. Trandolapril also reduced cardiovascular death (relative risk 0.75, p = 0.001), sudden death (relative risk 0.76, p = 0.03), and progression to severe/ resistant heart failure (relative risk 0.71, p = 0.003). Recurrent myocardial infarction (fatal or nonfatal) was not significantly reduced (relative risk 0.86, p = 0.29). More than 80% of patients in both treatment groups reached the target dose of 4 mg trandolapril or placebo at the end of dose titration. Nearly half of the patients in both treatment groups discontinued taking study medication before death or trial closure. The need for open-label ACE inhibition was the reason for discontinuation for 48 and 75 patients in the trandolapril and placebo groups, respectively. In conclusion, long-term treatment with trandolapril in patients with reduced left ventricular function shortly after myocardial infarction significantly reduced mortality and morbidity. Most patients received the target dose of 4 mg trandolapril daily. The benefit observed is likely to reflect the benefit in clinical practice because the majority of eligible patients were randomized and the difference in patients leaving the trial to receive open-label ACE inhibition was moderate.
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PMID:Angiotensin-converting enzyme inhibition after myocardial infarction: the Trandolapril Cardiac Evaluation Study. 867 62

The TRACE (TRAndolapril Cardiac Evaluation) study was designed to determine whether long-term treatment with an ACE inhibitor is beneficial in patients with early post-myocardial infarction cardiac failure. A total 6,676 consecutive patients with 7,001 myocardial infarctions were included; 2,606 patients had echocardiographic signes of left ventricular dysfunction (ejection fraction < 35%), 3 to 7 days after myocardial infarction; 1,749 patients were randomised and given either oral trandolapril (876 patients) or placebo (873 patients). Follow-up ranged from 24 to 50 months. Three hundred and four patients (34.7%) in the trandolapril group died, compared with 369 (42.3%) in the placebo group (p = 0.001). The relative risk of death in the trandolapril group compared with the placebo group was 0.78. Trandolapril was also associated with a statistically significantly lower risk of cardiovascular death and of sudden death. Progression to severe cardiac failure was also less frequent in the treatment group. On the other hand, the risk of recurrent myocardial infarction was not significantly reduced. In conclusion, long-term treatment with trandolapril in patients with early post-infarction left ventricular dysfunction significantly reduced the risk of cardiovascular mortality, sudden death and progression to severe cardiac failure.
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PMID:[Trandolapril in patients with left ventricular insufficiency after myocardial infarction]. 894 15

Angiotensin converting-enzyme (ACE) inhibition reduces mortality among patients surviving an acute myocardial infarction, but whether to give ACE-inhibitors to all patients or target their use to selected patients is unclear. Seven thousand and one consecutive enzyme-confirmed myocardial infarctions were screened. One thousand seven hundred and forty-nine patients with echocardiographic signs of left ventricular dysfunction were randomized to oral trandolapril (876 patients) or placebo (873 patients) starting from days three to seven following the infarction. Average follow-up was 27 months. There were 304 deaths (34.7 percent) among patients on trandolapril vs. 369 deaths (42.3 percent) among patients on placebo (p = 0.0013). Relative risk (RR) of death in the trandolapril group was 0.78 (95% confidence interval (CD 0.67-0.91). Trandolapril reduced cardiovascular death (RR 0.75, CI 0.63-0.89) and sudden death (RR 0.76, CI 0.59-0.98). Progression to severe/resistant heart failure was reduced (RR 0.71, CI 0.56-0.90). Recurrent myocardial infarction (fatal or non-fatal) was not significantly reduced (RR 0.86, CI 0.66-1.13). It is concluded that long-term treatment with trandolapril in patients with reduced left ventricular function shortly after myocardial infarction significantly reduced total mortality. The substantial mortality risk reduction was obtained in 25% of consecutive patients screened for entry encouraging a selective use of ACE inhibition following myocardial infarction.
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PMID:[The significance of trandelapril for mortality after AMI in patients with reduced left ventricular function. TRACE Study Group]. 909 45

