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PubMedDate not supplied

Enalapril and enalapril-hydrochlorothiazide in the treatment of essential hypertension. The Enalapril-Hydrochlorothiazide in Essential Hypertension Canadian Working Group.

A total of 217 patients with essential hypertension were enrolled by 25 Canadian centers in this double-blind, parallel study to compare the efficacy and safety of enalapril administered alone or in combination with hydrochlorothiazide. After a 4-week placebo period, patients were given 10 mg of enalapril for 2 weeks. At the end of the 2 weeks of therapy, patients were maintained on the same dose of enalapril, titrated to a higher dose of enalapril, or received combination therapy with hydrochlorothiazide if their diastolic blood pressure remained > 90 mmHg. Patients in group 1 received enalapril 10 mg or 20 mg and those in group 2 received enalapril 10 mg alone or combined with hydrochlorothiazide 25 mg. The maintenance phase lasted 8 weeks. A standard mercury sphygmomanometer was used to measure blood pressure at each visit. The mean decrease in supine diastolic blood pressure (SDBP) was 16 mmHg in groups 1 and 2; the mean decrease in supine systolic blood pressure (SSBP) was 19 mmHg in group 1 and 20 mmHg in group 2. Eighty percent of the patients in group 1 and 81% of those in group 2 had an SDBP < or = 90 mmHg at the final visit. To achieve this control, 67% of the patients received enalapril 10 mg and 33% received enalapril 20 mg in group 1. In group 2, 70% of the patients received enalapril 10 mg and 30% received enalapril 10 mg plus hydrochlorothiazide 25 mg. Eighteen patients in group 1 and 17 patients in group 2 experienced one or more minor adverse events. The most frequently reported adverse events were headache, asthenia, abdominal pain, nausea, and dizziness. No major adverse events were observed. We conclude that enalapril used alone reduces blood pressure in the majority of patients with mild to moderate essential hypertension. When blood pressure is not controlled by enalapril alone, hydrochlorothiazide can safely be added to the regimen.

Adult↗

PubMed1999

Comparison of two strategies for intensifying antihypertensive treatment: low-dose combination (enalapril + felodipine ER) versus increased dose of monotherapy (enalapril). LEVEL (Lexxel vs Enalapril) Study Group.

To compare two popular strategies for intensifying treatment for hypertension, a double-blind, randomized, prospective, parallel-group, and partial crossover study was done. After 2 weeks of placebo run-in (baseline) and 3 weeks of 5 mg enalapril once daily, 217 patients were randomized to 6 weeks of treatment with either a low-dose combination therapy (5 mg enalapril + 5 mg felodipine ER once daily, Lexxel, Astra Merck, Inc.), or a higher dose of monotherapy (10 mg enalapril once daily, Vasotec, Merck & Co., Inc.). The group randomized to the combination had significantly greater reductions in sitting systolic/diastolic blood pressure (BP)--14.2/10.6 mm Hg compared with baseline versus 9.6/7.4 mm Hg (P < .05/.01)--as well as a greater percentage of patients having achieved either diastolic BP < 90 mm Hg or a decline of at least 10 mm Hg (responders), 59% v 41% (P < .01). When patients originally taking 10 mg enalapril were crossed over to the combination therapy for a further 6 weeks, there was a further BP reduction and increase in response rate, with loss of significant differences compared with those treated continuously with the combination for the entire 12 weeks. The greater BP-lowering efficacy of the combination was independent of age, gender, and race. There were no significant differences in tolerability between the regimens. These data support the hypothesis that in patients who do not achieve goal BP reduction with a low dose of an antihypertensive agent, a combination of two drugs with complementary mechanisms of action is more effective than increasing the dose of the first agent.

Aged↗

PubMed2005

Pharmacokinetics and pharmacodynamics profiles of enalapril maleate in healthy volunteers following determination of enalapril and enalaprilat by two specific enzyme immunoassays.

