Doubling the RAS Blockade: A Bad ALTITUDE
Doubling the RAS Blockade: A Bad ALTITUDE
Hello. I'm Bret Stetka, Editorial Director at Medscape. Welcome to the F1000 Practice-Changing Minute, where we report commentaries from the Faculty of 1000 on highly rated studies. Our commentary today covers the study "Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes," from HH Parving and colleagues, published in the New England Journal of Medicine. The F1000 commentator has given this a ranking of Changes Clinical Practice, with the conclusion that dual blockade of the renin-angiotensin system with aliskiren should no longer be used in people with type 2 diabetes and chronic kidney disease (CKD). The following F1000 commentary on this study was written by Rudy Bilous, MD, FRCP, from James Cook University Hospital, Middlesbrough, United Kingdom.
In his commentary on this study, Dr. Bilous wrote:
"The Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE) study has finally been published after early discontinuation in December 2011. Despite a reduction in albuminuria of 14%, the addition of the renin antagonist aliskiren to conventional renin-angiotensin system (RAS) blockade using either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) in a randomized controlled trial (RCT) to 8561 type 2 diabetic subjects with increased albuminuria or a history of cardiovascular disease or both showed no clinical benefit on cardiorenal end points over a mean follow-up of 32.9 months. In fact, patients did worse on active therapy with a 10% absolute increase in hyperkalaemia >5 mmol/L.
"The rationale for ALTITUDE was the much shorter AVOID trial, where aliskiren was added to losartan in 599 people with type 2 diabetes and increased albuminuria >300 mg/g creatinine. In AVOID, a 20% reduction in albuminuria was observed after 6 months, much greater than in ALTITUDE and perhaps a reflection of their more advanced nephropathy. Intriguingly, blood pressure rose at 6 months in ALTITUDE, slightly less so in the aliskiren arm, but this is an unusual finding in studies using anti-hypertensive agents. Both of these observations require further analysis and explanation but may have mitigated any potential for benefit.
"Reduction in albuminuria has been associated with better cardiorenal outcome in observational and post hoc analyses. ALTITUDE underlines the critical importance of suitably powered trials with hard clinical end points in informing evidence-based treatments for our patients. This large trial, taken together with others, means that combination blockade of the RAS should not be used in people with diabetes."
This concludes today's commentary from Rudy Bilous for the F1000 Practice-Changing Minute. I am Bret Stetka. Thank you for listening.
Hello. I'm Bret Stetka, Editorial Director at Medscape. Welcome to the F1000 Practice-Changing Minute, where we report commentaries from the Faculty of 1000 on highly rated studies. Our commentary today covers the study "Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes," from HH Parving and colleagues, published in the New England Journal of Medicine. The F1000 commentator has given this a ranking of Changes Clinical Practice, with the conclusion that dual blockade of the renin-angiotensin system with aliskiren should no longer be used in people with type 2 diabetes and chronic kidney disease (CKD). The following F1000 commentary on this study was written by Rudy Bilous, MD, FRCP, from James Cook University Hospital, Middlesbrough, United Kingdom.
In his commentary on this study, Dr. Bilous wrote:
"The Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE) study has finally been published after early discontinuation in December 2011. Despite a reduction in albuminuria of 14%, the addition of the renin antagonist aliskiren to conventional renin-angiotensin system (RAS) blockade using either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) in a randomized controlled trial (RCT) to 8561 type 2 diabetic subjects with increased albuminuria or a history of cardiovascular disease or both showed no clinical benefit on cardiorenal end points over a mean follow-up of 32.9 months. In fact, patients did worse on active therapy with a 10% absolute increase in hyperkalaemia >5 mmol/L.
"The rationale for ALTITUDE was the much shorter AVOID trial, where aliskiren was added to losartan in 599 people with type 2 diabetes and increased albuminuria >300 mg/g creatinine. In AVOID, a 20% reduction in albuminuria was observed after 6 months, much greater than in ALTITUDE and perhaps a reflection of their more advanced nephropathy. Intriguingly, blood pressure rose at 6 months in ALTITUDE, slightly less so in the aliskiren arm, but this is an unusual finding in studies using anti-hypertensive agents. Both of these observations require further analysis and explanation but may have mitigated any potential for benefit.
"Reduction in albuminuria has been associated with better cardiorenal outcome in observational and post hoc analyses. ALTITUDE underlines the critical importance of suitably powered trials with hard clinical end points in informing evidence-based treatments for our patients. This large trial, taken together with others, means that combination blockade of the RAS should not be used in people with diabetes."
This concludes today's commentary from Rudy Bilous for the F1000 Practice-Changing Minute. I am Bret Stetka. Thank you for listening.
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