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Background: In the past decade, many studies have indicated that the combination of low doses of different classes of antihypertensive agents may be more efficacious than monotherapy while minimizing the likelihood of dose-dependent adverse effects (AEs).Objective: The aim of this study was to determine whether combination therapy with lower doses of candesartan and a calcium antagonist, felodipine, would be more effective and tolerable in controlling mild to moderate hypertension compared with either drug used alone.Methods: In this 18-week, single-center, double-blind, crossover study, patients with mild to moderate essential hypertension were randomized to 1 of 2 treatment groups after a 2-week placebo washout period. Patients in group 1 received candesartan 16 mg once daily and patients in group 2 received felodipine 5 mg once daily, for 6 weeks. All patients then received half-dose combination therapy (candesartan 8 mg plus felodipine 2.5 mg, once daily) for 6 weeks. Finally, patients received 6 weeks of monotherapy with the alternate medication (group 1 received felodipine 5 mg once daily and group 2 received candesartan 16 mg once daily).Results: Thirty patients (18 men, 12 women; mean [SD] age, 54.0 [4.9] years; range, 39–62 years) were included in the study. During both monotherapy periods, candesartan and felodipine significantly reduced blood pressure (BP) (both P<0.001). BP further decreased with combination therapy (P<0.001 in both groups). Overall, 90.0% (27/30) of the patients achieved the target BP at the end of combination therapy. The incidence of AEs was similar with combination therapy compared with either monotherapy.Conclusions: In this study population, candesartan and felodipine had additive effects when used in combination, even at low doses, in the treatment of hypertension. Therefore, the combination of candesartan and felodipine is an effective alternative to that of candesartan and hydrochlorothiazide. [Copyright &y& Elsevier]

Background: The high incidence of ventricular arrhythmias in patients with hypertension and left ventricular hypertrophy (LVH) is well documented. However, few studies have been conducted on the prevalence of ventricular arrhythmias in patients with isolated systolic hypertension without LVH.Objectives: The objectives of this study were to (1) determine the prevalence of ventricular arrhythmias in patients with systolic hypertension without LVH and (2) estimate the effect of a perindopril/indapamide combination, which does not have an antiarrhythmic effect, on the incidence of ventricular arrhythmias.Methods: Patients with newly diagnosed isolated systolic hypertension (systolic blood pressure [SBP] >160 mm Hg) and a control group of normotensive patients were enrolled. During the 2-week washout period, patients underwent physical examination (including blood pressure measurements), ambulatory electrocardiography monitoring, echocardiography, and laboratory urine and blood tests. Absence of LVH was confirmed by echocardiographic examination. The group of hypertensive patients received 1 tablet of 2 mg perindopril/0.625 mg indapamide per day for a total of 4 weeks. Physical examinations and ambulatory electrocardiographic monitoring were repeated after treatment.Results: A total of 60 hypertensive (mean age, 63.1 years; mean SBP, 176.8 ± 3.1 mm Hg; mean diastolic blood pressure, 82.6 ± 2.9 mm Hg) and 60 normotensive patients were enrolled. Ambulatory electrocardiographic monitoring indicated that 18 of the 60 hypertensive patients (30%) had ventricular arrhythmias: 17 had ventricular premature contractions (>100/24 h) and 1 had ventricular tachycardia plus ventricular premature contractions. In the control group, 7 of 60 subjects (11.7%) had ventricular premature contractions. The difference between the 2 groups in incidence of ventricular arrhythmias was significant (P < 0.01). After treatment, mean SBP decreased to 136.1 ± 3.2 mm Hg, and ventricular premature contractions were found in 9 of 60 hypertensive patients (15%) (P < 0.02 vs pretreatment).Conclusions: The results of this study suggest that in patients with isolated systolic hypertension without LVH, (1) the prevalence of ventricular arrhythmia is higher than in normotensive patients and (2) treatment with perindopril/indapamide decreases the incidence of ventricular arrhythmias. [Copyright &y& Elsevier]

Abstract: Background:: In addition to their cholesterol-lowering effects, hydroxymethylglutaryl coenzyme A reductase inhibitors (“statins”) might have pleiotropic, nonlipid effects. Insulin resistance syndrome is known to increase the risk for cardiovascular disease. However, the effects of statins on insulin resistance are a subject of controversy. Objective:: We aimed to investigate the effects of atorvastatin on insulin resistance in hyperlipidemic patients. Methods:: This 12-week, prospective, nonrandomized, open-label study was conducted at the outpatient cardiology clinic, Ege University Medical School, Bornova-Izmir, Turkey. Hyperlipidemic patients aged ≥18 years with insulin resistance and no other components of the metabolic syndrome were included in the study. Atorvastatin 10 mg QD (after the evening meal) was administered by mouth (tablet) over a 12-week period. At baseline and after 12 weeks of treatment, insulin sensitivity was assessed using homeostasis model assessment (HOMA) index methodology. Serum lipid parameters and fasting levels of plasma glucose and insulin (FPG and FPI, respectively) were measured at the same 2 time points. The tolerability of atorvastatin was assessed using laboratory analysis and physical examination, including vital sign measurements. Results:: Fifteen white patients (9 women, 6 men; mean [SD] age, 52 [8] years) participated in the study. No significant changes in HOMA index were found (mean [SD], 3.1 [1.5] vs 3.2 [1.9]). The lipid profile was improved significantly at 12 weeks compared with baseline (mean [SD] low-density lipoprotein cholesterol, 173.2 [21.3] vs 110.8 [43.6] mg/dL; total cholesterol, 270.9 [21.5] vs 201.2 [46.7] mg/dL; and triglycerides, 269.5 [46.3] vs 205.5 [49.3] mg/dL; all, P < 0.001). No significant change in mean (SD) plasma high-density lipoprotein cholesterol level (45.5 [6.6] vs 43.7 [8.1] mg/dL) was found. In addition, no significant changes in FPG (85.3 [12.71 vs 84.8 [10.4] mg/dL), or FPI (13.5 [9.7] vs 13.9 [10.1] μU/mL) were found. None of the patients required withdrawal of medication due to an adverse event. Conclusion:: In this pilot study in hyperlipidemic patients with insulin resistance, 12 weeks of treatment with atorvastatin 10 mg QD was effective in controlling hyperlipidemia but did not reduce the severity of insulin resistance. [Copyright &y& Elsevier]