BACKGROUND AND OBJECTIVES: Most of the pharmacokinetic (PK) parameters for enalapril and enalaprilat were established following determination of the drug and its metabolite, using angiotensin converting enzyme (ACE) inhibition assays. In these methods, enalapril has to be hydrolysed to enalaprilat first and then assayed. The purpose of this study was to re-estimate the PK parameters of enalapril and enalaprilat in healthy volunteers using two specific enzyme immunoassays for enalapril and enalaprilat. METHODS: The rate and extent of absorption of enalapril and enalaprilat from a 10-mg dose of two enalapril maleate commercial brands (Renetic and Enalapril) were estimated using a two-way-cross over design with 1-week washout period. Blood pressure was also measured at specified time intervals and correlated to enalaprilat plasma concentrations. RESULTS: For enalapril, the AUC(o-->infinity) values (Mean+/-SD) were 450.0+/-199.5 and 479.6+/-215.6 ng h/mL, Cmax values were 313.5+/-139.6 and 310.1+/-186.6 ng/mL, Tmax values were 1.06+/-0.30 h and 1.13+/-0.22 h, and t1/2 ranged between 0.3 to 6.1 h (1.6+/-1.5) and 0.40 to 5.05 h (1.3+/-1.0), for the two brands. For enalaprilat, the AUC(o-->infinity) values were 266.9+/-122.7 and 255.9+/-121.8 ng h/ml, Cmax values were 54.8+/-29.5 and 57.2+/-29.0 ng/mL, Tmax values were 4.6+/-1.6 h and 4.3+/-1.45 h, and t1/2 ranged between 1.1 to 10.5 h (4.5+/-2.9) and 0.6 to 9.4 h (3.5+/-2.5) for the two brands. CONCLUSIONS: Cmax values for enalapril are about 10 times those published in the literature and the rate and extent of absorption of the two brands of enalapril and their deesterification to enalaprilat following the administration of either brand were bioequivalent. Secondly, enalaprilat concentrations at 12-24 h following a single oral dose of enalapril in healthy volunteers were lower than those reported in the literature. The values reported here correlated with the return of blood pressure to predose level. Thirdly, enzyme immunoassays for enalapril and enalaprilat are better than ACE inhibition assays and can be used in bioequivalence assessment of enalapril and enalaprilat and for therapeutic drug monitoring in a clinical laboratory setting.

Absorption↗

PubMed1992

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)

BACKGROUND: Long-term administration of angiotensin-converting--enzyme (ACE) inhibitors has been shown to improve survival in patients with symptomatic left ventricular failure and to attenuate left ventricular dilatation in patients with myocardial infarction. We studied whether mortality could be reduced during the 6 months after an acute myocardial infarction with use of the ACE inhibitor enalapril. METHODS: At 103 Scandinavian centers patients with acute myocardial infarctions and blood pressure above 100/60 mm Hg were randomly assigned to treatment with either enalapril or placebo, in addition to conventional therapy. Therapy was initiated with an intravenous infusion of enalapril (enalaprilat) within 24 hours after the onset of chest pain, followed by administration of oral enalapril. RESULTS: Of the 6090 patients enrolled, 3046 were assigned to placebo and 3044 to enalapril. The life-table mortality rates in the two groups at one and six months were not significantly different (6.3 and 10.2 percent in the placebo group vs. 7.2 and 11.0 percent in the enalapril group, P = 0.26). The relative risk of death in the enalapril group was 1.10 (95 percent confidence interval, 0.93 to 1.29). Death due to progressive heart failure occurred in 104 patients (3.4 percent) in the placebo group and 132 (4.3 percent) in the enalapril group (P = 0.06). Therapy had to be changed because of worsening heart failure in 30 percent of the placebo group and 27 percent of the enalapril group (P less than 0.006). Early hypotension (systolic pressure less than 90 mm Hg or diastolic pressure less than 50 mm Hg) occurred in 12 percent of the enalapril group and 3 percent of the placebo group (P less than 0.001). CONCLUSIONS: Enalapril therapy started within 24 hours of the onset of acute myocardial infarction does not improve survival during the 180 days after infarction.

