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Low glomerular filtration rate, recurrent stroke risk, and effect of renin-angiotensin system modulation.

ABSTRACT: To investigate the association of low estimated glomerular filtration rate (eGFR) <60 mL/min with recurrent stroke risk and to evaluate whether add-on renin-angiotensin system modulator therapy is associated with lower recurrent stroke risk in patients with low eGFR.We analyzed the database of a multicenter trial involving 18,666 patients with recent ischemic stroke followed for 2.5 years. Primary outcome was time to first recurrent stroke. Independent associations of low eGFR with outcome in the entire cohort and add-on telmisartan treatment with outcome among those with low eGFR were evaluated.Low eGFR was observed in 3630 (20.1%) patients. Patients with low eGFR were older, more likely women, with a known history of hypertension. In unadjusted analyses, patients with low eGFR were more likely to experience a recurrent stroke (hazard ratio, 1.34; 95% confidence interval, 1.20-1.49). After adjusting for confounders, low eGFR was still associated with recurrent stroke but to a lesser extent (hazard ratio, 1.16; 95% confidence interval, 1.04-1.31). Telmisartan treatment among patients with low eGFR was not independently associated with recurrent stroke (hazard ratio, 1.08; 95% confidence interval, 0.89-1.31).Low eGFR is independently associated with a higher risk of recurrent stroke, but short-term add-on telmisartan therapy does not seem to mitigate this risk.http://www.clinicaltrials.gov. Unique identifier: NCT00153062.

SUBMITTER: Ovbiagele B

PROVIDER: S-EPMC4134879 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Low glomerular filtration rate, recurrent stroke risk, and effect of renin-angiotensin system modulation.

Ovbiagele Bruce B Bath Philip M PM Cotton Daniel D Sha Nanshi N Diener Hans-Christoph HC

Stroke 20130829 11

<h4>Background and purpose</h4>To investigate the association of low estimated glomerular filtration rate (eGFR) <60 mL/min with recurrent stroke risk and to evaluate whether add-on renin-angiotensin system modulator therapy is associated with lower recurrent stroke risk in patients with low eGFR.<h4>Methods</h4>We analyzed the database of a multicenter trial involving 18,666 patients with recent ischemic stroke followed for 2.5 years. Primary outcome was time to first recurrent stroke. Independ ...[more]

PMID: 23988639

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Project description:ImportanceIt is uncertain whether and when angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) treatment should be discontinued in individuals with low estimated glomerular filtration rate (eGFR).ObjectiveTo investigate the association of ACE-I or ARB therapy discontinuation after eGFR decreases to below 30 mL/min/1.73 m2 with the risk of mortality, major adverse cardiovascular events (MACE), and end-stage kidney disease (ESKD).Design, setting, and participantsThis retrospective, propensity score-matched cohort study included 3909 patients from an integrated health care system that served rural areas of central and northeastern Pennsylvania. Patients who initiated ACE-I or ARB therapy from January 1, 2004, to December 31, 2018, and had an eGFR decrease to below 30 mL/min/1.73 m2 during therapy were enrolled, with follow-up until January 25, 2019.ExposuresIndividuals were classified based on whether they discontinued ACE-I or ARB therapy within 6 months after an eGFR decrease to below 30 mL/min/1.73 m2.Main outcomes and measuresThe association between ACE-I or ARB therapy discontinuation and mortality during the subsequent 5 years was assessed using multivariable Cox proportional hazards regression models, adjusting for patient characteristics at the time of the eGFR decrease in a propensity score-matched sample. Secondary outcomes included MACE and ESKD.ResultsOf the 3909 individuals receiving ACE-I or ARB treatment who experienced an eGFR decrease to below 30 mL/min/1.73 m2 (2406 [61.6%] female; mean [SD] age, 73.7 [12.6] years), 1235 discontinued ACE-I or ARB therapy within 6 months after the eGFR decrease and 2674 did not discontinue therapy. A total of 434 patients (35.1%) who discontinued ACE-I or ARB therapy and 786 (29.4%) who did not discontinue therapy died during a median follow-up of 2.9 years (interquartile range, 1.3-5.0 years). In the propensity score-matched sample of 2410 individuals, ACE-I or ARB therapy discontinuation was associated with a higher risk of mortality (hazard ratio [HR], 1.39; 95% CI, 1.20-1.60]) and MACE (HR, 1.37; 95% CI, 1.20-1.56), but no statistically significant difference in the risk of ESKD was found (HR, 1.19; 95% CI, 0.86-1.65).Conclusions and relevanceThe findings suggest that continuing ACE-I or ARB therapy in patients with declining kidney function may be associated with cardiovascular benefit without excessive harm of ESKD.

Project description:ObjectiveTo qualitatively and quantitatively investigate the link between a low estimated glomerular filtration rate (eGFR) at baseline and risk of future stroke.DesignSystematic review and meta-analysis of prospective studies.Data sourcesPubMed (1966-October 2009) and Embase (1947-October 2009). Selection criteria Inclusion criteria were studies that prospectively collected data within cohort studies or clinical trials, estimated glomerular filtration rate at baseline using the modification of diet in renal disease or Cockcroft-Gault equations, assessed incident stroke, had a follow-up of at least one year, and reported quantitative estimates of multivariate adjusted relative risk and 95% confidence interval for stroke associated with an eGFR of 60-90 ml/min/1.73 m(2) or <60 ml/min/1.73 m(2). Data abstraction Two investigators independently abstracted data from eligible studies. Estimates were combined using a random effects model. Heterogeneity was assessed by P value of χ(2) statistics and I(2). Publication bias was assessed by visual examination of funnel plots.Results21 articles derived from 33 prospective studies: 14 articles assessed eGFR <60 ml/min/1.73 m(2) and seven assessed eGRF at both <60 ml/min/1.73 m(2) and 60-90 ml/min/1.73 m(2) for a total of 284 672 participants (follow-up 3.2-15 years) with 7863 stroke events. Incident stroke risk increased among participants with an eGFR <60 ml/min/1.73 m(2) (relative risk 1.43, 95% confidence interval 1.31 to 1.57; P<0.001) but not among those with an eGFR of 60-90 ml/min/1.73 m(2) (1.07, 0.98 to 1.17; P=0.15). Significant heterogeneity existed between estimates among patients with an eGFR <60 ml/min/1.73 m(2) (P<0.001). In subgroup analyses among participants with an eGFR <60 ml/min/1.73 m(2), heterogeneity was significant in Asians compared with non-Asians (1.96, 1.73 to 2.23 v 1.25, 1.16 to 1.35; P<0.001), and those with an eGFR of 40-60 ml/min/1.73 m(2) v <40 ml/min/1.73 m(2) (1.28, 1.04 to 1.56 v 1.77, 1.32 to 2.38; P<0.01).ConclusionsA baseline eGFR <60 ml/min/1.73 m(2) was independently related to incident stroke across a variety of participants and study designs. Prompt and appropriate implementation of established strategies for reduction of vascular risk in people with know renal insufficiency may prevent future strokes.

Project description:BackgroundEquations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values.ObjectiveTo develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.DesignCross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates.SettingResearch studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006.Participants8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES.MeasurementsGFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age.ResultsIn the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%).LimitationThe sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR.ConclusionThe CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use.Primary funding sourceNational Institute of Diabetes and Digestive and Kidney Diseases.

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Low glomerular filtration rate, recurrent stroke risk, and effect of renin-angiotensin system modulation.

Publications

Low glomerular filtration rate, recurrent stroke risk, and effect of renin-angiotensin system modulation.

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