Prediction of the effect of dapagliflozin on kidney and heart failure outcomes based on short-term changes in multiple risk markers

Abstract Background Besides improving glucose control, sodium-glucose co-transporter 2 inhibition with dapagliflozin reduces blood pressure, body weight and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes (T2DM). The parameter response efficacy (PRE) score was developed to predict how short-term drug effects on cardiovascular risk markers translate into long-term changes in clinical outcomes. We applied the PRE score to clinical trials of dapagliflozin to model the effect of the drug on kidney and heart failure (HF) outcomes in patients with T2DM and impaired kidney function. Methods The relationships between multiple risk markers and long-term outcome were determined in a background population of patients with T2DM with a multivariable Cox model. These relationships were then applied to short-term changes in risk markers observed in a pooled database of dapagliflozin trials (n = 7) that recruited patients with albuminuria to predict the drug-induced changes to kidney and HF outcomes. Results A total of 132 and 350 patients had UACR >200 mg/g and >30 mg/g at baseline, respectively, and were selected for analysis. The PRE score predicted a risk change for kidney events of −40.8% [95% confidence interval (CI) −51.7 to −29.4) and −40.4% (95% CI −48.4 to −31.1) with dapagliflozin 10 mg compared with placebo for the UACR >200 mg/g and >30 mg/g subgroups. The predicted change in risk for HF events was −27.3% (95% CI −47.7 to −5.1) and −21.2% (95% CI −35.0 to −7.8), respectively. Simulation analyses showed that even with a smaller albuminuria-lowering effect of dapagliflozin (10% instead of the observed 35% in both groups), the estimated kidney risk reduction was still 26.5 and 26.8%, respectively. Conclusions The PRE score predicted clinically meaningful reductions in kidney and HF events associated with dapagliflozin therapy in patients with diabetic kidney disease. These results support a large long-term outcome trial in this population to confirm the benefits of the drug on these endpoints.

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Drug-Induced Changes in Risk/Biomarkers and Their Relationship with Renal and Cardiovascular Long-Term Outcome in Patients with Diabetes

Clinical Chemistry ◽

10.1373/clinchem.2010.148395 ◽

2011 ◽

Vol 57 (2) ◽

pp. 186-195 ◽

Cited By ~ 2

Author(s):

Yan Miao ◽

Paul A Smink ◽

Dick de Zeeuw ◽

Hiddo J Lambers Heerspink

Keyword(s):

Risk Management ◽

Short Term ◽

Drug Induced ◽

Term Outcome ◽

Long Term Outcome ◽

Patients With Diabetes ◽

Changes In Risk ◽

Risk Biomarkers ◽

Induced Changes

BACKGROUND Optimal renal and cardiovascular risk management in diabetic patients includes optimal maintenance of blood pressure and control of glucose and lipids. Although the optimal control of these risk factors or “risk/biomarkers” has proven to be effective, it often is difficult to achieve. Consequently, the risk for renal and cardiovascular complications remains devastatingly high. Many risk/biomarkers have been discovered that accurately predict long-term renal and cardiovascular outcome. However, the aim of measuring risk/biomarkers may not be only to determine an individual's risk, but also to use the risk/biomarker level to guide therapy and thereby improve long-term clinical outcome. CONTENT This review describes the effects of various drugs on novel risk/biomarkers and the relationship between (drug induced) short-term changes in risk/biomarkers and long-term renal and cardiovascular outcome in patients with diabetes. SUMMARY In post hoc analyses of large trials, the short-term reductions in albuminuria, transforming growth factor-β, and N-terminal pro-B–type natriuretic peptide (NT-proBNP) induced by inhibitors of the renin-angiotensin-aldosterone system were associated with a decreased likelihood of long-term adverse renal and cardiovascular outcomes. However, the few studies that systematically investigated the utility of prospectively targeting novel risk/biomarkers such as hemoglobin or NT-proBNP failed to demonstrate long-term cardiovascular protection. The latter examples suggest that although a risk/biomarker may have superior prognostic ability, therapeutically changing such a risk/biomarker does not necessarily improve long-term outcome. Thus, to establish the clinical utility of other novel risk/biomarkers, clinical trials must be performed to prospectively examine the effects of therapeutically-induced changes in single or multiple risk/biomarkers on long-term risk management of patients with diabetes.