Administration, Oral↗

PubMedDate not supplied

Long-term efficacy, tolerability, and safety of the combination of enalapril and felodipine ER in the treatment of hypertension. Enalapril-Felodipine ER Factorial Study Group.

A recent 8-week, double-masked, placebo-controlled, 3 x 4 factorial-design study demonstrated that enalapril-felodipine extended-release (ER) combinations had statistically significant additive effects for reducing both sitting systolic blood pressure (SiSBP) and sitting diastolic blood pressure (SiDBP) and were generally well tolerated in hypertensive patients with SiDBPs ranging from 95 to 115 mm Hg. The present open-label study was undertaken to assess the long-term efficacy, tolerability, and safety of such combinations. Patients from the factorial study were eligible for the 1-year, open-label extension. Initially, all patients received enalapril 5 mg-felodipine ER 2.5 mg once daily; if SiDBP was not controlled (< 90 mm Hg) after 4 weeks of treatment, the dose was titrated upward at 2- to 4-week intervals to a maximum of enalapril 10 mg-felodipine ER 10 mg. Hydrochlorothiazide (HCTZ) 12.5 mg was added to the regimen of patients whose hypertension was not controlled at the highest enalapril-felodipine ER dose. A total of 507 patients were enrolled, of whom 502 were assessable. At their last study visit, 391 (78%) of the assessable patients were receiving only an enalapril-felodipine ER combination. The enalapril-felodipine ER combinations resulted in mean trough SiDBPs of 85 to 89 mm Hg (decreases of 13 to 16 mm Hg from baseline) and SiSBPs of 137 to 140 mm Hg (decreases of 13 to 21 mm Hg). Overall, 407 (81%) of the 502 assessable patients achieved an SiDBP < 90 mm Hg or a reduction from baseline > or = 10 mm Hg (responders); such a response was recorded in 331 patients (66%) taking a combination of enalapril-felodipine ER alone and 76 patients (15%) taking the combination with the addition of HCTZ 12.5 mg. Blood pressure reductions were maintained throughout the treatment period. Drug-related adverse events were relatively infrequent, often transient, usually mild, and apparently not dose related. The most frequently reported drug-related adverse events were edema/swelling, asthenia/fatigue, dizziness, cough, and headache. These results suggest that combination therapy with enalapril-felodipine ER is effective for long-term blood pressure reduction, has an excellent safety profile, and is generally well tolerated. Addition of low-dose HCTZ to the enalapril-felodipine ER combination appears to provide further blood pressure control without increasing drug-related adverse events.

Adult↗

PubMedDate not supplied

Controlled clinical evaluation of enalapril in dogs with heart failure: results of the Cooperative Veterinary Enalapril Study Group. The COVE Study Group.

The clinical efficacy and safety of enalapril were evaluated in dogs with moderate or severe heart failure. This study was conducted at 19 centers and included 211 client-owned dogs with heart failure caused by mitral regurgitation (MR) due to acquired valvular disease or dilated cardiomyopathy (DCM). Dogs of various breeds, ages, and weights were included in the study. Replicates of 2 dogs each were formed, using separate allocation schedules for dogs with MR or DCM. One dog within each replicate received placebo tablets (vehicle tablets without enalapril) PO sid or bid, and the other dog received enalapril tablets at approximately 0.5 mg/kg sid or bid, based on individual need. In addition to the experimental drug, all dogs, except 1 in the placebo group, received furosemide; 73.3% of the dogs in the placebo group and 78.3% of those in the enalapril group received digoxin. Doses of enalapril or placebo were administered for approximately 28 days. In the placebo group, 68.6% of the dogs completed the study compared with 84.9% in the enalapril group; the difference between groups was significant (P < .01). Significantly (P < .01) more dogs in the placebo group compared with the enalapril group died or were removed from the study because of progression of heart failure. On day 28, all 14 clinical variables measured improved significantly (P < .01) in the enalapril group compared with the placebo group. Five dogs (3 from the placebo group and 2 from the enalapril group) had to be removed from the study as a result of azotemia.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Reduction in left ventricular hypertrophy in hypertensive patients treated with enalapril, losartan or the combination of enalapril and losartan.

