Low-dose combination therapy as first-line hypertension treatment for blacks and nonblacks

To assess the efficacy and safety of bisoprolol/6.25-mg hydrochlorothiazide (HCTZ), amlodipine, and enalapril in black and nonblack patients, data from two comparative studies were pooled and subgroup analyses performed. Both studies had similar designs and included all three active treatments. The second study also included a placebo group. Subjects (n = 541) with a sitting diastolic blood pressure of 95-114 mmHg were titrated to achieve a diastolic blood pressure < or = 90 mmHg. The studies included 114 blacks and 427 nonblacks. Results of an intention-to-treat analysis of mean change from baseline after 12 weeks of treatment showed the following: 1) blood pressure was significantly lowered by all three active drugs compared with baseline or placebo; 2) in blacks, bisoprolol/6.25-mg HCTZ resulted in significantly greater reductions of systolic and diastolic blood pressure than enalapril or placebo, but was not significantly different from amlodipine; 3) in nonblacks, bisoprolol/6.25-mg HCTZ resulted in significantly greater reduction of diastolic blood pressure than amlodipine, enalapril, or placebo. The placebo-corrected change in blood pressure was greater for blacks than whites on the bisoprolol/6.25-mg HCTZ combination, but this was not statistically significant. Bisoprolol/6.25-mg HCTZ controlled diastolic blood pressure to < or = 90 mmHg in significantly more patients than enalapril or placebo in blacks and nonblacks. The difference in control rates was not significant versus amlodipine. The incidence of drug-related adverse events was similar between treatments; however, bisoprolol/6.25-mg HCTZ had a lower discontinuation rate due to lack of blood pressure control or adverse experiences in both blacks and nonblacks.     

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.     

Duloxetine in the treatment of major depressive disorder: comparisons of safety and tolerability in male and female patients

BACKGROUND: While some studies have suggested sex differences in the efficacy of antidepressant medications, there have been few investigations into potential sex differences related to safety and/or tolerability. Pooled data from double-blind, placebo-controlled studies were utilized to assess the safety and tolerability of duloxetine in the treatment of major depressive disorder (MDD) in male and female patients. METHODS: Safety data were pooled from seven double-blind, placebo-controlled clinical trials of duloxetine. Patients (aged >or=18 years) meeting DSM-IV criteria for MDD received duloxetine (40-120 mg/day, male: N=318, female: N=578) or placebo (male: N=242, female: N=484) for up to 9 weeks. Safety was assessed using discontinuation rates, spontaneously reported treatment-emergent adverse events, changes in vital signs and laboratory analyses. RESULTS: Discontinuation rates due to adverse events among duloxetine-treated patients were 18.6% for males and 13.5% for females. The most common treatment-emergent adverse events in both male and female patients included nausea, headache, dry mouth, diarrhea and constipation. The only event occurring at significantly different rates in male and female patients was nausea (Breslow Day p-value=0.008), and the significant difference was driven by a placebo nausea rate that was almost three times greater in females compared with males. No significant differential sex effects were found for pulse, blood pressure or weight. No laboratory analyte had an incidence of abnormal high or low values that differed significantly between male and female patients. LIMITATIONS: This was a post-hoc analysis of pooled data from acute phase clinical trials. Plasma concentrations of duloxetine were not obtained. Adverse event rates were based on spontaneous reports and differential dose-response effects were not evaluated. CONCLUSIONS: No evidence of clinically meaningful sex differences in the safety and tolerability of duloxetine were uncovered.     

Once daily dosing of enalapril in congestive heart failure

Enalapril 40 mg or tolerated dose was given once daily to 21 patients with congestive heart failure (CHF), NYHA class III, in addition to treatment with digoxin and/or diuretics. After an 8-week open period, 19 patients were randomized to continue enalapril or to receive a placebo in a double-blind manner. After the first enalapril dose of 10 mg, maximal reduction of blood pressure (BP) occurred after 4 hours (mean 34/17 mmHg; p less than 0.001). No further reduction was found after higher doses. After the open period significant improvement was shown as judged by NYHA class (p less than 0.01), stroke volume (p less than 0.05), maximal working capacity (p less than 0.05), heart volume (p less than 0.01) and maximum rate pressure product (RPPmax) (p less than 0.001). Urinary aldosterone markedly decreased (p less than 0.01), whereas serum potassium and serum creatinine slightly increased (p less than 0.05). At the end of the blind period enalapril was superior to placebo concerning NYHA class (p less than 0.01), heart volume (p less than 0.05) and RPPmax (p less than 0.05). Other parameters, including aldosterone in urine, did not differ between the groups. Carry-over effects may have diminished the differences between enalapril and placebo. Diarrhoea (n = 5) and hypotension (n = 5) were the most common side-effects. Overall, enalapril was well tolerated and seems to be useful in single daily doses in the treatment of CHF.     