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In-hospital brain natriuretic peptide and N-terminal prohormone brain natriuretic peptide variations are predictors of short-term and long-term outcome in acute decompensated heart failure

Critical Care ◽

10.1186/cc9970 ◽

2011 ◽

Vol 15 (1) ◽

pp. 116 ◽

Cited By ~ 6

Author(s):

Salvatore Di Somma ◽

Laura Magrini ◽

Enrico Ferri

Keyword(s):

Heart Failure ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Acute Decompensated Heart Failure ◽

Decompensated Heart Failure ◽

Short Term ◽

Term Outcome ◽

Long Term Outcome

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Systolic blood pressure and outcome in patients admitted with acute heart failure: a pooled analysis from 4 randomized clinical trials

European Heart Journal Acute Cardiovascular Care ◽

10.1093/ehjacc/zuab020.045 ◽

2021 ◽

Vol 10 (Supplement_1) ◽

Author(s):

J Grand ◽

K Miger ◽

A Sajadieh ◽

L Kober ◽

C Torp-Pedersen ◽

...

Keyword(s):

Heart Failure ◽

Composite Endpoint ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Term Outcome ◽

Ventricular Ejection Fraction ◽

Long Term Outcome ◽

All Cause Mortality ◽

Short And Long Term

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Background In acute heart failure (AHF), low systolic blood pressure (SBP) has been associated with poor outcome. Less is known of the risk related to normal versus elevated SBP and interaction with left ventricular ejection fraction. Purpose The aim of the present study was to assess the association between baseline SBP and short- and long-term outcome in a large cohort of AHF-patients. Methods A pooled cohort of four randomized controlled trials investigating the vasodilator serelaxin versus placebo in patients admitted with AHF and an SBP from 125 to 180 mmHg. Endpoints were 180-day all-cause mortality and a short-term composite endpoint (worsening heart failure, all-cause mortality or hospital readmission for HF through Day 14). Left ventricular ejection fraction (LVEF) was categorized into HFrEF (<40%) and HFpEF (= >40%). Multivariable Cox regression was used and adjusted for age, sex, baseline body mass index, HFrEF, serum estimated glomerular filtration rate, allocated treatment (placebo/serelaxin), diabetes mellitus, ischemic heart disease, and atrial fibrillation/flutter. Measurements and Main Results A total of 10.533 patients with a mean age of 73 (±12) years and median SBP of 140 (130-150) mmHg were included within mean 8.2 hours from admission. LVEF was assessed in 8493 (81%), and of these, 4294 (51%) had HFrEF. Increasing SBP as a continuous variable was inversely associated with 180-day mortality (HRadjusted: 0.93 [0.88-0.98], p = 0.004 per 10 mmHg increase) and with the composite endpoint (HRadjusted: 0.90 [0.85-0.95], p < 0.0001 per 10 mmHg increase). A significant interaction was observed regarding LVEF, revealing that SBP was not associated with mortality in patients with HFpEF (HRadjusted: 1.01 [0.94-1.09], p = 0.83 per 10 mmHg increase), but SBP was associated with increased mortality in HFrEF (HRadjusted: 0.80 [0.73-0.88], p < 0.001 per 10 mmHg increase) (Figure). Conclusions Elevated SBP is independently associated with favorable short- and long-term outcome in AHF-patients. The association between SBP and mortality was, however, not present in patients with preserved LVEF. Abstract Figure. Survival plots by SBP and LVEF

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Maternal Vaginal Ureaplasma spp. Colonization in Early Pregnancy Is Associated with Adverse Short- and Long-Term Outcome of Very Preterm Infants

Children ◽

10.3390/children8040276 ◽

2021 ◽

Vol 8 (4) ◽

pp. 276

Author(s):

Judith Rittenschober-Böhm ◽

Tanja Habermüller ◽

Thomas Waldhoer ◽

Renate Fuiko ◽

Stefan M. Schulz ◽

...

Keyword(s):

Preterm Infants ◽

Early Pregnancy ◽

Short Term ◽

Term Outcome ◽

Long Term Outcome ◽

Very Preterm Infants ◽

Very Preterm ◽

Vaginal Colonization ◽

Short And Long Term

Vaginal colonization with Ureaplasma (U.) spp. has been shown to be associated with adverse pregnancy outcome; however, data on neonatal outcome are scarce. The aim of the study was to investigate whether maternal vaginal colonization with U. spp. in early pregnancy represents a risk factor for adverse short- or long-term outcome of preterm infants. Previously, 4330 pregnant women were enrolled in an observational multicenter study, analyzing the association between vaginal U. spp. colonization and spontaneous preterm birth. U. spp. colonization was diagnosed via PCR analysis from vaginal swabs. For this study, data on short-term outcome were collected from medical records and long-term outcome was examined via Bayley Scales of Infant Development at 24 months adjusted age. Two-hundred-and-thirty-eight children were born <33 weeks gestational age. After exclusion due to asphyxia, malformations, and lost-to-follow-up, data on short-term and long-term outcome were available from 222 and 92 infants, respectively. Results show a significant association between vaginal U. spp. colonization and severe intraventricular hemorrhage (10.4% vs. 2.6%, p = 0.03), retinopathy of prematurity (21.7% vs. 10.3%, p = 0.03), and adverse psychomotor outcome (24.3% vs. 1.8%, OR 13.154, 95%CI 1.6,110.2, p = 0.005). The data suggest an association between vaginal U. spp. colonization in early pregnancy and adverse short- and long-term outcome of very preterm infants.

