A Prospective Comparative Study of Efficacy and Pleiotropic Effect of Telmisartan versus Enalapril in Hypertensive Patients with Dyslipidaemia in a Tertiary Care Hospital in Visakhapatnam

BACKGROUND Hypertension is a silent killer, an asymptomatic chronic disorder if left untreated which results in major health problems. Goal of treatment is to decrease the morbidity and mortality associated with cardiovascular and cerebrovascular complications of hypertension when it is associated with dyslipidaemia. The renin angiotensin system plays an important role in the regulation of blood pressure and in the pathogenesis of hypertension. Telmisartan is an ARB (angiotensin receptor blocker) and Enalapril is an ACE inhibitor. The purpose of this study is to compare the efficacy of Telmisartan with Enalapril in patients of essential hypertension with dyslipidaemia, and to observe the effects of Telmisartan and Enalapril on blood lipid levels of these patients. METHODS This is a prospective, randomized, comparative and open label study conducted among 70 patients who were included in the study and were divided in to two groups. Group A - consisting of 35 patients receiving Telmisartan 40 mg, and Group B receiving Enalapril 5 mg orally once a day. Informed consent was obtained from all the patients. Follow up was done after 4, 8 and 12 weeks. Blood pressure was recorded at every visit and lipid profile was done at the time of enrolment and after 12 weeks of study period. RESULTS Baseline demographic attributes were comparable between both the groups including total cholesterol and low-density lipoprotein (LDL). The mean reduction in systolic and diastolic blood pressure (BP) after 12 weeks was highly significant (P value < 0.001) in both the groups but when mean reduction in SBP & DBP was compared, there was no significant difference (P > 0.05) between the drugs. Blood levels of total cholesterol, LDL, triglyceride had significantly reduced (P < 0.05) in Telmisartan group compared to Enalapril group after 12 weeks of follow up and mean high density lipoprotein (HDL) level significantly increased in Telmisartan group (P < 0.05) but no increment was seen in Enalapril group. CONCLUSIONS Telmisartan and Enalapril had comparable antihypertensive effect and significant reduction in blood pressure was seen after 12 weeks of therapy in both the groups. In addition, Telmisartan showed more beneficial effects on lipid profile when compared to Enalapril. KEYWORDS Hypertension, Dyslipidemia, Lipid Profile, Telmisartan, Enalapril

Angiotensin-converting enzyme inhibition and pre-superior cavopulmonary connection haemodynamics in infants with single-ventricle physiology

Introduction: Preliminary animal and human data suggest that angiotensin-converting enzyme inhibition has a role in pulmonary vascular remodelling. We sought to assess the effect of ACEi versus placebo on pulmonary artery pressure and transpulmonary gradient amongst infants undergoing single-ventricle palliation. Materials and methods: Using the publicly available Pediatric Heart Network Infant Single-Ventricle trial dataset, we compared mean PA pressure at pre-superior cavopulmonary connection catheterisation (primary outcome), transpulmonary gradient, pulmonary-to-systemic flow ratio, and post-SCPC oxygen saturation (secondary outcomes) in infants receiving enalapril versus placebo. Results: A total of 179 infants underwent pre-SCPC catheterisation, of which 85 (47%) received enalapril. There was no difference between the enalapril and placebo group in the primary and the secondary outcomes. Mean PA pressure in the enalapril group was 13.1 ± 2.9 compared to 13.7 ± 3.4 mmHg in the placebo group. The transpulmonary gradient was 6.7 ± 2.5 versus 6.9 ± 3.2 mmHg in the enalapril and placebo groups, respectively. The pulmonary-to-systemic flow ratio was 1.1 ± 0.5 in the enalapril group versus 1.0 ± 0.5 in the placebo group and the post-SCPC saturation was 83.1 ± 5.0% in the enalapril group versus 82.2 ± 5.3% in the placebo group. In the pre-specified subgroup analyses comparing enalapril and placebo according to ventricular morphology and shunt type, there was no difference in the primary and secondary outcomes. Conclusion: ACEi did not impact mean pulmonary artery pressure or transpulmonary gradient amongst infants with single-ventricle physiology prior to SCPC palliation.

