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Biomedical subjects

H Pouleur

Publications and source records attributed to H Pouleur.

At least 37 records · Page 2Linked to original sources

Neurohormones in patients with ischemic left ventricular dysfunction.

Measurements of plasma neurohormones in patients with left ventricular dysfunction are generally performed for research purpose rather than for diagnostic purpose or to guide therapy. These studies have shown that in patients with left ventricular dysfunction, several neurohormonal systems were activated, even in the absence of symptoms of congestive heart failure. This suggested that the cardiovascular system was not in a steady state and pointed out potential culprits for the progression of the disease. It has also been shown that the levels of several of these markers, particularly plasma norepinephrine, had an important prognostic value. Another value of neurohormonal studies obviously is the design of new therapeutic approaches aimed at improving symptoms and prognosis. In this respect, important therapeutic successes have been obtained with agents that interfere with the actions of some of these neurohormonal systems, such as with the use of the angiotensin-converting enzyme (ACE) inhibitors, particularly captopril and enalapril, and to a lesser extent, with beta-blockers. It can therefore be expected that, in the future, most patients with severe ischemic dysfunction will be treated with an ACE inhibitor. Nonetheless, neurohormonal control is not complete with these drugs; powerful vasoconstrictor forces, such as endothelin-1, remain activated, and an escape of angiotensin II from the control of ACE inhibition may exist. Thus, morbidity (e.g., progression towards congestive heart failure and angina pectoris) and mortality remain high despite treatment with ACE inhibitors. In the search for future improvements, the new generation of long-acting dihydropyridines is worth considering. Their afterload reducing action, coupled with powerful coronary vasodilation, might hypothetically delay the progression of ischemic LV dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Effects of nisoldipine therapy on myocardial perfusion and neuro-hormonal status in patients with severe ischaemic left ventricular dysfunction.

The effects of nisoldipine on regional myocardial perfusion and neuro-hormonal status were assessed in a double-blind, placebo-controlled study of 32 patients. All patients had ischaemic left ventricular dysfunction, with a left ventricular ejection fraction between 25% and 35%; per protocol, they were stratified according to concomitant use of ACE inhibitors. After baseline measurements at rest, including single photon emission computed tomography (SPECT) with Tc-MIBI, plasma neuro-hormones (norepinephrine, renin, arginine vasopressin, atrial natriuretic peptide) and echocardiography, the patients were randomized to nisoldipine (core coat tablet, 20 mg once daily; n = 16) or placebo (n = 16). Measurements were repeated after 8 weeks. SPECT data were analysed qualitatively (visual comparison by blinded observer) and quantitatively to derive an index of hypoperfusion representing the percentage of the left ventricular mass with Tc-MIBI activity below normal. At baseline, all patients had left ventricular areas with reduced Tc-MIBI uptake and 29 patients also had increases in plasma neuro-hormones. With nisoldipine, the extent of hypoperfusion (quantitative analysis) was reduced in 8/14 patients vs only 2/14 patients with placebo (P = 0.046, 2-tailed test). The benefit of nisoldipine was similar in patients with or without ACE inhibitor therapy and was also confirmed by the visual analysis of the data. Further, none of the neuro-hormones examined was significantly modified by nisoldipine. Thus, chronically underperfused areas are present at rest in patients with ischaemic left ventricular dysfunction, and nisoldipine significantly improved Tc-MIBI uptake in these areas without evidence of detrimental changes in plasma neuro-hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Vasopressin↗

Cardiac involvement in Ribbing's disease.

Cardiac involvement was assessed in 14 patients with Ribbing's disease, a rare hereditary sclerosing bone dysplasia. When compared to age-, sex- and blood pressure-matched controls, the patients with Ribbing's disease had significant alterations in left ventricular systolic and diastolic function and an impaired exercise tolerance. Supraventricular and ventricular arrhythmias also tended to be more frequent in these patients than in controls. In conclusion, Ribbing's disease, initially described as a skeletal disease only, also involves the cardiovascular system. Despite its rarity, the expression of the disease is easily followed and identification of the genetic defect could shed some new light on the pathophysiological mechanisms linking hypertension, myocardial hypertrophy and diastolic dysfunction.