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3291Achieved biventricular pacing during the first year of follow-up predicts long-term outcome in patients with heart failure treated with cardiac resynchronization therapy

European Heart Journal ◽

10.1093/eurheartj/ehy563.3291 ◽

2018 ◽

Vol 39 (suppl_1) ◽

Author(s):

J Jacobsson ◽

C Reitan ◽

R Borgquist ◽

P Platonov

Keyword(s):

Heart Failure ◽

Biventricular Pacing ◽

Cardiac Resynchronization ◽

First Year ◽

Resynchronization Therapy ◽

Term Outcome ◽

Long Term Outcome ◽

Patients With Heart Failure

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Comparative short-term and long-term outcomes between internal and external intestinal plication in the management of small bowel obstruction

BMC Surgery ◽

10.1186/s12893-021-01304-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Song Liu ◽

Qiongyuan Hu ◽

Lihua Shao ◽

Xiaofeng Lu ◽

Xiaofei Shen ◽

...

Keyword(s):

Small Bowel ◽

Small Bowel Obstruction ◽

Bowel Obstruction ◽

Short Term ◽

Term Outcome ◽

Long Term Outcome ◽

Gut Dysfunction ◽

Gut Function

Abstract Background Small bowel obstruction (SBO) is common and usually requires surgical intervention. Intestinal plication is a traditional but critical strategy for SBO in certain scenarios. This study is to compare the short-term and long-term outcome between internal and external plications in the management of SBO. Methods All patients receiving intestinal plication in our hospital were retrospectively collected. Short-term outcome including postoperative complications, reoperation, postoperative ICU stay, starting day of liquid diet and postoperative hospitalization, as well as long-term outcome including recurrence of obstruction, readmission, reoperation and death were compared between groups. Gut function at annual follow-up visits was evaluated as well. Results Nine internal and 11 external candidates were recruited into each group. The major causes of plication were adhesive obstruction, abdominal cocoon, volvulus and intussusception. Lower incidence of postoperative complication (p = 0.043) and shorter postoperative hospitalization (p = 0.049) was observed in internal group. One patient receiving external plication died from anastomosis leakage. During the 5-year follow-up period, the readmission rate was low in both groups (22.2 % vs. 9.1 %), and none of patients required reoperation or deceased. None of patients exhibited gut dysfunction, and all patients restored normal gut function after 4 years. Patients in external group demonstrated accelerated recovery of gut function after surgery. Conclusions This study compares short-term and long-term outcome of patients receiving internal or external intestinal plication. We suggest a conservative attitude toward external plication strategy. Surgical indication for intestinal plication is critical and awaits future investigations.

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Long-term outcome of children undergoing surgery for suspected perilymph fistula

The Journal of Laryngology & Otology ◽

10.1017/s0022215108003046 ◽

2008 ◽

Vol 123 (3) ◽

pp. 298-302 ◽

Cited By ~ 2

Author(s):

R J Sim ◽

A H Jardine ◽

E J Beckenham

Keyword(s):

Hearing Loss ◽

Case Series ◽

Outcome Data ◽

Rank Test ◽

Short Term ◽

Term Outcome ◽

Long Term Outcome ◽

Signed Rank ◽

Signed Rank Test

AbstractA number of authors have suggested that surgery for suspected perilymph fistula is effective in preventing deterioration of hearing and in improving hearing in some cases in the short term. We present long-term hearing outcome data from 35 children who underwent exploration for presumed perilymph fistula at The Children's Hospital, Sydney, Australia, between 1985 and 1992.Methods:The pre-operative audiological data (mean of 500, 1000, 2000 and 4000 Hz results) were compared with the most recently available data (range two to 15 years) and the six-month post-operative data.Results:The short-term results showed no significant change in hearing at six months, with a subsequent, statistically significant progression of hearing loss in both operated and non-operated ears (Wilcoxon signed rank test: operated ear, p < 0.017; non-operated ear, p < 0.009).Conclusion:In this case series, exploratory surgery for correction of suspected perilymph fistula did not prevent progression of long-term hearing loss.

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