Comparison between moexipril and atenolol in obese postmenopausal women with hypertension

The present study investigated the effect of the new ACE-inhibitor moexipril versus the β₁-adrenergic blocker atenolol on metabolic parameters, adverse events (AEs) and sitting systolic (SSBP) and sitting diastolic blood pressure (SDBP) in obese postmenopausal women with hypertension (stage I and II). After a 4-week placebo run-in phase, 116 obese, postmenopausal women with primary hypertension were randomised into two treatment groups receiving once daily dosages of either moexipril 7.5 mg or atenolol 25 mg initially (mean age: 57±7 years in both groups; mean weight: 94 kg in the moexipril group and 89 kg in the atenolol group, corresponding to a body mass index (BMI) of 35.2 kg/m² and 34.1 kg/m² in both groups, respectively). After 4 and 8 weeks, the dosages were uptitrated to moexipril 15 mg, or if necessary to moexipril 15 mg/hydrochlorothiazide (HCTZ) 25 mg, or to atenolol 50 mg and atenolol 50 mg/HCTZ 25 mg, in patients whose blood pressure was not sufficiently controlled. At endpoint, metabolic parameters (total cholesterol, triglycerides, LDL, HDL, glucose, insulin) were not significantly altered in either treatment group. Most frequent adverse events under monotherapy (moexipril/atenolol) were asthenia (5.3/13.0%), headache (13.2/21.7%), cough (7.9/6.5%), pharyngitis (21.1/8.7%) and peripheral oedema (5.3/13.0%). Overall at least one AE was reported in 66% of the patients treated with moexipril and in 78% of those treated with atenolol. Reduction of SSBP/SDBP at endpoint was 14.7±1.9/10.0±1.1 and 8.7±1.9/8.4±1.1 mmHg after treatment with moexipril and atenolol, respectively. The results showed that moexipril and atenolol are equally effective in reducing blood pressure without adversely affecting blood lipids and carbohydrate metabolism.     

A multicenter,open-label study evaluating safety and clinical outcomes in children (1.4–7.5 years) with Hunter syndrome receiving idursulfase enzyme replacement therapy

PurposeThe primary objective of this study was to determine the safety of idursulfase in Hunter syndrome patients aged 5 years or younger.MethodsIdursulfase (0.5 mg/kg) was administered intravenously on a weekly basis (52 infusions per patient) in an open-label study. Safety monitoring included adverse events, anti-idursulfase antibodies, vital signs, physical examination, 12-lead electrocardiogram, concomitant medications or procedures, and laboratory testing (clinical chemistry, hematology, and urinalysis). The following exploratory efficacy outcomes were assessed at baseline and at weeks 18 or 36 or 53: urinary glycosaminoglycan levels, liver or spleen size, developmental milestones, and growth indices. Pharmacokinetic parameters were assessed at week 27.ResultsTwenty-eight boys aged 1.4–7.5 years were enrolled (one discontinued for noncompliance) in the study. All the patients reported adverse events (16 patients (57%) reported possibly or probably treatment-related adverse events). The only severe adverse event was sleep apnea (two patients); others were mild or moderate. Sixteen patients had infusion-related adverse events, a similar proportion as previously reported. Thirteen patients (46%) experienced at least one serious adverse event: pyrexia and bronchopneumonia were the most common (three patients each). No clinically important drug-related changes in laboratory parameters or vital signs or electrocardiograms were reported. Nineteen patients (68%) developed anti-idursulfase immunoglobulin G antibodies. Growth rates remained within normal age-related ranges. Developmental quotients were lower than normal but remained stable. By week 18, organ size and urinary glycosaminoglycan levels decreased as compared with baseline and remained stable throughout the study.ConclusionIdursulfase safety, tolerability, and efficacy were similar to that previously reported in males ≥5 years.Genet Med16 6, 435–441.     

A retrospective analysis of the efficacy and safety of metformin in the African-American patient.

