George Bakris
Publications
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Blood pressure-lowering efficacy of the fixed-dose combination of azilsartan medoxomil and chlorthalidone: a factorial study.
Journal of clinical hypertension (Greenwich, Conn.). 05/2012; 14(5):284-92.
J Clin Hypertens (Greenwich). 2012; 14:284-292. ©2012 Wiley Periodicals, Inc. This study compared the efficacy and safety of fixed-dose combinations (FDCs) of the angiotensin II receptor blocker azilsartan medoxomil (AZL-M) and the thiazide-like diuretic chlorthalidone (CLD) with the individual mono... [more] J Clin Hypertens (Greenwich). 2012; 14:284-292. ©2012 Wiley Periodicals, Inc. This study compared the efficacy and safety of fixed-dose combinations (FDCs) of the angiotensin II receptor blocker azilsartan medoxomil (AZL-M) and the thiazide-like diuretic chlorthalidone (CLD) with the individual monotherapies in a double-blind factorial study. A total of 1714 patients with clinic systolic blood pressure (SBP) 160 mm Hg to 190 mm Hg inclusive were randomized to AZL-M 0 mg, 20 mg, 40 mg, or 80 mg and/or chlorthalidone 0 mg, 12.5 mg, or 25 mg. The primary efficacy end point was change from baseline to 8 weeks in trough (hour 22-24) SBP by ambulatory blood pressure (BP) monitoring (ABPM). Patients' mean age was 57 years; 47% were men and 20% were black. Baseline trough BP was approximately 165/95 mm Hg and 151/91 mm Hg by clinic and ABPM measurements, respectively. For the pooled AZL-M/CLD 40/25-mg and 80/25-mg FDC groups, SBP reduction by ABPM at trough was 28.9 mm Hg and exceeded AZL-M 80 mg and CLD 25 mg monotherapies by 13.8 mm Hg and 13 mm Hg, respectively (P<.001 for both comparisons). Discontinuation rates and elevations in serum creatinine were dose-dependent and occurred more often in the AZL-M/CLD groups. In patients with stage 2 hypertension, treatment with the combination of AZL-M and CLD resulted in substantially greater SBP reduction compared with either agent alone.
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1.77Impact points
Kidney Dysfunction, Cardiorespiratory Fitness, and the Risk of Death in Women.
Journal of women's health (2002). 04/2012;
Abstract Background: Chronic kidney disease (CKD) is associated with increased risk of cardiovascular (CV) events and death. However, the effect of cardiorespiratory fitness on the CKD-mortality relationship remains unknown, particularly in women. Methods: We used Cox regression to estimate hazard r... [more] Abstract Background: Chronic kidney disease (CKD) is associated with increased risk of cardiovascular (CV) events and death. However, the effect of cardiorespiratory fitness on the CKD-mortality relationship remains unknown, particularly in women. Methods: We used Cox regression to estimate hazard ratios (HR) for the effect of kidney function and fitness on all-cause mortality in a prospective cohort of 5716 women free of CKD and CV disease symptoms. Serum creatinine (Cr) was used to estimate glomerular filtration rate (eGFR), and spot urine protein and maximal stress tests were performed at baseline. Results: Mean age at baseline was 52.5±10.8 years, and 86% of the sample was Caucasian. Mean Cr was 1.11±0.14 mg/dL, and mean eGFR was 53.7±8.3 mL/min/1.73 m(2) at baseline. The mean follow-up was 15.9±2.2 years, with 589 deaths identified. Cr <1.4 was associated with an HR of death of 1.59 (p=0.03). After adjustment for traditional CV risk factors and fitness, the risk of death decreased by 3% (p<0.001) for every mL/min/1.73 m(2) increase in eGFR. Compared to women with an eGFR <45 mL/min/1.73 m(2), the risk of death was reduced by 36% and 47%, for eGFR 45-59.9 mL/min/1.73 m(2) and eGFR ≥60 mL/min/1.73 m(2), respectively (p<0.001). At every level of eGFR, fitness remained an independent predictor of mortality, with the lowest level of fitness (<5 metabolic equivalents [METs]) at the highest risk of mortality regardless of eGFR level. Conclusions: Fitness remains an independent predictor of mortality regardless of eGFR. eGFR was a stronger predictor of mortality compared to Cr or the presence of proteinuria. These findings have important implications for clinical practice and health policy, as the level of cardiorespiratory fitness predicts risk of death in the presence of asymptomatic CKD.
