Why Vono
Vonoprazan, a novel class of Potassium Competitive Acid Blocker has been introduced in the space of Anti-peptic ulcerants post 3 long decades of PPI existence as the best alternative. This superior molecule promises to be the future with its key attributes of 24-hour pH > 4 holding time ratio, peak action with its first dose, and immediate symptomatic relief & no restriction of mealtime dosing for best patient outcomes. Dr. Reddys who has been at the forefront in Gastroenterology therapy are among the first few top Indian Pharma Companies to launch the patented molecule Vono ( Vonoprazan) along with a non-exclusive patent licensing agreement with manufacturers to commercialize Vono (Vonoprazan) in India.
A recent study demonstrated that the early administration of dapagliflozin during the acute heart failure (AHF) hospitalization is safe and serves as a component of guideline-directed medical therapy (GDMT) optimization. Additionally, dapagliflozin may be associated with improved diuresis in patients with AHF. This study's findings were published in the Journal of the American College of Cardiology.
A total of 240 patients were enrolled in this multicenter trial, where they were randomized to receive either dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration within a period of 24 hours of hospital admission for hypervolemic AHF. The primary outcome of the study, diuretic efficiency, was assessed by comparing the cumulative weight change per cumulative loop diuretic dose between the two treatment groups.
Administration of dapagliflozin resulted in a reduction in loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] compared to 800 mg [Q1-Q3: 380-1,715 mg]) and a reduced need for intravenous diuretic adjustments to achieve comparable weight loss as standard treatment. Commencing dapagliflozin early did not elevate the occurrence of safety issues related to diabetes, kidney function, or cardiovascular health. Additionally, dapagliflozin was linked to an enhancement in median 24-hour natriuresis and urine output, facilitating quicker hospital discharge throughout the study duration.
Thus, it can be concluded that the early use of dapagliflozin during AHF hospitalization is considered safe and fulfills a component of optimizing GDMT. Additionally, dapagliflozin may lead to improved diuresis in individuals with AHF.
A recent study demonstrated that the early administration of dapagliflozin during the acute heart failure (AHF) hospitalization is safe and serves as a component of guideline-directed medical therapy (GDMT) optimization. Additionally, dapagliflozin may be associated with improved diuresis in patients with AHF. This study's findings were published in the Journal of the American College of Cardiology.
A total of 240 patients were enrolled in this multicenter trial, where they were randomized to receive either dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration within a period of 24 hours of hospital admission for hypervolemic AHF. The primary outcome of the study, diuretic efficiency, was assessed by comparing the cumulative weight change per cumulative loop diuretic dose between the two treatment groups.
Administration of dapagliflozin resulted in a reduction in loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] compared to 800 mg [Q1-Q3: 380-1,715 mg]) and a reduced need for intravenous diuretic adjustments to achieve comparable weight loss as standard treatment. Commencing dapagliflozin early did not elevate the occurrence of safety issues related to diabetes, kidney function, or cardiovascular health. Additionally, dapagliflozin was linked to an enhancement in median 24-hour natriuresis and urine output, facilitating quicker hospital discharge throughout the study duration.
Thus, it can be concluded that the early use of dapagliflozin during AHF hospitalization is considered safe and fulfills a component of optimizing GDMT. Additionally, dapagliflozin may lead to improved diuresis in individuals with AHF.
A recent study found that the administration of intravenous ferric derisomaltose (FDI) in patients diagnosed with both iron deficiency anemia and heart failure with reduced left ventricular ejection fraction has been found to improve their quality of life and may decrease cardiovascular events. This study’s results were published in the Journal of Cardiac Failure.
In the IRONMAN trial, patients with heart failure, iron deficiency (ferritin <100 µg/L or transferrin saturation of <20%), and a left ventricular ejection fraction of ≤45% were enrolled. Out of the total, 68% (n= 771) had anemia (hemoglobin less than 12 g/dL for women and less than 13 g/dL for men). Patients were then randomly assigned to either FDI (n = 397) or usual care (n = 374) and were followed for a median duration of 2.6 years. The primary endpoint of the study was recurrent hospitalization for heart failure and cardiovascular death.
