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Results for “Targeted dosing”

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PubMed1988

The induction of chromosome aberrations during the course of radiation therapy for morbus Hodgkin.

In a patient with Morbus Hodgkin, structural aberrations of the chromosome type in peripheral lymphocytes were analyzed during radiation therapy (accumulated target dose 44.6 Gy: 22 fractions of 1.8 Gy each and 2 fractions of 2.5 Gy each at the end of the therapy). The blood was sampled about 5 min after a fraction and/or 24, 48, or 72 h thereafter. The frequency of dicentric chromosomes:acentric fragments:centric ring chromosomes is 37:14:1 throughout the therapy. Independent of the time of blood sampling after a fraction, the distributions of dicentrics and acentrics are overdisperse and represent negative binomial distributions. The yields from these aberrations, as determined during the course of radiotherapy, are best fitted to a linear-quadratic function with a negative quadratic term. The two dose-effect curves (blood sampling about 5 min and 24 to 72 h after a fraction) of dicentrics and acentrics do not differ significantly. Up to an accumulated target dose of about 20 Gy the percentages of cells with chromosome aberrations increase to about 48 to 65% and, at this level, remain constant until the end of therapy.

Adult↗

PubMedDate not supplied

An algorithm for generation of implant plans for high-dose-rate irradiators.

An algorithm is described for generating a treatment plan with minimal input from the user for a remote high-dose-rate afterloading irradiator. The algorithm generates a plan after locating all catheters involved and an area of interest on each catheter, and two additional numbers are specified: a radial distance and a target dose. The treatment volume becomes the locus of all points that are within the specified radial distance from any point within the area of interest on any catheter (except for the end points). For a single catheter, the volume may be alternately outlined on an x-ray film of the implant. The routine uses a linear programming formulism to compute which dwell positions are to be used, as well as the dwell time at each position, to irradiate the treatment volume to the target dose while minimizing the total volume integrated dose to the patient.

Algorithms↗

PubMed1987

Amphotericin-B nephrotoxicity in humans decreased by sodium supplements with coadministration of ticarcillin or intravenous saline.

Previous observations suggest that salt loading can help reverse amphotericin-B induced nephrotoxicity. Evidence is presented indicating that sodium supplements provide prophylaxis against the development of amphotericin-B nephrotoxicity. In a retrospective study at Vanderbilt University, 14/21 patients receiving amphotericin B (target dose, 25 mg/day) without salt supplements developed impaired renal function; in 10 instances amphotericin B was temporarily withdrawn. In contrast, only 2/17 patients who received amphotericin B with ticarcillin (with its obligatory sodium supplement) developed nephrotoxicity (P less than 0.01). All four patients, who were receiving the combination of amphotericin B and ticarcillin and who had their ticarcillin therapy stopped, developed nephrotoxicity in the subsequent week. In a prospective observational study at Essen, 20 patients had 24 courses of amphotericin B (target dose, 40 mg/day) with routine supplementation of 1 liter of 0.9% sodium chloride daily. Only two patients showed evidence of nephrotoxicity and no dosage modification of amphotericin B was required in any patient. Four patients with initial evidence of mildly impaired renal function received full supplements without adverse effects or the development of nephrotoxicity. These observations suggest that routine parenteral administration of sodium supplements can help minimize the nephrotoxic potential of amphotericin B.

Amphotericin B↗

PubMed1990

[Long-term results of postoperative and primary radiotherapy of carcinoma of the salivary glands: importance of dosage and target volume].

Longterm results in 92 patients after primary or postoperative irradiation for carcinoma of the major or minor salivary glands of the head are analyzed. Target volume included the region of the primary tumor; ipsilateral cervical lymph nodes were included in patients with metastases of the lymph nodes. Target doses were 25 to 35 X 2.0 Gy or in some cases 16 to 18 X 3.30 Gy. Local control was 93% in tumors of limited extension (I), 84% in extensive but macroscopically complete resected tumors (II) and 26% in biopsied or partially resected tumors (III). There were no major complications. Recurrence in the lymph nodes were observed in less than 5% of the group I + II NO and could be controlled permanently by secondary surgery plus irradiation. According to the own and published results the following target volumes are adequate: region of the primary tumor in adenoid-cystic carcinoma NO plus the ipsilateral cervical-supraclavicular region in patients with other high grade cancers or evidence for metastases. Target doses between 5940 and 7020 cGy are recommended.