Abstract 17063: Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure

Background: In patients with heart failure, chronic kidney disease (CKD) is associated with a higher risk of renal events than in patients without CKD, irrespective of the ejection fraction. We assessed the renal effects of angiotensin/neprilysin inhibition in patients with heart failure in a pooled analysis of 13,195 patients with reduced and preserved ejection fraction. Methods: We combined data from PARADIGM-HF (LVEF eligibility≤40%; n=8,399) and PARAGON-HF (LVEF eligibility≥45%; n=4,796) in a prespecified pooled analysis. We assessed the effect of treatment (sacubitril/valsartan compared with enalapril or valsartan) on the renal composite outcome, defined as the time to first occurrence of either: ≥50% reduction in eGFR, end-stage renal disease, or death from renal causes. We also assessed the influence of therapy on eGFR slope. Results: At randomization, eGFR was 68±20 ml/min/1.73m 2 in PARADIGM-HF and 63±19 ml/min/1.73m 2 in PARAGON-HF. The composite renal outcome occurred in 70 of the 6594 patients (1.1%) in the sacubitril/valsartan group and 123 of the 6601 patients (1.9%) in the valsartan or enalapril group, with a risk reduction of 44% (HR 0.56, 95%CI 0.42-0.75; P<0.001). The treatment effect on the composite renal endpoint did not differ according to the baseline eGFR (<60 vs ≥ 60 ml/min/1.73 m 2 ; P-interaction=0.46) or baseline ejection fraction (P-interaction=0.35). From randomization, the mean decline in eGFR was -1.8 (95%CI -1.9 to -1.7) ml/min/1.73 m 2 per year for the sacubitril/valsartan group, compared with -2.4 (95%CI -2.5 to -2.2) ml/min/1.73 m 2 per year for the valsartan or enalapril group, with an adjusted mean difference of 0.6 (95%CI 0.4 to 0.7; P<0.001) ml/min/1.73 m 2 per year. Conclusions: In patients with heart failure, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, compared with valsartan or enalapril, across the spectrum of ejection fraction.

Effect of enalapril in children with steroid resistant primary nephrotic syndrome

Background A significant proportion of children with nephrotic syndrome become steroid dependent or steroid resistant who need further medication with cytostatic or other immunosuppressive drugs such as cyclophosphamide or chlorambucil. Unfortunately studies show that the drugs give no good results and cause adverse effects.Objective To establish the effect of enalapril in decreasing proteinuria in children with steroid resistant nephrotic syndrome.Methods We conducted a clinical trial in Nephrology Division, Pediatrics Department, Dr. Sardjito General Hospital from January 2004 to October 2005. Subjects were randomized to either receive prednisone and enalapril (Enalapril Group) or prednisone and cyclophosphamide (CPA Group). The main parameter was proteinuria level, which was examined at the beginning of the study and then every two weeks for eight weeks.Results Remission rate in enalapril group was 96% whereas in CPA group was 82% (P=0.09). Proteinuria level reduction in Enalapril Group from the beginning until the end was 606.92 mg/dl (99%) whereas in CPA Group the reduction was 712.97 mg/dl (91%). Statistically, there was no significant difference in the average decrease of proteinuria level between both groups (P=0.30). Odds ratio for overall adverse events in combined prednisone and enalapril therapy group compared to combined prednisone and cyclophosphamide therapy group was 0.29 (CI 95% 0.17;0.41).Conclusion Combined prednisone and enalapril has similar effect tocombined prednisone and cyclophosphamide in children with steroidresistant nephrotic syndrome. Overall adverse events in combinedprednisone and enalapril group was lower than that in combinedprednisone and cyclophosphamide group.

Contribution of captopril thiol group to the prevention of spontaneous hypertension

We aimed to compare the effect of angiotensin converting enzyme (ACE) inhibitors captopril (containing thiol group) and enalapril (without thiol group) on the development of spontaneous hypertension and to analyze mechanisms of their actions, particularly effects on oxidative stress and NO production. Six-week-old SHR were divided into three groups: control, group receiving captopril (50 mg/kg/day) or enalapril (50 mg/kg/day) for 6 weeks. At the end of experiment, systolic blood pressure (SBP) increased by 41 % in controls. Both captopril and enalapril prevented blood pressure increase, however, SBP in the captopril group (121+/-5 mmHg) was significantly lower than that in the enalapril group (140+/-5 mmHg). Concentration of conjugated dienes in the aorta was significantly lower in the captopril group compared to the enalapril group. Captopril and enalapril increased NO synthase activity in the heart and aorta to the similar level. Neither captopril nor enalapril was, however, able to increase the expression of eNOS. Both ACE inhibitors increased the level of cGMP. However, cGMP level was significantly higher in the aorta of captopril group. We conclude that captopril, beside inhibition of ACE, prevented hypertension by increasing NO synthase activity and by simultaneous decrease of oxidative stress which resulted in increase of cGMP concentration.