The occurrence of recurrent hospitalization for heart failure and cardiovascular death was less frequent among individuals assigned to FDI (rate ratio 0.78, 95% confidence interval of 0.61-1.01, and the p-value = 0.063). Similarly, the first event analysis for cardiovascular hospitalization or death for heart failure showed similar results (hazard ratio of 0.77, 95% confidence interval of 0.62-0.96 ; p-value = 0.022). Additionally, patients who were randomized to FDI reported better quality of life scores for overall (p-value = 0.013) and physical domain (p-value = 0.00093) at 4 months, as measured by the Minnesota Living with Heart Failure questionnaire.
The above study demonstrated that the administration of intravenous FDI improves the quality of life in patients diagnosed with both iron deficiency anemia and heart failure with reduced left ventricular ejection fraction, and it may also lead to a decrease in cardiovascular events.
A recent study found that the administration of intravenous ferric derisomaltose (FDI) in patients diagnosed with both iron deficiency anemia and heart failure with reduced left ventricular ejection fraction has been found to improve their quality of life and may decrease cardiovascular events. This study’s results were published in the Journal of Cardiac Failure.
In the IRONMAN trial, patients with heart failure, iron deficiency (ferritin <100 µg/L or transferrin saturation of <20%), and a left ventricular ejection fraction of ≤45% were enrolled. Out of the total, 68% (n= 771) had anemia (hemoglobin less than 12 g/dL for women and less than 13 g/dL for men). Patients were then randomly assigned to either FDI (n = 397) or usual care (n = 374) and were followed for a median duration of 2.6 years. The primary endpoint of the study was recurrent hospitalization for heart failure and cardiovascular death.
The occurrence of recurrent hospitalization for heart failure and cardiovascular death was less frequent among individuals assigned to FDI (rate ratio 0.78, 95% confidence interval of 0.61-1.01, and the p-value = 0.063). Similarly, the first event analysis for cardiovascular hospitalization or death for heart failure showed similar results (hazard ratio of 0.77, 95% confidence interval of 0.62-0.96 ; p-value = 0.022). Additionally, patients who were randomized to FDI reported better quality of life scores for overall (p-value = 0.013) and physical domain (p-value = 0.00093) at 4 months, as measured by the Minnesota Living with Heart Failure questionnaire.
The above study demonstrated that the administration of intravenous FDI improves the quality of life in patients diagnosed with both iron deficiency anemia and heart failure with reduced left ventricular ejection fraction, and it may also lead to a decrease in cardiovascular events.
A recent study showed that the use of an "inclisiran first" approach resulted in a more significant reduction in low-density lipoprotein cholesterol (LDL-C) levels when compared to standard care, without negatively impacting the use of statins or giving rise to any additional safety concerns. This research findings were published in the Journal of the American College of Cardiology.
The VICTORION-INITIATE trial involved 450 patients who were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg at days 0, 90, and 270) along with standard care (lipid management determined by the treating physician) or standard care alone. The primary endpoints of the study assessed the percentage change in LDL-C levels from the baseline and the rates of statin discontinuation.
The "inclisiran first" strategy resulted in significantly larger reductions in LDL-C levels from baseline to day 330 compared to standard care (60.0% vs. 7.0%; P < 0.001). The discontinuation rates of statins with the "inclisiran first" approach (6.0%) were found to be noninferior to standard care (16.7%). A higher proportion of patients in the "inclisiran first" group achieved their LDL-C goals compared to standard care (<70 mg/dL: 81.8% vs. 22.2%; <55 mg/dL: 71.6% vs. 8.9%; P < 0.001). Rates of treatment-emergent adverse events (TEAE) and serious TEAE were comparable between the two treatment strategies (62.8% vs. 53.7% and 11.5% vs. 13.4%, respectively).
The above study demonstrated that adopting an "inclisiran first" strategy led to a greater decrease in LDL-C levels compared to conventional treatment, while maintaining the use of statins and without posing any additional safety issues.
A recent study showed that the use of an "inclisiran first" approach resulted in a more significant reduction in low-density lipoprotein cholesterol (LDL-C) levels when compared to standard care, without negatively impacting the use of statins or giving rise to any additional safety concerns. This research findings were published in the Journal of the American College of Cardiology.
