B1tta/Drug-ACE huggingface dataset:
[Title]: Low Dose Combination Therapy vs. High Dose Monotherapy in the Management of Hypertension.
[Abstract]: A common approach to the management of hypertension suggests the use of an initial drug and the addition of a second agent if goal blood pressures (BPs) are not achieved. The Sixth Report of the Joint National Committee (JNC VI) suggests that the use of low dose combination therapy may be an appropriate alternative to initial treatment. In this prospective, randomized, open label, blinded end point (PROBE) study, following a 2 week single blind placebo washout period, qualified patients were started on a calcium channel blocker, felodipine 5 mg for 2 weeks. Patients who were nonresponders (DBP equals 90 mm Hg) were randomized to either felodipine 10 mg (n equals 17, mean age 52.4, 12 males), an ACE inhibitor, enalapril 5 mg/felodipine 5 mg (n equals 20 mean, mean age 52.1, 13 males), or another ACE inhibitor, benazepril 10 mg/amlodipine 5 mg (n equals 18, mean age 53.9, 15 males) for an additional 6 weeks. Ambulatory BP monitoring was performed at the end of the single blind placebo washout period and again at the end of the study. All three treatment groups had significant reductions in mean 24 hour systolic and diastolic BP compared to baseline. The reduction in mean 24 hour systolic and diastolic BPs in the benazepril/amlodipine treated patients (-17.2/-9.7 mm Hg) was significantly greater (p equals 0.05) than in the felodipine 10 mg treated patients (-11.9/-6.4 mm Hg) and was also numerically but not statistically significantly greater than in the enalapril/felodipine treated patients (-14.2/-8.2 mm Hg). Similar differences were seen when assessing daytime BP (06:00-21:59) and nighttime BP (10:00-05:59). The reductions in morning systolic and diastolic BP (6 am-noon) in the benazepril/amlodipine treated patients (-18.6/-10.7 mm Hg) were numerically but not statistically significantly greater than the enalapril/felodipine treated patients (-13.6/-7.5 mm Hg) and the felodipine 10 mg treated patients (-14.9/-8.3 mm Hg). The data from this study suggests that using low dose combination therapy in patients who are nonresponders to first line monotherapy with a calcium channel blocker provides greater blood pressure control than up titration to higher dose monotherapy. Low dose combination therapy may therefore be an important early alternative to up titration of monotherapy in patients who are nonresponders. These data confirm other observations with combination therapy with A -blockers/ diuretics, ACE inhibitors/diuretics, and angiotensin II (AII) receptor blockers/diuretics. (c)1999 by Le Jacq Communications, Inc.
[Drug-Disease]: benazepril - goal blood pressures
[Title]: Low Dose Combination Therapy vs. High Dose Monotherapy in the Management of Hypertension.
[Abstract]: A common approach to the management of hypertension suggests the use of an initial drug and the addition of a second agent if goal blood pressures (BPs) are not achieved. The Sixth Report of the Joint National Committee (JNC VI) suggests that the use of low dose combination therapy may be an appropriate alternative to initial treatment. In this prospective, randomized, open label, blinded end point (PROBE) study, following a 2 week single blind placebo washout period, qualified patients were started on a calcium channel blocker, felodipine 5 mg for 2 weeks. Patients who were nonresponders (DBP equals 90 mm Hg) were randomized to either felodipine 10 mg (n equals 17, mean age 52.4, 12 males), an ACE inhibitor, enalapril 5 mg/felodipine 5 mg (n equals 20 mean, mean age 52.1, 13 males), or another ACE inhibitor, benazepril 10 mg/amlodipine 5 mg (n equals 18, mean age 53.9, 15 males) for an additional 6 weeks. Ambulatory BP monitoring was performed at the end of the single blind placebo washout period and again at the end of the study. All three treatment groups had significant reductions in mean 24 hour systolic and diastolic BP compared to baseline. The reduction in mean 24 hour systolic and diastolic BPs in the benazepril/amlodipine treated patients (-17.2/-9.7 mm Hg) was significantly greater (p equals 0.05) than in the felodipine 10 mg treated patients (-11.9/-6.4 mm Hg) and was also numerically but not statistically significantly greater than in the enalapril/felodipine treated patients (-14.2/-8.2 mm Hg). Similar differences were seen when assessing daytime BP (06:00-21:59) and nighttime BP (10:00-05:59). The reductions in morning systolic and diastolic BP (6 am-noon) in the benazepril/amlodipine treated patients (-18.6/-10.7 mm Hg) were numerically but not statistically significantly greater than the enalapril/felodipine treated patients (-13.6/-7.5 mm Hg) and the felodipine 10 mg treated patients (-14.9/-8.3 mm Hg). The data from this study suggests that using low dose combination therapy in patients who are nonresponders to first line monotherapy with a calcium channel blocker provides greater blood pressure control than up titration to higher dose monotherapy. Low dose combination therapy may therefore be an important early alternative to up titration of monotherapy in patients who are nonresponders. These data confirm other observations with combination therapy with A -blockers/ diuretics, ACE inhibitors/diuretics, and angiotensin II (AII) receptor blockers/diuretics. (c)1999 by Le Jacq Communications, Inc.