A retrospective analysis was conducted to determine the effects of metformin on glycosylated hemoglobin (HbA1c), body weight, and adverse events in an African-American population. Thirty-six patients who were receiving combination therapy with metformin and either a sulfonylurea or insulin were identified from a hospital pharmacy database. Nineteen patients met the criteria for efficacy analysis. The combination of metformin with either a sulfonylurea or insulin resulted in a decrease of the average HbA1c from a baseline of 10.07% to 7.92% (delta = 2.15%). The effect of combination therapy on weight was variable; however, twice as many patients lost weight compared with those who gained weight. Metformin appeared to be well-tolerated, with gastrointestinal symptoms being the most commonly reported adverse events.     

Duloxetine in the treatment of major depressive disorder: comparisons of safety and efficacy

BACKGROUND: Pooled data from double-blind, placebo-controlled studies were utilized to compare the safety and efficacy of duloxetine in the treatment of major depressive disorder (MDD) in African-American and Caucasian patients. METHODS: Efficacy and safety data were pooled from seven double-blind, placebo-controlled clinical trials of duloxetine. Patients (aged > or =18 years) meeting DSM-IV criteria for MDD received duloxetine (40-120 mg/day; African Americans, N=69; Caucasians, N=748) or placebo (African Americans, N=59; Caucasians, N=594) for up to nine weeks. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAMD17) total score, the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and Visual Analog Scales (VAS) for pain. Safety was assessed using discontinuation rates, spontaneously reported treatment-emergent adverse events, vital signs and laboratory analyses, RESULTS: Based upon mean changes in HAMD17, CGI-S and PGI-I scales, the magnitude of duloxetine's treatment effects did not differ significantly between African-American and Caucasian patients. Discontinuation rates due to adverse events among duloxetine-treated patients were 13.0% for African Americans and 17.0% for Caucasians. No adverse event led to discontinuation in more than one African-American patient. The most common treatment-emergent adverse events in both ethnic groups included nausea, headache, constipation, dizziness and insomnia. The rate of occurrence of these events did not differ significantly between African-American and Caucasian patients. Mean changes from baseline for pulse, blood pressure, weight and laboratory analytes were small and showed no significant differences between African-American and Caucasian patients. CONCLUSION: In this analysis of data from seven clinical trials, no convincing evidence was found to suggest that the overall safety and tolerability profile or the efficacy profile for duloxetine in this cohort of African-American patients differed from that observed in a comparator group of Caucasian patients. The results from these analyses provide supportive evidence for the efficacy and safety of duloxetine in the treatment of MDD in African-American patients.     

Spotlight on Imatinib Mesylate in Chronic Myeloid Leukemia

Imatinib mesylate (Gleevec, Glivec) is an orally administered competitive inhibitor of the BCR-ABL tyrosine kinase created by the Philadelphia chromosome (Ph+) in chronic myeloid leukemia (CML). In patients with newly diagnosed and previously untreated (apart from hydroxyurea and/or anagrelide) CML in the chronic phase, imatinib mesylate 400 mg/day, compared with interferon-alpha (IFNalpha) plus cytarabine, resulted in higher hematologic response (HR) and cytogenetic response (CR) rates and fewer patients progressing to the accelerated phase or blast crisis in a large comparative trial. Preliminary results indicate that, compared with IFNalpha plus cytarabine, imatinib mesylate treatment was associated with similar total costs, but resulted in a higher health-related quality of life (HR-QOL). Imatinib mesylate was also effective in patients with chronic-phase CML refractory to or intolerant of treatment with IFNalpha (as 400 mg/day) and in those with blast-crisis or accelerated-phase CML (600 mg/day). In the latter groups, HR and CR rates were lower than those in patients with chronic-phase CML. Imatinib mesylate-associated adverse events were common in clinical trials, but were mostly mild to moderate in severity. The most frequently reported adverse events were superficial edema, nausea, muscle cramps, diarrhea, vomiting, and skin rash. Myelosuppression (thrombocytopenia and neutropenia) was also reported, especially in patients with advanced disease. In patients with previously untreated chronic-phase CML, serious adverse events (both hematologic and nonhematologic) were less common with imatinib mesylate than with IFNalpha plus cytarabine treatment. CONCLUSION: Imatinib mesylate is a valuable therapy for patients with newly diagnosed Ph+ chronic-phase CML. It is better tolerated and produces higher HR, CR and freedom from progressive disease rates than conventional therapy with IFNalpha plus cytarabine. Preliminary results indicate that, compared with IFNalpha plus cytarabine, imatinib mesylate treatment was associated with similar total costs, but resulted in a higher HR-QOL. Imatinib mesylate is also effective in patients with accelerated-phase and blast-crisis CML, and patients with chronic-phase CML who have failed IFNalpha therapy. Given its efficacy and generally manageable adverse event profile, imatinib mesylate offers an important early treatment option for patients with CML.     