The VICTORION-INITIATE trial involved 450 patients who were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg at days 0, 90, and 270) along with standard care (lipid management determined by the treating physician) or standard care alone. The primary endpoints of the study assessed the percentage change in LDL-C levels from the baseline and the rates of statin discontinuation.
The "inclisiran first" strategy resulted in significantly larger reductions in LDL-C levels from baseline to day 330 compared to standard care (60.0% vs. 7.0%; P < 0.001). The discontinuation rates of statins with the "inclisiran first" approach (6.0%) were found to be noninferior to standard care (16.7%). A higher proportion of patients in the "inclisiran first" group achieved their LDL-C goals compared to standard care (<70 mg/dL: 81.8% vs. 22.2%; <55 mg/dL: 71.6% vs. 8.9%; P < 0.001). Rates of treatment-emergent adverse events (TEAE) and serious TEAE were comparable between the two treatment strategies (62.8% vs. 53.7% and 11.5% vs. 13.4%, respectively).
The above study demonstrated that adopting an "inclisiran first" strategy led to a greater decrease in LDL-C levels compared to conventional treatment, while maintaining the use of statins and without posing any additional safety issues.
According to a recent study, it was validated that nomogram can predict cancer-specific survival and develop a risk stratification system for patients with primary gastrointestinal melanoma. The findings of the study were published in The Turkish Journal of Gastroenterology.
Results from a database of 433 patients with primary gastrointestinal melanoma were included in the study after randomly dividing the participants into training and validation cohorts (8:2). The nomogram was constructed based on the risk factors identified in the multivariate Cox regression analysis. Based on the nomogram, a risk stratification system was developed. Time-dependent receiver operating characteristic, calibration curve, and decision curve analysis were performed.
All cases were randomly divided into either the training (n = 347, 80%) or validation cohort (n = 86, 20%). For all patients, the median cancer-specific survival (CSS) time was 18.0 months (95% CI: 14.7-21.3). The median CSS was 18.0 months (95% CI: 14.5-21.5) and 18.0 months (95% CI: 10.7-25.3) in the training and validation cohorts, respectively (log-rank test, P = .241).
It was found that CSS under the curves of the nomogram for 6-, 12-, and 18-month were 0.789, 0.757, and 0.726 for internal validation, and 0.796, 0.763, and 0.795 for the external validation. Furthermore, the patients were divided into 2 risk sub-groups to study the risk stratification, low-risk (point: 0-182) and high-risk (point: 183-333). The median CSS was 31.0 months (95% CI: 24.5-37.5) in the low-risk subgroup and 8.0 months (95% CI: 6.2-9.8) in the high-risk subgroup. The Kaplan-Meier analysis and the log-rank test demonstrated that the risk stratification was well-differentiated in patients with varying risks of cancer-specific survival.
Thus, it can be concluded that the nomogram prediction model may be practical for validation of cancer-specific survival and development of a risk stratification system in patients with primary gastrointestinal melanoma.
According to a recent study, it was validated that nomogram can predict cancer-specific survival and develop a risk stratification system for patients with primary gastrointestinal melanoma. The findings of the study were published in The Turkish Journal of Gastroenterology.
Results from a database of 433 patients with primary gastrointestinal melanoma were included in the study after randomly dividing the participants into training and validation cohorts (8:2). The nomogram was constructed based on the risk factors identified in the multivariate Cox regression analysis. Based on the nomogram, a risk stratification system was developed. Time-dependent receiver operating characteristic, calibration curve, and decision curve analysis were performed.
All cases were randomly divided into either the training (n = 347, 80%) or validation cohort (n = 86, 20%). For all patients, the median cancer-specific survival (CSS) time was 18.0 months (95% CI: 14.7-21.3). The median CSS was 18.0 months (95% CI: 14.5-21.5) and 18.0 months (95% CI: 10.7-25.3) in the training and validation cohorts, respectively (log-rank test, P = .241).
