Unmet Need for Further LDL-C Lowering in India despite Statin Therapy: Lipid Association of India Recommendations for the Use of Bempedoic Acid

Lipid-lowering therapy plays a crucial role in reducing adverse cardiovascular (CV) events in patients with established atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia. Lifestyle interventions along with high-intensity statin therapy are the first-line management strategy followed by ezetimibe. Only about 20–30% of patients who are on maximally tolerated statins reach recommended low-density lipoprotein cholesterol (LDL-C) goals. Several factors contribute to the problem, including adherence issues, prescription of less than high-intensity statin therapy, and de-escalation of statin dosages, but in patients with very high baseline LDL-C levels, including those with familial hypercholesterolemia and those who are intolerant to statins, it is critical to expand our arsenal of LDL-C-lowering medications. Moreover, in the extreme risk group of patients with an LDL-C goal of ?30 mg/dL according to the Lipid Association of India (LAI) risk stratification algorithm, there is a significant residual risk requiring the addition of non-statin drugs to achieve LAI recommended targets. This makes bempedoic acid a welcome addition to the existing non-statin therapies such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. A low frequency of muscle-related side effects, minimal drug interactions, a significant reduction in high-sensitivity C-reactive protein (hsCRP), and a lower incidence of new-onset or worsening diabetes make it a useful adjunct for LDL-C lowering. However, the CV outcomes trial results are still pending. In this LAI consensus document, we discuss the pharmacology, indications, contraindications, advantages, and evidence-based recommendations for the use of bempedoic acid in clinical practice.

Recombinant Macrophage Targeted Enzyme Replacement Therapy for Gaucher Disease in India.

Objective: Gaucher disease in India has been reported only in a few case reports from India. The aim of the study was to assess the response to enzyme replacement therapy in Indian patients with Gaucher disease. Design: Retrospective analysis of patients receiving CHO-derived recombinant macrophage-targetted glucocorebrosidase. Setting: Five centers from India with experience in treating lysosomal storage disorders. Patients: The diagnosis of Gaucher disease was confirmed by low glucocerebrosidase levels, though it was first made on splenectomy in 8 and on bone marrow examination in 9 patients. Twenty five of 52 patients diagnosed with Gaucher disease (17 Type I, 8 mild Type III) received treatment for >6 months. Indications for treatment included symptomatic anemia, thrombocytopenia, organomegaly, bone disease or mild neurological symptoms leading to impairment of quality of life. Patients with significant neurological involvement were excluded. The drug infusions were given intravenously every 15 days. Main Outcome measures: Hemoglobin, platelet counts, liver and spleen volumes and growth parameters. Results: 22 of the 25 children who survived were analyzed. After 6 months of treatment, the mean (range) increase in hemoglobin was 1.5 (-3.4 to 6.1) g/dL (P=0.01) and in platelet count was 32 x 109/L (-98.5 x 109 to 145.5 x109) /L (P=0.02). The mean (range) increase in weight was 3 kg (-5.6 to 10.5) (P=0.04) and in height was 7.1 cm (0 to 26.5) (P=0.0003). Liver size decreased by a mean (range) of 38.5% (- 5.5 to 86.7) (P=0.0003) and the spleen size by 34.8% (0 to 91.7) (P=0.004). All patients had improvement in bone pains and in 2 patients, neurological symptoms improved with others remaining static. Conclusions: This is the first reported cohort of patients in India reporting our experience with imiglucerase enzyme replacement therapy for treatment of Gaucher Disease in India.

Efficacy of nimesulide alone and in combination with cetirizine in acute allergic rhinitis.

OBJECTIVE: To study the effect of cetirizine and nimesulide given alone and in combination in allergic rhinitis. METHOD: A double blind, double dummy, randomised, parallel controlled clinical study in three groups consisting of 18 patients each suffering from allergic rhinitis was conducted. Group A was given nimesulide alone (100 mg BD), Group B received combination (nimesulide 100 mg + cetirizine 10 mg) and Group C was given cetirizine alone (10 mg) for one week. The efficacy of each treatment in reducing nasal stuffiness, nasal discharge, itching nose and watery eyes was assessed at base line (day 0), on days four and eight of treatment. Patients used diary cards twice daily to rate symptom severity on a four point scale. RESULTS: Nimesulide and cetirizine alone could decrease nasal discharge, nasal stuffiness and sneezing significantly in allergic rhinitis patients by day four. Cetirizine was more effective in relieving nasal discharge and sneezing compared to nimesulide. By combining cetirizine and nimesulide four symptoms of allergic rhinitis, i.e., nasal discharge, nasal stuffiness, sneezing and watery eyes decreased significantly. CONCLUSION: Present study has shown that nimesulide alone could decrease three symptoms of allergic rhinitis like certirizine and combination of cetirizine (anti-histaminic) and nimesulide (anti-inflammatory) exerts synergistic action in reducing symptoms in patients of allergic rhinitis.