1 Characteristics of cyclic GMP- and cyclic AMP-mediated relaxation in aortic segments of rats with chronic heart failure (CHF) and the effects of chronic treatment with an angiotensin I converting enzyme (ACE) inhibitor, trandolapril, were examined 8 weeks after coronary artery ligation. 2 Cardiac output indices of coronary artery-ligated and sham-operated rats were 125+/-8 and 189+/-10 ml min(-1) kg(-1), respectively (P<0.05), indicating the development of CHF at this period. 3 The maximal relaxant response of aortic segments to 10 microM acetylcholine in rats with CHF and sham-operated rats was 64.0+/-5.7 and 86.9+/-1.9%, respectively (P<0.05), whereas the relaxant response to sodium nitroprusside (SNP) remained unchanged. Tissue cyclic GMP content in rats with CHF was lower than that of sham-operated rats. 4 In endothelium-intact segments of rats with CHF, the maximal relaxant response to 10 microM isoprenaline (44.5+/-6.7%) was lower that sham-operated rats (81.3+/-2.5%, P<0.05) and the concentration-response curve for NKH477, a water-soluble forskolin, was shifted to the right without a reduction in the maximal response. Isoprenaline-induced relaxation of aortic segments was attenuated by NG-nitro-L-arginine methyl ester (L-NAME) in sham-operated rats, but not in rats with CHF. Relaxation to 30 microM dibutyryl cyclic AMP in rats with CHF (26.8+/-2.7%) was lower than that in sham-operated rats (63.4+/-11.8%, P<0.05). 5 Trandolapril (3 mg kg(-1) day(-1)) was orally administered from the 2nd to 8th week after the operation. Aortic blood flow of rats with CHF (38.5+/-3.6 ml min(-1)) was lower than that of sham-operated rats (55.0+/-3.0 ml min(-1)), and this reduction was reversed (54.1+/-3.4 ml min(-1)) by treatment with trandolapril. The diminished responsiveness described above was normalized in the trandolapril-treated rat with CHF (i.e., the maximal relaxation to acetylcholine, 94.7+/-1.0%; that to isoprenaline, 80.5+/-2.8%; that to dibutyryl cyclic AMP, 54.7+/-6.2%). However, aortic segments of trandolapril-treated rats with CHF, L-NAME did not attenuate isoprenaline-induced relaxation and the tissue cyclic GMP level was not fully restored, suggesting that the ability of the endothelium to produce NO was still partially damaged. 6 The results suggest that vasorelaxation in CHF, diminished mainly due to dysfunction in endothelial nitric oxide (NO) production and cyclic AMP-mediated signal transduction, was partially restored by long-term treatment with trandolapril. The mechanism underlying the restoration may be attributed in part to prevention of CHF-induced endothelial dysfunction.
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PMID:The effect of chronic treatment with trandolapril on cyclic AMP-and cyclic GMP-dependent relaxations in aortic segments of rats with chronic heart failure. 948 24

