Fixed-dose Combination Therapy Research Articles

Triple Fixed-dose combination of Dapagliflozin, Sitagliptin, and Metformin for People with Type 2 Diabetes in Indian Settings

Objective: This study assessed the bioequivalence of a fixed-dose combination (FDC) therapy containing extended-release Metformin (Metformin XR), Dapagliflozin, and Sitagliptin for treating type 2 diabetes (T2D). The objective was to compare the absorption rate and extent of the FDC with two reference products: Sitagliptin 100mg tablets (R1) and a combination of Dapagliflozin 10mg plus Metformin 1000mg extended-release tablets (R2) in healthy adult males under fed conditions. Methods: An open-label, randomized, cross-over study was conducted with 24 healthy male participants. Each participant received a single dose of the test FDC and the reference products, with blood samples collected over 72 hours to evaluate pharmacokinetic parameters (Cmax, AUC0-t, AUC0-inf, Tmax, Kel, AUC_% Extrap_obs, and t1/2). Bioequivalence was determined based on the 90% confidence intervals (CIs) of the geometric mean ratios for AUC0-t and Cmax, within a predefined range of 80.00%-125.00%. Safety and tolerability were also assessed. Results: Pharmacokinetic analysis was performed on 22 subjects. The geometric mean ratios for the FDC compared to the reference products were within the predefined bioequivalence range, indicating that the absorption profiles of the FDC and the reference products were similar. The mean plasma concentration-time curves for Dapagliflozin, Sitagliptin, and Metformin XR were almost identical between the FDC and reference products, demonstrating consistent drug release and absorption. No significant differences were observed in Tmax, t1/2, or other pharmacokinetic parameters, further supporting bioequivalence. Additionally, the FDC was well-tolerated, with no serious adverse events reported, and all subjects completed the study without complications. Conclusion: The study confirmed that the FDC of Dapagliflozin, Sitagliptin, and Metformin XR is bioequivalent to the reference products in healthy adult males under fed conditions. This bioequivalence supports the use of the FDC as an effective treatment option to improve glycemic control in adults with T2D, particularly in the Indian context, promoting the benefits of combined therapy in managing diabetes. Keywords: Bioequivalence, Fixed-dose combination (FDC), Type 2 diabetes (T2D), Pharmacokinetics, Dapagliflozin, Metformin XR, Sitagliptin

Abstract P438: Is aprocitentan also sympatholytic in patients with resistant hypertension?

Background: Aprocitentan is an endothelin ET A /ET B receptor antagonist (ERA) approved for the treatment of hypertension not adequately controlled on other drugs. Resistant hypertension is associated with sympathetic activation. The insufficient blood pressure (BP) lowering of many patients at night (non-dipping) and an often-increased heart rate are signs of sympathetic activation. Because ET A and ET B receptors participate in adrenaline and noradrenaline release and dual ERAs have been shown to decrease catecholamines, we hypothesized that aprocitentan might, among the various effects of dual blockade, behave as a sympathetic inhibitor. To assess this hypothesis, we investigated the effect of aprocitentan on nighttime BP and heart rate, both influenced by the sympathetic system. Methods: In the PRECISION study, where enrolled subjects were still hypertensive despite being on a standard fixed-dose background combination therapy composed of amlodipine, valsartan and hydrochlorothiazide, 730 patients were randomized to receive aprocitentan 12.5 mg, 25 mg or placebo for the first 4 weeks (double-blind placebo-controlled phase). 24-hour ambulatory BP monitoring (ABPM) was recorded in all randomized patients at baseline and Week 4. Results: At baseline, 60% of patients were non-dippers at night . Among those, 25%, 39% and 37% were reverted to dippers in the placebo, aprocitentan 12.5 and 25 mg groups, respectively, at Week 4. Accordingly, aprocitentan 12.5 mg and 25 mg decreased nighttime BP by -8.1 and -11 mmHg, respectively, vs -2.6 mmHg on placebo at Week 4. This reduction in nighttime BP by aprocitentan was larger than the reduction in daytime BP (-6.2 and -7.8 mmHg decrease at 12.5 and 25 mg, respectively, vs -2.3 mmHg on placebo). At baseline, mean heart rate, measured by office BP measurement at trough, was 74 beats/min. At Week 4, aprocitentan 12.5 mg and 25 mg, despite the respective 15.3 and 15.5 mmHg reduction of office BP from baseline, did not increase heart rate (-3.3 and -2.6 beats/min at 12.5 and 25 mg, respectively, versus -2.7 beats/min on placebo). Conclusion: We conclude that, by blocking ET A and ET B receptors, aprocitentan may have downstream sympatholytic effects, which may help its efficacy on nighttime BP – a prognostic factor for CV events in hypertension – and allow marked BP lowering without any reactive tachycardia.