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2.97Impact points
Pros and cons of aggressive blood pressure lowering in patients with type 2 diabetes.
Current vascular pharmacology. 03/2012; 10(2):156-61.
The goal of treating hypertension in patients with diabetes is reduction of macrovascular and microvascular complications. Most current guidelines recommend more aggressive treatment goals with blood pressure (BP) targets of < 130/80 mmHg. Retrospective data analyses suggest an association betwee... [more] The goal of treating hypertension in patients with diabetes is reduction of macrovascular and microvascular complications. Most current guidelines recommend more aggressive treatment goals with blood pressure (BP) targets of < 130/80 mmHg. Retrospective data analyses suggest an association between a lower BP and slower declines in chronic kidney disease (CKD) as well as greater cardiovascular (CV) risk reduction in patients with type 2 diabetes. Such recommendations, however, are not supported by appropriately powered prospective outcome trials. Indeed, several important questions regarding aggressive lowering of BP levels are still unanswered. Major limitations of most existing clinical trials of BP lowering in diabetes is the failure to either target or achieve mean systolic BP values below 130 mmHg. Data from more recent randomized trials that evaluated different levels of BP do not support a BP below 130/80 mmHg as providing further CV risk reduction and compared to levels below 140/90 mmHg. One consistent benefit of a lower BP level, however, is on reduction of cerebrovascular events. There is reasonable evidence that a lower BP level does further slow progression of advanced proteinuric kidney disease such that a BP goal < 130/80 mmHg is defensible. This review examines the data for and against aggressive BP lowering in patients with diabetes.
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4.36Impact points
Management of cardiac toxicity in patients receiving vascular endothelial growth factor signaling pathway inhibitors.
American heart journal. 02/2012; 163(2):156-63.
Interfering with angiogenesis is an effective, widely used approach to cancer therapy, but antiangiogenic therapies have been associated with important systemic cardiovascular toxicities such as hypertension, left ventricular dysfunction, heart failure, and myocardial ischemia and infarction. As the... [more] Interfering with angiogenesis is an effective, widely used approach to cancer therapy, but antiangiogenic therapies have been associated with important systemic cardiovascular toxicities such as hypertension, left ventricular dysfunction, heart failure, and myocardial ischemia and infarction. As the use of vascular endothelial growth factor signaling pathway (VSP) inhibitors broadens to include older patients and those with existing cardiovascular disease, the adverse effects are likely to be more frequent, and cardiologists will increasingly be enlisted to help oncologists manage patients who develop adverse cardiovascular effects. The Cardiovascular Toxicities Panel of the National Cancer Institute reviewed the published literature and abstracts from major meetings, shared experience gained during clinical development of VSP inhibitors, and contributed extensive clinical experience in evaluating and treating patients with cancer with cardiovascular disease. This report was edited and approved by the National Cancer Institute Investigational Drug Steering Committee. It presents the panel's expert opinion on the current clinical use and future investigation for safer, more expansive use of these drugs. The panel recommends that physicians (1) conduct and document a formal risk assessment for existing cardiovascular disease and potential cardiovascular complications before VSP inhibitor treatment recognizing that preexisting hypertension and cardiovascular disease are common in patients with cancer, (2) actively monitor for blood pressure elevations and cardiac toxicity with more frequent assessments during the first treatment cycle, and (3) aggressively manage blood pressure elevations and early symptoms and signs of cardiac toxicity to prevent clinically limiting complications of VSP inhibitor therapy.
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9.81Impact points
Blood pressure components and end-stage renal disease in persons with chronic kidney disease: the Kidney Early Evaluation Program (KEEP).
Archives of internal medicine. 01/2012; 172(1):41-7.
