A study of the prevalence of significant increases in serum creatinine following angiotension-converting enzyme inhibitor administration

Thorp, Micah L.; Ditmer, Diane; Nash, Mike; Wise, R.; Jaderholm, P L; Smith, J. Douglas; Chan, Wing Cheuk

doi:10.1038/sj.jhh.1001832

Cited by 7 publications

(8 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings are consistent with previous studies involving AZL‐M plus CLD . Evidence from clinical studies with RAS inhibitors suggests that acute serum creatinine elevations are associated with long‐term renal protection, in spite of short‐term decreases in GFR, and thus appear to reflect a benefit of therapy rather than an AE …”

Section: Discussionsupporting

confidence: 90%

“…Similarly, hypokalemia was reported more frequently in patients who required addition of CLD. The hypokalemic effects of CLD and other diuretics are well characterized and evidence suggests that inhibition of RAS activity with agents such as AZL‐M may counteract this effect . For instance, in a recent 8‐week, double‐blind factorial study, mean changes in potassium were 0.08 mmol/L with AZL‐M, −0.42 mmol/L with CLD, and −0.08 mmol/L with AZL‐M/CLD …”

Section: Discussionmentioning

confidence: 99%

“…The primary efficacy endpoint was the change in trough clinic sitting DBP measured during the double-blind reversal phase (weeks [26][27][28][29][30][31][32]. The secondary efficacy endpoint was the change in trough clinic sitting SBP for the same period.…”

Section: Endpoints and Assessmentsmentioning

confidence: 99%

See 2 more Smart Citations

Safety, Tolerability, and Efficacy of Azilsartan Medoxomil With or Without Chlorthalidone During and After 8 Months of Treatment for Hypertension

Kipnes

Handley

Lloyd

et al. 2015

J of Clinical Hypertension

View full text Add to dashboard Cite

A phase 3, 26‐week, open‐label, titrate‐to‐target study (n=418) assessed the safety of azilsartan medoxomil (AZL‐M) alone and with chlorthalidone (CLD), followed by a 6‐week, double‐blind, placebo‐controlled reversal phase with change in clinic diastolic blood pressure (DBP) as the primary endpoint. Target blood pressure (BP) was <140/90 mm Hg (<130/80 mm Hg with diabetes/chronic kidney disease). AZL‐M was initiated at 40 mg once a day (QD), force‐titrated to 80 mg at week 4. CLD 25 mg QD could be added (weeks 8–22), if required, to reach target, followed by additional antihypertensives from week 12. At the end of the open‐label phase, mean change in systolic BP (SBP)/DBP from baseline was −23/−16 mm Hg. The most common adverse events, irrespective of treatment, were dizziness (8.9%) and headache (7.2%). Serious AEs were reported in eight patients (1.9%). Consecutive creatinine elevations ≥50% with values exceeding the upper limit of normal (ULN) were reported in nine (2.2%) patients. All returned to below the 50% threshold; most also returned to below the ULN after drug discontinuation. Mean DBP was maintained through the reversal phase in patients receiving AZL‐M, but increased with placebo (difference: −7.8 mm Hg, 95% confidence interval, −9.8 to −5.8; P<.001). AZL‐M alone or with CLD showed good long‐term safety and stable BP improvements in a titrate‐to‐target approach. BP improvements caused by AZL‐M therapy were safely reversible upon AZL‐M withdrawal.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Safety, Tolerability, and Efficacy of Azilsartan Medoxomil With or Without Chlorthalidone During and After 8 Months of Treatment for Hypertension

Kipnes

Handley

Lloyd

et al. 2015

J of Clinical Hypertension

View full text Add to dashboard Cite

show abstract

“…Acute serum creatinine elevations have been previously reported in patients receiving RAS‐inhibiting drugs, including both angiotensin‐converting enzyme inhibitors and ARBs . This might be expected based on their mechanism of action—as RAS blockade inhibits angiotensin II‐mediated vasoconstriction of efferent glomerular arterioles, it causes a decrease in intraglomerular pressure, thus leading to a reversible acute decrease of glomerular filtration rate .…”

Section: Discussionmentioning

confidence: 96%

Comparison of long‐term safety of fixed‐dose combinations azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide

