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DALLAS – High-potency statin therapy given post acute coronary syndrome did not raise serum creatinine or cause more risk of acute kidney injury than low-potency statin regimens did in a new analysis of two published landmark randomized clinical trials.
"Considering the recently updated AHA/American College of Cardiology lipid guidelines, which call for the use of high-potency statins in millions more patients, these findings provide important reassurance that a high-potency statin regimen will not increase the incidence of adverse renal events," Dr. Amy Sarma said in presenting the study results at the American Heart Association scientific sessions.
She noted that a recent Canadian observational study utilizing Canadian and U.S. administrative databases totaling more than 2 million patients over age 40 who were newly placed on statin therapy showed an adjusted 1.34-fold increased rate of hospitalization for acute kidney injury within the first 120 days in those on a high- as compared to a low-potency regimen, and a 1.11-fold increased risk beyond 120 days through the end of the first year (BMJ 2013;346:f880). Both risk elevations were statistically significant.
However, observational studies such as this are prone to bias in the form of potentially crucial differences between the patients given a prescription for statins and those who aren’t. For this reason, Dr. Sarma and her coinvestigators turned for guidance to two randomized trials of high- versus low-dose statins, since this study design obviates the risks of confounding. The trials were PROVE IT-TIMI 22 (N. Engl. J. Med. 2004;350:1495-504) and the A-to-Z trial (JAMA 2004;292:1307-16).
PROVE IT included 4,122 patients randomized within 10 days post ACS to standard background therapy plus either pravastatin at 40 mg/day or atorvastatin at 80 mg/day. A-to-Z involved 4,497 patients who were placed on simvastatin at either 20 or 80 mg/day within 5 days post ACS. Both trials had a median follow-up of 2 years, and both featured serial measurements of serum creatinine. Two-thirds of subjects in PROVE IT had a baseline estimated glomerular filtration rate below 90 mL/min per 1.73 m2, while two-thirds of those in A-to-Z had a baseline eGFR less than 60, noted Dr. Sarma of Brigham and Women’s Hospital, Boston.
In both studies, mean serum creatinine rose equally during the first 30 days of statin therapy, regardless of treatment potency, and then levels declined. In PROVE IT, for example, serum creatinine in the pravastatin and atorvastatin arms rose by 0.96% and 0.97% above baseline, respectively, at 30 days. Values then dropped by 2.88% and 3.85% from baseline at 4 months, and by 3.88% and 5.83% at 16 months.
In both studies, there was no difference between the high- and low-potency statin groups in the incidence of any increase in serum creatinine of at least 1.5-fold, 2.0-fold, or 3.0-fold greater than baseline. In other words, there was no hint of a safety signal, she added.
Dr. Sarma reported having no financial conflicts of interest.
I’m not convinced by the PROVE IT and A-to-Z data. In the combined analysis, the high-potency statin group had a 15% greater risk of acute kidney injury compared with the low-potency statin group during the first 4 months of treatment. Although that wasn’t a statistically significant difference due to limited patient numbers and broad confidence intervals, it was quite similar to the long-term 11% increased risk seen in the Canadian observational database study with 2 million patients.
Moreover, an even bigger recent observational study led by investigators at the University of North Carolina, Chapel Hill, involving 3.9 million U.S. statin initiators found a 42% greater rate of acute kidney injury during the first year on high- as compared to lower-dose simvastatin in commercially insured patients and a 24% increased risk in the Medicare population. Both risk increases were statistically significant due to the huge patient numbers (Pharmacoepidemiol. Drug Saf. 2013;22:1061-70).
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Also, PROVE IT and A-to-Z featured patient populations who were of a younger average age and less likely to be male and to have diabetes than the general American population of acute MI patients as depicted in the National Cardiovascular Data Registry (J. Am. Coll. Cardiol. 2013;62:1931-47). Advancing age, diabetes, and male gender are predisposing factors for acute kidney disease.
The Canadian observational study defined high-potency statin therapy as at least 20 mg/day of atorvastatin or 40 mg or simvastatin. The University of North Carolina study also defined high-potency simvastatin as at least 40 mg/day as opposed to the 80 mg/day employed in the A-to-Z trial. One wonders whether they would have seen an even larger magnitude of association had they used a higher threshold to define high potency.
I don’t necessarily disagree with Dr. Sarma’s conclusion that for most people after ACS a high-potency statin will be warranted. I just think we need to be cautious and think about the individual patient when we consider the risks and benefits.
It may well be the case that high-potency statin therapy means fewer cardiovascular events at the cost of a greater risk of acute kidney injury and other adverse events. With lower-potency statins, the trade-off may be more cardiovascular events but a lower acute kidney injury risk.
Dr. Tara Chang is a nephrologist at Stanford (Calif.) University. She was the discussant of the paper at the meeting. Dr. Chang disclosed having no financial conflicts.
I’m not convinced by the PROVE IT and A-to-Z data. In the combined analysis, the high-potency statin group had a 15% greater risk of acute kidney injury compared with the low-potency statin group during the first 4 months of treatment. Although that wasn’t a statistically significant difference due to limited patient numbers and broad confidence intervals, it was quite similar to the long-term 11% increased risk seen in the Canadian observational database study with 2 million patients.