Strategies to Address Statin Medication Intolerance Among Patients at Risk of Cardiovascular Disease Identified Through Electronic Health Records: A Literature Review and Pooled Analysis.

Statins are a group of medications that lower lipid and are used for primary and secondary prevention of cardiovascular diseases (CVD). Patients can either be partially (15%) or completely (5%) intolerant to statins. Symptoms of statin intolerance can include muscle aches (myalgia), weakness, cramps, myopathy, diabetes mellitus, and elevated creatine kinase levels. Decreasing statin intolerance also improves statin adherence, which in turn results in lower number of CVD events among patients. Studies on statin intolerance is often embedded within studies of statin adherence. However, relevant data can be obtained from digital health systems. This preliminary literature review looks at studies from the past 10 years to identify and determine the effectiveness of strategies to address statin intolerance. The NLA definition for statin intolerance was used in this review. The initial search results on EMBASE, PubMed, SCOPUS, and CINAHL showed 91 articles and applying the inclusion and exclusion criteria, four articles were used in this review and pooled analysis. The study patients were identified through electronic health records. The pooled analysis was done using the Metafor package in R, applying a random-effect model to estimate pooled effect size. The findings suggest that using fixed dose combination therapy and switching from a lipophilic statin to a hydrophilic statin, while correcting metabolic abnormalities, or initiating evolocumab alongside statin can address statin intolerance. The overall relative risk (RR) was 0.40 (95% CI, 0.09 to 1.70) with I2 90%, and the overall odds ratio (OR) was 0.11 (95% CI, 0.01 to 1.59) with I2 94%, suggesting that the interventions work well in addressing statin intolerance. Since statin intolerance is has a vast range of effects, further research works may be done on exploring the possibility of using digital health systems to identify and provide targeted interventions to patients.

Assessment of treatment outcomes of daily fixed-dose combination therapy among drug-sensitive pulmonary tuberculosis patients: A prospective study from Bengaluru, India.

The annual incidence cases report depicts India as having the highest tuberculosis (TB) burden globally. Following a programmatic change, the daily fixed-dose combination (FDC) anti-TB treatment regimens were introduced by the Indian government's National Tuberculosis Elimination Program (NTEP). The aim of the study was to assess the treatment outcomes among drug-sensitive pulmonary TB patients receiving daily FDC drugs and the associated factors influencing the treatment outcomes. A prospective study was conducted among 300 drug-sensitive pulmonary TB cases in the Bruhat Bengaluru Mahanagara Palike (BBMP) area. The TB units and designated microscopic centers (DMCs) were selected by multistage random sampling. Data were collected through a pre-tested and semi-structured questionnaire. Patients were followed up until treatment completion. Data were compiled and analyzed using IBM Statistical Package for Social Sciences (SPSS) statistics version 20.0. Descriptive statistics and the Chi-square test were used for interpretation. A P-value less than 0.05 was considered statistically significant. Around 86.33% of patients were cured, 4% had completed treatment, and 1% had treatment failure. Older age, human immunodeficiency virus (HIV) reactive status, alcohol intake, tobacco use, and migrants were associated with poor outcomes. The daily FDC regimen had better outcomes than intermittent regimens. Smokers, alcoholics, migrants, and patients with co-morbidity need to be given priority in management as they are prone to poorer outcomes.

Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars)

BackgroundWe aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting.MethodsThe PolyPars Study is a two-arm...

Development and Validation of Ultra-Performance Liquid Chromatography (UPLC) Method for Simultaneous Quantification of Hydrochlorothiazide, Amlodipine Besylate, and Valsartan in Marketed Fixed-Dose Combination Tablet

