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.
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.
A recent study found that initial oral treprostinil improved survival while those who started treprostinil after a clinical worsening in the placebo group and tolerated the drug for up to 48 weeks, enjoyed substantial functional gains. This study was published in the journal, Advances in Therapy.
This trial was an open-label extension (OLE) of the FREEDOM-EV study which enrolled 470 patients who had experienced an investigator-assessed clinical worsening event. All OLE participants were kept on open-label oral treprostinil. Those participants who had previously been assigned to placebo or previously assigned treprostinil, continued with the dose titration. Assessments included measured N-terminal pro-brain natriuretic peptide (NT-proBNP) at week 48, functional class, and 6-min walk distance (6MWD) at 12-week intervals. Survival was studied using the Kaplan-Meier analysis while hazard ratio (HR) was measured using Cox proportional hazards.
At the end of the study, it was seen that initial administration of oral treprostinil reduced mortality. Those who were randomized to the placebo group and initiated on oral treprostinil after clinical worsening, showed a reduction in NT-proBNP of - 778 pg/mL, functional class shifts, and 6MWD improvements of + 84 m when compared to the OLE baseline. Modest trends were observed in those participants who were initially assigned placebo and did not show clinical worsening and also those participants who were on the study drug without clinical worsening but continued with the drug through week 48.
Based on the above results, it can be concluded that with initial treprostinil, improved survival in the entire data set may be observed while those participants in the placebo arm, who were kept on treprostinil after a clinical worsening and tolerated the drug at week 48, may exhibit substantial functional gains.
A recent study found that initial oral treprostinil improved survival while those who started treprostinil after a clinical worsening in the placebo group and tolerated the drug for up to 48 weeks, enjoyed substantial functional gains. This study was published in the journal, Advances in Therapy.
This trial was an open-label extension (OLE) of the FREEDOM-EV study which enrolled 470 patients who had experienced an investigator-assessed clinical worsening event. All OLE participants were kept on open-label oral treprostinil. Those participants who had previously been assigned to placebo or previously assigned treprostinil, continued with the dose titration. Assessments included measured N-terminal pro-brain natriuretic peptide (NT-proBNP) at week 48, functional class, and 6-min walk distance (6MWD) at 12-week intervals. Survival was studied using the Kaplan-Meier analysis while hazard ratio (HR) was measured using Cox proportional hazards.
At the end of the study, it was seen that initial administration of oral treprostinil reduced mortality. Those who were randomized to the placebo group and initiated on oral treprostinil after clinical worsening, showed a reduction in NT-proBNP of - 778 pg/mL, functional class shifts, and 6MWD improvements of + 84 m when compared to the OLE baseline. Modest trends were observed in those participants who were initially assigned placebo and did not show clinical worsening and also those participants who were on the study drug without clinical worsening but continued with the drug through week 48.
Based on the above results, it can be concluded that with initial treprostinil, improved survival in the entire data set may be observed while those participants in the placebo arm, who were kept on treprostinil after a clinical worsening and tolerated the drug at week 48, may exhibit substantial functional gains.
According to a recent study, the pulmonary hypertension (pH) due to left heart disease (LHD) noninvasive nomogram demonstrates exceptional diagnostic value and clinical applicability, enabling a more precise assessment of the risk of pH in individuals with LHD. This study’s results were published in the journal, Heart & Lung.
In this study, a total of 361 patients with left heart disease (LHD) who had undergone right heart catheterization were enrolled. These patients were then randomly divided into two groups: a training cohort consisting of 253 patients (70%) and a validation cohort consisting of 108 patients (30%). The presence of pH was determined by a resting mean pulmonary arterial pressure (mPAP) of ≥25 mmHg, as measured through the right heart catheterization (RHC) examination. To analyze the data, the Lasso regression model was used for dimension reduction and feature selection. Subsequently, a nomogram was constructed based on multivariable logistic regression analysis.
175 individuals with left heart disease were diagnosed with pulmonary hypertension during their hospitalization, accounting for 48.5% of the sample cohort. Factors such as elevated New York Heart Association functional class, excessive resting heart rate, increased red blood cell distribution width, pulmonary artery systolic pressure, and right ventricular end-diastolic diameter assessed via echocardiography were independently linked to the prevalence of pH-LHD. The incorporation of these 5 variables in the nomogram demonstrated optimal calibration (Hosmer-Lemeshow test, P = 0.791) and strong discrimination (AUC = 0.866 [95% CI, 0.820-0.911]) for the validation set.