Adolescent↗

Improving patient care: some unresolved issues in heart failure.

Angiotensin-converting enzyme (ACE) inhibitors are considered as the cornerstone of the treatment of congestive heart failure with systolic dysfunction, proving beneficial in all grades of heart failure, from I to IV on the New York Heart Association scale. However, despite these positive results, a brief glance at the published mortality data or an hour spent in any heart failure clinic easily demonstrates that the problems of heart failure are far from being solved. Among the unresolved issues that will be addressed in this brief review are: the high incidence of deaths due to pump failure and sudden death in patients receiving ACE inhibitor therapy; methods of further improving exercise tolerance and quality of life, and, finally, current views regarding prevention of heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

Effects of endothelin-1 at pathophysiologic concentrations on coronary perfusion and mechanical function of normal and postischemic myocardium.

We assess hemodynamic, vascular, and hormonal effects of endothelin-1 (ET-1) at pathophysiologic levels on normal and ischemic myocardium. Thirty conscious chronically instrumented dogs were studied before, during, and after a 10-min coronary artery occlusion (CAO) performed either during ET-1 infusion (2.5 ng/kg.min, n = 15) or during placebo infusion (n = 15). ET-1 infusion produced an increase in plasma ET-1 (from 1.3 +/- 0.1 to 11.5 +/- 1.1 pM, p < 0.0001) during CAO (pathophysiologic value). Left anterior descending artery (LAD) blood flow (measured by Doppler flow probe) decreased similarly during CAO with ET-1 or placebo (p = 0.0001, NS, ET-1 vs. placebo). Both endocardial and epicardial blood flows in ischemic regions also decreased (p = 0.0001) during CAO but were threefold greater with ET-1 than with placebo (endocardium 42 +/- 7 vs. 14 +/- 2 ml/min/100 g, p = 0.003). No significant difference in myocardial blood flows between groups was observed in control regions. CAO produced increases (p < 0.005) in heart rate (HR), mean aortic pressure (AOP), and ventricular pressures but no change in atrial pressures. The changes in these parameters were comparable in the ET-1 and placebo groups. Despite the greater residual flow during CAO, however, ET-1 decreased the function of the ischemic zone during reperfusion as assessed by systolic shortening (p < 0.05). Atrial natriuretic factor (ANF), unchanged during CAO with placebo, increased from 38.3 +/- 6.1 to 53.3 +/- 10 pM with ET-1 (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Safety of concomitant potassium-sparing diuretics in angiotensin-converting enzyme inhibitor therapy in severe congestive heart failure. Xamoterol in Severe Heart Failure Study Group.

The safety of concomitant use of angiotensin-converting enzyme (ACE) inhibitors and potassium-sparing diuretics (PSD) in severe heart failure remains a controversial issue. The database of the recently reported double-blind international trial, "Xamoterol in Severe Heart Failure," was investigated to elucidate this question. Of 516 patients with New York Heart Association (NYHA) class III-IV, despite diuretics and ACE inhibitor therapy, 352 were randomized to xamoterol, a beta 1 partial agonist, and 164 were randomized to placebo. During the 13-week study, 28% of all patients (xamoterol, 104; placebo, 42) received potassium-sparing diuretics. All groups were comparable in hemodynamics and dose of other diuretics. At study end, patients with or without PSD showed no significant differences in serum K+ or creatinine, independent of xamoterol or placebo therapy. Mortality rate was consistently lower: 4.6% in patients with PSD and 8.5% in patients without PSD, although statistical significance was not reached. As compared with baseline, K+ values of 6 patients with and 17 patients without PSD had increased by > 5.0 mM at study end (p = NS); 1 patient with and 11 patients without PSD had a creatinine level > 180 microM (p = NS). For 3 patients receiving PSD, and 2 patients not receiving PSD because of renal impairment, study was discontinued because of hyperpotassemia. No significant differences were noted in long and short action or different dosages of ACE inhibitors. PSD may be administered concomitantly with ACE inhibitors, but serum K+ should be monitored as with other diuretics.