Moreover, an even bigger recent observational study led by investigators at the University of North Carolina, Chapel Hill, involving 3.9 million U.S. statin initiators found a 42% greater rate of acute kidney injury during the first year on high- as compared to lower-dose simvastatin in commercially insured patients and a 24% increased risk in the Medicare population. Both risk increases were statistically significant due to the huge patient numbers (Pharmacoepidemiol. Drug Saf. 2013;22:1061-70).
|
|
Also, PROVE IT and A-to-Z featured patient populations who were of a younger average age and less likely to be male and to have diabetes than the general American population of acute MI patients as depicted in the National Cardiovascular Data Registry (J. Am. Coll. Cardiol. 2013;62:1931-47). Advancing age, diabetes, and male gender are predisposing factors for acute kidney disease.
The Canadian observational study defined high-potency statin therapy as at least 20 mg/day of atorvastatin or 40 mg or simvastatin. The University of North Carolina study also defined high-potency simvastatin as at least 40 mg/day as opposed to the 80 mg/day employed in the A-to-Z trial. One wonders whether they would have seen an even larger magnitude of association had they used a higher threshold to define high potency.
I don’t necessarily disagree with Dr. Sarma’s conclusion that for most people after ACS a high-potency statin will be warranted. I just think we need to be cautious and think about the individual patient when we consider the risks and benefits.
It may well be the case that high-potency statin therapy means fewer cardiovascular events at the cost of a greater risk of acute kidney injury and other adverse events. With lower-potency statins, the trade-off may be more cardiovascular events but a lower acute kidney injury risk.
Dr. Tara Chang is a nephrologist at Stanford (Calif.) University. She was the discussant of the paper at the meeting. Dr. Chang disclosed having no financial conflicts.
I’m not convinced by the PROVE IT and A-to-Z data. In the combined analysis, the high-potency statin group had a 15% greater risk of acute kidney injury compared with the low-potency statin group during the first 4 months of treatment. Although that wasn’t a statistically significant difference due to limited patient numbers and broad confidence intervals, it was quite similar to the long-term 11% increased risk seen in the Canadian observational database study with 2 million patients.
Moreover, an even bigger recent observational study led by investigators at the University of North Carolina, Chapel Hill, involving 3.9 million U.S. statin initiators found a 42% greater rate of acute kidney injury during the first year on high- as compared to lower-dose simvastatin in commercially insured patients and a 24% increased risk in the Medicare population. Both risk increases were statistically significant due to the huge patient numbers (Pharmacoepidemiol. Drug Saf. 2013;22:1061-70).
|
|
Also, PROVE IT and A-to-Z featured patient populations who were of a younger average age and less likely to be male and to have diabetes than the general American population of acute MI patients as depicted in the National Cardiovascular Data Registry (J. Am. Coll. Cardiol. 2013;62:1931-47). Advancing age, diabetes, and male gender are predisposing factors for acute kidney disease.
The Canadian observational study defined high-potency statin therapy as at least 20 mg/day of atorvastatin or 40 mg or simvastatin. The University of North Carolina study also defined high-potency simvastatin as at least 40 mg/day as opposed to the 80 mg/day employed in the A-to-Z trial. One wonders whether they would have seen an even larger magnitude of association had they used a higher threshold to define high potency.
I don’t necessarily disagree with Dr. Sarma’s conclusion that for most people after ACS a high-potency statin will be warranted. I just think we need to be cautious and think about the individual patient when we consider the risks and benefits.
It may well be the case that high-potency statin therapy means fewer cardiovascular events at the cost of a greater risk of acute kidney injury and other adverse events. With lower-potency statins, the trade-off may be more cardiovascular events but a lower acute kidney injury risk.
Dr. Tara Chang is a nephrologist at Stanford (Calif.) University. She was the discussant of the paper at the meeting. Dr. Chang disclosed having no financial conflicts.
DALLAS – High-potency statin therapy given post acute coronary syndrome did not raise serum creatinine or cause more risk of acute kidney injury than low-potency statin regimens did in a new analysis of two published landmark randomized clinical trials.
"Considering the recently updated AHA/American College of Cardiology lipid guidelines, which call for the use of high-potency statins in millions more patients, these findings provide important reassurance that a high-potency statin regimen will not increase the incidence of adverse renal events," Dr. Amy Sarma said in presenting the study results at the American Heart Association scientific sessions.
She noted that a recent Canadian observational study utilizing Canadian and U.S. administrative databases totaling more than 2 million patients over age 40 who were newly placed on statin therapy showed an adjusted 1.34-fold increased rate of hospitalization for acute kidney injury within the first 120 days in those on a high- as compared to a low-potency regimen, and a 1.11-fold increased risk beyond 120 days through the end of the first year (BMJ 2013;346:f880). Both risk elevations were statistically significant.