Neutel

Cushman

Lloyd

et al. 2017

J of Clinical Hypertension

View full text Add to dashboard Cite

This 52-week, randomized, open-label study evaluated long-term safety/tolerability of fixed-dose combination azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs fixed-dose combination olmesartan medoxomil/hydrochlorothiazide (OLM/HCTZ) in patients with essential hypertension (stage 2; clinic systolic blood pressure 160-190 mm Hg). Initial AZL-M/CLD 40/12.5 mg/d (n=418) or OLM/HCTZ 20/12.5 mg/d (n=419) could be uptitrated during weeks 4 to 52 (AZL-M/CLD to 80/25 mg; OLM/HCTZ to 40/25 mg [United States] or 20/25 mg [Europe]) to meet blood pressure targets. Treatment-emergent adverse events/serious adverse events occurred in 78.5%/5.7% of patients taking AZL-M/CLD vs 76.4%/6.2% taking OLM/HCTZ. The most frequent adverse events were dizziness (16.3% vs 12.6%), blood creatinine increase (21.5% vs 8.6%), headache (7.4% vs 11.0%), and nasopharyngitis (12.2% vs 11.5%). Hypokalemia was uncommon (1.0% vs 0.7%). Greater blood pressure reductions with AZL-M/CLD by week 2 were maintained throughout the study, despite less uptitration (32.3% vs 48.9% with OLM/HCTZ). Fixed-dose combination AZL-M/CLD showed an encouraging benefit-risk profile when used per standard clinical practice in a titrate-to-target strategy.

show abstract

“…Early studies with RAAS inhibitors excluded patients with advanced renal insufficiency (creatinine clearance >3.0 mg ⁄ dL) on the basis that these agents could further increase serum creatinine or electrolytes (ie, potassium). 46,47 However, more recent studies have shown that RAAS inhibitors continue to confer renoprotective benefits in patients with advanced renal insufficiency (serum creatinine >3.0 mg ⁄ dL) 48,49 and at higher-than-usual doses, 42 while infrequently incurring hyperkalemia. Therefore, a preexisting elevated serum creatinine level should not deter clinicians from using ACE inhibitors or ARBs.…”

Section: Monitoring Kidney Functionmentioning

confidence: 99%

Identification and Management of Albuminuria in the Primary Care Setting

Kuritzky

Toto

Buren

2011

The Journal of Clinical Hypertension

View full text Add to dashboard Cite

Albuminuria is an important risk marker for adverse cardiovascular (CV) and renal outcomes and mortality. The relationship between albuminuria and risk is continuous and linear, like that of blood pressure and cardiovascular risk. Evidence now supports increased risk even at levels traditionally considered within normal limits. In high-risk patients, routine annual screening can detect changes in urine albumin excretion and improve the timely identification of albuminuria, and therefore should be considered in patients with diabetes, hypertension, and chronic kidney disease. Preferred simple screening methods appropriate for use in the primary care setting include microalbumin-specific dipsticks and urinary albumin:creatinine ratio determination (from a spot urine sample). Cornerstones of albuminuria treatment include risk factor management, ongoing monitoring, and, in patients with hypertension, chronic kidney disease, or diabetes, the use of renin-angiotensin-aldosterone system (RAAS)-blocking agents. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have demonstrated utility in this regard; data from studies of direct renin inhibition are promising. The combined use of an ACE inhibitor and ARB was once considered a viable option for the treatment of albuminuria; however, results of the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) raised important questions regarding the benefits and limitations of dual RAAS blockade. Ongoing studies should provide important insight into the effects of this approach on renal outcomes.

show abstract

A study of the prevalence of significant increases in serum creatinine following angiotension-converting enzyme inhibitor administration

Cited by 7 publications

References 10 publications

Safety, Tolerability, and Efficacy of Azilsartan Medoxomil With or Without Chlorthalidone During and After 8 Months of Treatment for Hypertension

Safety, Tolerability, and Efficacy of Azilsartan Medoxomil With or Without Chlorthalidone During and After 8 Months of Treatment for Hypertension

Comparison of long‐term safety of fixed‐dose combinations azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide

Identification and Management of Albuminuria in the Primary Care Setting

Contact Info

Product

Resources

About