Adverse Events with the Pfizer-BioNTech COVID-19 Vaccine among Korean Healthcare Workers

The Pfizer-BioNTech COVID-19 vaccine has shown excellent clinical effectiveness; however, adverse events of the vaccine remain a concern in Korea. We surveyed adverse events in 2498 healthcare workers vaccinated with the Pfizer-BioNTech COVID-19 vaccine at a university hospital. The survey was conducted using a diary card for 7 days following each injection. The questionnaire response rate was 75.1% (1876/2498) for the first dose and 73.8% (1840/2493) for the second dose. Among local reactions, pain was the most commonly reported (84.9% after the first dose and 90.4% after the second dose). After the second dose, two people visited the emergency room due to severe local pain, but no hospitalization or skin necrosis occurred. Among systemic reactions, fatigue was most frequently reported (52.8% after the first dose and 77.0% after the second dose), followed by myalgia (49.0% and 76.1%), headache (28.7% and 59.2%), chills (16.7% and 54.0%), and arthralgia (11.4% and 39.2%). One or more critical adverse events occurred in 0.2% and 0.7% of the vaccinees. Except for urticaria, more adverse events were reported after the second dose than after the first dose. In the future, adverse events should be investigated in older adults, and a future study with a longer observation period should be conducted.     

老年高血压患者脉压和心电图变化

目的:分析老年高血压患者脉压(PP)与心电图变化。方法:对291名老年高血压患者进行基本信息调查,并进行血压与心电图的测量,分析不同PP患者血压现状和心电图异常的差异。结果:在老年高血压患者中,1期高血压所占比例最大,为68.73%,86.95%的高血压患者PP值偏高,1期和2期高血压患者中,PP在41～60mmHg者所占比例最高,3期高血压患者中,PP>61mmHg者所占比例最高,且明显高于1期和2期高血压患者,差异均有统计学意义(P<0.05或P<0.01)。PP≥61mmHg组患者各种心电图异常率均高于PP≤40mmHg组(心律失常除外)和PP在40～60mmHg组(左室高电压除外),差异有统计学意义(P<0.05或P<0.01)。结论:高血压患者PP值普遍偏高,PP增加可加重心电图异常发生率,监测PP并行有效干预有助于预防心血管事件的发生。     

Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis

Chimeric antigen receptor (CAR) T cell therapy is approved in the United States for the treatment of acute lymphocytic leukemia and aggressive B cell lymphomas. Multiple cardiovascular adverse events (CVEs) associated with CAR-Ts have been observed in small studies, but no large-scale studies exist. Leveraging the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), we identified all reported adverse events (AEs) associated with CAR-T therapy (tisagenlecleucel and axicabtagene ciloleucel) from 2017 to 2019. Reports with missing age and sex were excluded. CVEs were classified into arrhythmias, heart failure (HF), myocardial infarction (MI), and other CVEs. Logistic regression and hierarchical clustering were used to identify factors associated with CVEs. A total of 996 reported AEs were observed (39.1% associated with tisagenlecleucel and 60% with axicabtagene ciloleucel). Of all patients experiencing AEs, the median age was 54 (interquartile range, 21 to 65) years; 38.9% were females. In total, 19.7% (196) of all AEs reported to the FDA were CVEs. The most common CVEs were arrhythmia (77.6%), followed by HF (14.3%) and MI (0.5%). In adjusted analysis a positive association was observed between those presenting with CVE with neurotoxicity (odds ratio, 1.76; 95% confidence interval, 1.20 to 2.60; P = .004). Additionally, when both CVE and cytokine release syndrome (CRS) are present, neurotoxicity is the most common noncardiac AE, which clusters with them (Jaccard similarity: 73.1). The mortality rate was 21.1% overall but 30.1% for those reporting CVEs. In FAERS, reported CVEs with CAR-T are associated with high reported mortality. The development of either CRS or neurotoxicity should prompt vigilance for cardiovascular events.     