Proven cardiovascular benefit from angiotensin-converting enzyme (ACE) inhibition is a cornerstone of evidence-based medicine. The first study to show dramatic benefits from ACE inhibition was the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS-I), in which a 31% decrease in the rate of death was observed in patients with severe heart failure at the end of 1 year of enalapril treatment (p = 0.001). This result led to large long-term studies-including Survival and Ventricular Enlargement (SAVE), Acute Infarction Ramipril Efficacy (AIRE), Trandolapril Cardiac Evaluation (TRACE), and Study of Left Ventricular Dysfunction (SOLVD)-which verified that ACE inhibition decreases heart failure, myocardial infarction (MI), and mortality, and that striking benefit could be observed within 30 days. Short-term studies of patients in the acute phase of a heart attack verified that ACE inhibition provided rapid benefits. A meta-analysis of short-term (up to 8 weeks) studies of ACE inhibition (including CONSENSUS-II, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico [GISSI]-3, International Study of Infarct Survival [ISIS]-4, and the Chinese Captopril Study [CCS]-1) demonstrated that post-MI risk was reduced by 10% within the first day of treatment. The immediacy of the benefit suggested that ACE inhibition not only improved cardiovascular function in failing hearts but also affected important mechanisms in patients without overt heart failure. Effects on more general mechanisms of heart disease suggested that patients with problems other than hypertension or heart failure might benefit from ACE inhibitors. The Heart Outcomes Prevention Evaluation (HOPE) study investigated the hypothesis that ACE inhibition would confer benefits to patients who were at high risk for cardiovascular events, but who were without left ventricular dysfunction or heart failure. Long-term reductions in MI, stroke, cardiac arrest, and heart failure, as well as improvements in mortality, were observed in this population after treatment with ACE inhibitors. Substudies of the HOPE study revealed that ACE inhibition reduced progression of atherosclerosis and improved myocardial remodeling. Taken together, these studies provide evidence that supports treatment of a broad population of patients at risk for cardiovascular events with ACE inhibitors. The next step is to combine ACE inhibition with other treatments to maximize patient benefit. The Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) will compare the efficacy of an ACE inhibitor (ramipril) with an angiotensin receptor blocker (telmisartan), and determine whether these treatments in combination will further reduce morbidity and mortality from cardiovascular disease.
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PMID:Angiotensin II and trials of cardiovascular outcomes. 1183 5

In well designed studies in patients with mild to moderate hypertension, combinations of the sustained-release (SR) formulation of the nondihydropyridine calcium channel antagonist verapamil 120 to 240 mg/day and the ACE inhibitor trandolapril 0.5 to 8 mg/day were significantly more effective in reducing sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline than placebo. In most randomised studies, combinations of verapamil SR 120 to 240 mg/day and trandolapril 0.5 to 8 mg/day were significantly more effective in lowering sitting DBP and SBP than the corresponding monotherapies administered at the same dosage. Trandolapril/verapamil SR 2/180 mg/day provided significantly more effective 24-hour ambulatory blood pressure (BP) control than of the corresponding monotherapies. Moreover, trandolapril/verapamil SR reduced BP in patients inadequately controlled with either of the corresponding monotherapies. The antihypertensive efficacy of trandolapril/verapamil SR 2/180 mg/day was generally similar to that of other combinations of antihypertensive agents (metoprolol/hydrochlorothiazide, atenolol/chlorthalidone, lisinopril/hydrochlorothiazide, enalapril/hydrochlorothiazide) in patients with hypertension, including those with type 2 diabetes mellitus. Trandolapril/verapamil SR reduced BP in patients with hypertension and type 2 diabetes or primary renal disease, Black patients and elderly patients. Trandolapril/verapamil SR was more effective than the individual components administered as monotherapy in reducing proteinuria in patients with type 2 diabetes or primary renal disease. Trandolapril/verapamil SR had a neutral or beneficial effect on metabolic parameters (glucose, insulin, lipids) in patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR preserved left ventricular function in patients with heart failure. Fewer cardiac events occurred after therapy with trandolapril/verapamil SR than after trandolapril alone in post-myocardial infarction patients with congestive heart failure. The incidence of adverse events in recipients of trandolapril/verapamil SR was similar to that of the individual components, and that of other combination therapies. In placebo-controlled trials conducted in the US, headache, upper respiratory tract infections, cough, constipation, atrioventricular block (first degree) and dizziness were the most commonly reported adverse events in recipients of combinations of verapamil SR (120 to 240 mg/day) and trandolapril (0.5 to 8 mg/day). In conclusion, the fixed-dose combination of trandolapril/verapamil SR is an effective treatment for patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR tended to be more effective than monotherapy with either verapamil SR or trandolapril, and generally showed antihypertensive efficacy similar to that of other combination antihypertensive therapies. Current data support the use of trandolapril/verapamil SR as an alternative treatment when monotherapy with either agent is not effective. Data from large clinical trials currently being conducted will assist in fully defining the role of trandolapril/verapamil SR as a cardio- and renoprotective agent.
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PMID:Fixed combination trandolapril/verapamil sustained-release: a review of its use in essential hypertension. 1242 Nov 12

