By Angela Chu, PharmD, BCPS, and Martin S. Lipsky, MD
Dr. Chu is Assistant Professor of Pharmacy Practice, College of Pharmacy, Roseman University of Health Sciences, South Jordan, UT. Dr. Lipsky is Chancellor, South Jordan Campus, Roseman University of Health Sciences, South Jordan, UT.
Drs. Chu and Lipsky report no financial relationships relevant to this field of study.
SYNOPSIS: For patients at risk of or who already have been diagnosed with cardiovascular disease and are taking atorvastatin, an added benefit is improved kidney function in a dose-dependent manner.
SOURCE: Vogt L, Bangalore S, Fayyad R, et al. Atorvastatin has a dose-dependent beneficial effect on kidney function and associated cardiovascular outcomes: Post hoc analysis of 6 double-blind randomized controlled trials. J Am Heart Assoc 2019;8:1-9.
Data from six randomized, controlled trials evaluating patients on atorvastatin for cardiovascular outcomes were pooled and analyzed in this post hoc analysis. Participants were included if they had follow up data of ≥ 12 months; were older than 18 years of age; had more than two serum creatinine values documented; and were assigned to a fixed dose of either placebo, atorvastatin 10 mg, or atorvastatin 80 mg in their respective studies. Patients with known primary renal disease, including end-stage renal disease, were excluded. Participant data were collected from the ASCOT, CARDS, ASPEN, SPARCL, TNT, and SAGE trials.1-6 A total of 10,057 placebo group patients, 12,763 atorvastatin 10 mg patients, and 7,801 atorvastatin 80 mg patients were studied. From the reciprocal of serum creatinine levels, a slope of kidney function line was calculated and used to evaluate primary and secondary outcomes. This slope linearly correlates to glomerular filtration rates (GFR).
The primary outcome was kidney function decline over time, with slopes of reciprocal serum creatinine (standard deviations) of 0.009 (0.0008), 0.011 (0.0006), and 0.014 (0.0006) mg/dL-1/year for placebo patients, atorvastatin 10 mg patients, and atorvastatin 80 mg patients, respectively (P < 0.0001), across all groups. One study that included atorvastatin 10 mg vs. 80 mg showed similar dose-dependent renal improvement of 0.012 (0.0007) vs. 0.015 (0.0007) mg/dL-1/year, respectively (P = 0.0009).5 Vogt et al showed that kidney function improves over time, with the greatest improvement seen with a dose of atorvastatin 80 mg.
The secondary outcome was the effect of kidney function on major cardiovascular events, cardiovascular deaths, and all-cause mortality. This study showed statistically significant protective benefits in all secondary outcomes across all three arms. When adjusted for the study, sex, age, body mass index, low-density lipoprotein value, blood pressure, use of concurrent renin-angiotensin-aldosterone system inhibitors, aspirin or diuretics, and history of cardiovascular disease, a protective effect was found in both atorvastatin groups in major cardiovascular events (P < 0.0001), cardiovascular death (hazard ratio [HR], 0.92; P = 0.0367 in atorvastatin 10 mg and HR, 0.87; P = 0.0448 in atorvastatin 80 mg) and all-cause mortality (HR, 0.88; P < 0.0044 in atorvastatin 80 mg). Vogt et al showed that improved renal function is associated with improved cardiovascular outcomes, with the greatest benefit seen with atorvastatin 80 mg.
Statins are among the most commonly used class of medications, and atorvastatin is one of the most frequently prescribed statins.7 Studies indicate that statins reduce the risk of heart attack, stroke, and death from heart disease by about 25% to 35%.
Recognizing the link between kidney function and cardiovascular disease,8 Vogt et al speculated whether atorvastatin also might affect kidney function decline. They found that in patients with or at risk of cardiovascular disease, atorvastatin improved kidney function in a dose-dependent manner over time. Even though guidelines differ for treating hyperlipidemia, research suggests that despite the known benefits of statins, there is a significant gap between patients on statins and patients who should be on statins.9,10 For patients who receive a statin, there also is an inconsistency in intensity of statin prescribed (i.e., patients who are clinically indicated for high-intensity therapy often receive low-intensity therapy).10 The findings by Vogt et al reveal an additional benefit on kidney function from atorvastatin. Further, it appears high-intensity treatment yields additional benefit over lower-intensity therapy. These findings provide additional motivation for primary care physicians to be more aggressive about adhering to recommendations for statin use. A question that often arises in the minds of primary care physicians is: Are all statins created equal? In the case of kidney function, they may not be. A study comparing the effects of atorvastatin and rosuvastatin on kidney function decline among patients with diabetes revealed that rosuvastatin was associated with a more rapid decline in kidney function.11 Another study demonstrated that while simvastatin was associated with a decrease in proteinuria, it did not demonstrate a renoprotective effect on GFR.12 However, this study used mild- to moderate-intensity simvastatin, and it is possible higher-intensity simvastatin therapy might yield a renoprotective effect. Vogt et al noted that the beneficial effects of atorvastatin in their study may not be applicable to all statins. Undoubtedly, as more researchers explore the effects of statins on kidney function, new data will direct the primary care physician about how to optimize statin therapy to help preserve kidney function.
- Sever PS, Dahlöf B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm (ASCOT-LLA): A multicentre randomised controlled trial. Lancet 2003;361:1149-1158.
- Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): Multicentre randomised placebo-controlled trial. Lancet 2004;364:685-696.
- Knopp RH, d’Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: The Atorvastatin Study for the Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care 2006;29:1478-1485.
- Amarenco P, Bogousslavsky J, Callahan A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549-559.
- LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425-1435.
- Deedwania P, Stone PH, Bairey Merz CN, et al. Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: Results of the Study Assessing Goals in the Elderly (SAGE). Circulation 2007;115:700-707.
- GoodRx. The GoodRx Top 10, July 2019. Available at: . Accessed Aug. 26, 2019.
- Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and risks of death, cardiovascular events and hospitalizations. N Engl J Med 2004;351:1296-1305.
- Chen G, Farris MS, Cowling T, et al. Treatment with low-density cholesterol management in patients diagnosed with clinical atherosclerotic cardiovascular disease in Alberta. Can J Cardiol 2019;35:884-891.
- Johansen ME, Green LA, Sen A, et al. Cardiovascular risk and statin use in the United States. Ann Fam Med 2014;12:215-223.
- Han E, Kim G, Lee JY, et al. Comparison between atorvastatin and rosuvastatin in renal function decline among patients with diabetes. Endocrinol Metab (Seoul) 2017;32:274-280.
- Satirapoj B, Promrattanakun A, Supasyndh O, Choovichian P. The effects of simvastatin on proteinuria and renal function in patients with chronic kidney disease. Int J Nehprol 2015;2015:485839.