Specific low-density lipoprotein (LDL) cholesterol treatment targets were removed from guidelines on managing lipids in patients with chronic kidney disease (CKD) released by Kidney Disease: Improving Global Outcomes (KDIGO) in November (2013). Instead, the decision to initiate cholesterol-lowering treatment, specifically statin therapy, should be based on the absolute risk of coronary events, and evidence that a therapy will help lower that risk, Marcello Tonelli, MD, of the University of Alberta in Edmonton, and Christoph Wanner, MD, of the University Hospital of Würzburg in Germany wrote in a synopsis of the guidelines published online Monday in Annals of Internal Medicine. They served as co-chairs of KDIGO’s lipid guideline development work group. The change in approach mirrors that advocated in the prevention guidelines released in November (2013) by the American Heart Association (AHA) and American College of Cardiology (ACC), which sparked controversy surrounding the number of people recommended for statin therapy and the accuracy of a new risk calculator. “Previous studies convincingly demonstrated that the prevalence of statin use among persons with CKD who were at risk for cardiovascular events was lower than among otherwise similar persons with normal kidney function,” Tonelli and Wanner wrote. “We are optimistic that the current guideline will help to close this quality gap by emphasizing the high cardiovascular risk associated with CKD (regardless of LDL cholesterol levels) while also reducing complexity for practitioners and enhancing implementation.”
The new guidelines “provide a roadmap of simplicity for healthcare professionals to mitigate cardiovascular risk in their patients affected by renal disorders,” commented Catherine Staffeld-Coit, MD, of Ochsner Medical Center in New Orleans, who added that they will “most likely be controversial.” “Persons with renal disease are already on numerous medications and are at increased risk of drug-drug interactions. Patients often complain about their current pill burden and cost of medicines, and this will only add to it. The best strategy will be education of patients and providers to understand why taking more medicine will benefit them.”
LDL Insufficient for Determining Risk
Tonelli and Wanner, who provided a summary for general internists of eight of the 13 recommendations from the full KDIGO guidelines, noted that LDL cholesterol levels are not sufficient for determining coronary risk in patients with CKD.
“Although higher levels of LDL cholesterol are associated with higher risk, dialysis patients with the lowest levels of LDL cholesterol and total cholesterol are also at very high risk for all-cause and cardiovascular mortality, likely because of confounding by inflammation and malnutrition,” they wrote. “Among persons with non-dialysis-dependent CKD, the magnitude of the excess risk associated with increased LDL cholesterol levels decreases at lower eGFRs [estimated glomerular filtration rates].” “The weaker and potentially misleading association between LDL cholesterol and coronary risk among those with lower levels of kidney function (who are at the highest absolute risk for coronary events) argues against the use of LDL cholesterol for identifying CKD patients who should receive pharmacologic cholesterol-lowering treatment,” they wrote.
Anupam Agarwal, MD, of the University of Alabama at Birmingham, commented that the “guidelines highlight the limitations of LDL cholesterol as a marker of cardiovascular risk in CKD and draw caution for using changes in LDL cholesterol as a gauge for prescribing statins in patients with CKD.” The optimal risk threshold for initiating cholesterol-lowering treatment was unclear but “a 10-year risk for coronary death or nonfatal myocardial infarction (MI) that exceeds 10% is a reasonable working definition,” Tonelli and Wanner said, noting that any validated risk prediction tool can be used. “The 10-year risk for coronary death or nonfatal MI among CKD patients older than 50 years (both men and women) is consistently greater than 10%, even in those without diabetes or previous MI.” As for the type of cholesterol-lowering treatment that should be used in patients with CKD, the strongest randomized evidence supports the use of statins with or without ezetimibe (Zetia), according to the recommendations.
After a review of the most recent randomized trials that included patients with CKD, the authors crafted the following eight recommendations regarding the assessment of lipid status and the use of pharmacologic lipid-lowering therapy in adult patients:
- Adults with newly diagnosed CKD should be evaluated with a lipid profile.