Impact of nutritional supplements on hematological profile of pregnant women.

Eighty one pregnant women (20 +/- 2 weeks of gestation) were assessed for their nutritional status. They were divided into three groups; Group I women (n = 30) were given 200 mg ferrous sulphate (FeSO4) tablet per day for 15 weeks, Group II women (n = 25) were given FeSO4 tablets along with 2,000,000 IU of vitamin A as single dose in beginning of study; and Group III women (n = 26) were not given any supplements and served as controls. To study impact of supplements on hematological profile of pregnant women, Hb, PCV, RBC, TS%, TIBC and serum levels of iron, zinc, copper, manganese and vitamin A were assessed at 20 +/- 2 weeks and 36 +/- 2 weeks of gestation by standard techniques. Pregnant women in Group I (Fe suppl) and group II (Fe + vitamin A suppl) had significantly (p < 0.01) higher Hb, PCV, RBC, TS% and serum iron levels than the controls. Group II had significantly (p < 0.05) higher values of these indices as compared to Group I. Levels of serum zinc, copper, manganese were not affected by supplements. Iron supplements improved the hematological profile of pregnant mothers but Fe + vitamin A supplements were more beneficial.

Urodynamic study of children with voiding problems.

Twenty high risk children aged 5-12 years with various voiding problems were studied prospectively by urodynamics to evaluate the function of their urinary bladder and its continence mechanism. None of them had neuropathic bladder or any obstruction distal to bladder neck. Fourteen out of twenty (70%) had abnormal findings on urodynamics evaluation; 8 (40%) had non-neurogenic neurogenic bladder (NNNB); 3 (15%) had small capacity hypertonic bladder (SCHB); 2 (10%) had atonic bladder (AB) and 1 (5%) had hyperreflexic bladder (HB). We conclude that urodynamic abnormalities are as frequent in high risk Indian children as they are in developed countries. The high risk children should be subjected to urodynamic studies more frequently than being done hitherto and be directed to proper therapeutic modality.

Simple predictors to differentiate acute asthma from ARI in children: implications for refining case management in the ARI Control Programme.

There is a considerable overlap in the clinical presentation of acute asthma and ARI. According to the current ARI Control Programme recommendations, a child with cough and rapid breathing is overtreated for ARI (pneumonia) with antibiotics and undertreated for asthma with bronchodilators. The present study, therefore, evaluated simple predictors to differentiate these two conditions to refine the recommended case management. In a case control comparison, children between 6 to 60 months age who presented with cough and rapid breathing due to acute asthma (n = 100) and ARI (n = 100) were evaluated. Only 34% of asthmatics had an audible wheeze. Significant independent predictors on multiple logistic regression analysis were number of earlier similar attacks and fever (or temperature). The best predictor for asthma was two or more earlier similar episodes (sensitivity 84%, specificity 84%) followed by temperature < 37.6 degrees C (sensitivity 73% and specificity 84%). Absence of fever, audible wheeze and a family history of asthma had excellent specificities (98-100%) but low sensitivities (20-34%). It is concluded that simple clinical predictors can differentiate acute asthma and ARI. The recommended case management can, therefore, be refined by either: (i) Prescribing bronchodilators and no antibiotics with two or more earlier similar episodes of cough and rapid breathing; or (ii) To further minimize undertreatment for pneumonia, prescribing bronchodilators as above, but denying antibiotics in such cases only if there is audible wheeze or family history of asthma or no fever.

Impact of nutrition and health education on rural pre-school children.

Pre-school children (n = 155) belonging to low socio-economic group from eight creches in villages around Chandigarh, were imparted nutrition and health education (NHE) for one year. Appropriate teaching material in the form of songs, rhymes and roleplays were scientifically developed for the purpose. For impact evaluation, objective tools in the form of checklists were formulated and used. NHE on three aspects, i.e., personal hygiene (PH), food hygiene (FH) and recognition of foods (RF) was imparted by Balsevikas (BSs) incharge of the creches, daily in a non-formal manner, for one year and evaluated periodically. On PH only, children of the lowest income group improved significantly. On FH and RF, all children registered significant improvement as these two aspects, were under the direct control of BSs who enthused and involved the children by providing an interacting and stimulating environment. The results are encouraging and indicate the pre-school children are educable in NHE provided participatory and appropriate material and methods are used.