OBJECTIVE: To compare the regression of left ventricular hypertrophy in patients with moderate hypertension treated with enalapril, losartan or a combination of the two drugs at lower doses. METHODS: Patients of both sexes with moderate hypertension confirmed by ambulatory monitoring of arterial blood pressure and with left ventricular hypertrophy on echocardiogram were assigned to three groups: enalapril (35 mg/day, n=15), losartan (175 mg/day, n=15) and enalapril losartan (15 mg+100 mg/day, n=16). The patients received the drugs for 10 months. RESULTS: The three therapeutic regimens were equally effective in reducing blood pressure and left ventricular mass index (LVMI, g/m2): 141+/-3.9 to 123+/-3.6 in the enalapril group (p<0.05), from 147+/-3.8 to 133+/-2.8 in the losartan group (p<0.05), and from 146+/-3.0 to 116+/-4.0 in the enalapril+losartan group (p<0.05). However, the percent reduction of LVMI was significantly greater (p<0.01) in the enalapril+losartan group (20.5+/-5.0%) than in enalapril (12.4+/-3.2%) and the losartan (9.1+/-2.1%) groups. Normalization of LVMI was obtained in 10 out of the 16 patients who received enalapril+ losartan, in 6 out of the 15 patients who received only enalapril and in 4 out of the 15 patients treated with losartan. CONCLUSION: The combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist (AT1 receptor antagonist) in patients produced an additional effect on the reduction of left ventricular hypertrophy. This finding may depend on a more complete inhibition of the cardiac renin-angiotensin.

Adult↗

PubMed1987

Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS).

To evaluate the influence of the angiotensin-converting-enzyme inhibitor enalapril (2.5 to 40 mg per day) on the prognosis of severe congestive heart failure (New York Heart Association [NYHA] functional class IV), we randomly assigned 253 patients in a double-blind study to receive either placebo (n = 126) or enalapril (n = 127). Conventional treatment for heart failure, including the use of other vasodilators, was continued in both groups. Follow-up averaged 188 days (range, 1 day to 20 months). The crude mortality at the end of six months (primary end point) was 26 percent in the enalapril group and 44 percent in the placebo group--a reduction of 40 percent (P = 0.002). Mortality was reduced by 31 percent at one year (P = 0.001). By the end of the study, there had been 68 deaths in the placebo group and 50 in the enalapril group--a reduction of 27 percent (P = 0.003). The entire reduction in total mortality was found to be among patients with progressive heart failure (a reduction of 50 percent), whereas no difference was seen in the incidence of sudden cardiac death. A significant improvement in NYHA classification was observed in the enalapril group, together with a reduction in heart size and a reduced requirement for other medication for heart failure. The overall withdrawal rate was similar in both groups, but hypotension requiring withdrawal occurred in seven patients in the enalapril group and in no patients in the placebo group. After the initial dose of enalapril was reduced to 2.5 mg daily in high-risk patients, this side effect was less frequent. We conclude that the addition of enalapril to conventional therapy in patients with severe congestive heart failure can reduce mortality and improve symptoms. The beneficial effect on mortality is due to a reduction in death from the progression of heart failure.

Aged↗

PubMed1990

Comparative efficacy and safety of enalapril and sustained-release nifedipine in patients with mild to moderate hypertension. The Enalapril vs Nifedipine French Study Group.