Fixed-dose combination therapy is considered a practical approach in the treatment of various diseases, as it can simultaneously target different mechanisms of action that achieve the required therapeutic efficacy through a synergistic effect. A combination of hydrochlorothiazide (HTZ), amlodipine (AMD), and valsartan (VLS) has been created for the treatment of hypertension. Therefore, the aim of this study was to develop an optimized UPLC method for the simultaneous quantification of this combination. A DoE at a level of 32 was used to investigate the effects of column temperature (20, 30, and 40 °C) and formic acid concentration (0.05, 0.15, and 0.25%) on the retention time of each active pharmaceutical ingredient (API), the peak area, and the peak symmetry, as well as the resolution between HTZ-AMD and AMD-VLS peaks. The optimized analytical method was validated and used to extract the three APIs from the marketed product. The optimized analytical condition with a column temperature of 27.86 °C and a formic acid concentration of 0.172% showed good separation of the three APIs in 1.62 ± 0.006, 3.59 ± 0.002, and 3.94 ± 0.002 min for HTZ, AMD, and VST, respectively. The developed method was linear with the LOQ for a HTC, AMD, and VST of 0.028, 0.038, and 0.101 ppm, respectively. Moreover, the developed assay was sustainable and robust, with an RSD % of less than 2%. The application of this method in the extraction of HTZ, AMD, and VST from the Exforge® marketed product showed good separation with a measurable drug content of 23.5 ± 0.7, 9.68 ± 0.1, and 165.2 ± 5.2 mg compared to the label claims of 25/10/160 for HTZ, AMD, and VST, respectively.

Controlling blood pressure and progression of hypertension-dependent cardiovascular continuum by amlodipine and perindopril A single pill fixed‑dose combination: focus on endothelial dysfunction and metabolic risks

Due to its broad spectrum of pathogenic target points, fixed-dose combination therapy is considered a benchmark approach to successful treatment of arterial hypertension (HTN) and HTN-associated cardiovascular conditions. This results from endothelium insufficiency of various origin, so the use of combination of angiotensinconverting enzyme inhibitors and calcium channel blockers is an optimal treatment choice. The review highlights key points of single pill amlodipine and perindopril A combination use and its key position in modern concept of hypertension management. We have focused on the metabolic neutrality of fixed-dose amlodipine and perindopril A combination, its ability to delay rapid progression of already acquired metabolic changes. We briefly highlight fundamental observational and randomized studies, in particular, those regarding effectiveness of the drug components and its effect on the end points as a fixed-dose combination. The last but not least, we emphasize vasoand cardioprotective properties of the drug as well as its safety profile.

Bioequivalence of Elagolix/Estradiol/Norethindrone Acetate Fixed-Dose Combination Product: Phase 1 Results in Healthy Pre- and Postmenopausal Women.

Fixed-dose combination (FDC) therapies can enhance patient convenience and adherence to prescribed treatment regimens. Elagolix is a novel oral gonadotropin-releasing hormone receptor antagonist approved for management of moderate to severe pain associated with endometriosis and heavy menstrual bleeding associated with uterine fibroids. Hormonal add-back therapy can attenuate the reversible hypoestrogenic effects of elagolix. An FDC formulation containing elagolix/estradiol (E2)/norethindrone acetate (NETA) 300/1/0.5mg as the morning dose and an elagolix 300mg capsule as the evening dose, were evaluated in 2 bioequivalence studies including the effects of food. Study 1 in premenopausal women assessed the bioavailability of the elagolix 300-mg capsule relative to the commercially available elagolix 300-mg tablet. Study 2 in postmenopausal women, elagolix/E2/NETA (300mg/1mg/0.5mg) FDC capsule was assessed relative to the elagolix 300-mg tablet coadministered with E2/NETA 1-mg/0.5-mg tablet, the regimen that was studied in Phase 3 uterine fibroid studies. Under fasting conditions, the test elagolix 300-mg capsule was bioequivalent to the reference elagolix 300-mg tablet. Under fasting conditions, the elagolix/E2/NETA FDC capsule was bioequivalent to the coadministered elagolix 300-mg tablet and E2/NETA 1/0.5-mg tablet. Following administration of elagolix/E2/NETA FDC capsule after a high-fat breakfast, elagolix mean maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) were 38% and 28% lower, relative to fasting conditions. NETA mean Cmax was 51% lower and AUC from time 0 to infinity was 20% higher, while baseline-adjusted total estrone mean Cmax and AUC were 46% and 14% lower, respectively. No safety concerns were identified. These results enabled bridging the elagolix/E2/NETA FDC capsule.

Fixed-dose combination therapy in pulmonary arterial hypertension: Pros & cons

Quality of life of patients suffering from chronic diseases is inevitably conditioned by the number of pills taken during the day. To improve patients' tolerability, compliance and quality of life and reduce healthcare costs, pharmaceutical companies are focusing on the commercialization of fixed-dose combination (FDC) therapies.The last ESC/ERS guidelines for the treatment of pulmonary arterial hypertension (PAH) recommend initial dual combination therapy for newly diagnosed patients at low or intermediate mortality risk. In this regard, polypills including an endothelin receptor antagonist (ERA) and a phosphodiesterase 5 inhibitor (PDE5-i) could represent an useful therapeutic strategy, although with some limitations. To date, evidence about the use of FDCs in PAH is limited but future studies evaluating their safety and efficacy are welcome.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease.

