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Aim: To evaluate the antihypertensive efficacy and safety of the fixed-dose combination (FDC) of Efonidipine and S (-) Metoprolol in adult patients with hypertension. Study Design: Multicentric, double-blind, randomized, parallel, comparative Phase III trial. Methodology: This clinical trial was conducted at five geographically distributed sites across India and enrolled 240 hypertensive patients. They were randomized (1:1) to receive either FDC of Efonidipine 40 mg + S (-) Metoprolol 25 mg tablet (E+S(-)M group) or FDC of Cilnidipine 10 mg + Metoprolol 50 mg tablet (C+M group) once daily for 90 days. Patients were evaluated for changes in their blood pressure (BP) from baseline to Day 30, 60 and 90. The study site staff, investigator and patients were blinded to the treatment allocation. Blood pressure was recorded as the mean of 3 consecutive measurements taken in a sitting position. Patients achieving target BP (<140/90 mmHg) were evaluated and the safety and tolerability were assessed based on the incidences of adverse events (AEs). Results: This study focused on evaluating the mean Systolic BP (SBP) and Diastolic BP (DBP) reduction from baseline to Day 30, 60 and 90. At baseline, patients had a mean (±SD) SBP and DBP of 154.60 (±11.33) mmHg and 98.68 (±8.18) mmHg respectively. After 30 days of the E+S(-)M treatment, the mean SBP/DBP was 136.06±10.55/ 86.68±5.51 mmHg (p<0.0001) and on Day 60 it was 129.48±10.51/ 84.17±5.51mmHg (P <0.0001), corresponding to mean reductions in SBP/DBP of 18.09/11.66 and 24.78/14.17 mmHg, respectively. There was a statistically significant (p <0.0001) reduction to 123.59 ± 15.21 mmHg in SBP and 82.38 ± 5.05 mmHg in DBP observed on Day 90 as compared to baseline. Post-treatment with E+S(-)M group, SBP/DBP reduction of 31.01/16.29 mmHg in hypertensive patients was observed. A total of 95% of the patients achieved a pre-defined target BP <140/90 mmHg on the administration of E+S(-)M. Furthermore, it was observed that 93% of Stage I and 96% of Stage II hypertensive patients achieved the target BP goal. A total of 5.78% of patients experienced adverse events (AEs) in the E+S(-)M group which was similar to that of C+M group. All AEs were mild in severity and resolved without any sequelae at the end of the study. No unexpected adverse events were reported, and the E+S(-)M dosage regimen was well tolerated by the patients. Both the treatment groups were non-inferior to each other. Conclusion: The study results demonstrated clinically meaningful reductions in blood pressure after administration of FDC of Efonidipine 40 mg + S(-) Metoprolol 25 mg over a period of 90 days. The treatment was efficacious, safe, and well?tolerated in the study population.
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Background:Patients with hypertension in India been reported with high heart rate owing to sympathetic overdrive (SO). Beta-blockers provides several positive effects to reduce SO in patients with hypertension. The aim of present survey studywasto understand current real-world prevalence of SO in Indian patients with hypertension and usage of beta-blocker therapy in them.Methods:A cross sectional, observational, questionnaire-based survey conducted across India between June 2020 to October 2020. A specially designed validated questionnaire was shared with 157 registered health care practitioners (HCP),their anonymous inputs were captured and analysed in qualitative manner. Categorical data was summarized by number (n) and percentage (%). Results:Total 157 HCP participated and completed the survey. Around 53% of HCP observed that patients with average heart rate above 75 beats/min were associated with negative prognosis. Around 43% of HCP reported that raised heart rate is associated with advancedage and increased body mass index (BMI). Two-third of HCP reported that tachycardia is associated with stage-2 hypertension and marked by restlessness and anxiety which is suggestive of SO. Over 70% HCP agreed that the HR below 75 beats/min is associated with good prognosis. Around 89% HCP reported beta-blockers as the drug of choice in patients with augmented SO. S-Metoprololwas reported to bethemost preferred beta-blocker agent and was recommended by 76% HCP in patients with hypertension and coexisting SO.Conclusions:SO been reported prevalent conditionin Indian patients with hypertension which likely worsensthe prognosis in these patients. Beta-blockers reported to be the preferred choice of anti-hypertensive and S-Metoprololseem to be themost preferred agent amongst the available beta-blockers against SO in patients with hypertension in India.
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A selective, sensitive and high throughput liquid chromatography-tandem mass spectro-metry (LC-ESI-MS/MS) method has been developed for separation and quantification of metoprolol enantiomers on a chiral Lux Amylose-2 (250 mm×4.6 mm, 5 mm) column. Solid phase extraction of (S)-(-)- and (R)-(t)-metoprolol and rac-metoprolol-d6 as an internal standard (IS) was achieved on Lichrosep DVB HL cartridges employing 200 mL human plasma. Both the analytes were chromatographically separated with a resolution factor of 2.24 using 15 mM ammonium acetate in water, pH 5.0 and 0.1% (v/v) diethyl amine in acetonitrile (50:50, v/v) as the mobile phase within 7.0 min. The precursor-product ion transitions for the enantiomers and IS were monitored in the multiple reaction monitoring and positive ionization mode. The method was validated over the concentration range of 0.500-500 ng/mL for both the enantiomers. Matrix effect was assessed by post-column analyte infusion experiment and the mean extraction recovery was greater than 94.0% for both the enantiomers at all quality control levels. The stability of analytes was evaluated in plasma and whole blood under different storage conditions. The method was successfully applied to a clinical study in 14 healthy volunteers after oral administration of 200 mg metoprolol tablet under fasting conditions. The assay reproducibility is shown by reanalysis of 68 incurred samples. The suitability of the developed method was assessed in comparison with different chromatographic methods developed for stereoselective analysis of metoprolol in biological matrices.