Treatment of hypertension is difficult in chronic kidney disease (CKD), and blood pressure goals remain controversial. The association between each blood pressure component and end-stage renal disease (ESRD) risk is less well known. We studied associations of systolic and diastolic blood pressure (S... [more] Treatment of hypertension is difficult in chronic kidney disease (CKD), and blood pressure goals remain controversial. The association between each blood pressure component and end-stage renal disease (ESRD) risk is less well known. We studied associations of systolic and diastolic blood pressure (SBP and DBP, respectively) and pulse pressure (PP) with ESRD risk among 16,129 Kidney Early Evaluation Program (KEEP) participants with an estimated glomerular filtration rate of 60 mL/min/1.73 m(2) using Cox proportional hazards. We estimated the prevalence and characteristics associated with uncontrolled hypertension (SBP ≥ 150 or DBP ≥ 90 mm Hg). The mean (SD) age of participants was 69 (12) years; 25% were black, 6% were Hispanic, and 43% had diabetes mellitus. Over 2.87 years, there were 320 ESRD events. Higher SBP was associated with higher ESRD risk, starting at SBP of 140 mm Hg or higher. After sex and age adjustment, compared with SBP lower than 130 mm Hg, hazard ratios (HRs) were 1.08 (95% CI, 0.74-1.59) for SBP of 130 to 139 mm Hg, 1.72 (95% CI, 1.21-2.45) for SBP of 140 to 149 mm Hg, and 3.36 (95% CI, 2.51-4.49) for SBP of 150 mm Hg or greater. After full adjustment, HRs for ESRD were 1.27 (95% CI, 0.88-1.83) for SBP of 140 to 149 mm Hg and 1.36 (95% CI, 1.02-1.85) for SBP of 150 mm Hg or higher. Persons with DBP of 90 mm Hg or higher were at higher risk for ESRD compared with persons with DBP of 60 to 74 mm Hg (HR, 1.81; 95% CI, 1.33-2.45). Higher PP was also associated with higher ESRD risk (HR, 1.44 [95% CI, 1.00-2.07] for PP ≥ 80 mm Hg compared with PP < 50 mm Hg). Adjustment for SBP attenuated this association. More than 33% of participants had uncontrolled hypertension (SBP ≥ 150 mm Hg or DBP ≥ 90 mm Hg), mostly due to isolated systolic hypertension (54%). In this large, diverse, community-based sample, we found that high SBP seemed to account for most of the risk of progression to ESRD. This risk started at SBP of 140 mm Hg rather than the currently recommended goal of less than 130 mm Hg, and it was highest among those with SBP of at least 150 mm Hg. Treatment strategies that preferentially lower SBP may be required to improve BP control in CKD.
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6.19Impact points
Renal outcomes in hypertensive Black patients at high cardiovascular risk.
Kidney international. 12/2011; 81(6):568-76.
The ACCOMPLISH trial (Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension) was a 3-year multicenter, event-driven trial involving patients with high cardiovascular risk who were randomized in a double-blinded manner to benazepril plus either hydro... [more] The ACCOMPLISH trial (Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension) was a 3-year multicenter, event-driven trial involving patients with high cardiovascular risk who were randomized in a double-blinded manner to benazepril plus either hydrochlorothiazide or amlodipine and titrated in parallel to reach recommended blood pressure goals. Of the 8125 participants in the United States, 1414 were of self-described Black ethnicity. The composite kidney disease end point, defined as a doubling in serum creatinine, end-stage renal disease, or death was not different between Black and non-Black patients, although the Blacks were significantly more likely to develop a greater than 50% increase in serum creatinine to a level above 2.6 mg/dl. We found important early differences in the estimated glomerular filtration rate (eGFR) due to acute hemodynamic effects, indicating that benazepril plus amlodipine was more effective in stabilizing eGFR compared to benazepril plus hydrochlorothiazide in non-Blacks. There was no difference in the mean eGFR loss in Blacks between therapies. Thus, benazepril coupled to amlodipine was a more effective antihypertensive treatment than when coupled to hydrochlorothiazide in non-Black patients to reduced kidney disease progression. Blacks have a modestly higher increased risk for more advanced increases in serum creatinine than non-Blacks.
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The United nations high level meeting addresses noncommunicable diseases, but where is hypertension?
Journal of clinical hypertension (Greenwich, Conn.). 11/2011; 13(11):787-90.