The long acting angiotensin-converting enzyme inhibitor enalapril was compared with the calcium channel blocker nifedipine as sustained-release formulation in 136 patients with mild to moderate hypertension. This multicentre study was carried out in a double-blind, double-dummy fashion by 28 cardiologists in private practice. After a 2-week placebo period, patients were randomly allocated to 2 treatment groups; the first group received enalapril 20 mg daily (n = 68), and the second group received sustained-release nifedipine 20 mg twice daily (n = 68). The duration of treatment was 12 weeks. In both groups, hydrochlorothiazide 25 mg was added at week 4 if diastolic blood pressure remained greater than 90 mm Hg. At week 8, if the target diastolic pressure of less than 90 mm Hg was not achieved, the dosage of hydrochlorothiazide was increased to 50mg. The clinical characteristics of the patients in each group were comparable. After 4 weeks of treatment, the reduction in supine diastolic blood pressure was similar in both groups (12.1 mm Hg in the enalapril group vs 10.3 mm Hg in the nifedipine group). Moreover, although the difference between the groups was more noticeable after 12 weeks of treatment (16.3 vs 13.9 mm Hg, respectively), it did not reach significance. The number of patients experiencing clinical adverse effects was significantly greater in the nifedipine group than in the enalapril group [33 (48.5%) vs 18 (26.5%), respectively]. The most common complaints of patients administered nifedipine included swollen ankles, flushing and headaches, whereas complaints in the enalapril group included cough, asthenia, and epigastralgia. Three patients were withdrawn from the study because of side effects in the enalapril group and 10 were withdrawn from the nifedipine group. These results indicate that enalapril and sustained-release nifedipine are equally effective in controlling mild to moderate hypertension. However, enalapril was much better tolerated in this study.

Double-Blind Method↗

PubMed2005

Enalapril and diltiazem co-administration and respiratory side effects of enalapril.

A persistent, chronic dry cough is the most common adverse effect of angiotensin converting enzyme (ACE) inhibitors therapy. The mechanism of this respiratory adverse effect is related to the inhibition of ACE and the accumulation of bradykinin, substance P, prostanoids and other inflammatory neuropeptides in the airways. The aim of this study was to follow the relationship between 15-day administration of enalapril and the defense reflexes (cough and bronchoconstriction) of the airways in experimental animals, as well as the possibility of their pharmacological restriction with simultaneous diltiazem administration. Cough reflex was investigated by the method of mechanical irritation of laryngopharyngeal and tracheobronchial area in non-anesthetized cats. The reactivity of tracheal smooth muscles of the airways to bronchoconstrictor mediators (histamine 10 nM - 1 mM, acetylcholine 10 nM - 1 mM and KCl 1 mM - 100 mM) was evaluated by an in vitro method in guinea pigs. Enalapril 5 mg/kg/day and diltiazem 30 mg/kg/day were administered perorally for 15 days. The results showed that long-lasting administration of enalapril resulted in a significant increase of measured cough parameters and increased reactivity of tracheal smooth muscle to histamine and KCl. Simultaneous administration of enalapril together with diltiazem significantly decreased the enalapril induced cough, and decreased enalapril induced hyperreactivity of tracheal smooth muscles to KCl. The results showed a partially protective effect of diltiazem and enalapril co-administration on the respiratory adverse effects induced by enalapril therapy.

Animals↗

PubMed1985

A parallel study of enalapril and captopril and 1 year of experience with enalapril treatment in moderate-to-severe essential hypertension.

Angiotensin converting enzyme (ACE) inhibitors, enalapril (5 to 20 mg twice daily) or captopril (25 to 100 mg thrice daily) and matching ACE inhibitor placebos were given to 32 moderate-to-severe essential hypertension patients who were already on 50 mg hydrochlorothiazide daily. Alpha-methyldopa (250 to 500 mg twice daily) was given to 16 patients following 6 weeks of ACE inhibitor therapy. Both enalapril and captopril significantly (p less than 0.05) lowered the supine and upright blood pressures (BPs) (acutely and long-term) without significant reflex heart rate changes. The BPs of enalapril patients were, however, significantly lower (supine diastolic p less than 0.03, supine systolic p less than 0.05, and upright diastolic p less than 0.04) than those of captopril patients when compared by repeated measures of analysis of variance. Eleven enalapril patients have been followed for 1 year with continued BP control. Skin rash occurred in one captopril patient and reversible renal insufficiency developed in two enalapril patients during the first 16 weeks. It is concluded that (although both ACE inhibitors lowered BP, enalapril was more effective than captopril and twice-daily enalapril was well tolerated during 52 weeks of treatment.

