CHICAGO — Intensive lipid lowering with high-dose atorvastatin significantly reduces the incidence of major cardiovascular events in coronary patients who have both type 2 diabetes and chronic kidney disease, Dr. James Shepherd reported at the annual scientific sessions of the American Diabetes Association.
In a new subanalysis of diabetic patients in the Pfizer-funded Treating to New Targets (TNT) study, “Individuals got greater benefit in relative terms and far greater benefit in absolute terms if they had the combination of diabetes and renal disease, because they had much greater risk to begin with,” said Dr. Shepherd, professor and head of pathological biochemistry at the Royal Infirmary and the University of Glasgow (Scotland).
The main finding of the TNT study of 10,001 patients with stable coronary heart disease was a 22% reduction in the risk of major cardiovascular events with using 80 mg of atorvastatin per day relative to 10 mg/day at a median follow-up of 5 years (N. Engl. J. Med. 2005;352:1425–35). A subsequent sub-analysis of the 1,501 diabetics in that study showed a 25% event reduction with 80 mg versus 10 mg (Diabetes Care 2006;29:1220–6). However, another study of 1,255 patients who had type 2 diabetes and end-stage renal disease (ESRD) and were undergoing hemodialysis showed no cardiovascular benefit of 20 mg of atorvastatin per day, compared with placebo (N. Engl. J. Med. 2005;353:238–48).
To further investigate the potential role of atorvastatin treatment in patients with both diabetes and kidney disease, Dr. Shepherd and his associates analyzed the TNT outcomes of 1,431 of the diabetic patients in the study for whom renal data were available. There were 546 patients with chronic kidney disease (CKD) — defined as having an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m
At baseline, those with CKD had greater cardiovascular morbidity than those without, including higher systolic blood pressure (136.1 vs. 133.6 mm Hg); a greater proportion had a history of hypertension (76% vs. 67%), as well as higher rates of peripheral vascular disease, coronary bypass grafting, and congestive heart failure. There were also more women in the CKD group (42% vs. 18%). The 80-mg dose of atorvastatin lowered LDL equally in both groups, from about 98 mg/dL at baseline to 75 mg/dL at follow-up, Dr. Shepherd reported.
Major cardiovascular events (coronary heart disease death, nonfatal myocardial infarction, resuscitation after cardiac arrest, fatal or nonfatal stroke) occurred in 13.4% of the diabetics with normal GFR and 17.4% for those with both diabetes and CKD. (The rates were 7.8% among those without diabetes or CKD and 10% for the nondiabetics with CKD.) Compared with 10 mg of atorvastatin, the 80-mg dose reduced the relative risk of major cardiovascular events by 35% in the diabetic patients with CKD, compared with just 10% among the diabetics without CKD. “Those patients with the greatest risk got the greatest benefit from intensive intervention with atorvastatin,” Dr. Shepherd commented.
The drug was well tolerated overall, with no evidence of myopathy and less than 1% with elevated liver enzymes. “The high dose of atorvastatin created no penalty with regard to side effects,” he noted.
Although not an end point in the study, improvements in GFR were seen with both atorvastatin doses over the 5 years of the study, but were greater with 80 mg, he said.
When asked by an audience member why atorvastatin did not benefit the patients with ESRD in the earlier study, Dr. Shepherd responded, “I think it's a function of the degree of kidney compromise. If you have patients with ESRD on dialysis, you're asking far too much of a drug to reverse that. But you can see a reversal if you have compromise but still-viable glomerular filtration rates.”
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