Adult↗

Regional remodeling and nonuniform changes in diastolic function in patients with left ventricular dysfunction: modification by long-term enalapril treatment. The SOLVD Investigators.

OBJECTIVES: The purpose of the present study was to assess the process of late regional remodeling and the changes in regional diastolic function at the base and apex of the left ventricle in patients with chronic systolic dysfunction. BACKGROUND: Remodeling has been suggested to play an important role in the progression of left ventricular dysfunction and heart failure. However, the regional difference in the process of late remodeling and its relation to diastolic function remain unclear. METHODS: In 32 patients with previous myocardial infarction and left ventricular ejection fraction < or = 35%, left ventricular hemodynamic and angiographic data were studied before and 1 year after randomization to conventional therapy with placebo (n = 12) or enalapril, 10 mg twice daily (n = 20). Left ventricular regional wall dynamics were analyzed in the basal and apical regions by the area method. RESULTS: In the placebo group, left ventricular end-diastolic and end-systolic regional areas increased significantly over time at the base but were unchanged at the apex. At the base, the diastolic left ventricular pressure-regional area relation shifted rightward and the regional stiffness constant decreased (6.9 +/- 4.3 to 5.0 +/- 3.1 x 10(-3) mm-2, p < 0.05), indicating an increase in regional distensibility. At the apex, however, the diastolic pressure-regional area relation shifted upward slightly, and the regional stiffness constant increased from 11.5 +/- 4.4 to 14.4 +/- 5.6 x 10(-3) mm-2 (p = 0.08). The regional peak filling rate was maintained at the base but decreased at the apex (1,014 +/- 436 to 762 +/- 306 mm2/s, p < 0.05); further, the changes in regional peak filling rate during follow-up were inversely related to the changes in the regional stiffness constant (r = -0.78, p < 0.001) at the apex. In contrast, in the enalapril group, end-diastolic and end-systolic regional areas significantly decreased over time both at the base and at the apex. Diastolic pressure-regional area relations shifted leftward, but the regional stiffness constant and regional peak filling rate did not change significantly either at the base or at the apex. CONCLUSIONS: These findings suggest that in patients with severe systolic left ventricular dysfunction, there was a regional difference in the process of late remodeling between the base and apex of the left ventricle, which was associated with nonuniform changes in regional diastolic function in the placebo group. The data also suggest that the nonuniform progression of regional remodeling and diastolic dysfunction was prevented by long-term enalapril treatment.

Cardiac Catheterization↗

Wall motion asynchrony is a major determinant of impaired left ventricular filling in patients with healed myocardial infarction.

Left ventricular (LV) diastolic filling is impaired in hearts with healed myocardial infarction. Possible hemodynamic parameters related to impaired LV filling include left atrial pressure, time constant of isovolumic relaxation, chamber stiffness and wall motion asynchrony. Previous studies demonstrated univariate correlations between each of these parameters and LV filling. The current study was designed to compare relative importance of these parameters in patients with a myocardial infarction. Left ventriculograms with simultaneous LV pressure measurement were analyzed in 15 patients with a myocardial infarction and in 10 control subjects. Every frame of the left ventriculogram was divided into 8 segments and the volume of each segment was obtained frame-by-frame by planimetry and area-length method. Asynchrony was quantitated as the sum of areas of discrepancy between each segmental and global volume-time curve. Patients with myocardial infarction had greater asynchrony (20 +/- 2 vs 10 +/- 1%, p < 0.01), greater atrial filling fraction (46 +/- 4 vs 35 +/- 5%, p < 0.05) and slower peak early filling rate (2.5 +/- 0.1 vs 4.1 +/- 0.4 end-diastolic volume/s, p < 0.01) than the control subjects. Multiple regression analyses with hemodynamic variables (asynchrony, LV pressure at mitral valve opening, time constant of LV isovolumic pressure decrease and LV chamber stiffness constant) showed that asynchrony and LV pressure at mitral valve opening were significant determinants of LV filling in patients with myocardial infarction, whereas LV pressure at mitral valve opening was the only significant determinant in control subjects.