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4.36Impact points
EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE): a cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome.
American heart journal. 10/2011; 162(4):620-626.e1.
Comprehensive safety evaluation of new drugs for diabetes mellitus is needed in the area of cardiovascular (CV) outcomes, particularly in populations with high CV risk. Alogliptin, a dipeptidyl peptidase 4 inhibitor, is under development for the treatment of type 2 diabetes mellitus alone or in comb... [more] Comprehensive safety evaluation of new drugs for diabetes mellitus is needed in the area of cardiovascular (CV) outcomes, particularly in populations with high CV risk. Alogliptin, a dipeptidyl peptidase 4 inhibitor, is under development for the treatment of type 2 diabetes mellitus alone or in combination with other antidiabetic therapies. Long-term CV safety of alogliptin is being established in a randomized, placebo-controlled clinical study in patients with acute coronary syndrome (ACS) using an analytical approach that has both an interim and final assessment. The primary CV end point for this trial is a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Approximately 5,400 men and women with type 2 diabetes and ACS (acute myocardial infarction or unstable angina) are being recruited and will be followed up for up to 4.5 years postrandomization. The statistical plan for the trial uses a design that evaluates the hazard ratio (HR) of alogliptin to placebo first based on the primary CV composite end point after accrual of 80 to 150 primary CV events and again when there are 550 to 650 primary CV events. In the first series of analyses, the upper bound of a group-sequential 1-sided repeated CI for the HR must be ≤1.8 for registration in the United States. At end of study, the upper bound of a subsequent group-sequential 1-sided repeated CI for the HR must be ≤1.3. For both group sequential analyses, the repeated CIs are calculated to insure simultaneous coverage probabilities of 97.5% for the true HR. Study progress: More than 2,000 ACS patients were randomized as of June 2011. EXAMINE will define the CV safety profile of this dipeptidyl peptidase 4 inhibitor in patients at high risk for CV events.
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4.13Impact points
Effects of combining simvastatin with rosiglitazone on inflammation, oxidant stress and ambulatory blood pressure in patients with the metabolic syndrome: the SIROCO study.
Diabetes, obesity & metabolism. 09/2011; 14(2):181-6.
Individually, statins and thiazolidinediones (TZDs) show positive effects on atherosclerosis progression in cellular and animal models as well as patients with diabetes; however, their combined effects have not been studied. This study examines the effects of simvastatin combined with rosiglitazone ... [more] Individually, statins and thiazolidinediones (TZDs) show positive effects on atherosclerosis progression in cellular and animal models as well as patients with diabetes; however, their combined effects have not been studied. This study examines the effects of simvastatin combined with rosiglitazone on vascular inflammation, oxidant stress, ambulatory blood pressure (BP) and other atherosclerotic factors in patients with the metabolic syndrome. This is a randomized, double blind, placebo-controlled study in 53 subjects with the metabolic syndrome. Participants were randomized to simvastatin 40 mg/day plus placebo vs. simvastatin 40 mg/day plus rosiglitazone 4 mg/day for 6 months. The primary endpoint was the between-group difference in high-sensitivity C-reactive protein (hs-CRP) and secondary variables including urinary isoprostanes, serum malondialdehyde (MDA), ambulatory BP, adiponectin, and lipid and glycaemic profiles. At study end, the group randomized to the simvastatin/rosiglitazone combination had a greater reduction in hs-CRP of 1.33 mg/dl, (p = 0.029) and showed a trend for a greater reduction in urinary isoprostane (-39%), (p = 0.056) compared to simvastatin/placebo group. Changes in MDA levels did not differed between groups (p = 0.81). 24-h systolic blood pressure (SBP) also showed a 4.5 mmHg reduction at 6 months (p = 0.06). Adiponectin levels increased by 3.91 µg/ml in the combination group over placebo, (p = 0.03) and blood glucose decreased in combination group vs. placebo. Our data show that patients with the metabolic syndrome given a statin/TZD combination manifest greater reductions in markers of vascular inflammation and oxidant stress, 24-h ambulatory BP and increases in adiponectin as well as improved glycaemic indices.
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5.15Impact points
Comparison of measured GFR, serum creatinine, cystatin C, and beta-trace protein to predict ESRD in African Americans with hypertensive CKD.