However, observational studies such as this are prone to bias in the form of potentially crucial differences between the patients given a prescription for statins and those who aren’t. For this reason, Dr. Sarma and her coinvestigators turned for guidance to two randomized trials of high- versus low-dose statins, since this study design obviates the risks of confounding. The trials were PROVE IT-TIMI 22 (N. Engl. J. Med. 2004;350:1495-504) and the A-to-Z trial (JAMA 2004;292:1307-16).
PROVE IT included 4,122 patients randomized within 10 days post ACS to standard background therapy plus either pravastatin at 40 mg/day or atorvastatin at 80 mg/day. A-to-Z involved 4,497 patients who were placed on simvastatin at either 20 or 80 mg/day within 5 days post ACS. Both trials had a median follow-up of 2 years, and both featured serial measurements of serum creatinine. Two-thirds of subjects in PROVE IT had a baseline estimated glomerular filtration rate below 90 mL/min per 1.73 m2, while two-thirds of those in A-to-Z had a baseline eGFR less than 60, noted Dr. Sarma of Brigham and Women’s Hospital, Boston.
In both studies, mean serum creatinine rose equally during the first 30 days of statin therapy, regardless of treatment potency, and then levels declined. In PROVE IT, for example, serum creatinine in the pravastatin and atorvastatin arms rose by 0.96% and 0.97% above baseline, respectively, at 30 days. Values then dropped by 2.88% and 3.85% from baseline at 4 months, and by 3.88% and 5.83% at 16 months.
In both studies, there was no difference between the high- and low-potency statin groups in the incidence of any increase in serum creatinine of at least 1.5-fold, 2.0-fold, or 3.0-fold greater than baseline. In other words, there was no hint of a safety signal, she added.
Dr. Sarma reported having no financial conflicts of interest.
DALLAS – High-potency statin therapy given post acute coronary syndrome did not raise serum creatinine or cause more risk of acute kidney injury than low-potency statin regimens did in a new analysis of two published landmark randomized clinical trials.
"Considering the recently updated AHA/American College of Cardiology lipid guidelines, which call for the use of high-potency statins in millions more patients, these findings provide important reassurance that a high-potency statin regimen will not increase the incidence of adverse renal events," Dr. Amy Sarma said in presenting the study results at the American Heart Association scientific sessions.
She noted that a recent Canadian observational study utilizing Canadian and U.S. administrative databases totaling more than 2 million patients over age 40 who were newly placed on statin therapy showed an adjusted 1.34-fold increased rate of hospitalization for acute kidney injury within the first 120 days in those on a high- as compared to a low-potency regimen, and a 1.11-fold increased risk beyond 120 days through the end of the first year (BMJ 2013;346:f880). Both risk elevations were statistically significant.
However, observational studies such as this are prone to bias in the form of potentially crucial differences between the patients given a prescription for statins and those who aren’t. For this reason, Dr. Sarma and her coinvestigators turned for guidance to two randomized trials of high- versus low-dose statins, since this study design obviates the risks of confounding. The trials were PROVE IT-TIMI 22 (N. Engl. J. Med. 2004;350:1495-504) and the A-to-Z trial (JAMA 2004;292:1307-16).
PROVE IT included 4,122 patients randomized within 10 days post ACS to standard background therapy plus either pravastatin at 40 mg/day or atorvastatin at 80 mg/day. A-to-Z involved 4,497 patients who were placed on simvastatin at either 20 or 80 mg/day within 5 days post ACS. Both trials had a median follow-up of 2 years, and both featured serial measurements of serum creatinine. Two-thirds of subjects in PROVE IT had a baseline estimated glomerular filtration rate below 90 mL/min per 1.73 m2, while two-thirds of those in A-to-Z had a baseline eGFR less than 60, noted Dr. Sarma of Brigham and Women’s Hospital, Boston.
In both studies, mean serum creatinine rose equally during the first 30 days of statin therapy, regardless of treatment potency, and then levels declined. In PROVE IT, for example, serum creatinine in the pravastatin and atorvastatin arms rose by 0.96% and 0.97% above baseline, respectively, at 30 days. Values then dropped by 2.88% and 3.85% from baseline at 4 months, and by 3.88% and 5.83% at 16 months.
In both studies, there was no difference between the high- and low-potency statin groups in the incidence of any increase in serum creatinine of at least 1.5-fold, 2.0-fold, or 3.0-fold greater than baseline. In other words, there was no hint of a safety signal, she added.
Dr. Sarma reported having no financial conflicts of interest.
AT THE AHA SCIENTIFIC SESSIONS
Major finding: Patients randomized to a high-potency statin regimen shortly after an acute coronary syndrome did not have higher serum creatinine levels or a greater risk of acute kidney injury than those randomized to a low-potency statin.
Data source: PROVE IT-TIMI 22 and the A-to-Z trial were randomized, double-blind clinical trials in which a total of 8,619 patients with a recent acute coronary syndrome were assigned to high- or lower-potency statin therapy and prospectively followed for a median of 2 years.
Disclosures: Dr. Sarma reported having no financial conflicts of interest.
