Renal function, concomitant medication use and outcomes following acute coronary syndromes

Chronic kidney disease (CKD) is highly prevalent in patients with cardiovascular disease. We explored the associations of CKD with outcomes using combined data from two large acute coronary syndrome (ACS) trials. We also explored the associations of CKD with prescription patterns for common cardiovascular medications and the association of these prescription patterns with clinical outcomes.

Patients were stratified by CKD stage using creatinine clearance (CrCl, ml/min) estimated by the modified MDRD equation using baseline core laboratory creatinine measures. Serum creatinine > or =1.5 mg/dl was an exclusion criterion for the SYMPHONY trials. Baseline characteristics and outcomes across CKD categories were compared and Cox proportional hazards regression was used to assess the relationship of renal insufficiency with clinical outcomes after adjusting for previously identified outcome predictors. Interactions between the use of specific medications and calculated CrCl were tested in the final Cox proportional hazards model predicting time to mortality.

Of 13 707 patients analysed, 6840 had CKD stage I (CrCl > or =90 ml/min), 5909 stage II (CrCl 60-89 ml/min), 955 stage III (CrCl 30-59 ml/min) and three stage IV (CrCl <30 ml/min). Patients with more advanced CKD (III) were older, more often female, non-smokers and more likely to have co-morbid diseases including diabetes mellitus, hypertension and congestive heart failure. Cardiovascular medications were used less frequently in patients with CKD. Unadjusted survival was poorer in patients with CKD stages > or =II. In adjusted analyses, for those with CrCl < or =91, each 10 ml/min increase in CrCl was associated with a significantly decreased risk of mortality (hazards ratio 0.897, 95% confidence interval 0.815-0.986) (P = 0.024). The interaction between use of angiotensin-converting enzyme (ACE) inhibitors and CrCl was significantly associated with outcomes; the benefit of drug therapy was greater among patients with CKD.

CKD is an independent predictor of risk among ACS patients, and is associated with less frequent use of proven medical therapies. More aggressive use of conventional cardiovascular therapies in patients with CKD and ACS may be warranted.