American journal of kidney diseases : the official journal of the National Kidney Foundation. 09/2011; 58(6):886-93.
Identification of persons with chronic kidney disease (CKD) who are at highest risk to progress to end-stage renal disease (ESRD) is necessary to reduce the burden of kidney failure. The relative utility of traditional markers of kidney function, including estimated glomerular filtration rate (eGFR)... [more] Identification of persons with chronic kidney disease (CKD) who are at highest risk to progress to end-stage renal disease (ESRD) is necessary to reduce the burden of kidney failure. The relative utility of traditional markers of kidney function, including estimated glomerular filtration rate (eGFR) and serum creatinine level, and emerging markers of kidney function, including cystatin C and beta-trace protein (BTP) levels, to predict ESRD and mortality has yet to be established. Randomized clinical trial followed by an observational cohort study. 865 African American individuals with hypertensive CKD enrolled in a clinical trial of 2 levels of blood pressure control and 3 different antihypertensive drugs as initial therapy and subsequently followed by an observational cohort study. Quintile of measured GFR (mGFR) by iothalamate clearance, serum creatinine, serum creatinine-based eGFR, cystatin C, and BTP values. Incidence of ESRD and mortality. 246 participants reached ESRD during a median follow-up of 102 months. The incidence rate of ESRD was higher with higher quintiles of each marker. The association between higher BTP level and ESRD was stronger than those for the other markers, including mGFR. All markers remained significantly associated with ESRD after adjustment for mGFR and relevant covariates (all P < 0.05), with BTP level retaining the strongest association (HR for highest vs lowest quintile, 5.7; 95% CI, 2.2-14.9). Associations with the combined end point of ESRD or mortality (n = 390) were weaker, but remained significant for cystatin C (P = 0.05) and BTP levels (P = 0.004). The ability of these markers to predict ESRD and mortality in other racial and ethnic groups and in individuals with CKD due to other causes is unknown. Plasma BTP and cystatin C levels may be useful adjuncts to serum creatinine level and mGFR in evaluating risk of progression of kidney disease.
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1.40Impact points
Blood pressure targets for patients with diabetes or kidney disease.
Current hypertension reports. 09/2011; 13(6):452-5.
The most recent scientific guideline statements from foundations and societies dealing with diabetes and kidney disease argue for blood pressure (BP) goals lower than 130/80 mm Hg, but whether the evidence from properly done clinical trials supports this BP level remains questionable. A review of al... [more] The most recent scientific guideline statements from foundations and societies dealing with diabetes and kidney disease argue for blood pressure (BP) goals lower than 130/80 mm Hg, but whether the evidence from properly done clinical trials supports this BP level remains questionable. A review of all the evidence suggests that almost all of the data come from retrospective data analyses of randomized cardiovascular and chronic kidney disease (CKD) trials. Meta-analyses of all clinical trials to date demonstrate that reducing BP reduces risk for stroke and coronary heart disease, but none have achieved a mean BP goal of less than 130/80 mm Hg. In fact, only two prospective trials achieved a BP lower than 130/80 mm Hg in people with type 2 diabetes, as did three trials in advanced proteinuric CKD. Of these, one of the two diabetes trials showed a benefit for overall cardiovascular risk reduction, and two of the three kidney disease trials showed a benefit on slowing of advanced CKD. Of note, however, these two trials in CKD had baseline average proteinuria rates of more than 500 mg/day. No benefit of a lower BP was seen in microalbuminuric CKD. Therefore, the totality of the prospective randomized trial evidence indicates that a BP less than 130/80 mm Hg is not defensible to slow nephropathy progression unless proteinuria levels are at least 500 mg/day, and it does not reduce overall cardiovascular events in diabetes. Stroke benefit was uniformly seen at BP levels less than 130/80 mm Hg, however. Therefore, newer guidelines are emerging that state that the BP goal for most people is lower than 140/90 mm Hg with level IA or IB evidence, and that levels lower than 130/80 mm Hg are defensible only if advanced proteinuric CKD is present or stroke risk is very high (i.e., history of prior stroke or several risk factors for stroke, including hypertension, smoking, diabetes mellitus, dyslipidemia).
