Cardiovascular risk reduction in CKD patients: let's get SHARP!
While many have generally felt that extending the standards of practice for the general population to the CKD population is not harmful--and the CSN has, in fact, endorsed this approach in their Clinical Practice Guidelines for CKD (Levin et al., 2008)--many have been uncertain about the benefits given the lack of evidence in the literature. Despite the fact that the 4D and Aurora trial results were negative, there were promising small improvements in cardiac events and MI that were intriguing to researchers. This led to the design of the Study of Heart and Renal Protection (SHARP)--the results of which were first revealed at the American Society of Nephrology meeting in October of last year. The SHARP trial results were met with enthusiasm--this was the first trial to demonstrate a clear and safe benefit from the use of lipid-lowering agents in CKD patients (Baigent et al., 2011).
The SHARP study objective was to assess the safety and efficacy of lowering LDL cholesterol using a combination of ezetimibe and simvastatin daily in men or women aged 40 years or over without known heart disease and with CKD. This was a randomized, double-blind trial including more than 9,000 patients; 3,000 on dialysis (PD or hemodialysis) and 6,000 not on dialysis. The participants had no known history of MI or coronary intervention (e.g., angioplasty). After agreeing to participate, patients were randomized to receive either a combination of ezitimibe 10 mg and simvastatin 20 mg per day, or to receive a placebo. Observation during the study period consisted of routine follow-up appointments and blood safety monitoring at two, six, and 12 months, and then every six months for at least four years. The study was double-blind; neither patient nor clinicians knew what group the patient was in and whether or not they were receiving the real drug or the placebo. From a research perspective, this is an important point. This type of trial prevents the potential for contamination of the data through the removal of unintentional bias.
The results reported that 9,270 patients were randomized, with 4,650 patients receiving active treatment and 4,620 patients receiving placebos. All variables among groups were similar, which strengthens the findings (this way, the researchers have convinced us that we are comparing two similar groups of people and, therefore, the findings cannot be attributed to a difference in one group's characteristics). An in-depth review of the findings along with statistical analysis is beyond the scope of this article. However, nephrology nurses should be aware of the following study outcomes reported in the literature:
* there was no increase in risk of myopathy, liver and biliary disorders, cancer or nonvascular mortality
* there was no substantial effect on kidney disease progression (this confirms the safety profile of the medications)
* two-thirds compliance with the combination of simvastatin and ezitamibe reduced the risk of major atherosclerotic events by 17%
* full compliance with the simvastatin/ezitamibe combination would reduce the risk of major atherosclerotic events by one quarter, or 30 to 40 events per 1,000 patients treated over a five-year period (this confirms the efficacy of the medications).
One-quarter reduction in risk of major atherosclerotic events is a meaningful change. This suggests that widespread use of LDL-lowering agents in CKD patients would have a substantial impact on cardiovascular disease complications. From a "What's in it for me?" point of view, this is an important study that has answered questions for nephrology teams with respect to the use of lipid-lowering agents in patients with CKD. Dr. Adeera Levin from Vancouver, B.C., one of the trial investigators, has commented that "The [SHARP trial] results should change practice, by providing a clear answer to physicians, who have 'been all over the map ...' variability in practice was huge, and there was a lot of misunderstanding. Everyone worried these drugs might be unsafe [in chronic kidney disease patients] and that they didn't work. Now what SHARP says is, these drugs are safe and they work" (Canadian Heart Research Centre, n.d.).
More importantly, as nephrology nurses, awareness of the impact of this trial to your clinical practice will be of benefit to your patients. Discuss these findings amongst your teams at rounds or medication reviews. Ask your physician or NP colleagues about the impact of these findings on practice in your clinics or dialysis programs. Is this evidence leading to a change in prescribing practice? Is there an opportunity to discuss individual cases in your programs to determine if protocol changes are needed? Has your patient now been prescribed simvastatin and ezitimibe? If so, perhaps you can support them with education as to the rationale for this change.
Want to know more about the SHARP trial? Check out the website at http://www.ctsu.ox.ac.uk/~sharp/
Baigent, C., Landray, M.J., Reith, C., Emberson, J., Wheeler, D.C., et al. (2011). The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): A randomized placebo-controlled trial. The Lancet, 377(9784), 2181-2192.
Canadian Heart Research Centre. (n.d.). SHARP Trial Investigator, Dr. Adeera Levin comments to The Heart.org.
Retrieved from http://www.chrc.net/LDLINCKD/comments.html
Collins, R., Armitage, J., Parish, S., Sleight, P., & Peto, R. (2002). MRC/BHF Heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebocontrolled trial. The Lancet, 360(9326), 7-22.
Fellstrom, B., Jardine, A., Schmieder, R., & the AURORA Study Group. (2009). Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. New England Journal of Medicine, 360, 1395-1407.
Levin, A., Hemmelgarn, B., Culleton, B., et al. (2008). Guidelines for the management of chronic kidney disease. Canadian Medical Association Journal, 179(11), 1154-1162.
Tonelli, M., Isles, C., Curhan, G., et al. (2004). Effect of pravastatin on cardiovascular events in people with chronic kidney disease. Circulation, 110, 1557-1563.
Wanner, C., Krane, V., Marz, W., et al., & the German Diabetes and Dialysis Study Investigators. (2005). Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. New England Journal of Medicine, 353, 238-248.
By Alison Thomas, RN(EC), MN, CNeph(C)
Alison Thomas, RN(EC), MN, CNeph(C), Nurse Practitioner, Hemodialysis, St. Michael's Hospital, Toronto, ON.
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|Title Annotation:||chronic kidney disease, Study of Heart and Renal Protection; Research review|
|Date:||Jul 1, 2011|
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