- Most patients do not require follow-up measurements of lipid levels, with additional assessments performed only if they will alter management.
- Adults 50 and older who have an eGFR under 60 mL/min/1.73 m2 but who do not require chronic dialysis and have not had a kidney transplant should be treated with a statin with or without ezetimibe.
- Treatment with a statin is recommended in adults 50 and older with CKD who have an eGFR of 60 mL/min/1.73 m2 or higher.
- For adults younger than 50 who have CKD but who are not on chronic dialysis and have not had a kidney transplant, a statin should be used in patients with at least one of the following conditions: known coronary disease, diabetes, prior ischemic stroke, or an estimated 10-year risk of coronary death or myocardial infarction exceeding 10%.
- It is suggested that statins with or without ezetimibe should not be started in dialysis-dependent patients with CKD.
- Patients with CKD who are already taking a statin with or without ezetimibe and who need to start dialysis should continue their cholesterol-lowering treatment.
- Patients who have undergone a kidney transplant should use a statin.
The authors underscored patient preference in the decision about starting a statin throughout the guidance, however, similar to the patient-physician risk discussion pushed in the AHA/ACC guidelines. The KDIGO guidelines provide a table to help physicians select the appropriate statin and dose once the decision has been made to initiate treatment. “Given the potential for toxicity with higher doses of statins and the relative lack of data evaluating the safety of these regimens in advanced CKD, the work group suggests that prescription of statins in persons with eGFR less than 60 mL/min/1.73 m2 or renal replacement therapy should be based on regimens and doses that have been shown to be beneficial in randomized trials done specifically in this population,” Tonelli and Wanner wrote.
Commenting on the new guidance, Dave Dixon, PharmD, of Virginia Commonwealth University in Richmond stated “I applaud the effort to expand the appropriate use of statins in the CKD population, as this subgroup of patients is well known to be at high risk for cardiovascular disease, but often under treated.” He said he was concerned, however, about certain aspects of the guidance, including the move away from treating to specific LDL cholesterol goals.”I am concerned this type of dogmatic approach may lead clinicians to under treat patients with a high degree of residual risk,” he said. “I also disagree that there is no role for monitoring serum lipids as they will remain useful to monitor patient adherence and to look for under-responders who may require more intensive statin therapy.” Linda Hemphill, MD, of Massachusetts General Hospital in Boston, said “the focus on getting treatment with statins for more patients with this disorder is valuable,” but questioned the risk threshold suggested in the guidelines.
“The recent 2013 ACC/AHA Cholesterol Guideline recommends statin therapy for the general population over the age of 40 (not 50) who have a 10-year cardiovascular risk of over 7.5% (not 10%),” she pointed out. “Perhaps the best way for clinicians to respond is to use whichever guideline is the most aggressive for their patient who is sitting in front of them.”
According to Moro Salifu, MD, MPH, MBA, of SUNY Downstate Medical Center in Brooklyn, the guidelines are “a great start to make people aware of the serious cardiovascular disease burden in CKD patients and the need to treat them with a statin irrespective of the LDL cholesterol level.” Salifu said that cardiovascular disease is the reason that most patients with CKD die before reaching end-stage renal disease and either initiating dialysis or receiving a kidney transplant. “Therefore, every effort must be made to recognize this disparity and design interventions to reduce mortality in these patients,” he said. “The use of statins as described in the guidelines is an attempt to close this gap and is on target.”
Tip of the Day
A sweet treat for your bones. This week choose a dessert rich in calcium such as pudding made with fat-free or low-fat milk
“And when he had sent them away, he departed into a mountain to pray.’
~ Mark 6:46
Jesus was never too hurried to spend hours in prayer. He prayed before every difficult task confronting him. He prayed with regularity-not a day began or closed on which he did not unfold his soul before his father. Hever stop praying no matter how dark and hopeless your case may seem.