People with chronic kidney disease (CKD) have an increased risk of heart disease that can block blood supply to the heart or brain causing heart attack or stroke. Drugs that prevent blood clots forming (antiplatelet agents) can prevent deaths caused by clots in arteries in the general adult population. However, there may be fewer benefits for people who have CKD, because blood clots in arteries is a less common cause of death or reason to be admitted to hospital compared with heart failure or sudden death in these people. People with CKD also have an increased tendency for bleeding due to changes in blood clotting mechanisms. Antiplatelet agents may therefore be more hazardous when CKD is present. This review evaluated the benefits and harms of antiplatelet agents to prevent cardiovascular disease and death, and improve dialysis vascular access function in people who have CKD. We identified 44 studies comparing antiplatelet agents with placebo or no treatment and six studies directly comparing one antiplatelet agent with another.
Antiplatelet agents prevent heart attack, but not death or stroke, and increase major and minor bleeding in people with CKD. Dialysis access (fistula or Gortex graft) is maintained with antiplatelet treatment, but antiplatelet drugs do not clearly improve fistula maturation or suitability for dialysis. Benefits (fewer deaths and heart attacks) and harms (bleeding) occur irrespective of the stage of CKD or type of antiplatelet used. More studies of anti-blood clotting drugs are needed in people who have CKD, especially in those who have received kidney transplants. We also need studies that compare one anti-clotting drug versus another, particularly newer drugs, and that determine the best treatment for people with both CKD and acute cardiovascular disease and that assess treatment to improve maturation of dialysis vascular access.
Antiplatelet agents reduce myocardial infarction but increase major bleeding. Risks may outweigh benefits among people with low annual risks of cardiovascular events, including those with early stages of CKD who do not have clinically-evident occlusive cardiovascular disease.
Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet treatment may be different in people with chronic kidney disease (CKD) for whom occlusive atherosclerotic events are less prevalent, and bleeding hazards might be increased.
To summarise the effects of antiplatelet treatment (antiplatelet agent versus control or other antiplatelet agent) for the prevention of cardiovascular and adverse kidney outcomes in individuals with CKD.
In January 2011 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cochrane Renal Group's Specialised Register without language restriction.
We selected randomised controlled trials of any antiplatelet treatment versus placebo or no treatment, or direct head-to-head antiplatelet agent studies in people with CKD. Studies were included if they enrolled participants with CKD, or included people in broader at-risk populations in which data for subgroups with CKD could be disaggregated.
Two authors independently extracted data from primary study reports and any available supplementary information for study population, interventions, outcomes, and risks of bias. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from numbers of events and numbers of participants at risk which were extracted from each included study. The reported RRs were extracted where crude event rates were not provided. Data was pooled using the random-effects model.
We included 50 studies, enrolling 27,139 participants; 44 studies (21,460 participants) compared an antiplatelet agent with placebo or no treatment, and six studies (5679 participants) directly compared one antiplatelet agent with another. Compared to placebo or no treatment, antiplatelet agents reduced the risk of myocardial infarction (17 studies; RR 0.87, 95% CI 0.76 to 0.99), but not all-cause mortality (30 studies; RR 0.93, 95% CI 0.81 to 1.06), cardiovascular mortality (19 studies; RR 0.89, 95% CI 0.70 to 1.12) or stroke (11 studies; RR 1.00, 95% CI 0.58 to 1.72). Antiplatelet agents increased the risk of major (27 studies; RR 1.33, 95% CI 1.10 to 1.65) and minor bleeding (18 studies; RR 1.49, 95% CI 1.12 to 1.97). In terms of dialysis access outcomes, antiplatelet agents reduced access thrombosis or patency failure but had no effect on suitability for dialysis. Meta-regression analysis indicated no differences in the relative benefit or harms of treatment (risk of all-cause mortality, myocardial infarction, or major bleeding) by type of antiplatelet agent or stage of CKD. Limited data were available for direct head-to-head comparisons of antiplatelet drugs, treatment in kidney transplant recipients, primary prevention, or risk of ESKD.