Adenocarcinoma↗

PubMed1991

The objective evaluation of alternative treatment plans: II. Score functions.

A series of six patients with adenocarcinoma of the prostate, Stages A2, B1, or B2, were planned for treatment using a four-field box technique at 25 MV. Plans were prepared by three techniques: composite, mid-plane, and conformal. The dose distributions at the central plane and at two planes offset by +/- 2 cm were evaluated by means of score functions which quantify the magnitude of regret for target dose gradient, target over- and under-dose, non-target tissue overdose, and for overdose to the rectum, bladder, and femoral heads. The score functions are normalized to give values in the range from 10 (ideal) to zero (limit of acceptability), with negative values indicating unacceptable deviations from the prescribed dose limits. The scores for off-axis conformal plans were found to be essentially the same as for mid-plane plans on the central plane. However, mid-plane planning was shown to be totally inadequate for off-axis planes, where the average target gradient and underdose scores were reduced by 10 units. Composite planning resulted in adequate target coverage on all planes, but at the expense of unacceptable overdose to non-target tissue. The effect of reducing the posterior beam weight to half that of the other three beams was to reduce the target gradient score by 1.6 +/- 0.5 units and to increase the rectal score by 0.9 +/- 0.3 units.

Adenocarcinoma↗

PubMed1992

The clinical application of a non-axial treatment plan for pancreatic and biliary malignancies.

Standard radiation therapy for adenocarcinoma of the pancreas treats a substantial portion of the renal parenchyma. It was hypothesized that rotating the plane of treatment to a non-axial orientation, with the anterior field entering the patient from an inferior oblique direction, would decrease the renal dose of radiation without increasing the liver dose or compromising the target dose. To test this hypothesis, patients referred for radical radiation treatment for tumors of the pancreas or distal common bile duct were prospectively evaluated by performing treatment planning using axial and non-axial field arrangements. Treatment plans were compared using dose volume histograms (DVHs) of both kidneys and the liver. In all 15 cases analyzed, the non-axial plan was superior to the axial plan with respect to renal dose, without significantly increasing the hepatic dose and was used for treatment. Treatment was not significantly more complex nor was gastrointestinal toxicity increased. These findings show that non-axial field arrangements can be used on a routine basis to decrease the renal dose of radiation for the treatment of pancreatic and biliary malignancies. It is anticipated that in the future, a combination of DVH-guided treatment planning and sophisticated renal function studies will be necessary to permit a more accurate prediction of the probability of renal complications resulting from radiation therapy.

Aged↗

PubMed1994

Organ-sparing treatment of advanced bladder cancer: a 10-year experience.

PURPOSE: Radical cystectomy is considered as standard therapy for muscle-invasive bladder cancer. We present 10-year results of bladder-sparing treatment by conservative surgery and radiotherapy +/- chemotherapy. METHODS AND MATERIALS: From 1982 through 1991, 245 consecutive patients, mean age 66 years, with invasive bladder cancer (T2-3 or poor prognostic T1, no distant metastases) entered a prospective protocol with the objective of bladder preservation. Treatment consisted of transurethral resection (complete, if possible) and definitive radiotherapy with 56 Gy maximum dose (50.4 Gy minimum target dose) in 28 fractions. Since 1985, 139 patients received a simultaneous chemotherapy on 5 days in the first and fifth treatment week with either 25 mg/m2 cisplatin daily (79 patients) or 65 mg/m2 carboplatin (60 patients). Cystectomy was performed as salvage treatment for residual or recurrent invasive disease. The median follow-up at the date of analysis (12-31-92) was 5.9 years. RESULTS: The overall survival was 47% after 5 years and 26% after 10 years. The 5-year survival according to the initial T-category was 60% for T1 (44 patients), 64% for T2 (47 patients), 43% for T3 (127 patients), and 16% for T4 (23 patients). The most important single prognostic factor was the amount of residual tumor after TUR (5-year survival 80% after R0, 53% after R1, and 31% after R2 resection, p < 0.01). Chemotherapy increased the rate of complete remission, but had no impact on 5-year survival (52% vs. 50%). Fifty-three salvage cystectomies were performed, all without severe complications, and 192 patients (79%) maintained a normal functioning bladder. The bladder preservation rate in 5-year survivors was 83%. CONCLUSIONS: Organ-sparing treatment of advanced bladder cancer by transurethral surgery and definitive radiotherapy or radiochemotherapy is feasible and effective. The survival in this series is as good as in any comparable cystectomy series. Eighty-three percent of long-term survivors maintained their functioning bladders.

