Thesis (Ph.D)-Cairo University, 2025.

Bibliography: pages 69-94.

Background and Objectives: Initiating sodium-glucose cotransporter 2
inhibitor empagliflozin early in hospitalized acute decompensated heart failure
(ADHF) patients was found to increase urine output and resulted in shorter hospital
stays, a decrease in heart failure events (HFEs), and an improvement in health-
related quality of life following hospital discharge. However, limited data is
available related to the early initiation of canagliflozin in ADHF patients. This trial
aims to investigate the effectiveness and safety of early initiation of canagliflozin
within 24 hours of hospital admission, in comparison to empagliflozin, in patients
with ADHF presenting with volume overload.
Methods: This was a multicenter, prospective, randomized equivalence trial.
ADHF diabetic and non-diabetic patients were randomized within 24 hours from
hospital admission to either receive 100 mg canagliflozin or 10 mg empagliflozin
in addition to the standardized protocol for intravenous loop diuretics. The primary
outcome was the median daily diuresis during the hospitalization period.
Secondary outcomes during the hospitalization period include diuretic response
(weight change per 40 mg of furosemide), clinical congestion score, dyspnea
assessment, change in level of NT-pro BNP, and hospital stay length. Patients were
followed-up for 90 days post-discharge to assess the level of NT-pro B-NP at day
30 post-hospital discharge, the change in patients 'quality of life as assessed by the
Kansas City cardiomyopathy questionnaire (KCCQ-23) and the development of
heart failure events (HFEs). In addition, safety outcomes, including volume
depletion, renal adverse effects, hypoglycemia, and ketoacidosis, were assessed
throughout the entire study period.
Results: A total of 142 patients were randomized, with 71 patients assigned
to each group. The median daily diuresis during the hospitalization period was
4200 ml in the canagliflozin group, which was statistically equivalent to


Abstract



VII

empagliflozin (4117 ml) with a difference of 83 ml, which falls within the
predefined equivalence margin (±10% of the median daily diuresis of
empagliflozin; Δ = ±411.7 mL), confirming equivalence via bootstrap TSOT p <
0.001. During hospitalization no difference was observed in diuretic response,
dyspnea score, orthodema congestion score or length of hospital stay. After 30 days
of hospital discharge, the NT-proBNP levels were lower in the canagliflozin
(median, 1098 pg/mL) compared to the empagliflozin groups (median, 1768
pg/mL). However, this did not reach statistical significance (p = 0.025). Statistical
significance was defined as P-values < 0.0125 to correct for multiple comparisons.
For the analysis of KCCQ-23 domains (KCCQ-Total Symptom Score, KCCQ-
Clinical Summary Score, and KCCQ-Overall Summary Score), no statistically
significant differences in mean changes from baseline to day 90 post hospital
discharge were observed between groups. The incidence of HFEs until the end of
the trial was 16 (23.9%) in the canagliflozin group and 17(27%) in the
empagliflozin group (p = 0.684). There were no significant differences in the
incidence of safety events.
Conclusion: Early initiation of canagliflozin within 24 hours of hospital
admission for patients with ADHF, independent of their diabetes condition, was
equivalent to empagliflozin in diuresis effect. Canagliflozin also resulted in
comparable decreases in congestion and NT-proBNP levels, lowering HF events
and enhancing patients' quality of life but the study was not powered for the
secondary outcomes. These findings suggest that the initiation of canagliflozin
could be a part of usual care for hospitalized ADHF patients and an alternative to
empagliflozin without safety concerns.

كانت هذه دراسة معادلة، عشوائية، متعددة المراكز، استشرافية ، هدفت إلى تقييم البدء المبكر بعقار كاناجليفلوزين مقارنة بإمباغليفلوزين في 142 مريضًا أدخلوا إلى المستشفى بسبب قصور القلب الحاد اللاتعويضي (ADHF) مع وجود احتباس سوائل. خلال أول 24 ساعة من دخول المستشفى، تم توزيع المرضى عشوائيًا بغض النظر عن إصابتهم بالسكري لتلقّي إما 100 ملغ من كاناجليفلوزين أو 10 ملغ من إمباغليفلوزين، مع العلاج القياسي بمدرات البول الحلقية الوريدية.
كان المعيار الأساسي للدراسة هو متوسط الإدرار البول اليومي خلال فترة الاستشفاء، وقد أظهرت النتائج تكافؤًا إحصائيًا بين المجموعتين (كاناجليفلوزين: 4200 مل؛ إمباغليفلوزين: 4117 مل؛ p < 0.001 ). لم تُسجل فروق ذات دلالة إحصائية في النتائج الثانوية داخل المستشفى، بما في ذلك الاستجابة لمدرات البول، درجة الاحتقان الوذمي، أو مدة الإقامة في المستشفي. بعد مرور 30 يومًا من الخروج من المستشفى، كانت مستويات NT-proBNP أقل في مجموعة الكاناجليفلوزين مقارنةً بمجموعة الإمباغليفلوزين، إلا أن هذا الفرق لم يصل إلى مستوى الدلالة الإحصائية (p = 0.025). كذلك، كانت نتائج جودة الحياة ومعدل الأحداث المرتبطة بقصورعضلة القلب خلال 90 يومًا متقاربة بين المجموعتين . كما لم تُلاحظ فروق تُذكر في معدلات أحداث السلامة بين المجموعتين.

Issues also as CD.

Text in English and abstract in Arabic & English.