[Drug-Disease]: enalapril - goal blood pressures
[Title]: Low Dose Combination Therapy vs. High Dose Monotherapy in the Management of Hypertension.
[Abstract]: A common approach to the management of hypertension suggests the use of an initial drug and the addition of a second agent if goal blood pressures (BPs) are not achieved. The Sixth Report of the Joint National Committee (JNC VI) suggests that the use of low dose combination therapy may be an appropriate alternative to initial treatment. In this prospective, randomized, open label, blinded end point (PROBE) study, following a 2 week single blind placebo washout period, qualified patients were started on a calcium channel blocker, felodipine 5 mg for 2 weeks. Patients who were nonresponders (DBP equals 90 mm Hg) were randomized to either felodipine 10 mg (n equals 17, mean age 52.4, 12 males), an ACE inhibitor, enalapril 5 mg/felodipine 5 mg (n equals 20 mean, mean age 52.1, 13 males), or another ACE inhibitor, benazepril 10 mg/amlodipine 5 mg (n equals 18, mean age 53.9, 15 males) for an additional 6 weeks. Ambulatory BP monitoring was performed at the end of the single blind placebo washout period and again at the end of the study. All three treatment groups had significant reductions in mean 24 hour systolic and diastolic BP compared to baseline. The reduction in mean 24 hour systolic and diastolic BPs in the benazepril/amlodipine treated patients (-17.2/-9.7 mm Hg) was significantly greater (p equals 0.05) than in the felodipine 10 mg treated patients (-11.9/-6.4 mm Hg) and was also numerically but not statistically significantly greater than in the enalapril/felodipine treated patients (-14.2/-8.2 mm Hg). Similar differences were seen when assessing daytime BP (06:00-21:59) and nighttime BP (10:00-05:59). The reductions in morning systolic and diastolic BP (6 am-noon) in the benazepril/amlodipine treated patients (-18.6/-10.7 mm Hg) were numerically but not statistically significantly greater than the enalapril/felodipine treated patients (-13.6/-7.5 mm Hg) and the felodipine 10 mg treated patients (-14.9/-8.3 mm Hg). The data from this study suggests that using low dose combination therapy in patients who are nonresponders to first line monotherapy with a calcium channel blocker provides greater blood pressure control than up titration to higher dose monotherapy. Low dose combination therapy may therefore be an important early alternative to up titration of monotherapy in patients who are nonresponders. These data confirm other observations with combination therapy with A -blockers/ diuretics, ACE inhibitors/diuretics, and angiotensin II (AII) receptor blockers/diuretics. (c)1999 by Le Jacq Communications, Inc.
[Drug-Disease]: felodipine - goal blood pressures
[Title]: Low Dose Combination Therapy vs. High Dose Monotherapy in the Management of Hypertension.