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1.39Impact points
Predictors of systolic BP <140 mmHg and systolic BP level by randomly assigned treatment group (benazepril plus amlodipine or hydrochlorothiazide) in the ACCOMPLISH Study.
Blood pressure. 08/2011;
Abstract Background. The ACCOMPLISH Trial investigated intensive antihypertensive combination treatment with benazepril + amlodipine (B+A) or benazepril + hydrochlorothiazide (B+H) on cardiovascular outcomes in patients with systolic hypertension. We analyzed the baseline predictors of achieving a s... [more] Abstract Background. The ACCOMPLISH Trial investigated intensive antihypertensive combination treatment with benazepril + amlodipine (B+A) or benazepril + hydrochlorothiazide (B+H) on cardiovascular outcomes in patients with systolic hypertension. We analyzed the baseline predictors of achieving a systolic blood pressure (SBP) <140 mmHg and achieved SBP level by the end of 12 months in both treatment groups. Methods. Baseline and 12-month SBP was available in 10,506 patients, of whom 6250 had diabetes. Univariate and multivariate logistic regression models were used for SBP control at 12 months and multivariable regression models were used for the prediction of SBP at 12 months. A stepwise procedure was used to select significant (p < 0.001) predictors in multivariate analyses. Results. Mean (± SD) BP fell from 145.4/80.1 (± 18.3/10.7) mmHg at randomization to 132.8/74.7 (± 16.0/9.6) mmHg at 12 months. The main baseline predictors of SBP control <140 mmHg were region (USA >Nordic region) and Caucasian ethnicity in both randomization arms. A higher diastolic BP and the use of lipid lowering agents indicated favorable effects in the B+H arm only. The predictors of uncontrolled SBP were: (i) higher baseline SBP values, (ii) higher number of previous antihypertensive medications in both arms, (iii) the previous use of insulin in the B+A arm, and (iv) pre-trial calcium channel blocker (CCB) use in the B+H arm. Additionally, pre-trial use of thiazides and electrocardiogram (ECG)-left ventricular hypertrophy (LVH) at baseline predicted higher, and smoking lower absolute SBP in the B+A arm and the use of thiazides and proteinuria a higher SBP in the B+H arm. Conclusion. Irrespective of treatment, patients in the USA and Caucasians achieved better SBP control, whereas higher baseline SBP and more previous antihypertensive medications indicated less control. Concomitant use of lipid lowering treatment indicated a better SBP control in the benazepril + hydrochlorothiazide arm. Lastly, insulin use and ECG-LVH in the benazepril + amlodipine arm and proteinuria in the benazepril + hydrochlorothiazide arm indicated poor control.
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Comparison of the novel angiotensin II receptor blocker azilsartan medoxomil vs valsartan by ambulatory blood pressure monitoring.
Journal of clinical hypertension (Greenwich, Conn.). 07/2011; 13(7):467-72.
Azilsartan medoxomil (AZL-M) is a unique angiotensin II receptor blocker (ARB) under development for the treatment of hypertension. To compare this ARB with another in the class, the authors studied the effects of AZL-M and valsartan (VAL) in 984 patients with primary hypertension in a randomized, d... [more] Azilsartan medoxomil (AZL-M) is a unique angiotensin II receptor blocker (ARB) under development for the treatment of hypertension. To compare this ARB with another in the class, the authors studied the effects of AZL-M and valsartan (VAL) in 984 patients with primary hypertension in a randomized, double-blind, multicenter study using ambulatory and clinic blood pressure (BP) measurements. The primary end point was change from baseline in 24-hour mean ambulatory systolic BP following 24 weeks of treatment. Hierarchical analysis testing for noninferiority was followed by superiority testing of AZL-M (80 mg then 40 mg) vs VAL. The mean age of participants was 58 years, 52% were men, and 15% were black. Baseline 24-hour mean systolic BP was similar (approximately 145.6 mm Hg) in each group. AZL-M 40 mg and 80 mg lowered 24-hour mean systolic BP (-14.9 mm Hg and -15.3 mm Hg, respectively) more than VAL 320 mg (-11.3 mm Hg; P<.001 for 40-mg and 80-mg comparisons vs VAL). Clinic systolic BP reductions were consistent with the ambulatory results (-14.9 mm Hg for AZL-M 40 mg and -16.9 mm Hg for AZL-M 80 mg vs -11.6 mm Hg for VAL; P=.015 and P<.001, respectively). The reductions in 24-hour mean and clinic diastolic BPs were also greater with both doses of AZL-M than with VAL (P≤.001 for all comparisons). Small, reversible changes in serum creatinine occurred more often with AZL-M than with VAL; otherwise, safety and tolerability parameters were similar among the three groups. These data demonstrate that AZL-M across the effective dose range had superior efficacy to VAL at its maximal recommended dose without any meaningful increase in adverse events. These findings suggest that AZL-M could provide higher rates of hypertension control compared with other ARBs in the class.