Analysis of Variance↗

Angiotensin-converting enzyme inhibitors in the treatment of clinical heart failure.

During the last decade, angiotensin-converting enzyme inhibitors (ACE-I) have become cornerstones in the treatment of clinical congestive heart failure. There is convincing evidence that they improve survival and that, in this respect, they are superior to ordinary vasodilators. ACE-I administration also improves New York Heart Association functional class and the left-ventricular function, but their long-term effects on exercise tolerance and quality of life appear modest. During prolonged administration to patients with ischemic left-ventricular dysfunction, ACE-I also significantly reduce the incidence of new ischemic events (myocardial infarction, unstable angina).

Angiotensin-Converting Enzyme Inhibitors↗

High or low dose of angiotensin-converting enzyme inhibitor in patients with left ventricular dysfunction?

Although it is widely accepted that angiotensin-converting enzyme inhibitors have become a cornerstone in the treatment of congestive heart failure, controversy still exists regarding the optimal doses of these drugs to use, and important variations in the daily dose used are seen among different physicians and countries. Nevertheless, objective data indicate that the efficacy of these drugs increases with dose and that most patients with heart failure tolerate the relatively high doses that have been used in large mortality trials. Presently, therefore, and unless new contradictory data become available, every effort should be made to use high doses of angiotensin-converting enzyme inhibitor in heart failure patients.

Angiotensin-Converting Enzyme Inhibitors↗

Nisoldipine in severe ischaemic left ventricular dysfunction.

The use of calcium antagonists in patients with severe dysfunction is controversial because agents like verapamil, diltiazem and nifedipine have been shown to worsen or precipitate congestive heart failure. However, successive improvements in our understanding of the clinical pharmacology of these drugs, of their pharmacokinetics and of their action on several neuro-humoral regulatory mechanisms have led to a continuous improvement of the molecules available. Promising results have been obtained with nisoldipine in patients with ischaemic left ventricular dysfunction (improved exercise tolerance, improved diastolic filling probably related to a relative improvement of chronically ischaemic areas) and other studies are exploring the effects of the combination of nisoldipine with an ACE-inhibitor. Soon, these trials should tell us if there is a real clinical benefit in the use of this agent not only to improve symptoms but also to slow down progression of the ventricular dysfunction.

Coronary Circulation↗

Calcium antagonists or beta-blockers in chronic ischaemic left ventricular dysfunction?

Angina pectoris in patients with severe left ventricular dysfunction (LVD), with or without heart failure, is important clinically and socioeconomically. In the Studies of Left Ventricular Dysfunction (SOLVD), more than 36% of the patients had angina pectoris. Although angiotensin-converting enzyme (ACE) inhibitors improve survival and reduce the incidence of new, acute ischaemic events in these patients, they have no significant impact on the incidence of anginal attacks. Treatment of these patients must, therefore, primarily rely on nitrates, beta-blockers and calcium channel blockers. The beta-blockers, by lowering heart rate, improve the balance between myocardial oxygen supply and demand during exercise, and are among the most effective anti-anginal agents available. In addition, by reducing resting heart rate and by preventing excessive catecholamine stimulation of the myocardium, beta-blockers may slow the progression of ischaemic LVD. This may contribute to the improved survival observed when these agents are used following myocardial infarction. By reducing cardiac sympathetic stimulation, however, beta-blockers may depress right and left ventricular pump function. This depression is generally of no clinical consequence when the ejection fraction remains above 40%, but when the ejection fraction is below 35%, only 30% of patients without heart failure and 10% of those with heart failure seem to tolerate a full dose of beta-blocker. This limits their therapeutic use in angina in this setting. Moreover, beta-blockers do not act on the mechanisms underlying some anginal attacks, namely the vasoconstriction of large coronary vessels at the level of atherosclerotic plaques and the reflex vasoconstriction of small coronary arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Effects of D-nebivolol and L-nebivolol on left ventricular systolic and diastolic function: comparison with D-L-nebivolol and atenolol.