[Abstract]: A common approach to the management of hypertension suggests the use of an initial drug and the addition of a second agent if goal blood pressures (BPs) are not achieved. The Sixth Report of the Joint National Committee (JNC VI) suggests that the use of low dose combination therapy may be an appropriate alternative to initial treatment. In this prospective, randomized, open label, blinded end point (PROBE) study, following a 2 week single blind placebo washout period, qualified patients were started on a calcium channel blocker, felodipine 5 mg for 2 weeks. Patients who were nonresponders (DBP equals 90 mm Hg) were randomized to either felodipine 10 mg (n equals 17, mean age 52.4, 12 males), an ACE inhibitor, enalapril 5 mg/felodipine 5 mg (n equals 20 mean, mean age 52.1, 13 males), or another ACE inhibitor, benazepril 10 mg/amlodipine 5 mg (n equals 18, mean age 53.9, 15 males) for an additional 6 weeks. Ambulatory BP monitoring was performed at the end of the single blind placebo washout period and again at the end of the study. All three treatment groups had significant reductions in mean 24 hour systolic and diastolic BP compared to baseline. The reduction in mean 24 hour systolic and diastolic BPs in the benazepril/amlodipine treated patients (-17.2/-9.7 mm Hg) was significantly greater (p equals 0.05) than in the felodipine 10 mg treated patients (-11.9/-6.4 mm Hg) and was also numerically but not statistically significantly greater than in the enalapril/felodipine treated patients (-14.2/-8.2 mm Hg). Similar differences were seen when assessing daytime BP (06:00-21:59) and nighttime BP (10:00-05:59). The reductions in morning systolic and diastolic BP (6 am-noon) in the benazepril/amlodipine treated patients (-18.6/-10.7 mm Hg) were numerically but not statistically significantly greater than the enalapril/felodipine treated patients (-13.6/-7.5 mm Hg) and the felodipine 10 mg treated patients (-14.9/-8.3 mm Hg). The data from this study suggests that using low dose combination therapy in patients who are nonresponders to first line monotherapy with a calcium channel blocker provides greater blood pressure control than up titration to higher dose monotherapy. Low dose combination therapy may therefore be an important early alternative to up titration of monotherapy in patients who are nonresponders. These data confirm other observations with combination therapy with A -blockers/ diuretics, ACE inhibitors/diuretics, and angiotensin II (AII) receptor blockers/diuretics. (c)1999 by Le Jacq Communications, Inc.
[Drug-Disease]: amlodipine - goal blood pressures
[Title]: Cardiovascular effects of sildenafil in neonates and infants with congenital diaphragmatic hernia and pulmonary hypertension.
[Abstract]: BACKGROUND: Pulmonary hypertension is a common problem in patients with congenital diaphragmatic hernia (CDH). In a subset of these patients, pulmonary hypertension persists despite optimized ventilatory management and supportive care. Sildenafil, a phosphodiestrase V inhibitor, has been used in the treatment of pulmonary hypertension in adults and children. Cardiovascular effects of sildenafil in patients with CDH and pulmonary hypertension are not known. OBJECTIVE: To describe the changes in cardiovascular and respiratory parameters in newborn infants with CDH and persistent pulmonary hypertension refractory to inhaled nitric oxide (iNO) during the first 2 weeks of sildenafil administration. METHODS: Retrospective data analysis of seven patients with CDH (birth weight = 2,573 +/- 1,019 g; gestational age = 35.6 +/- 4.3 weeks) receiving oral sildenafil for pulmonary hypertension refractory to iNO. Findings of serial echocardiograms and data on cardiovascular and respiratory status were assessed. RESULTS: Right cardiac output increased and left cardiac output tended to increase 1.5-4 h after initiation of sildenafil and the increase was sustained throughout the study. Echocardiographic indices of pulmonary hypertension showed an apparent reduction in abnormally high pulmonary vascular resistance. Systemic blood pressure tended to decrease. Shortening fraction did not change. Ventilatory index and the need for iNO tended to decrease in the five surviving infants. CONCLUSIONS: These preliminary findings suggest that sildenafil may improve cardiac output by reducing pulmonary hypertension refractory to iNO in patients with CDH.
[Drug-Disease]: sildenafil - CDH
[Title]: Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine: consistency across subgroups in the African-American Heart Failure Trial.
[Abstract]: BACKGROUND: We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality. METHODS AND RESULTS: Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P&lt;0.001) and a 39% reduction in the risk for first hospitalization for HF (P&lt;0.001). These benefits appeared to emerge early (at approximately 50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012). CONCLUSIONS: FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.
[Drug-Disease]: hydralazine hydrochloride - Heart Failure
[Title]: Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine: consistency across subgroups in the African-American Heart Failure Trial.
[Abstract]: BACKGROUND: We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality. METHODS AND RESULTS: Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P&lt;0.001) and a 39% reduction in the risk for first hospitalization for HF (P&lt;0.001). These benefits appeared to emerge early (at approximately 50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012). CONCLUSIONS: FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.
[Drug-Disease]: isosorbide dinitrate - Heart Failure
[Title]: Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen.
[Abstract]: BACKGROUND: In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. METHODS AND FINDINGS: In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. CONCLUSIONS: This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin-cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features.
[Drug-Disease]: cyclophosphamide - breast cancer
[Title]: Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen.
[Abstract]: BACKGROUND: In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. METHODS AND FINDINGS: In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. CONCLUSIONS: This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin-cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features.
[Drug-Disease]: epirubicin - breast cancer