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I2 = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I2 = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.

The Rationale for Using Fixed-Dose Combination Therapy in the Management of Hypertension in Colombia: A Narrative Review.

Hypertension is a major risk factor for cardiovascular disease and the leading cause of death in Colombia. While the rate of hypertension awareness in Colombia is generally high, rates of treatment initiation, adherence, and blood pressure (BP) control are suboptimal. Major international hypertension guidelines recommend starting treatment with a combination of antihypertensive agents, and the use of a single-pill combination (SPC) to maximize adherence. In contrast, Colombian hypertension guidelines recommend starting treatment with diuretic monotherapy in most patients, and only initiating combination therapy in those with BP > 160/100 mmHg. Therefore, the aim of the current narrative review is to examine the rationale for using SPCs to treat hypertension in Colombia, in the context of the major issues for BP controlthere. There is evidence of widespread therapeutic inertia in hypertension management, particularly in primary care, in Colombia. Moreover, combination therapy, angiotensin-converting enzyme inhibitors, and long-acting calcium channel blockers, which are internationally recommended as first-line drug therapies, are underutilized there. Adherence to antihypertensive therapy is low in Colombia and may be enhanced by use of SPCs as well as better patient education and follow-up. While there are promising national initiatives to improve BP management, more needs to be done by individual physicians. Antihypertensive SPCs are available on the national essential medicines list and may help to overcome some of the problems with suboptimal adherence, therapeutic inertia, and low rates of BP control that contribute to the high cardiovascular death rate in Colombia.

Cost-effectiveness of cardiomyopathy ambulatory care with sacubitril/valsartan vs standard therapy after COVID-19 in Kazakhstan

The aim of this study is to evaluate the cost-effectiveness of 2 different therapies of cardiomyopathy (CM) after COVID -19. The focus of the study is fixed dose combination (FDC) of sacubitril/valsartan and standard therapy in Kazakhstan. This is written from the point of view of the health insurance institution. Information for the age, gender, CM therapy, number of hospitalizations, COVID-19 infection, and past cardiovascular surgeries of 237 patients with incidents of CM which required a hospitalization after a COVID-19 infection was collected. Selected patients were divided into two groups: the cost of FDC and standard therapy and the annual cost of their therapy was calculated. The incremental cost-effectiveness ratio was calculated by dividing the cost of medication therapy by the number of hospitalizations between the two compared groups. Robustness of the results was tested with deterministic and probabilistic sensitivity analyses. The study was performed in City cardiology centre of Almaty in Kazakhstan during 2020–2022. Results show that FDC is more costly but more effective, leading to fewer hospitalizations. ICER accounts for €-2,743.08 per hospitalization saved in the group on FDC vs standard of therapy. Sacubitril/valsartan is cost-effective in ambulatory conditions in comparison with standard therapy of cardiomyopathy after COVID-19 leading to savings due to the decrease in the number of hospitalizations.

Effectiveness of perindopril/amlodipine fixed-dose combination in the treatment of hypertension: a systematic review.

Background: Uncontrolled blood pressure is a major risk factor for cardiovascular diseases. Fixed-dose combination (FDC) therapy offers a promising approach to addressing this challenge by providing a convenient single-tablet solution that enhances the effectiveness of blood pressure control. In our systematic review, we assess the effectiveness of perindopril/amlodipine FDC in managing blood pressure. Methods: We conducted a comprehensive search across four primary electronic databases, namely, PubMed, Virtual Health Library (VHL), Global Health Library (GHL), and Google Scholar, as of 8 February 2022. Additionally, we performed a manual search to find relevant articles. The quality of the selected articles was evaluated using the Study Quality Assessment Tools (SQAT) checklist from the National Institute of Health and the ROB2 tool from Cochrane. Results: Our systematic review included 17 eligible articles. The findings show that the use of perindopril/amlodipine FDC significantly lowers blood pressure and enhances the quality of blood pressure control. Compared to the comparison group, the perindopril/amlodipine combination tablet resulted in a higher rate of blood pressure response and normalization. Importantly, perindopril/amlodipine FDC contributes to improved patient adherence with minimal side effects. However, studies conducted to date have not provided assessments of the cost-effectiveness of perindopril/amlodipine FDC. Conclusion: In summary, our analysis confirms the effectiveness of perindopril/amlodipine FDC in lowering blood pressure, with combination therapy outperforming monotherapy and placebo. Although mild adverse reactions were observed in a small subset of participants, cost-effectiveness assessments for this treatment remain lacking in the literature.