(D-L) Nebivolol is a new beta 1-selective adrenoceptor blocker which in normal individuals preserves rest and exercise hemodynamics. We assessed the effects of the enantiomers (L- and D-nebivolol) on left ventricular (LV) systolic and diastolic function and compared their effects with those of the racemic mixture. LV angiography (+Millar) was performed before and after intravenous (i.v.) infusion of either D- or L-nebivolol (1.25-2.5 mg, n = 22) in patients with ischemic heart disease and previous myocardial infarction. Neither L- nor D-nebivolol produced significant changes in heart rate (HR), peak (+) dP/dt, (dP/dt) DP40, cardiac index (CI) or ejection fraction (EF). Diastolic distensibility, evaluated from the shift of the pressure-volume data at the time of mitral valve opening, did not improve after D- or L-enantiomers administration. In contrast, both D-L-nebivolol 2.5 mg (n = 9) and atenolol 15 mg (n = 9) significantly reduced HR and peak (+) dP/dt, but in comparison to atenolol D-L nebivolol improved EF (+4% after D-L nebivolol vs. -4% after atenolol; p < 0.05 D-L nebivolol vs. atenolol) and maintained cardiac output CO, (+2% vs. -21%; p < 0.05 between groups). Moreover, unlike any of the other drugs in the study, the racemate shifted the diastolic pressure-volume data downward, suggesting improved LV distensibility. The beneficial effects of nebivolol on LV systolic and diastolic function appears to require the presence of both D- and L-enantiomers.

Adrenergic beta-Antagonists↗

Endothelin-1 exacerbates diastolic stunning in conscious dogs.

The purpose of this study was to examine the effects of endothelin-1 (ET-1) on "diastolic stunning" in the postischemic myocardium. In 14 conscious dogs receiving either placebo (n = 7) or ET-1 (2.5 ng.kg-1.min-1, n = 7), left ventricular (LV) hemodynamics and regional wall motion (systolic segmental shortening by sonomicrometry and the ischemic-nonischemic regional asynchrony during isovolumic relaxation) were assessed at baseline, during 10 min of left anterior descending coronary artery occlusion (CAO) and at 60 min after reflow (R-60). During CAO, the ischemic segment shortening was severely depressed and both regional asynchrony and LV relaxation time constant were significantly increased in the placebo and ET-1 groups. At R-60, this LV diastolic dysfunction recovered to baseline conditions in the placebo group but was still present in the ET-1 group. Because coronary and myocardial blood flow returned to the baseline level at R-60 in both groups, the deleterious effects of ET-1 on diastolic stunning are probably mediated by its direct action on the myocardium.

Animals↗

Effects of long-term enalapril therapy on left ventricular diastolic properties in patients with depressed ejection fraction. SOLVD Investigators.