Effect of antihypertensive drugs on the myocardial microvessels in rats with nitric oxide blockade

In the present study, myocardial microvessels were investigated by stereology in rats with nitric oxide blockade and concomitant antihypertensive treatment for 40 days. The following five groups (10 rats each) were studied: control; L-NAME; L-NAME + spironolactone; L-NAME + enalapril; L-NAME + verapamil. The blood pressure (BP) increased every week in the L-NAME group; after an initial increase BP decreased in the treated groups and was not different from the control group. Compared to control animals, the myocardium had hypertrophied myocytes and capillary rarefaction; the tunica media and the tunica intima of small arteries were thickened, and an increase in collagen fibrils in L-NAME treated animals was noted. The enalapril, verapamil and spironolactone groups showed uniform myocardium, quite similar to the control group. The volume density of vessels, in comparison with the L-NAME group, was greater in the spironolactone group (57%), in the enalapril group (76%) and in the verapamil group (81%). The length density of vessels was, respectively, 56%, 50%, and 76% greater in the spironolactone, enalapril and verapamil groups than in the L-NAME group. The surface density of the vessels of the L-NAME group was, respectively, 88%, 96%, and 113% lower than in the spironolactone, enalapril and verapamil groups. These results are compatible with the occurrence of angiogenesis in the verapamil rats.     

Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure

BACKGROUND: Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available. METHODS: We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies. RESULTS: At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02). CONCLUSIONS: Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.     

The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II.

BACKGROUND. In a sample of 30,195 randomly selected hospital records, we identified 1133 patients (3.7 percent) with disabling injuries caused by medical treatment. We report here an analysis of these adverse events and their relation to error, negligence, and disability. METHODS. Two physician-reviewers independently identified the adverse events and evaluated them with respect to negligence, errors in management, and extent of disability. One of the authors classified each event according to type of injury. We tested the significance of differences in rates of negligence and disability among categories with at least 30 adverse events. RESULTS. Drug complications were the most common type of adverse event (19 percent), followed by wound infections (14 percent) and technical complications (13 percent). Nearly half the adverse events (48 percent) were associated with an operation. Adverse events during surgery were less likely to be caused by negligence (17 percent) than nonsurgical ones (37 percent). The proportion of adverse events due to negligence was highest for diagnostic mishaps (75 percent), noninvasive therapeutic mishaps ("errors of omission") (77 percent), and events occurring in the emergency room (70 percent). Errors in management were identified for 58 percent of the adverse events, among which nearly half were attributed to negligence. CONCLUSIONS. Although the prevention of many adverse events must await improvements in medical knowledge, the high proportion that are due to management errors suggests that many others are potentially preventable now. Reducing the incidence of these events will require identifying their causes and developing methods to prevent error or reduce its effects.     

Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction

BACKGROUND: Black patients with heart failure have a poorer prognosis than white patients, a difference that has not been adequately explained. Whether racial differences in the response to drug treatment contribute to differences in outcome is unclear. To address this issue, we pooled and analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials, two large, randomized trials comparing enalapril with placebo in patients with left ventricular dysfunction. METHODS: We used a matched-cohort design in which up to four white patients were matched with each black patient according to trial, treatment assignment, sex, left ventricular ejection fraction, and age. A total of 1196 white patients (580 from the prevention trial and 616 from the treatment trial) were matched with 800 black patients (404 from the prevention trial and 396 from the treatment trial). The average duration of follow-up was 35 months in the prevention trial and 33 months in the treatment trial. RESULTS: The black patients and the matched white patients had similar demographic and clinical characteristics, but the black patients had higher rates of death from any cause (12.2 vs. 9.7 per 100 person-years) and of hospitalization for heart failure (13.2 vs. 7.7 per 100 person-years). Despite similar doses of drug in the two groups, enalapril therapy, as compared with placebo, was associated with a 44 percent reduction (95 percent confidence interval, 27 to 57 percent) in the risk of hospitalization for heart failure among the white patients (P<0.001) but with no significant reduction among black patients (P=0.74). At one year, enalapril therapy was associated with significant reductions from base line in systolic blood pressure (by a mean [+/-SD] of 5.0+/-17.1 mm Hg) and diastolic blood pressure (3.6+/-10.6 mm Hg) among the white patients, but not among the black patients. No significant change in the risk of death was observed in association with enalapril therapy in either group. CONCLUSIONS: Enalapril therapy is associated with a significant reduction in the risk of hospitalization for heart failure among white patients with left ventricular dysfunction, but not among similar black patients. This finding underscores the need for additional research on the efficacy of therapies for heart failure in black patients.     