Blood Pressure↗

PubMed1992

Renal function in severe congestive heart failure during treatment with enalapril (the Cooperative North Scandinavian Enalapril Survival Study [CONSENSUS] Trial).

The effect on renal function of long-term treatment with either enalapril (n = 123) or placebo (n = 120) in addition to conventional therapy was studied in a randomized trial in patients with severe congestive heart failure (New York Heart Association functional class IV; the Cooperative North Scandinavian Enalapril Survival Study). Enalapril was administered in a dose of 2.5 to 40 mg/day. The analysis was restricted to the first 6 months of treatment. There was an average initial increase of 10 to 15% (10 to 20 mumol/liter) irrespective of baseline serum creatinine within the first 3 weeks of enalapril treatment, whereafter mean serum creatinine remained on a similar level during the first 6 months. Enalapril was well-tolerated by most patients, and serum creatinine was reduced in 24%. Serum creatinine increased by greater than 100% in 13 patients (11%) in the enalapril group (mainly as a consequence of intercurrent disease or severe hypotension, and usually transiently) and in 4 (3%) in the placebo group. The maximal increase in serum creatinine in the enalapril group was inversely correlated to the diastolic blood pressure (p = 0.008) at baseline and to the mean diastolic and systolic blood pressures measured at the time of the maximal increase in serum creatinine (p = 0.0001). According to multivariate regression analysis, the maximal increase in serum creatinine was also slightly influenced by the dose of furosemide taken. The development of hypotension emerged as the strongest factor explaining an abnormal increase in serum creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

Effect on exercise performance of enalapril therapy initiated early after myocardial infarction. Nordic Enalapril exercise Trial.

OBJECTIVES: The Nordic Enalapril Exercise Trial was a multicenter subtrial of the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II) designed to evaluate the effect on maximal exercise performance of a 6-month period of enalapril treatment initiated early after myocardial infarction. BACKGROUND: When begun early after myocardial infarction, converting enzyme inhibition therapy has been shown to attenuate infarct expansion and reduce left ventricular volume. Therapy has been associated with improved exercise performance. METHODS: Three hundred twenty-seven men (mean age 63.3 +/- 10.9 years) with documented acute myocardial infarction were randomized to treatment with enalapril or placebo on a double-blind basis. Intravenous enalaprilat or placebo therapy was initiated within 24 h after the onset of symptoms. Oral therapy was continued at a target dose of 20 mg/day. Patients exercised maximally at 1 month and 6 months after infarction to symptom-limited end points on a cycle ergometer with a 20 W/min incremental protocol. RESULTS: The treatment and control groups were comparable in patient age, concurrent therapy and type and site of infarction. At 1 month, for all patients, mean total work performed was 34.9 +/- 20.9 kJ in the enalapril group (n = 169) versus 28.5 +/- 20.6 kJ in the placebo group (n = 158) (difference = 18.4%, p < 0.01). This between-group difference in favor of enalapril was greatest in patients > 70 years old (difference = 41.4%, p < 0.01, n = 105) and those with clinical evidence of heart failure (difference = 33.0%, p < 0.01, n = 122). At 6 months for all patients, mean total work performed was 35.4 +/- 23.8 kJ in the enalapril group versus 34.0 +/- 23.9 kJ in the placebo group (difference = 4.1%, NS). CONCLUSIONS: This trial found that chronic converting enzyme inhibition initiated early after myocardial infarction was associated with significantly greater exercise capacity in men tested at 1 month. This difference was independent of type or site of infarction, patient age or the presence of clinical heart failure. The difference between the treatment and control groups was not significant at 6 months because of improvement in the placebo group. Further research is needed to elucidate the potential mechanisms involved, profile those patients most likely to profit from early therapy and establish the optimal timing and duration for intervention.

Administration, Oral↗

PubMed2004

Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial.