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3.96Impact points
Newer renin-angiotensin-aldosterone system blocker combinations: is there an advantage?
Current opinion in nephrology and hypertension. 06/2011; 20(5):471-5.
The necessity for new and more effective management approaches to achieve blood pressure goals is still present in spite of the number of antihypertensive medications available. One of the cornerstones of successful therapy is implementation of drug combinations that act on complementary biological ... [more] The necessity for new and more effective management approaches to achieve blood pressure goals is still present in spite of the number of antihypertensive medications available. One of the cornerstones of successful therapy is implementation of drug combinations that act on complementary biological pathways. This review article focuses on the evaluation of recent data supporting newer combinations involving inhibition of the renin-angiotensin-aldosterone system (RAAS) with other drug classes such as calcium channel blockers (CCBs) and diuretics. New angiotensin receptor blockers as well as renin inhibitors, with a more robust blood pressure-lowering effect than their predecessors, have emerged recently. The data presented in this text also strongly supports a combination therapy approach as initial therapy to achieve blood pressure goals in a timely fashion. Additionally, the blood pressure-lowering effect is more robust with lower-dose, single-pill combinations than with highest doses of single agents alone. Therefore, using combination agents is less prone to side effects. The challenges for such single-pill combinations remain affordability. For this reason, payers and patients have traditionally not preferred such agents in spite of better blood pressure control and adherence rates. The new combinations of renin inhibitors and the new angiotensin receptor blocker combinations add to the armamentarium of agents to control blood pressure. Whereas the new angiotensin receptor blocker offers greater efficacy on blood pressure control over other agents in the class and the availability of the only chlorthalidone combination, no outcome data exist yet with any of the new agents.
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14.82Impact points
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12.54Impact points
ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension.
Journal of the American College of Cardiology. 05/2011; 57(20):2037-114.
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5.15Impact points
National Kidney Foundation's Kidney Early Evaluation Program (KEEP) annual data report 2010: executive summary.
American journal of kidney diseases : the official journal of the National Kidney Foundation. 03/2011; 57(3 Suppl 2):S1-3.
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5.15Impact points
Sustainable community-based CKD screening methods employed by the National Kidney Foundation's Kidney Early Evaluation Program (KEEP).
American journal of kidney diseases : the official journal of the National Kidney Foundation. 03/2011; 57(3 Suppl 2):S4-8.
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5.15Impact points
Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) study equations: prevalence of and risk factors for diabetes mellitus in CKD in the Kidney Early Evaluation Program (KEEP).
American journal of kidney diseases : the official journal of the National Kidney Foundation. 03/2011; 57(3 Suppl 2):S24-31.
