Statin Use

Q: I have a dialysis patient whose cholesterol numbers were getting quite high. I gave him a prescription for a lipid-lowering medication. He brought the prescription back, saying the nephrology AP told him it would make no difference since he was a dialysis patient. Is this true? 

This is an excellent question that has been researched and debated over the past 10 years. Cardiovascular disease is the leading cause of death in patients with CKD and those in the dialysis population. So intuitively, it makes sense in these patients to control cholesterol—one of the main risk factors for cardiovascular disease. However, the research that has been done to date contradicts that hypothesis in dialysis patients.⁹

With a 2002 observational study, Iseki et al¹⁰ became the first researchers to document that cholesterol levels are inversely related to mortality in patients undergoing dialysis. However, this study team did not adjust for inflammation or infection—which, in addition to malnutrition, reduce HDL and LDL levels (and increase mortality).¹⁰

The goal of the Deutsche Diabetes and Dialysis (4D) trial,¹¹ funded by a pharmaceutical company and involving 1,255 subjects, was to demonstrate the benefits of atorvastatin use in diabetic patients on dialysis. Although the agent was shown to improve patients’ lipid parameters, no statistically significant effect was found on the primary endpoints: all-cause mortality and cardiovascular and cerebrovascular events. In fact, the incidence of fatal stroke was significantly higher in the atorvastatin-treated patients, compared with those taking placebo.¹¹

In the Evaluation of the Use of Rosuvastatin in Subjects on Regular Hemodialysis (AURORA) study,¹² in which 2,776 patients were enrolled, the primary endpoint was time to major cardiovascular events (including fatal and nonfatal MI and stroke). No statistically significant changes were reported in mortality or primary or secondary endpoints in either treatment arm. However, the AURORA study did demonstrate an increased risk for fatal hemorrhagic stroke in the treatment arm.¹²

Most recently, in the seven-year-long Study of Heart and Renal Protection (SHARP),¹³ researchers investigated the benefits of cholesterol-lowering therapy, enrolling 9,270 patients with CKD and 3,023 patients undergoing dialysis. In the treatment arm of the CKD group (ie, those receiving simvastatin plus ezetimibe), a 17% reduction was reported in major atherosclerotic events. In the dialysis patients randomized to receive treatment, however, no significant reduction was found in mortality rates or cardiovascular events, compared with patients taking placebo.¹³

Thus, no cardioprotective benefit has yet been reported for statin use in patients receiving dialysis. In fact, these agents may increase patients’ risk for stroke. They surely increase the pill burden and treatment costs for dialysis patients. As for patients with CKD, a number of studies (including the SHARP study¹³) have demonstrated a benefit in statin use for primary prevention of cardiovascular events.

Susan Busch, MSN, CNP, Cleveland Clinic; Family NP Program
Kent State University, Ohio

For see next page for references... 

REFERENCES
1. CDC. 2011 National Diabetes Fact Sheet. www.cdc.gov/diabetes/pubs/estimates11.htm. Accessed May 23, 2012.

2. US Renal Data System, National Institute of Diabetes and Kidney Disease, NIH. 2010 Annual Data Report, vol II: Atlas of End-Stage Renal Disease in the United States. www.usrds.org/2010/pdf/v2_00a_intros.pdf. Accessed May 23, 2012.

3. Cowie CC, Port FK, Wolfe RA, et al. Disparities in incidence of diabetic end-stage renal disease according to race and type of diabetes. N Engl J Med. 1989;312(16):1074-1079.

4. Vora JP, Ibrahim HAA. Clinical manifestations and natural history of diabetic nephropathy. In: Johnson R, Feehally J, eds. Comprehensive Clinical Nephrology. Philadelphia, PA: Mosby; 2003:425-438.

5. Packham DK, Alves TP, Dwyer JP, et al. Relative incidence of ESRD versus cardiovascular mortality in proteinuric type 2 diabetes and nephropathy: results from the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database. Am J Kidney Dis. 2012;59(1):75-83.

6. Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification and stratification. Ann Intern Med. 2003;139(2):137-147.

7. Tangri N, Stevens LA, Griffith J, et al. A predictive model for progression of chronic kidney disease to kidney failure. JAMA. 2011;305(15):1553-1559.

8. Prochaska JO, Velicer WF, Rossi JS, et al. Stages of change and decisional balance for 12 problem behaviors. Health Psychol. 1994;13(1):39-46.

9. Olyaei A, Lerma EV. Three strikes and statins out: a case against use of statins in dialysis patients for primary prevention. Dialysis Transplant. 2011;40(4):148-151.

10. Iseki K, Yamazato M, Tozawa M, Takishita S. Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int. 2002;61(5):1887-1893.

11. Wanner C, Krane V, März W, et al; German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353(3):238-248.

12. Fellström BC, Jardine AG, Schmeider RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009; 360(14):1395-1407.

13. SHARP Collaborative Group. Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease. Am Heart J. 2010;160(5):785-794.