BACKGROUND: Recent reports suggest that existing antihypertensive agents may not have sufficient efficacy to control blood pressure (BP) in many patients. Omapatrilat, an agent under development, has been shown to have significantly greater antihypertensive efficacy than existing agents, but may also carry increased risk of angioedema. We compared the efficacy and safety of omapatrilat to a representative angiotensin-converting enzyme (ACE) inhibitor, enalapril. METHODS: The Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial is a multicenter, randomized, double-blind, active-controlled, 24-week trial in 25,302 patients with untreated or uncontrolled hypertension conducted in 3298 office-based sites in 12 countries. Subjects were randomized to omapatrilat 10 mg or enalapril 5 mg as initial therapy for hypertension (group 1, n = 9292), replacement for existing antihypertensive therapy (group 2, n =11,224), or in addition to existing antihypertensive therapy (group 3, n = 4751). Study drug was force-titrated at week 2 and electively titrated at weeks 4 and 6 to a maximum of omapatrilat 80 mg or enalapril 40 mg once daily. At weeks 8 and 16, adjunctive antihypertensive medications were added electively to achieve target BP. RESULTS: Omapatrilat reduced systolic BP 3.6 mm Hg more than enalapril at week 8, and was associated with less use of adjunctive antihypertensive therapy by week 24 (19% v 27%; P < 0.001 for both comparisons). Subjects randomized to omapatrilat were more likely to reach BP target, regardless of demographics or comorbid conditions and whether omapatrilat was used as initial therapy, replacement for existing therapy, or in addition to existing therapy. Angioedema was more frequent with omapatrilat than enalapril (2.17% v 0.68%). Two omapatrilat-treated subjects experienced angioedema with airway compromise, which was successfully treated. CONCLUSIONS: Omapatrilat provided broadly superior antihypertensive efficacy when used in a setting resembling clinical practice. Angioedema was more common than with enalapril but life-threatening angioedema was rare. The risk-benefit profile for omapatrilat in clinical use therefore appears likely to be favorable in appropriate patients.

Adolescent↗

PubMed1997

Combined enalapril and felodipine extended release (ER) for systemic hypertension. Enalapril-Felodipine ER Factorial Study Group.

This multicenter, placebo-controlled, double-blind trial of factorial design evaluated the safety and efficacy of combination treatment with the angiotensin-converting enzyme inhibitor, enalapril, and the vascular selective calcium antagonist felodipine extended release (ER) in patients with essential hypertension. After a 4-week, single-blind placebo baseline period, 707 patients with sitting diastolic blood pressures (BPs) in the range of 95 to 115 mm Hg received placebo, enalapril (5 or 20 mg), felodipine ER (2.5, 5, or 10 mg), or their combinations for an 8-week double-blind treatment period. All doses of enalapril and felodipine ER had a statistically significant (p < 0.05) additive effect in reducing both systolic and diastolic BP. The trough to peak ratios for the combinations ranged from 0.63 (enalapril 5 mg-felodipine ER 2.5 mg) to 0.79 (enalapril 20 mg-felodipine ER 10 mg) and were consistent with effective BP control with 1 dose/day. Patients aged > or = 65 years demonstrated a greater reduction in diastolic BP. Combinations of enalapril-felodipine ER were associated with less drug-induced peripheral edema (4.1%) compared to felodipine ER monotherapy (10.8%). There were no serious drug-related adverse effects observed during the study. In this trial, the combination of enalapril and felodipine ER effectively lowered BP and was generally well tolerated with an excellent safety profile when used in the treatment of hypertension.

Aged↗

PubMed1994

Long-term efficacy and safety of pimobendan in moderate heart failure. A double-blind parallel 6-month comparison with enalapril. The Pimobendan-Enalapril Study Group.