Diabetes is a leading cause of chronic kidney disease (CKD). Whether reclassification of CKD stages based on glomerular filtration rate estimated using the CKD Epidemiology Collaboration (CKD-EPI) equation versus the Modification of Diet in Renal Disease (MDRD) Study equation modifies estimates of p... [more] Diabetes is a leading cause of chronic kidney disease (CKD). Whether reclassification of CKD stages based on glomerular filtration rate estimated using the CKD Epidemiology Collaboration (CKD-EPI) equation versus the Modification of Diet in Renal Disease (MDRD) Study equation modifies estimates of prevalent risk factors across stages is unknown. This is a cross-sectional analysis of data from the Kidney Early Evaluation Program (KEEP), a community-based health screening program targeting individuals 18 years and older with diabetes, hypertension, or a family history of diabetes, hypertension, or kidney disease. Of 109,055 participants, 68.2% were women and 31.8% were African American. Mean age was 55.3 ± 0.05 years. Clinical, demographic, and laboratory data were collected from August 2000 through December 2009. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations. CKD was present in 25.6% and 23.5% of the study population using the MDRD Study and CKD-EPI equations, respectively. Diabetes was present in 42.4% and 43.8% of participants with CKD, respectively. Prevalent risk factors for diabetes included obesity (body mass index >30 kg/m(2)), 44.0%; hypertension, 80.5%; cardiovascular disease, 23.2%; family history of diabetes, 55.9%; and dyslipidemia, 43.0%. In a logistic regression model after adjusting for age and other risk factors, odds for diabetes increased significantly compared with no CKD with each CKD stage based on the CKD-EPI equation and similarly with stages based on the MDRD Study equation. Using a CKD-EPI-adjusted model, ORs were: stage 1, 2.08 (95% CI, 1.90-2.27); stage 2, 1.86 (95% CI, 1.72-2.02); stage 3, 1.23 (95% CI, 1.17-1.30); stage 4, 1.69 (95% CI, 1.42-2.03); and stage 5, 2.46 (95% CI, 1.46-4.14). Using the CKD-EPI equation led to a lower prevalence of CKD but to similar diabetes prevalence rates associated with CKD across all stages compared with the MDRD Study equation. Diabetes and other CKD risk factor prevalence was increased compared with the non-CKD population.
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5.15Impact points
Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) study equations: risk factors for and complications of CKD and mortality in the Kidney Early Evaluation Program (KEEP).
American journal of kidney diseases : the official journal of the National Kidney Foundation. 03/2011; 57(3 Suppl 2):S9-16.
The National Kidney Foundation has recommended that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation replace the Modification of Diet in Renal Disease (MDRD) Study equation. Before implementing this change in the Kidney Early Evaluation Program (KEEP), we compared characteris... [more] The National Kidney Foundation has recommended that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation replace the Modification of Diet in Renal Disease (MDRD) Study equation. Before implementing this change in the Kidney Early Evaluation Program (KEEP), we compared characteristics of reclassified individuals and mortality risk predictions using the new equation. Of 123,704 eligible KEEP participants, 116,321 with data available for this analysis were included. Glomerular filtration rate (GFR) was estimated using the MDRD Study (eGFR(MDRD)) and CKD-EPI (eGFR(CKD-EPI)) equations with creatinine level calibrated to standardized methods. Participants were characterized by eGFR category: >120, 90-119, 60-89, 45-59, 30-44, and <30 mL/min/1.73 m(2). Clinical characteristics ascertained included age, race, sex, diabetes, hypertension, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and anemia. Mortality was determined over a median of 3.7 years of follow-up. The prevalence of eGFR(CKD-EPI) <60 mL/min/1.73 m(2) was 14.3% compared with 16.8% using eGFR(MDRD). Using eGFR(CKD-EPI), 20,355 participants (17.5%) were reclassified to higher eGFR categories, and 3,107 (2.7%), to lower categories. Participants reclassified upward were younger and less likely to have chronic conditions, with a lower risk of mortality. A total of 3,601 deaths (3.1%) were reported. Compared with participants classified to eGFR of 45-59 mL/min/1.73 m(2) using both equations, those with eGFR(CKD-EPI) of 60-89 mL/min/1.73 m(2) had a lower mortality incidence rate (6.4 [95% CI, 5.1-7.7] vs 18.5 [95% CI, 17.1-19.9]). Results were similar for all eGFR categories. Net reclassification improvement was 0.159 (P < 0.001). The CKD-EPI equation reclassifies people at lower risk of CKD and death into higher eGFR categories, suggesting more accurate categorization. The CKD-EPI equation will be used to report eGFR in KEEP.
Following (16)
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Richard E Gilbert
St. Michael's Hospital -
Elijah Saunders
University of Maryland -
Keith C Norris
Charles R. Drew University of Medicine and Science -
William C Cushman
University of Tennessee -
Jack Stockert
University of Chicago
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