The above study demonstrated that the noninvasive nomogram for pH-LHD exhibits excellent diagnostic efficacy and clinical applicability, facilitating a more accurate evaluation of the pH risk in individuals with LHD.
According to a recent study, the pulmonary hypertension (pH) due to left heart disease (LHD) noninvasive nomogram demonstrates exceptional diagnostic value and clinical applicability, enabling a more precise assessment of the risk of pH in individuals with LHD. This study’s results were published in the journal, Heart & Lung.
In this study, a total of 361 patients with left heart disease (LHD) who had undergone right heart catheterization were enrolled. These patients were then randomly divided into two groups: a training cohort consisting of 253 patients (70%) and a validation cohort consisting of 108 patients (30%). The presence of pH was determined by a resting mean pulmonary arterial pressure (mPAP) of ≥25 mmHg, as measured through the right heart catheterization (RHC) examination. To analyze the data, the Lasso regression model was used for dimension reduction and feature selection. Subsequently, a nomogram was constructed based on multivariable logistic regression analysis.
175 individuals with left heart disease were diagnosed with pulmonary hypertension during their hospitalization, accounting for 48.5% of the sample cohort. Factors such as elevated New York Heart Association functional class, excessive resting heart rate, increased red blood cell distribution width, pulmonary artery systolic pressure, and right ventricular end-diastolic diameter assessed via echocardiography were independently linked to the prevalence of pH-LHD. The incorporation of these 5 variables in the nomogram demonstrated optimal calibration (Hosmer-Lemeshow test, P = 0.791) and strong discrimination (AUC = 0.866 [95% CI, 0.820-0.911]) for the validation set.
The above study demonstrated that the noninvasive nomogram for pH-LHD exhibits excellent diagnostic efficacy and clinical applicability, facilitating a more accurate evaluation of the pH risk in individuals with LHD.
A new study found that standard dose triple combination therapy of chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg was safe and effective for treating primary hypertension. This study’s results were published in the Journal of Clinical Hypertension.
This phase 3, multicenter, randomized, double-blind, active-controlled trial enrolled 374 patients. The participants were randomized to TEL/AML/CHTD group (triple combination), receiving telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg or TEL/AML group (dual combination), receiving telmisartan 40 mg/amlodipine 5 mg. This was followed by dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. Change of mean sitting systolic blood pressure (MSSBP) at week 8 was the primary endpoint of the study.
It was observed that the baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. 8 weeks post-treatment, the change of MSSBPs was found to be -19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and -11.4 ± 14.7 mm Hg (TEL/AML). The achievement rates of target BP and responder rate were significantly higher in TEL/AML/CHTD. No adverse events due to medication were reported. Among the triple combination group, female patients or those aged≥ 65 years old showed a higher rate of target BP achievement than relatively young males.
Based on the above results, it was evident that the standard dose triple combination was safe and efficacious in treating primary hypertension and may be more pronounced in females or older patients.
A new study found that standard dose triple combination therapy of chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg was safe and effective for treating primary hypertension. This study’s results were published in the Journal of Clinical Hypertension.
This phase 3, multicenter, randomized, double-blind, active-controlled trial enrolled 374 patients. The participants were randomized to TEL/AML/CHTD group (triple combination), receiving telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg or TEL/AML group (dual combination), receiving telmisartan 40 mg/amlodipine 5 mg. This was followed by dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. Change of mean sitting systolic blood pressure (MSSBP) at week 8 was the primary endpoint of the study.
It was observed that the baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. 8 weeks post-treatment, the change of MSSBPs was found to be -19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and -11.4 ± 14.7 mm Hg (TEL/AML). The achievement rates of target BP and responder rate were significantly higher in TEL/AML/CHTD. No adverse events due to medication were reported. Among the triple combination group, female patients or those aged≥ 65 years old showed a higher rate of target BP achievement than relatively young males.
Based on the above results, it was evident that the standard dose triple combination was safe and efficacious in treating primary hypertension and may be more pronounced in females or older patients.
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