Q: I have a dialysis patient whose cholesterol numbers were getting quite high. I gave him a prescription for a lipid-lowering medication. He brought the prescription back, saying the nephrology AP told him it would make no difference since he was a dialysis patient. Is this true? 

This is an excellent question that has been researched and debated over the past 10 years. Cardiovascular disease is the leading cause of death in patients with CKD and those in the dialysis population. So intuitively, it makes sense in these patients to control cholesterol—one of the main risk factors for cardiovascular disease. However, the research that has been done to date contradicts that hypothesis in dialysis patients.⁹

With a 2002 observational study, Iseki et al¹⁰ became the first researchers to document that cholesterol levels are inversely related to mortality in patients undergoing dialysis. However, this study team did not adjust for inflammation or infection—which, in addition to malnutrition, reduce HDL and LDL levels (and increase mortality).¹⁰

The goal of the Deutsche Diabetes and Dialysis (4D) trial,¹¹ funded by a pharmaceutical company and involving 1,255 subjects, was to demonstrate the benefits of atorvastatin use in diabetic patients on dialysis. Although the agent was shown to improve patients’ lipid parameters, no statistically significant effect was found on the primary endpoints: all-cause mortality and cardiovascular and cerebrovascular events. In fact, the incidence of fatal stroke was significantly higher in the atorvastatin-treated patients, compared with those taking placebo.¹¹

In the Evaluation of the Use of Rosuvastatin in Subjects on Regular Hemodialysis (AURORA) study,¹² in which 2,776 patients were enrolled, the primary endpoint was time to major cardiovascular events (including fatal and nonfatal MI and stroke). No statistically significant changes were reported in mortality or primary or secondary endpoints in either treatment arm. However, the AURORA study did demonstrate an increased risk for fatal hemorrhagic stroke in the treatment arm.¹²

Most recently, in the seven-year-long Study of Heart and Renal Protection (SHARP),¹³ researchers investigated the benefits of cholesterol-lowering therapy, enrolling 9,270 patients with CKD and 3,023 patients undergoing dialysis. In the treatment arm of the CKD group (ie, those receiving simvastatin plus ezetimibe), a 17% reduction was reported in major atherosclerotic events. In the dialysis patients randomized to receive treatment, however, no significant reduction was found in mortality rates or cardiovascular events, compared with patients taking placebo.¹³

Thus, no cardioprotective benefit has yet been reported for statin use in patients receiving dialysis. In fact, these agents may increase patients’ risk for stroke. They surely increase the pill burden and treatment costs for dialysis patients. As for patients with CKD, a number of studies (including the SHARP study¹³) have demonstrated a benefit in statin use for primary prevention of cardiovascular events.

Susan Busch, MSN, CNP, Cleveland Clinic; Family NP Program
Kent State University, Ohio

For see next page for references... 

REFERENCES
1. CDC. 2011 National Diabetes Fact Sheet. www.cdc.gov/diabetes/pubs/estimates11.htm. Accessed May 23, 2012.

2. US Renal Data System, National Institute of Diabetes and Kidney Disease, NIH. 2010 Annual Data Report, vol II: Atlas of End-Stage Renal Disease in the United States. www.usrds.org/2010/pdf/v2_00a_intros.pdf. Accessed May 23, 2012.

3. Cowie CC, Port FK, Wolfe RA, et al. Disparities in incidence of diabetic end-stage renal disease according to race and type of diabetes. N Engl J Med. 1989;312(16):1074-1079.

4. Vora JP, Ibrahim HAA. Clinical manifestations and natural history of diabetic nephropathy. In: Johnson R, Feehally J, eds. Comprehensive Clinical Nephrology. Philadelphia, PA: Mosby; 2003:425-438.

5. Packham DK, Alves TP, Dwyer JP, et al. Relative incidence of ESRD versus cardiovascular mortality in proteinuric type 2 diabetes and nephropathy: results from the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database. Am J Kidney Dis. 2012;59(1):75-83.

6. Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification and stratification. Ann Intern Med. 2003;139(2):137-147.

7. Tangri N, Stevens LA, Griffith J, et al. A predictive model for progression of chronic kidney disease to kidney failure. JAMA. 2011;305(15):1553-1559.

8. Prochaska JO, Velicer WF, Rossi JS, et al. Stages of change and decisional balance for 12 problem behaviors. Health Psychol. 1994;13(1):39-46.

9. Olyaei A, Lerma EV. Three strikes and statins out: a case against use of statins in dialysis patients for primary prevention. Dialysis Transplant. 2011;40(4):148-151.

10. Iseki K, Yamazato M, Tozawa M, Takishita S. Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int. 2002;61(5):1887-1893.

11. Wanner C, Krane V, März W, et al; German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353(3):238-248.

12. Fellström BC, Jardine AG, Schmeider RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009; 360(14):1395-1407.

13. SHARP Collaborative Group. Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease. Am Heart J. 2010;160(5):785-794.