In view of growing scepticism as to the efficacy and safety of agents with predominant phosphodiesterase inhibiting properties in heart failure, the clinical efficacy and safety of pimobendan, a calcium-sensitizing and partially phosphodiesterase-inhibiting compound, was compared with enalapril in 242 patients with mild to moderate heart failure (NYHA classification II-III) despite diuretics and digitalis, and abnormal haemodynamics at baseline. Patients were randomly assigned to either pimobendan (average 10.3 mg.day-1, n = 119), or enalapril (average 10.7 mg.day-1, n = 123) in a double-blind fashion for 6 months. Forty-two pimobendan and 37 enalapril patients stopped the treatment, five pimobendan and six enalapril due to worsening of failure without death, whereas 13 and eight patients, respectively, died from cardiac disorders (ns). Other reasons for discontinuation and adverse events not leading to discontinuation were also comparable. Although Holter analysis at 14 days, but not at 6 months, indicated increased ventricular extrasystoles in pimobendan patients, these did not lead to serious clinical events. NYHA classification improved similarly in both groups, from 2.51 to 2.16 (pimobendan) and from 2.40 to 2.06 (enalapril). The number of patients needing a change in background therapy or hospitalization did not differ between the two groups. Haemodynamic variables at rest were improved by both compounds after 6 months. In contrast, only enalapril improved haemodynamics during exercise, and reduced the cardiothoracic ratio. The primary endpoint, exercise capacity, increased significantly during the first 3 months by 45 and 53 s, under pimobendan and enalapril, respectively, but, although unchanged thereafter, the improvement was no longer statistically significant at 6 months in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗

PubMed1984

Enalapril in essential hypertension: a comparative study with propranolol. Enalapril in Hypertension Study Group (UK).

We report the first comparative study on enalapril maleate, a new angiotensin converting enzyme inhibitor, in patients with uncomplicated mild to moderate essential hypertension. Fifty-four patients were randomly assigned to treatment with enalapril or propranolol for 16 weeks following a placebo run-in-phase. The study was double-blind. Enalapril and propranolol both reduced blood pressure, though the changes were significantly treated with enalapril were normotensive at the end of the study. Enalapril treatment was associated with a significant reduction in weight. Both drugs raised plasma potassium and urea. No haematological abnormalities occurred with enalapril and there were no reports of rash, taste disturbance or proteinuria. At the end of the trial the mean daily dose of enalapril was 20 mg and that of propranolol was 180 mg.

Adult↗

PubMedDate not supplied

Acute and short-term hemodynamic, echocardiographic, and clinical effects of enalapril maleate in dogs with naturally acquired heart failure: results of the Invasive Multicenter PROspective Veterinary Evaluation of Enalapril study. The IMPROVE Study Group.

The efficacy of enalapril maleate in dogs with naturally acquired class III or class IV heart failure was evaluated in a multicenter study. Fifty-eight dogs with dilated cardiomyopathy (35 dogs), mitral regurgitation (22 dogs), or aortic regurgitation (1 dog) receiving conventional therapy for heart failure (furosemide with or without digoxin) were included in a randomized double-blind study. Thirty-one dogs received enalapril tablets PO at approximately 0.5 mg/kg body weight bid, and 27 dogs received placebo tablets PO bid. Physical, electrocardiographic, hemodynamic, echocardiographic, radiographic, and clinical examinations were performed on each dog before treatment and at the end of the approximately 21-day study. After treatment on day 0, the enalapril-treated dogs had significantly (P < .05) lower heart rate, mean systemic arterial blood pressure, and mean pulmonary arterial blood pressure than the placebo-treated dogs. Pulmonary capillary wedge pressure was marginally decreased (P = .0567) in the enalapril-treated dogs. When compared with those in the placebo-treated dogs, scores for pulmonary edema were significantly (P < .05) decreased on day 2 in the enalapril-treated dogs. At the end of the study, enalapril-treated dogs had significantly (P < .05) greater decreases in class of heart failure, pulmonary edema score, and mobility score relative to baseline, and had significantly (P < .05) better overall evaluation scores when compared with the placebo-treated dogs. This study shows the beneficial hemodynamic and clinical effects of adding enalapril to conventional therapy for dogs with heart failure.

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