Aged↗

PubMed1981

Chemical attraction in the absence of worm-mediated tactile behavior in Trichinella spiralis.

In vitro chemical attraction of Trichinella spiralis was studied using as migrators individual male or female worms. Both male and female worms exhibited a dose-dependent behavior at target doses of 20 to 80 worms, no significant differences in response at doses of 80 to 200 worms, and an inhibition of movement at doses of 200 to 400 worms. Single males were attracted less to a mixture of males and females as the source of pheromone than single males to a female source. Single females did not move significantly towards a mixture of males and females. Adult males and fourth-state, juvenile males were significantly attracted to fourth-stage females as the pheromone source. Fourth-stage males attracted adult females but not forth-stage juvenile females. Adult males and females and third-stage, juvenile males and females were not significantly attracted to a pheromone source from third-stage juvenile males and females. We postulate that the onset of pheromone production in T spiralis is during the fourth developmental stage.

Animals↗

PubMed1995

Biomarkers as tools in human health risk assessment.

Evaluation of occupational or environmental risk due to exposure to chemicals requires sufficient information on the toxic profiles, mechanisms of action, toxicokinetics, dose-response relation, exposure, and the target dose. Usually exposure is estimated by measuring concentrations of the agent in air, food, water, soil, dust, or other media with which a population or an individual is in contact. However, this external exposure is only a rough estimate for the internal exposure (agent dose or its metabolite at the critical target in the organism). Factors of influence are bioavailability of the chemicals, variations in concentrations and routes of exposure, physical activity, and individual variation in rates of metabolism, distribution, and excretion. All these affect the concentration of the toxic agent at the critical target, which is the most precise information for risk assessment. Thus, internal exposure is best measured by determining the concentration of the toxicant or its ultimate metabolite at the critical site in the target organ or by determining adducts with cellular macromolecules such as proteins, amino acids, DNA, or its bases. The latter are easily available in experimental toxicology from animal experiments but only occasionally from humans. For health surveillance such data usually are not available, because they require invasive procedures such as biopsies. Therefore, more accessible body fluids or tissue are used, such as blood, urine, or adipose tissue, or adducts with macromolecules such as albumin or hemoglobin in the blood, DNA adducts in peripheral lymphocytes, or altered DNA bases in urine such as 8-hydroxyguanine. All of these are indicators for exposure, whereas risk can only be estimated if the correlation between their deviations from normal and the dose-response at the critical target is known.

Animals↗

PubMed1993

Three-dimensional conformal radiation therapy may improve the therapeutic ratio of high dose radiation therapy for lung cancer.

PURPOSE: The specific aim of 3-dimensional conformal radiation therapy is to improve the target dose distribution while concomitantly reducing normal tissue dose. Such an approach should permit dose escalation until the limits of acceptable normal tissue toxicity are reached. To evaluate the feasibility of tumor dose escalation for nine patients with lung cancer, we determined the dose distribution to the target and normal tissues with 3-dimensional conformal radiation therapy and conventional planning. METHODS AND MATERIALS: Plans were compared to assess adequacy of dose delivery to target volumes, dose-volume histograms for normal tissue, and normal tissue complication probabilities (NTCP) for nine patients with lung tumors. RESULTS: The mean percentage of gross disease which received < or = 70.2 Gy with 3-dimensional conformal radiation therapy (3DCRT) was 40% of the mean percentage of gross disease which received < or = 70.2 Gy with conventional treatment planning (CTP). The mean NTCP for lung parenchyma with 3DCRT was 36% of the mean NTCP with CTP. The mean esophageal NTCP with 3DCRT was 88% of the mean NTCP with CTP. CONCLUSION: This preliminary analysis suggests that three dimensional conformal radiation therapy may provide superior delivery of high dose radiation with reduced risk to normal tissue, suggesting that this approach may have the potential to improve the therapeutic ratio of high dose radiation therapy for lung cancer.

Adenocarcinoma↗

PubMed1992

Prevention and therapy of radiation-induced bowel discomfort.