Q: I have a dialysis patient whose cholesterol numbers were getting quite high. I gave him a prescription for a lipid-lowering medication. He brought the prescription back, saying the nephrology AP told him it would make no difference since he was a dialysis patient. Is this true? 

This is an excellent question that has been researched and debated over the past 10 years. Cardiovascular disease is the leading cause of death in patients with CKD and those in the dialysis population. So intuitively, it makes sense in these patients to control cholesterol—one of the main risk factors for cardiovascular disease. However, the research that has been done to date contradicts that hypothesis in dialysis patients.⁹

With a 2002 observational study, Iseki et al¹⁰ became the first researchers to document that cholesterol levels are inversely related to mortality in patients undergoing dialysis. However, this study team did not adjust for inflammation or infection—which, in addition to malnutrition, reduce HDL and LDL levels (and increase mortality).¹⁰

The goal of the Deutsche Diabetes and Dialysis (4D) trial,¹¹ funded by a pharmaceutical company and involving 1,255 subjects, was to demonstrate the benefits of atorvastatin use in diabetic patients on dialysis. Although the agent was shown to improve patients’ lipid parameters, no statistically significant effect was found on the primary endpoints: all-cause mortality and cardiovascular and cerebrovascular events. In fact, the incidence of fatal stroke was significantly higher in the atorvastatin-treated patients, compared with those taking placebo.¹¹

In the Evaluation of the Use of Rosuvastatin in Subjects on Regular Hemodialysis (AURORA) study,¹² in which 2,776 patients were enrolled, the primary endpoint was time to major cardiovascular events (including fatal and nonfatal MI and stroke). No statistically significant changes were reported in mortality or primary or secondary endpoints in either treatment arm. However, the AURORA study did demonstrate an increased risk for fatal hemorrhagic stroke in the treatment arm.¹²

Most recently, in the seven-year-long Study of Heart and Renal Protection (SHARP),¹³ researchers investigated the benefits of cholesterol-lowering therapy, enrolling 9,270 patients with CKD and 3,023 patients undergoing dialysis. In the treatment arm of the CKD group (ie, those receiving simvastatin plus ezetimibe), a 17% reduction was reported in major atherosclerotic events. In the dialysis patients randomized to receive treatment, however, no significant reduction was found in mortality rates or cardiovascular events, compared with patients taking placebo.¹³

Thus, no cardioprotective benefit has yet been reported for statin use in patients receiving dialysis. In fact, these agents may increase patients’ risk for stroke. They surely increase the pill burden and treatment costs for dialysis patients. As for patients with CKD, a number of studies (including the SHARP study¹³) have demonstrated a benefit in statin use for primary prevention of cardiovascular events.

Susan Busch, MSN, CNP, Cleveland Clinic; Family NP Program
Kent State University, Ohio

For see next page for references... 

REFERENCES
1. CDC. 2011 National Diabetes Fact Sheet. www.cdc.gov/diabetes/pubs/estimates11.htm. Accessed May 23, 2012.

2. US Renal Data System, National Institute of Diabetes and Kidney Disease, NIH. 2010 Annual Data Report, vol II: Atlas of End-Stage Renal Disease in the United States. www.usrds.org/2010/pdf/v2_00a_intros.pdf. Accessed May 23, 2012.

3. Cowie CC, Port FK, Wolfe RA, et al. Disparities in incidence of diabetic end-stage renal disease according to race and type of diabetes. N Engl J Med. 1989;312(16):1074-1079.

4. Vora JP, Ibrahim HAA. Clinical manifestations and natural history of diabetic nephropathy. In: Johnson R, Feehally J, eds. Comprehensive Clinical Nephrology. Philadelphia, PA: Mosby; 2003:425-438.

5. Packham DK, Alves TP, Dwyer JP, et al. Relative incidence of ESRD versus cardiovascular mortality in proteinuric type 2 diabetes and nephropathy: results from the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database. Am J Kidney Dis. 2012;59(1):75-83.

6. Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification and stratification. Ann Intern Med. 2003;139(2):137-147.

7. Tangri N, Stevens LA, Griffith J, et al. A predictive model for progression of chronic kidney disease to kidney failure. JAMA. 2011;305(15):1553-1559.

8. Prochaska JO, Velicer WF, Rossi JS, et al. Stages of change and decisional balance for 12 problem behaviors. Health Psychol. 1994;13(1):39-46.

9. Olyaei A, Lerma EV. Three strikes and statins out: a case against use of statins in dialysis patients for primary prevention. Dialysis Transplant. 2011;40(4):148-151.

10. Iseki K, Yamazato M, Tozawa M, Takishita S. Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int. 2002;61(5):1887-1893.

11. Wanner C, Krane V, März W, et al; German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353(3):238-248.

12. Fellström BC, Jardine AG, Schmeider RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009; 360(14):1395-1407.

13. SHARP Collaborative Group. Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease. Am Heart J. 2010;160(5):785-794.