Chronic kidney disease (CKD) is a major risk factor for cardiovascular events. According to Yazid N. Al Hamarneh, BSc(Pharm), PhD, and colleagues, “patients with CKD are underserved when it comes to cardiovascular risk reduction efforts.” Approximately one in 10 adults in Canada are living with CKD and suboptimal treatment to reduce the risk of cardiovascular events is associated with an increased risk for progression to end-stage renal disease (ESRD). It is important to identify and manage patients with early stage CKD to slow the progression of kidney dysfunction, prevent or delay the development of ESRD, and reduce cardiovascular events among that patient population.
Cardiovascular disease accounts for approximately 40% of overall deaths in CKD patients; clinical guidelines now recommend including CKD as part of cardiovascular risk assessments, yet many patients report never having had a cardiovascular risk assessment from their primary care provider.
Pharmacists are well positioned to identify patients with CKD, determine cardiovascular risk, and assist in disease management. Pharmacists in Alberta, Canada, can order and interpret laboratory tests, conduct medication management assessment, and prescribe medications. Dr. Al Hamarneh and colleagues conducted a prespecified subgroup analysis based on results of the REACH trial, a multicenter randomized trial demonstrating that a community pharmacy-based case finding and intervention program led to a 21% reduction in cardiovascular risk over a 3-month period when compared with usual care. Results of the subgroup analysis were reported in the American Journal of Kidney Diseases [2018;71(1):42-51].
The pharmacist intervention included patient, laboratory, and individualized cardiovascular risk assessments; treatment recommendations; adaptation of prescriptions and/or initiation of prescriptions; and regular monthly follow-up for 3 months. The primary outcome of interest was change in estimated risk of cardiovascular events from baseline to 3 months following randomization. Secondary outcomes were change between baseline and 3 months following randomization in individual cardiovascular risk factors, the risk for developing ESRD, medication use and dosage, and the impact of rural versus urban residence on the difference in change in estimated cardiovascular risk.
The REACH trial enrolled 723 patients from January 2014 to June 2015; follow-up was completed in September 2015. Of the 723 patients in the total cohort, 290 had CKD and were randomly assigned to receive the intervention (n=147) or to receive usual pharmacist and physician care (n=143).
At baseline, the two groups were well balanced in demographic and clinical parameters. Mean age of the cohort was 65.5 years, 55.2% were men, 80.3% were white, 85.9% had at least a high school education, and 36.2% were employed. Mean body mass index was 33.2 kg/m2 and 24.5% of the participants were currently using tobacco. Hypertension was the most common comorbidity (90%), followed by dyslipidemia (86.6%), diabetes (82.1%), and vascular disease (35.5%).
Study inclusion criteria called for patients to have at least one poorly controlled risk factor: 76.5% of patients with diabetes had poor glycemic control as measured by hemoglobin A1c (HbA1c) concentration; 70.5% had poorly controlled blood pressure; 51% had poorly controlled dyslipidemia measured by low-density lipoprotein cholesterol concentration; and 24.5% were current tobacco users (categories not mutually exclusive).
Fifty-nine percent of the patients had known CKD; 41% had previously unrecognized CKD, 83% had elevated albumin-creatinine ratios, 9% had reduced estimated glomerular filtration rates (eGFRs), and 8% had abnormal results for both tests. Those with previously unrecognized CKD were referred to their treating clinician and received pharmacist care according to the study allocation.
Over the 3-month follow-up, in the intervention group the estimated cardiovascular risk was reduced from 25.7 to 20.9; in the control group the risk was reduced from 28.7 to 28.6. Following adjustment for baseline characteristics and center effect, the results corresponded to a relative reduction of 20% (absolute reduction, 5.03; 95% confidence interval [CI], 3.40-6.65; P<.001) in estimated cardiovascular risk over a 3-month period.
The largest contributor to the reduction in cardiovascular risk in patients with diabetes was reduction in HbA1c concentration, followed by reduction in systolic blood pressure, total cholesterol to high-density lipoprotein cholesterol, then self-reported tobacco cessation. In patients without diabetes, the largest contributor to the risk reduction was reduction in systolic blood pressure, followed by reduction in total cholesterol to high-density lipoprotein cholesterol ratio, and tobacco cessation.
In patients in the intervention group with eGFRs <60 mL/min/1.73 m2, the 5-year predicted risk of ESRD was reduced from 8.9% at baseline to 3.4% at 3 months; there was no change in risk of ESRD in the control group. This corresponded to a 27% relative reduction in predicted risk for ESRD (absolute difference, 2.38; 95% CI, –7.48 to 2.73). The reduction was not statistically significant.
Overall, the reduction in cardiovascular risk was larger in patients who lived in rural areas compared with patients who lived in urban areas.
Limitations to the analysis cited by the authors included the short follow-up period and the lack of a well-accepted risk assessment equation to calculate cardiovascular risk in patients with CKD; this analysis used the Framingham risk assessment equation, although that equation may underestimate cardiovascular risk in patients with CKD. The UK Prospective Diabetes Study risk assessment equation was used for patients with diabetes, and the International Model to Predict Recurrent Cardiovascular Disease risk assessment equation was used for patients with previous vascular disease.
In summary, the authors said, “This subgroup analysis demonstrated that a community pharmacy-based intervention program reduced cardiovascular risk and improved control of individual cardiovascular risk factors. This represents a promising approach to identifying and managing patients with CKD that could have important public health implications.”
- A subgroup analysis of results for the REACH trial was conducted to evaluate the effect of a community pharmacy-based intervention on estimated cardiovascular risk in a subset of patients with chronic kidney disease.
- The primary outcome of interest was change in the estimated cardiovascular risk from baseline to 3 months.
- The estimated cardiovascular risk in the intervention group was reduced from 25.7 to 20.9, compared with 28.7 to 28.6 in the control group over a 3-month period; after adjustment, the relative reduction was 20%.