In a double-blind randomized placebo-controlled study, including 70 patients treated with radiotherapy of localized malignancies in the pelvis, the effects of prophylactic sucralfate in preventing bowel discomfort were evaluated. Radiotherapy was delivered in a conventional manner with high-energy photons in a total dose of 62-66 Gy (target dose, 1.8-2.2 Gy) during 6.5 weeks. Dose granules of sucralfate or placebo were given 2 weeks after irradiation started and continued for 6 weeks. All analyses were performed blindly. The patients in the sucralfate group had significantly less problems with acute (5 weeks) and chronic (66 weeks) bowel discomfort. The consumption of loperamide was also reduced in the sucralfate group, and the weight decrease was less pronounced. No adverse effects were seen. Thus, sucralfate seems to be beneficial in minimizing the problems of bowel discomfort during and after irradiation of malignancies in the pelvis. These results are discussed in relation to other related observations.

Diarrhea↗

PubMed1988

Hydroxydesipramine in the elderly.

Elevation of the hydroxy metabolites of the tricyclic antidepressants in the elderly has been demonstrated for nortriptyline and suggested for desipramine by a study reporting elevated hydroxydesipramine (OH-DMI) plasma levels in four older patients. In the current study, patients treated with desipramine (DMI) were studied to determine whether OH-DMI was elevated in two larger samples of depressed elderly patients and to determine the magnitude of the increase, if present. In Sample I, which consisted of 68 patients of whom 23 were over 60 years of age, a fixed target dose of DMI was employed. Sample II, in which 20 of the 56 patients were over 60, received a dose adjusted to attain a fixed target DMI blood level. OH-DMI levels were higher in patients over 60 than in younger patients but the differences were not significant in either sample individually. In the two samples combined, average OH-DMI levels were 11 ng/ml higher in patients over 60 and the difference was significant (t = 2.30, p = 0.02). If variations in dose are accounted for, OH-DMI concentrations are positively correlated with age in both samples. OH-DMI/DMI ratios were not higher in the patients over 60 in these samples, but OH-DMI/DMI ratios may be higher in patients on lower doses with low DMI levels, as is common in the treatment of elderly patients. If comparable dosage is administered, nonlinear increases in DMI levels result in lower OH-DMI/DMI ratios similar to those in younger patients. Although our findings of elevated hydroxy levels in the elderly are consistent with prior reports, the clinical importance of an 11 ng/ml difference, particularly in relation to total drug levels averaging 220 ng/ml, is questioned.

Administration, Oral↗

PubMed1994

Is ambient ethene a cancer risk factor?

Ethene is, on a molar basis, a major urban air pollutant. It has been shown beyond doubt that a fraction of inhaled ethene is metabolized in mammals (including humans) via ethylene oxide, an electrophilic reagent that has been shown to be mutagenic and carcinogenic. To the extent that the linearity hypothesis for dose-response relationships at low levels is accepted, exposure to ethene is therefore expected to lead to a risk increment. In order to judge whether ethene as a single compound should be considered a risk factor, it has to be evaluated whether this risk increment is negligibly small or of concern to individuals or societies. The magnitude of the cancer risk from ethene cannot be inferred from animal experiments. Because of saturation of the metabolism of ethene, sufficient statistical power cannot be attained in long-term animal tests with about 100 animals per dose. By application of the radiation-dose equivalent of the unit of target dose of ethylene oxide and using the best (although still uncertain) value for the conversion factor (about 5%), exposure to 10 ppb ethene--a level occurring in urban areas--is expected to lead to a lifetime risk of cancer death amounting to approximately 70 per 100,000. According to a recent estimate the average exposure in Sweden to ethene is some six times lower. These figures are uncertain by a factor of at least three. They indicate ethene to be a risk factor of concern.

Air Pollutants↗

PubMed1986

Analysis of dose intensity for chemotherapy in early (stage II) and advanced breast cancer.

In chemotherapy of advanced breast cancer, the dose intensities of regimens containing cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) and cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) correlate with remission rate. The correlation is even better if dose intensity is calculated from doses actually given instead of from targeted doses. Also, in adjuvant chemotherapy of stage II breast cancer, the dose intensities of CMF-containing regimens correlate with relapse-free survival. The adjuvant trials analyzed included studies containing only 1 or 2 of C, M, or F or with L-phenylalanine mustard (melphalan) instead of C. Three-year relapse-free survival was clearly related to dose intensity whether the analysis was of trials containing all 4 prognostic groups [women less than 50 yr with 1-3 and greater than 3 positive nodes; and those greater than or equal to 50 yr with 1-3 and greater than 3 positive nodes (P less than .00001)] or of trials in which each of these 4 groups were analyzed separately (P less than .005). In multivariate analysis, dose intensity correlated with relapse-free survival (P less than .00001), independent of the number of positive nodes or menopausal status. Randomized trials will be required before we can determine if prospective increases of dose intensity will improve outcome of chemotherapy in breast cancer.

