Boston, MA - Although patients with kidney disease have a lower use of certain cardiac medications post-MI, this is unlikely to explain their worse long-term outcomes, a new study suggests [1].

The study, published online July 9, 2008 in the Clinical Journal of the American Society of Nephrology, was conducted by a team led by Dr Wolfgang Winkelmayer (Brigham and Women's Hospital, Boston, MA).

They note that kidney function has been recognized as a major cardiovascular risk factor, that patients with reduced kidney function are more likely to experience an MI, and that kidney function is further independently associated with short-term and long-term mortality after MI. It has been hypothesized that the relative underuse of certain cardiovascular medications in patients with kidney disease may, at least in part, be responsible for the increased mortality after MI in patients with reduced kidney function.

They thus conducted the current retrospective cohort study to evaluate whether the use of and adherence to recommended medications differed by kidney function in older survivors of an MI. Data were obtained from medical claims between 1995 and 2005 from two prescription drug coverage programs for eligible elderly patients in New Jersey and Pennsylvania. The researchers identified 21 484 patients who were discharged alive after having an MI and survived more than 30 days after discharge. Of those, 436 (2%) were identified as having end-stage renal disease (ESRD) and undergoing long-term dialysis, 3645 (17%) were categorized as having chronic kidney disease (CKD), and 17 403 (81%) had no previous diagnosis of kidney disease.

Results showed suboptimal use of several medication classes, with only 57% of patients receiving a beta blocker, 27% a statin, and 44% an ACE inhibitor or angiotensin-receptor blocker (ARB), although use improved considerably over the decade of observation. Compared with patients without any diagnosed kidney disease, patients who had ESRD and were on dialysis had a 43% lower use of ACE inhibitors/ARBs and 17% lower statin use. And patients with CKD had a 22% lower adjusted use of ACE inhibitors/ARBs but similar rates of beta-blocker and statin use.

They also found that adherence to these medications was similarly suboptimal, with only 54% to 64% (depending on the class of drug) of patients obtaining sufficient medication from the pharmacy to be covered for at least 80% of their days. Kidney-disease status was not a determinant of one-year adherence with these drugs, apart from patients who had ESRD and were on dialysis, who had lower adherence to initiated beta-blocker therapy than other patients.

The authors note that the relative underuse of ACE inhibitors/ARBs in patients with diagnosed CKD is striking, because these are exactly the ones who might benefit the most from these drugs, through both their cardiovascular and their renoprotective effects. "We can only speculate that this underuse might be related to providers' fears of adverse events such as hyperkalemia or sudden increases in serum creatinine, particularly because these patients both are older and have diagnosed CKD."

This study is novel in that it is the first one to evaluate putative differences across categories of kidney function in long-term adherence to initiated cardiovascular medications, the researchers say.

They say: "Because neither primary adjusted filling rates of prescribed drugs after discharge nor adjusted adherence to initiated medication regimens differed between patients with chronic kidney disease and those without diagnosed kidney disease, other mechanisms are likely responsible for the observed adjusted morbidity and mortality difference between patients with better vs more reduced kidney function," adding, "Improving medication use after MI may improve outcomes in the population overall but not necessarily serve to close the mortality gap across categories of kidney function."

But they make the point that few cardiovascular trials include patients with chronic disease and that high-quality randomized trials of sufficient statistical power designed on the basis of realistic event rates and meaningful risk reductions need to be conducted specifically in this population. "The development of candidate therapies and proof of their efficacy to reduce cardiovascular risk in kidney disease should be a top priority for the investment of private and public funds, especially given the high and increasing prevalence of kidney disease," they conclude.