Comparative efficacy of exenatide versus insulin glargine on glycemic control in type 2 diabetes mellitus patients inadequately treated with metformin monotherapy

PurposeComparative efficacy of exenatide versus insulin glargine primarily on glucemic control, and secondarily on body mass index (BMI), lipid profile and blood pressure, in type 2 diabetes mellitus (T2DM) patients suboptimally treated with metformin monotherapy.Material/MethodsForty-seven inadequately treated T2DM patients on metformin assigned to exenatide (n=18) or insulin glargine (n=29) for 26 weeks. Glycosylated hemoglobin (HbA1c), serum lipids, BMI, systolic and diastolic blood pressure, and adverse events, including episodes of hypoglycemia and gastrointestinal symptoms, were recorded.ResultsEither treatment had a similar favorable mean reduction in HbA1c. However, more patients in exenatide group achieved HbA1c ≤ 7% at the 26th week compared with insulin glargine group (p=0.036). Insulin glargine group had significantly more episodes of hypoglycemia compared with exenatide group (p=0.039). Gastrointestinal adverse events were non-significantly higher in the exenatide group. A significantly greater BMI reduction was observed in exenatide group, whereas BMI was not altered in insulin glargine group. Total and LDL cholesterol (p=0.012), and triglycerides (p=0.016) significantly decreased, whereas HDL cholesterol increased (p=0.021) in the exenatide group, whereas only total cholesterol decreased in insulin glargine group. Changes in systolic and diastolic blood pressure were insignificant in both groups.ConclusionsExenatide provided similar reduction in HbA1c, but fewer episodes of hypoglycemia, compared with insulin glargine. Exenatide had also a favorable effect on weight loss, although more gastrointestinal adverse events. Exenatide may provide a justified alternative in second line treatment of T2DM, but more trials are required to elucidate its long-term safety and cost-effectiveness.     

Volume-weighted mean nuclear volume and numerical nuclear density in the cardiomyocyte following enalapril and verapamil treatment

The estimation of the volume-weighted mean nuclear volume, nu(nu), and the numerical nuclear density in the plane, N(A), was used to analyze cardiomyocyte nuclei in the condition of cardiac hypertrophy caused by nitric oxide (NO) synthesis blockade and simultaneous antihypertensive treatment for 40 days (four groups of ten rats each: control, L-NAME, L-NAME+enalapril, L-NAME+verapamil). The blood pressure (BP) increased 71% in the L-NAME group. In the L-NAME+enalapril and L-NAME+verapamil groups, the BP did not show any alteration when compared with the respective controls. In comparison with the control group, nu(nu) was 250% greater, and the N(A) was 25% smaller in the L-NAME animals, while no difference occurred in the other two groups. With respect to cardiomyocyte nuclear size, the present results suggest a beneficial effect of the angiotensin-converting enzyme inhibitor enalapril and the calcium channel blocker verapamil when NO synthesis is blockaded.     

Long-term safety of once-daily budesonide in patients with early-onset mild persistent asthma: results of the Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study.

BACKGROUND: The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study is a worldwide, randomized, prospective study to investigate early intervention with inhaled corticosteroids in recent-onset mild persistent asthma. OBJECTIVE: To evaluate the safety and tolerability of long-term treatment with once-daily budesonide therapy in patients with mild persistent asthma. METHODS: Patients aged 5 to 66 years with mild persistent asthma for fewer than 2 years and no previous regular corticosteroid treatment received budesonide or placebo once daily for 3 years, in addition to their usual asthma therapy. The daily budesonide dose was 200 microg for children younger than 11 years and 400 microg for those 11 years or older. RESULTS: Overall, 7,221 patients were included in the safety analysis, and a total of 21,520 adverse events were reported (10,850 in the budesonide group and 10,670 in the placebo group). The most commonly reported events included respiratory infections, rhinitis, pharyngitis, bronchitis, viral infections, and sinusitis. The number of deaths and serious adverse events were similar for children and adults in both treatment groups. Fewer asthma-related serious adverse events were reported with budesonide (162) compared with placebo (276). Oral candidiasis was reported more frequently with budesonide (1.2%) than with placebo (0.5%); the frequencies of other adverse effects previously reported to be associated with inhaled corticosteroids (psychiatric disorders, skin disorders, and allergic reactions) were similar. CONCLUSIONS: Three-year treatment with budesonide once daily (200 or 400 microg) is safe and well tolerated in children and adults with newly detected mild persistent asthma.