Adult↗

PubMed1990

Radiation target sizes of the Na,K-ATPase and p-aminohippurate transport system in the basolateral membrane of renal proximal tubule.

Basolateral membrane vesicles made from rabbit kidney proximal tubules were frozen and irradiated with a high energy electron beam and the effects of irradiation on Na,K-ATPase activity, p-aminohippurate (PAH) transport, the membrane diffusion barrier and vesicle volume were measured. The vesicle volume and diffusion barrier were not significantly changed by radiation exposure. Na,K-ATPase activity was inactivated as a simple exponential function of radiation dose. Target size analysis of the data yielded a molecular size of 267 +/- 17 kDa, consistent with its existence as a (alpha beta)2 dimer. The carrier-mediated PAH uptake by basolateral membrane vesicles was also inactivated as a function of radiation dose. A target molecular size of 74 +/- 16 kDa was calculated for the PAH transport system. This study is the first measurement of the functional size of the organic acid transport system based directly on flux measurements.

Aminohippuric Acids↗

PubMed1990

The carcinogenic activity of commercial grade toluene diisocyanate in rats and mice in relation to the metabolism of the 2,4- and 2,6-TDI isomers.

Groups of 50 F344/N rats of each sex and 50 B6C3F1 mice of each sex were gavaged with corn oil or a mixture of toluene diisocyanate (TDI) in corn oil for 5 days per week for 105 or 106 weeks. Female rats and mice were given doses of 60 or 120 mg/kg body weight, while male rats received 30 or 60 mg/kg, and male mice received 120 or 240 mg/kg. The TDI reacted with the moisture in the corn oil vehicle resulting in doses that were 10% to 23% below the target dose concentrations. The chemical product used was commercial grade TDI, which was an 80%-20% mixture of the 2,4- and 2,6-isomers. Chemical disposition and metabolism studies were conducted with each of the radiolabelled TDI isomers in male rats. Absorption of both of the TDI isomers occurred, with the highest concentrations found in the stomach, cecum, large intestine, and bladder. Excretion occurred via the feces and urine. The major metabolic products from the metabolism of 2,4-TDI were shown to be identical with those from the metabolism of the carcinogen, 2,4-diaminotoluene, whereas the metabolism of the 2,6-TDI isomer yielded one major product, identified as 2,6-bis(acetylamino)toluene. Greater than 10% depression in body weight gain occurred in all dosed groups of rats throughout most of the study. The major non-neoplastic lesions that were observed in both sexes of the TDI-exposed rats were dose-related increases in acute broncho-pneumonia, characterized as chemical pneumonitis, with incidences as high as 50%. In mice mean body weight gain was depressed in dosed male and in high dose females. The principle non-neoplastic lesion in mice that was attributed to chemical treatment was cytomegaly of the kidney tubular epithelium in males. Survival in all groups of dosed rats was significantly lower than in controls. A dose-dependent pattern of mortality did not commence until 70 weeks of exposure, demonstrating that toluene diisocyanate elicited a cumulative toxic response. There was also significantly lower survival in high dose male, but not female mice, by comparison to controls. Despite the reduction of power and sensitivity in the rat studies caused by early mortality, statistically significant increases in tumor incidences were observed in many different target organs. TDI was carcinogenic in F344/N rats, causing subcutaneous fibromas and fibrosarcomas in males and females, pancreatic acinar cell adenomas in males, and pancreatic islet cell adenomas, neoplastic nodules of the liver, and mammary gland tumors in females.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

Carboplatin (CBDCA)-hexamethylmelamine (HMM)-oral etoposide (VP-16) first-line treatment of ovarian cancer patients with bulky disease: a phase II study.