This paper reviews the current literature pertaining to calcium channel blockers, including their classification, properties, and therapeutic indications, in light of several recent trials that have addressed their safety. Calcium channel blockers are a structurally and functionally heterogeneous group of medications that are used widely to control blood pressure and manage symptoms of angina. They are classified as dihydropyridines or nondihydropyridines. As a class, they are well tolerated and are associated with few side effects. The question of whether they may precipitate cardiovascular events has been largely settled by recent trials, such as the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the International Verapamil Slow-Release/Trandolapril Study (INVEST), and the Controlled Onset Verapamil Investigation of Cardiovascular Endpoints (CONVINCE) study, in which no such association was found. Even so, the use of these agents has been linked with an increased risk of heart failure. Thus, long-acting calcium channel blockers may be safely used in the management of hypertension and angina. However, as a class, they are not as protective as other antihypertensive agents against heart failure.
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PMID:Calcium channel blockers: an update. 1470 64

The INternational VErapamil SR-Trandolapril study (INVEST) had 6400 of 22,576 (28.3%) participants with diabetes at entry. The objectives of this prespecified analysis were to compare antihypertensive treatment strategies in the diabetes cohort (verapamil SR-based [n=3169] versus atenolol-based [n=3231]) and identify predictors for the primary outcome (a composite of first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke). During a mean follow-up of 2.7 years, 913 participants with diabetes experienced a primary outcome event, with no significant difference between treatment strategies (14.6%, verapamil SR versus 13.9%; atenolol hazard ratio, 1.05; 95% confidence interval, 0.92 to 1.19). Risk for the primary outcome increased with presence of baseline heart failure, renal impairment, US residency, age, previous stroke/transient ischemic attack, previous myocardial infarction, peripheral vascular disease, or smoking. High systolic and diastolic pressures during follow-up also were associated with increased risk, as were low diastolic pressures. Antihypertensive treatment with a verapamil SR or atenolol strategy resulted in similar rates of cardiovascular outcomes in coronary artery disease (CAD) patients with diabetes. Thus, a verapamil SR-based antihypertensive treatment strategy is an alternative to a beta-blocker-based strategy in adults with CAD and diabetes.
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PMID:Clinical outcomes in the diabetes cohort of the INternational VErapamil SR-Trandolapril study. 1536 99

Cardiovascular diseases are directly affected by arterial hypertension. When associated with diabetes mellitus, the potential deleterious effects are well amplified. Both conditions play a central role in the pathogenesis of coronary artery disease, heart failure, stroke, and renal insufficiency. Prevalence of hypertension is much higher among diabetic than non-diabetic patients, and the hypertensive patient is more likely to develop type 2 diabetes. Current international guidelines recommend aggressive reductions in blood pressure (BP) in hypertensive patients with additional risk factors, including cardiovascular risk factors, and emphasize the relevance of intensive reduction in patients with diabetes mellitus; a goal of 130/80 mm Hg is required. To achieve BP target a combination of antihypertensives will be needed, and the use of long-acting drugs that are able to provide 24-hour efficacy with a once-daily dosing confers the noteworthy advantages of compliance improvement and BP variation lessening. Lower dosages of the individual treatments of the combination therapy can be administered for the same antihypertensive efficiency as that attained with high dosages of monotherapy. Angiotensin-converting enzyme inhibitors and calcium-channel blockers as a combination have theoretically compelling advantages for vessel homeostasis. Trandolapril/verapamil sustained release combination has showed beneficial effects on cardiac and renal systems as well as its antihypertensive efficacy, with no metabolic disturbances. This combination can be considered as an effective therapy for the diabetic hypertensive population.
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PMID:Trandolapril/verapamil combination in hypertensive diabetic patients. 1758 77


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