BACKGROUND: The aim of the present study was to analyze the changes in left ventricular diastolic function that occur in patients with chronic severe left ventricular systolic dysfunction in the absence or presence of prolonged therapy with an angiotensin converting enzyme inhibitor. METHODS AND RESULTS: Left ventricular function data (cineangiography plus Millar, frame-by-frame analysis) and right ventricular volumes (radionuclide angiography) were obtained at baseline and after an average follow-up of 12.4 months in 42 patients with a left ventricular ejection fraction of 35% or less. After baseline measurements, the patients were randomized to placebo (n = 16) or enalapril (10 mg BID, n = 26). In the placebo group, the changes in left ventricular function were characterized by increases in end-diastolic (159 +/- 43 to 170 +/- 44 mL/m2) and end-systolic (119 +/- 38 to 128 +/- 49 mL/m2) volumes accompanied by a downward and rightward shift of the diastolic pressure-volume relation. In contrast, decreases in end-diastolic (166 +/- 43 to 156 +/- 47 mL/m2) and end-systolic (125 +/- 43 to 111 +/- 42 mL/m2) volumes accompanied by a slight upward and leftward shift of the diastolic pressure-volume relation were noted in the enalapril group. These changes in left ventricular volumes were significantly different between groups (both P < .005) but were not attended by changes in left ventricular end-diastolic pressure, in time constant of isovolumic pressure decrease, or in right ventricular volumes. However, the chamber stiffness constant beta decreased from 0.044 +/- 0.027 to 0.032 +/- 0.019 mL-1/m2 in the placebo group, whereas it increased insignificantly in the enalapril group (0.040 +/- 0.028 to 0.041 +/- 0.028 mL-1/m2). These changes in chamber stiffness constant beta between baseline and follow-up were significantly different between placebo and enalapril groups (P < .05). Another index of chamber compliance, delta V/delta P, also confirmed the presence of opposite changes in left ventricular chamber compliance in the placebo group and in the enalapril group. The mean diastolic wall stress increased with placebo but not with enalapril (+51 versus -13 kdyn/cm2; P < .04) whereas left ventricular mass and the indexes of left ventricular sphericity tended to improve in the enalapril group. The changes in plasma levels of norepinephrine, atrial natriuretic peptide, and arginine vasopressin were, however, comparable in both groups. CONCLUSIONS: The data indicate that in patients with severe systolic left ventricular dysfunction, the progressive left ventricular dilatation was accompanied by a decrease in left ventricular chamber stiffness; enalapril therapy was able to prevent or partially reverse these changes and tended to reduce left ventricular mass and ventricular sphericity. Those changes were suggestive of partial reversal of left ventricular remodeling by enalapril administration.

Adult↗

Cardiac mechanics during development of heart failure. SOLVD Investigators.

BACKGROUND: The changes in myocardial performance responsible for the progression from a stage of asymptomatic left ventricular dysfunction toward overt congestive heart failure are still poorly understood. Accordingly, using invasive methods, we examined the differences in baseline left ventricular function between a subgroup of patients enrolled in the treatment arm (presence of congestive heart failure) and in the prevention arm (asymptomatic patients) of the Studies of Left Ventricular Dysfunction. METHODS AND RESULTS: High-fidelity left ventricular pressures and frame-by-frame angiographic volumes were simultaneously obtained under baseline conditions in 65 patients with left ventricular ejection fraction < or = 35%. Sixteen patients had New York Heart Association congestive heart failure (class II or III), whereas the remaining 49 patients had no clinical signs of heart failure and did not receive therapy for this syndrome. A second set of data was obtained an average of 12.4 months later in 42 patients. The group with heart failure had significantly greater end-diastolic and end-systolic volumes than the asymptomatic group (both p < 0.001), but the stroke index at rest was similar in both groups. Accordingly, ejection fraction was significantly lower in the heart failure group (19.6 +/- 7.0% versus 26.3 +/- 7.2%; p < 0.02). Left ventricular end-diastolic pressure was greater and peak +dP/dt was lower in heart failure patients, but the difference did not reach statistical significance after Bonferroni correction for multiple comparisons. Moreover, the individual end-systolic stress/end-systolic volume data of the heart failure patients fell within the 95% confidence interval of the relation observed in the patients without heart failure both at baseline and after 1 year of follow-up irrespective of their changes in functional status. It was also noted that during follow-up, the changes in end-diastolic and end-systolic volumes correlated linearly, as if both dimensions always shifted in parallel, whereas alterations in contractility primarily influence end-systolic volume. CONCLUSIONS: These observations are compatible with the hypothesis that a depression in the mechanical performance of the viable myocardial areas is not the major determinant for the progression from asymptomatic to symptomatic left ventricular dysfunction. Abnormalities in left ventricular diastolic distensibility, on the other hand, might underlie the progressive ventricular dilation and create a vicious cycle through the afterload mismatch.

Adult↗

Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions.

An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions < or = 0.35 enrolled into the two Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n = 2569) and those without heart failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02; prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001; 355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group (risk reduction 23%, 95% CI 11-34%; p < 0.001). 595 placebo group patients developed unstable angina compared with 499 in the enalapril group (risk reduction 20%, 95% CI 9-29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615 enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths, myocardial infarction, and unstable angina was highly significant (20% risk reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions.

Angina, Unstable↗