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The SHARP trial: Lessons learnt; answers and more questions!
International Journal of Cardiology 156 (2012) e6
Contents lists available at ScienceDirect
International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d
Letter to the Editor
The SHARP trial: Lessons learnt; answers and more questions! Mohit Turagam a,⁎, Poonam Velagapudi b, 1 a b
Department of Medicine, University of Wisconsin School of Medicine and Public Health, 3116 MFCB, 1685 Highland Avenue, Madison, WI 53705, United States Division of Medicine, University of Illinois College of Medicine Urbana Champaign, 611 W Park St, Urbana, IL-61801, United States
a r t i c l e
i n f o
Article history: Received 22 July 2011 Accepted 25 July 2011 Available online 16 August 2011 Keywords: SHARP Chronic kidney disease Lipid lowering therapy
To the Editor, The key question in the SHARP trial was does lipid lowering therapy in chronic kidney disease (CKD) reduce the risk of atherosclerotic and vascular events and there is no doubt that the trial clearly does. Simvastatin plus ezetimibe was associated with an average 0·85 mmol/L reduction in LDL cholesterol and a 17% reduction in major atherosclerotic events (ratio 0·83, 95% CI 0·74– 0·94, p = 0.0021) [1]. Unlike previous trials in patients receiving dialysis, AURORA [2] and 4D [3] showed no benefit from statins on a composite cardiovascular endpoint. As it is well known dialysis patients usually suffer sudden cardiac death (heart failure and arrhythmias), unlike non-dialysis CKD patients who are at an increased likelihood of having an atherosclerotic/vascular event.
⁎ Corresponding author. Tel.: + 1 608 262 2434. E-mail addresses: [email protected] (M. Turagam), [email protected] (P. Velagapudi). 1 Tel.: + 1 217 383 4613. 0167-5273/$ – see front matter. Published by Elsevier Ireland Ltd. doi:10.1016/j.ijcard.2011.07.057
Hence, these previous studies were underpowered to answer that question. SHARP investigators smartly enrolled a wide spectrum of CKD patients both on and off dialysis and looked at events in systematic manner learning from past experiences. Secondly, the added benefit of ezetimibe to statin is debatable as the amount of LDL lowering seen in SHARP and the reduction in events it produced were similar to that seen for other trials that have used statins alone. Ezetimibe cancer findings are also an issue of debate and the SHARP study was not powered or designed to answer this question. To understand the role of ezetimibe, SHARP would also have needed a statin-only arm but then the required study sample would have been tripled or even quadrupled. It would be interesting to see a study on using statin monotherapy and statin/ezetimibe combination therapy in CKD patients' in the future to reveal more answers. All the authors have approved for the manuscript and have no conflict of interest to declare.
References [1] Baigent C, Landray MJ, Reith C, et al; and for the SHARP investigators. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebocontrolled trial. Lancet 2011, doi:10.1016/S0140-6736(11)60739-3 published online June 9. [2] Fellström BC, Jardine AG, Schmieder RE, et al; and for the AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009;360:1395–407. [3] Wanner C, Krane V, März W, et al; and for the German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;353:238–48.
Contents lists available at ScienceDirect
International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d
Letter to the Editor
The SHARP trial: Lessons learnt; answers and more questions! Mohit Turagam a,⁎, Poonam Velagapudi b, 1 a b
Department of Medicine, University of Wisconsin School of Medicine and Public Health, 3116 MFCB, 1685 Highland Avenue, Madison, WI 53705, United States Division of Medicine, University of Illinois College of Medicine Urbana Champaign, 611 W Park St, Urbana, IL-61801, United States
a r t i c l e
i n f o
Article history: Received 22 July 2011 Accepted 25 July 2011 Available online 16 August 2011 Keywords: SHARP Chronic kidney disease Lipid lowering therapy
To the Editor, The key question in the SHARP trial was does lipid lowering therapy in chronic kidney disease (CKD) reduce the risk of atherosclerotic and vascular events and there is no doubt that the trial clearly does. Simvastatin plus ezetimibe was associated with an average 0·85 mmol/L reduction in LDL cholesterol and a 17% reduction in major atherosclerotic events (ratio 0·83, 95% CI 0·74– 0·94, p = 0.0021) [1]. Unlike previous trials in patients receiving dialysis, AURORA [2] and 4D [3] showed no benefit from statins on a composite cardiovascular endpoint. As it is well known dialysis patients usually suffer sudden cardiac death (heart failure and arrhythmias), unlike non-dialysis CKD patients who are at an increased likelihood of having an atherosclerotic/vascular event.
⁎ Corresponding author. Tel.: + 1 608 262 2434. E-mail addresses: [email protected] (M. Turagam), [email protected] (P. Velagapudi). 1 Tel.: + 1 217 383 4613. 0167-5273/$ – see front matter. Published by Elsevier Ireland Ltd. doi:10.1016/j.ijcard.2011.07.057
Hence, these previous studies were underpowered to answer that question. SHARP investigators smartly enrolled a wide spectrum of CKD patients both on and off dialysis and looked at events in systematic manner learning from past experiences. Secondly, the added benefit of ezetimibe to statin is debatable as the amount of LDL lowering seen in SHARP and the reduction in events it produced were similar to that seen for other trials that have used statins alone. Ezetimibe cancer findings are also an issue of debate and the SHARP study was not powered or designed to answer this question. To understand the role of ezetimibe, SHARP would also have needed a statin-only arm but then the required study sample would have been tripled or even quadrupled. It would be interesting to see a study on using statin monotherapy and statin/ezetimibe combination therapy in CKD patients' in the future to reveal more answers. All the authors have approved for the manuscript and have no conflict of interest to declare.
References [1] Baigent C, Landray MJ, Reith C, et al; and for the SHARP investigators. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebocontrolled trial. Lancet 2011, doi:10.1016/S0140-6736(11)60739-3 published online June 9. [2] Fellström BC, Jardine AG, Schmieder RE, et al; and for the AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009;360:1395–407. [3] Wanner C, Krane V, März W, et al; and for the German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;353:238–48.