Antihypertensive efficacy of metoprolol XL/low dose chlorthalidone (6.25 mg) combination: a randomized, comparative study in indian patients with mild-to-moderate essential hypertension.

OBJECTIVE: High blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-to-moderate essential hypertension. METHODS: Total 130 eligible patients (65: metoprolol XL 25 mg/chlorthalidone 6.25 mg; 65: metoprolol XL 25 mg/HCTZ 12.5 mg) were enrolled in this randomized, comparative, multicentric, 12-weeks study. Sixty-two patients from each group completed the study. After 4-weeks of treatment, non-responders from chlorthalidone 6.25 mg combination group were shifted to metoprolol XL 50 mg/chlorthalidone 12.5 mg and non-responders from HCTZ 12.5 mg combination group were escalated to metoprolol XL 50 mg/HCTZ 12.5 mg. RESULTS: The study treatment groups were comparable with respect to demography and baseline disease characteristics. Both the starting therapies were comparable with respect to mean fall in SBP (p = 0.788) and DBP (p = 0.939), and response rates (p = 1.0) after 4-weeks of therapy. Also both the step-up therapies showed similar mean fall in SBP (p = 0.277) and DBP (p = 0.507) at the end of 12-weeks. However, significantly more number of patients from chlorthalidone 12.5 mg/metoprolol XL 50 mg group responded to therapy as compared to that from HCTZ 12.5 mg/metoprolol XL 50 mg group (p = 0.045). All the reported adverse events were of mild-to-moderate intensity. There were no clinically significant trends in electrolytes (Na (+), K(+), Cl(-)) and fasting blood sugar, evident across the treatment groups. CONCLUSION: Chlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option.

Clinical profile of chikungunya fever in patients in a tertiary care centre in Maharashtra, India.

BACKGROUND & OBJECTIVE: In India a chikungunya fever outbreak started in December 2005 when the country experienced more than 13 lakhs of chikungunya infected cases. We undertook this study to study detailed clinical profile of chikungunya fever in both indoor and outdoor patients in a tertiary care hospital in Nagpur, Maharashtra in 2006. METHODS: Suspected cases of chikungunya fever (n=405) during the period of July to September 2006, having clinical triad of fever, arthralgia and/or rashes were included in the study. Clinical profile was studied in all the cases. Of the 405 samples collected, 166 were tested for serum CHIK IgM antibodies. RESULTS: Of the 166 samples tested for CHIKV IgM antibodies, 87 (52.4%) were positive (confirmed cases). Male: female ratio was 2.3:1. Fever and arthralgia were present in all cases. Rash was present in 27 (31%) confirmed and 38 (12%) suspected cases. Lymphadenopathy was present in 12 (13.8 %) confirmed and 4 of suspected cases. Chronic polyarthritis was seen in 22 (25.3%) confirmed and 75 (23.6%) suspected cases. Neurological manifestations were observed in 08 (9%) confirmed and 10 (3.14%) suspected cases. Mortality was 7 (2.2%) in 318 suspected cases and 3 (3.4%) in 87 confirmed cases. INTERPRETATION & CONCLUSION: Our findings showed that about half of the serum samples for CHIKV IgM antibody tested positive from cases suspected to have chikungunya fever. Fever, joint pain and headache were major symptoms. Certain rare manifestations like lymphodenopathy, oral ulcers and encephalitis were also seen. Mortality in confirmed cases was about 3.4 per cent.

Clinical effectiveness of low-dose chlorthalidone (6.25 mg) + atenolol combination in stage I hypertensive patients: a multicenter, randomized, controlled study.

OBJECTIVE: To compare the efficacy and safety of low-dose chlorthalidone + atenolol combination with atenolol and atenolol + amlodipine combination in stage I hypertensive patients uncontrolled on active run-in monotherapy. METHODS: Newly diagnosed stage I hypertensive patients were randomized to active run-in monotherapy either with atenolol 25 mg (98/300) or chlorthalidone 6.25 mg (100/300) or amlodipine 2.5 mg (102/300). A total of 282/300 patients (atenolol 92, chlorthalidone 91, amlodipine 99) completed the active run-in phase successfully. Patients uncontrolled on active run-in monotherapy (atenolol 33, chlorthalidone 45, amlodipine 47) received the study treatment, namely atenolol 50 mg alone, chlorthalidone 6.25 mg+atenolol 25 mg and atenolol 25 mg+amlodipine 2.5 mg, respectively. Efficacy of the therapy was evaluated by BP measurement at weeks 12 and 20 post-therapy. RESULTS: Post-active run-in monotherapies, the study treatment groups showed a significant fall in mean SBP and DBP from baseline (p<0.05). The mean fall in SBP and DBP was comparable for study treatments (atenolol 50 mg, atenolol 25 mg+chlorthalidone 6.25 mg and atenolol 25 mg+amlodipine 2.5 mg) (p=0.337 for SBP and p=0.054 for DBP) at week 12 and (p=0.744 for SBP and p=0.855 for DBP) at week 20; also, the percentage of responders was comparable for the three study treatment groups (p=0.799) indicating that the low-dose chlorthalidone+atenolol combination is noninferior to the high-dose atenolol alone and atenolol+amlodipine combination. No serious laboratory/clinical adverse events were reported in this study. CONCLUSION: Chlorthalidone 6.25 mg in combination with atenolol 25 mg is effective and safe in stage I (JNC 7) essential hypertensive patients. This low dose of chlorthalidone could reduce dose-related concerns over metabolic adverse effects and may lead to wider usage of this proven antihypertensive agent in combination therapy.

Non-invasive detection of endothelial dysfunction in sickle cell disease by Doppler ultrasonography.

OBJECTIVE: The purpose of the study was to assess endothelial function in sickle cell disease (SCD), to compare endothelial dysfunction between sickle cell anemia (SS) and sickle cell trait (SA) cases and to evaluate correlation of endothelial dysfunction with duration of symptoms and vaso-occlusive crises per year (voc/year) [severity of disease]. METHODS: We investigated 37 steady state SCD cases, of which 19 were SS [mean age = 23.15 + 5.27 years and M/F = 10/9] and 18 were SA cases [Mean age = 22.05 +/- 5.17 years and M/F = 9/9]. Age, sex, and hemoglobin matched 33 controls [15 (Hb < or = 11g%) for SS cases and 18 (Hb > or = 11g%) for SA cases] were studied. Endothelial function was assessed by flow-mediated dilation (FMD) in brachial artery by vascular Doppler after pneumatic tourniquet stress at forearm (by Celermajer DS, 1992). RESULTS: FMD was significantly impaired in SCD cases [6.22% + 0.91% in SS cases vs. 16.85% + 1.06% in controls, P<0.05 and 12.56% + 0.90% in SA cases vs. 16.99% + 1.05% in controls, P < 0.05]. Endothelial function was impaired more in SS as compared to SA cases (p < 0.05). Decline in endothelial function was observed with increasing duration of symptoms and voc/year in SS cases. CONCLUSION: These results suggest that endothelial function is impaired in SCD and endothelial function is impaired more in SS as compared to SA cases.