Hexamethylmelamine (HMM) and oral etoposide (VP-16) have shown to be active against platinum-resistant epithelial ovarian cancer. On this basis a three-drug regimen including carboplatin (CBDCA) plus HMM and oral VP-16 was tested in previously untreated ovarian cancer patients with tumor size > 2 cm. Since October 1991, 29 chemotherapy-naive ovarian cancer patients with tumor larger than 2 cm (20 stage III and 9 stage IV) have been treated for a total of 153 courses. CBDCA was administered i.v. on Day 1. The dose was individualized using the Calvert formula (the target dose was AUC = 5). VP-16 was administered orally at the dose of 50 mg/m2 Days 1-14, HMM at the dose of 150 mg/m2 po Days 14-28. Therapy was repeated every 28 days for a total of 6 courses. In order to avoid severe leukopenia and delays in the treatment administration, G-CSF 5 micrograms/kg/day sc Days 8-14 (or until postnadir recovery of neutrophil count > 10,000/mm3) and Days 22-28 was administered. All patients were evaluable for toxicity. No treatment-related deaths occurred. Myelotoxicity was the main side effect. It was grade 3-4 in a total of 13/29(45%) patients. One patient discontinued treatment after the first course due to HMM-related gastrointestinal toxicity. The actual delivered dose intensity was 89% of the planned dose. At the time of this analysis (April 1994) 26 patients are evaluable for response. Fifteen patients achieved a clinical complete remission and 9 a partial response for a 92% overall response rate. Fourteen patients accepted second-look laparotomy. We observed 11 pathological complete regressions (42%; 95% CI, 21-63). At a median follow-up of 16 months 3 deaths have occurred. Only 2 patients with NED at second-look laparotomy have relapsed. We stopped the accrual since the 95% confidence interval of the pCR-rate observed exceeded 20%. This new first-line regimen seems to be highly effective in patients with poor-prognosis advanced ovarian cancer, although the data are not yet sufficiently mature for a final analysis of time to progression and overall survival.

Administration, Oral↗

PubMed2026

Efficacy and Safety of the Kidney Function-Based Finerenone Dosing Strategy Used in FINEARTS-HF.

BACKGROUND: Given that mineralocorticoid receptor antagonists have the potential to impair renal function and induce hyperkalemia, close monitoring of estimated glomerular filtration rate (eGFR) and serum potassium levels is essential to ensure the safe administration of this therapy. OBJECTIVES: In this prespecified analysis, the authors evaluated the efficacy and safety of the kidney function-based finerenone dosing strategy used in the FINEARTS-HF trial. METHODS: In FINEARTS-HF, patients with an eGFR of 25 to 60 mL/min/1.73 m2 at baseline were stratified at randomization to the low-dose group and started on 10 mg of finerenone once daily (titrated to a maximum 20 mg/d) or matching placebo, whereas those with an eGFR >60 mL/min/1.73 m2 at baseline were stratified to the high-dose group and started on 20 mg of finerenone once daily (titrated to a maximum 40 mg/d) or matching placebo. The primary outcome was the composite of total (first and recurrent) heart failure events and cardiovascular death. RESULTS: Among 5,986 (99.8%) analyzable patients, 3,159 were assigned to the higher eGFR/high-dose stratum and 2,827 to the lower eGFR/low-dose stratum group. The mean ± SD achieved dose was 32.3 ± 9.1 mg (finerenone) and 34.4 ± 7.8 mg (placebo) in the higher eGFR/high-dose stratum, and 15.6 ± 4.3 mg (finerenone) and 16.7 ± 4.0 mg (placebo) in the lower eGFR/low-dose stratum. The effect of finerenone on the primary outcome was consistent across the 2 dosing strata (higher eGFR/high-dose stratum: rate ratio: 0.77 [95% CI: 0.63-0.94] vs lower eGFR/low-dose stratum: rate ratio: 0.87 [95% CI: 0.74-1.03]; P for interaction = 0.34). Consistent benefits were observed for the components of the primary outcome and all-cause death. Safety was also consistent between dosing strata, except for hypokalemia, where the reduction in the odds of hypokalemia with finerenone compared to placebo was greater in the higher eGFR/high-dose stratum (P-interaction < 0.01). CONCLUSIONS: In FINEARTS-HF, an eGFR-based dosing strategy allowed effective and safe use of finerenone in patients with heart failure with mildly reduced ejection fraction/ heart failure with preserved ejection fraction with a baseline eGFR as low as 25 mL/min/1.73 m2. We recommend that clinicians implement the trial-validated dosing strategy and incorporate appropriate uptitration to the target dose to ensure optimal therapeutic outcomes. (FINEARTS-HF [Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40%; NCT04435626).

Aged↗