Enalapril to Prevent Cardiac Function Decline in Long-Term Survivors of Pediatric Cancer Exposed to Anthracyclines

Purpose To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer. Patients and Methods This was a randomized, double-blind, controlled clinical trial comparing enalapril to placebo in 135 long-term survivors of pediatric cancer who had at least one cardiac abnormality identified at any time after anthracycline exposure. Results There was no difference in the rate of change in MCI per year between enalapril and placebo groups (0.30 v 0.18 L/min/m2; P = .55). However, during the first year of treatment, the rate of change in LVESWS was greater in the enalapril group than in the placebo group (−8.59 v 1.85 g/cm2; P = .033) and this difference was maintained over the study period, resulting in a 9% reduction in estimated LVESWS by year 5 in the enalapril group. Six of seven patients removed from random assignment to treatment because of cardiac deterioration were initially treated with placebo (P = .11), and one has died as a result of heart failure. Side effects from enalapril included dizziness or hypotension (22% v 3% in the placebo group; P = .0003) and fatigue (10% v 0%; P = .013). Conclusion Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year; this reduction was maintained over the study period. Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions.

Improved Fibrinolysis after one Year of Treatment with Enalapril in Men and Women with Uncomplicated Myocardial Infarction

SummaryTo study long-term effects of enalapril on mass concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), tPA/PAI-1-complex and von Willebrand factor (vWF) in both genders with uncomplicated myocardial infarction.More than three months after an uncomplicated myocardial infarction 82 survivors (46 males, 36 females) were randomised to enalapril/placebo. PAI-1, tPA, tPA/PAI-1-complex and vWF were measured after two weeks, six and 12 months following randomisation. PAI-1 decreased significantly in both genders in the enalapril-treated group after two weeks, with a maximum decrease at six months (mean reduction: 31% equal to 9.8 µg X L–1, CI: 5.2 to 14.5 µg X L–1, p = 0.0001) and remained significantly lower at 12 months. Mass concentration of tPA decreased significantly (mean reduction; 1.81 µg X L–1, CI: 0.903 to 2.708 µg X L–1, p <0.001) after two weeks treatment in both genders but returned to baseline values at 12 months. The tPA/PAI-1-complex decreased and was significantly lower (mean reduction 0.96 µg X L–1, CI: 0.36 to 1.56 µg X L–1, p = 0.003) in the enalapril group after two weeks and six months (p = 0.037). No decrease of vWF was seen in the enalapril group.Enalapril treatment up to one year depressed mass concentrations of PAI-1 and transiently tPA and tPA/PAI-1 complex indicating an improvement of the fibrinolytic balance in both genders with uncomplicated myocardial infarction.

Comparative Evaluation of Enalapril and Hydrochlorothiazide in Elderly Patients with Mild to Moderate Hypertension

Initial treatment of elderly hypertensive patients with an angiotensin-converting enzyme inhibitor is currently discouraged due to such patients' typical low-renin profile. To validate this principle, we studied 38 elderly males (aged ≥ 65 years) with mild to moderate hypertension, comparing hemodynamic responses to and subjective impressions of enalapril or hydrochlorothiazide (HCTZ). After gradual withdrawal of existing antihypertensive therapy and a four-week, single-blind placebo period, each patient was randomized in a double-blind fashion to receive either enalapril 10-20 mg/d or HCTZ 12.5-25 mg/d for two to four weeks. Combination therapy with both agents was employed if either alone failed to reduce seated diastolic BP to ≤ 90 mm Hg. Equivalent proportions of patients receiving enalapril or HCTZ (8 of 19 and 10 of 19, respectively; p = ns) responded with significant reductions in systolic and diastolic BP in seated and standing positions. Combination therapy was most effective in patients receiving HCTZ prior to enalapril. In patients receiving enalapril before HCTZ, BP changes were minimal. No adverse effects were observed in the enalapril group but occurred in an equivalent fraction of patients in the other groups (4 of 10 HCTZ alone, 6 of 20 enalapril + HCTZ; p = ns). We conclude that enalapril may be considered a reasonable monotherapeutic antihypertensive agent in some elderly patients. Combination with HCTZ is beneficial in patients who fail to respond adequately to HCTZ alone.