Fixed-Dose Combination Formulations in Solid Oral Drug Therapy: Advantages, Limitations, and Design Features.

Whilst monotherapy is traditionally the preferred treatment starting point for chronic conditions such as hypertension and diabetes, other diseases require the use of multiple drugs (polytherapy) from the onset of treatment (e.g., human immunodeficiency virus acquired immunodeficiency syndrome, tuberculosis, and malaria). Successful treatment of these chronic conditions is sometimes hampered by patient non-adherence to polytherapy. The options available for polytherapy are either the sequential addition of individual drug products to deliver an effective multi-drug regimen or the use of a single fixed-dose combination (FDC) therapy product. This article intends to critically review the use of FDC drug therapy and provide an insight into FDC products which are already commercially available. Shortcomings of FDC formulations are discussed from multiple perspectives and research gaps are identified. Moreover, an overview of fundamental formulation considerations is provided to aid formulation scientists in the design and development of new FDC products.

Implementation study to introduce clinical guidelines on lipid metabolism disorders into routine practice: results of the first stage

Despite widespread knowledge in the management of patients with lipid metabolism disorders, their application in clinical practice is insufficient. Identification of barriers to the implementation of key principles of clinical guidelines in routine practice is the first step of the implementation study.Aim. To assess the organization and quality of care for patients with dyslipidemia in order to identify barriers to the implementation of the main principles of clinical guidelines in practice.Material and methods. An implementation study was planned, the initial stage of which was to conduct an anonymous online questionnaire among health care representatives of various levels in all Russian subjects.Results. The study involved 788 physicians, 124 heads of medical organizations and 48 chief freelance specialists from 84 Russian subjects. A wide range of barriers was identified: low availability of lipoprotein (a) testing (66,6% of physicians), coronary calcium index (79,4% of physicians, 71,8% of heads of a medical organizations, 79,2% of chief freelance specialists) and CT angiography (70,0% of physicians, 71,0% of heads of a medical organizations, 85,4% of chief freelance specialists). Lack of funds to manage lipid service (55,6% of heads of a medical organizations, 35,4% of chief freelance specialists). The key barrier to regular lipid-lowering therapy and achieving target low-density lipoprotein cholesterol (LDL-C) levels is lack of perceived need for treatment in patients (58,1% of physicians, 80,0% of heads of a medical organizations, 87,5% of chief freelance specialists), for PCSK9-targeted therapy — high cost (44,1% of physicians, 34,7% of heads of a medical organizations, 23,0% of chief freelance specialists). The possible fixed-dose combination therapy for dyslipidemia was positively perceived (59,7% of physicians, 42,0% of heads of a medical organizations, 35,4% of chief freelance specialists). Inclusion of innovative therapy in medicine assistance program will improve the situation in achieving target LDL-C levels (85,6% of physicians, 91,1% of heads of a medical organizations, 95,8% of chief freelance specialists).Conclusion. A wide range of barriers to the implementation of clinical guidelines on lipid metabolism disorders into practice have been identified. Based on the results obtained, the second stage of the implementation study will identify strategies aimed at eliminating the identified barriers.

Fixed triple combination of amlodipine, perindopril and atorvastatin in the focus of cardiovascular effectiveness and safety

The review outlines modern concepts of the relevance of fixed-dose combination therapy comprising angiotensin-converting enzyme inhibitor and dihydropyridine calcium channel antagonist as an antihypertensive component with the HMG-CoA reductase inhibitor when treating hypertensive patients. We have identified the realms of its possible clinical use taking into consideration the comorbidity peculiarities. In addition, we provide main features of the current drugs’ clinical pharmacodynamics and outline their role in real clinical practice. Nevertheless the emphasis was placed on the modern single-pill combination of amlodipin, atorvastatin and perindopril. We concisely report the results data collected from the large, randomized, double-blind major clinical trials regarding the effectiveness of single pill combination of amlodipine, atorvastatin and perindopril , primary focusing on their cardioprotective features and overall safety profile.

Fixed-Dose Combination Therapy for Prevention of Cardiovascular Diseases in CKD: An Individual Participant Data Meta-analysis.