It was found that CSS under the curves of the nomogram for 6-, 12-, and 18-month were 0.789, 0.757, and 0.726 for internal validation, and 0.796, 0.763, and 0.795 for the external validation. Furthermore, the patients were divided into 2 risk sub-groups to study the risk stratification, low-risk (point: 0-182) and high-risk (point: 183-333). The median CSS was 31.0 months (95% CI: 24.5-37.5) in the low-risk subgroup and 8.0 months (95% CI: 6.2-9.8) in the high-risk subgroup. The Kaplan-Meier analysis and the log-rank test demonstrated that the risk stratification was well-differentiated in patients with varying risks of cancer-specific survival.
Thus, it can be concluded that the nomogram prediction model may be practical for validation of cancer-specific survival and development of a risk stratification system in patients with primary gastrointestinal melanoma.
A recent study demonstrated that for patients at risk of renal injury undergoing coronary angiography for acute coronary syndromes (ACS), a short (5-day) regimen of once-daily inorganic nitrate resulted in decreased contrast-induced nephropathy (CIN), enhanced kidney outcomes at 3 months, and reduced major adverse cardiovascular events (MACE) at 1 year when compared with individuals who received a placebo. This study’s results were published in the European Heart Journal.
The NITRATE-CIN trial was a double-blind, randomized, placebo-controlled trial that included a total of 640 patients. These patients were randomized to receive either once daily potassium nitrate (n= 319; 12 mmol) or placebo (n= 321; potassium chloride) capsules for a period of 5 days. The primary endpoint of the trial was the incidence of CIN based on KDIGO criteria. Secondary outcomes measured included kidney function (eGFR) at 3 months, rates of procedural myocardial infarction, and MACE at 12 months.
Inorganic nitrate treatment led to a significant decrease in the rates of CIN compared to the placebo (9.1% vs 30.5%). This difference remained even after adjusting for baseline creatinine levels and diabetes status. Additionally, the use of inorganic nitrate exhibited positive outcomes in secondary outcomes, including a lower incidence of procedural myocardial infarction (2.7% vs 12.5%), improved renal function at 3 months (between-group change in estimated glomerular filtration rate of 5.17), and a reduced occurrence of MACE at 1 year (9.1% vs. 18.1%) compared to the placebo group.
Thus, it can be concluded that a 5-day regimen of once-daily inorganic nitrate may be beneficial for patients undergoing coronary angiography for ACS. This treatment resulted in a decrease in CIN, improved kidney outcomes at 3 months, and reduced MACE at 1 year compared to those who received a placebo.
A recent study demonstrated that for patients at risk of renal injury undergoing coronary angiography for acute coronary syndromes (ACS), a short (5-day) regimen of once-daily inorganic nitrate resulted in decreased contrast-induced nephropathy (CIN), enhanced kidney outcomes at 3 months, and reduced major adverse cardiovascular events (MACE) at 1 year when compared with individuals who received a placebo. This study’s results were published in the European Heart Journal.
The NITRATE-CIN trial was a double-blind, randomized, placebo-controlled trial that included a total of 640 patients. These patients were randomized to receive either once daily potassium nitrate (n= 319; 12 mmol) or placebo (n= 321; potassium chloride) capsules for a period of 5 days. The primary endpoint of the trial was the incidence of CIN based on KDIGO criteria. Secondary outcomes measured included kidney function (eGFR) at 3 months, rates of procedural myocardial infarction, and MACE at 12 months.
Inorganic nitrate treatment led to a significant decrease in the rates of CIN compared to the placebo (9.1% vs 30.5%). This difference remained even after adjusting for baseline creatinine levels and diabetes status. Additionally, the use of inorganic nitrate exhibited positive outcomes in secondary outcomes, including a lower incidence of procedural myocardial infarction (2.7% vs 12.5%), improved renal function at 3 months (between-group change in estimated glomerular filtration rate of 5.17), and a reduced occurrence of MACE at 1 year (9.1% vs. 18.1%) compared to the placebo group.
Thus, it can be concluded that a 5-day regimen of once-daily inorganic nitrate may be beneficial for patients undergoing coronary angiography for ACS. This treatment resulted in a decrease in CIN, improved kidney outcomes at 3 months, and reduced MACE at 1 year compared to those who received a placebo.
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