Fixed-dose combination treatments reduce cardiovascular disease in primary prevention. We aim to explore whether those benefits differ in the presence of chronic kidney disease (CKD). We conducted an individual participant data meta-analysis in 18,162 participants on the efficacy and safety of treatment for the primary prevention of cardiovascular disease. Combination therapies consisted of at least two blood pressure lowering drugs, and a statin, with or without aspirin versus placebo or usual care. Here we examine the differential effect of fixed-dose combination treatment on the risk of developing cardiovascular disease in participants with a low estimated glomerular filtration rate (eGFR <60 ml/min/1.73m2; CKD-EPI formula) compared to a normal eGFR (≥60 ml/min/1.73m2). The primary composite outcome was time to first occurrence of a combination of cardiovascular death, myocardial infarction, stroke, or arterial revascularization. At baseline, mean level of eGFR was 76 ml/min/1.73m2 (17). 3,315 (18%) participants had low eGFR at baseline. During a median follow-up of 5 years, among participants with normal eGFR, the primary outcome occurred in 232 (3%) of participants in the treatment group compared with 339 (5%) in control group (hazard ratio [HR], 0.68; 95% confidence interval [95%CI], 0.57-0.81; P<0.001). In participants with low eGFR, the primary outcome occurred in 64 (4%) of participants in the treatment group compared with 130 (8%) in control group (HR, 0.49; 95%CI, 0.36-0.66; P<0.001; P for interaction 0.047). The relative risk reduction among participants with low eGFR was larger for combination strategies including aspirin compared to treatments without aspirin. Apart from dizziness, other side effects didn't differ between treatment and control groups regardless of the stage of their kidney function. A fixed-dose combination treatment strategy is effective and safe at preventing cardiovascular disease, irrespective of eGFR but relative and absolute risk reductions are larger in individuals with low eGFR.

EE268 Temporal Trends in Adverse Event Costs with Nivolumab + Relatlimab Combination Therapy or Nivolumab Monotherapy for Patients with Unresectable or Metastatic Melanoma

This study described hospitalization costs of grade 3/4 all-cause adverse events (AEs) and treatment-related AEs (TRAEs) of nivolumab plus relatlimab fixed-dose combination therapy (Nivo+Rela) and nivolumab monotherapy (Nivo) for unresectable or metastatic melanoma.

Fixed dose combination therapies in primary cardiovascular disease prevention in different groups: an individual participant meta-analysis

ObjectiveTo evaluate the effects of fixed dose combination (FDC) medications on cardiovascular outcomes in different age groups in an individual participant meta-analysis of three primary prevention randomised trials.MethodsParticipants at intermediate...

Use of Fixed-dose Combination Therapy with Remogliflozin and Vildagliptin as an Add-on Drug in Improving the Glycemic Control of Type 2 Diabetes Mellitus: An Observational Study

Objective To evaluate whether a fixed dose combination (FDC) with remogliflozin and vildagliptin as an add-on therapy can improve the glycemic control in the management of type 2 diabetes mellitus and also the non-glycemic effects on physical profile, blood pressure, lipids, and insulin resistance. Materials and Methods An observational study that included 50 poorly controlled diabetics from April 2021 to September 2021. Patients were divided into two groups – those who were prescribed this FDC by their treating physician as an add-on drug were formed as group 1 ( n = 28). Comparison group was age-matched patients who received other standard anti-diabetic medications, categorized as group 2 ( n = 22). Fasting and postprandial sugars were done at baseline, the third and sixth month; glycated hemoglobin, body mass index, blood pressure, and lipids were done at baseline and the sixth month. Changes in blood sugar levels and glycated hemoglobin (HbA1C) at the third and sixth month from the baseline were compared using the Mann-Whitney U test. P-value less than 5% was considered statistically significant. Results A statistically significant reduction in mean HbA1c was noted in group 1 [–1.80 (−3.20, −0.15)] when compared to group 2 [0.50 (0.05, 0.80)] at the end of the third month. At the end of the sixth month, a significant reduction in the HbA1c level was noted in group 1 [(7.83 ± 0.87 %) when compared to baseline (10.3 ± 1.75%)]. Change in PPBS value at the third month from baseline was also statistically significant between groups 1 and 2 (−62.0 mg%, 19.0, P = 0.003). With respect to the body mass index and blood pressure, we did not find any significant difference. Conclusion The fixed drug combination improves glycemic control by significantly reducing mean HbA1c at the third and sixth month from baseline and there was no significant effect on body mass index, blood pressure, and lipids.