Antihypertensive Treatment Patterns in CKD Stages 3 and 4: The CKD-REIN Cohort Study

Abstract

Rationale & objective: Blood pressure (BP) control is essential for preventing cardiorenal complications in chronic kidney disease (CKD), but most patients fail to reach BP target. We assessed longitudinal patterns of antihypertensive drug prescription and systolic BP.

Study design: Prospective observational cohort study.

Setting & population: In total, 2,755 hypertensive patients with CKD stages 3-4, receiving care from a nephrologist, from the French CKD-Renal Epidemiology and Information Network (CKD-REIN cohort study).

Exposure: Patient factors, including sociodemographic characteristics, medical history, and laboratory data, and provider factors, including number of primary care physician and specialist encounters.

Outcomes: Changes in antihypertensive drug-class prescription during follow-up: add-on or withdrawal.

Analytical approach: Hierarchical shared-frailty models to estimate hazard ratios (HR) to deal with clustering at the nephrologist level and linear mixed models to describe systolic BP trajectory.

Results: At baseline, median age was 69 years, and mean estimated glomerular filtration rate was 33 mL/min/1.73 m². In total, 66% of patients were men, 81% had BP ≥ 130/80 mm Hg, and 75% were prescribed ≥2 antihypertensive drugs. During a median 5-year follow-up, the rate of changes of antihypertensive prescription was 50 per 100 person-years, 23 per 100 for add-ons, and 25 per 100 for withdrawals. After adjusting for risk factors, systolic BP, and the number of antihypertensive drugs, poor medication adherence was associated with increased HR for add-on (1.35, 95% confidence interval [CI], 1.01-1.80), whereas a lower education level was associated with increased HR for withdrawal (1.23, 95% CI, 1.02-1.49) for 9-11 years versus ≥12 years. More frequent nephrologist visits (≥4 vs none) were associated with higher HRs of add-on and withdrawal (1.52, 95% CI, 1.06-2.18; 1.57, 95% CI, 1.12-2.19, respectively), whereas associations with visit frequency to other physicians varied with their specialty. Mean systolic BP decreased by 4 mm Hg following drug add-on but tended to increase thereafter.

Limitations: Lack of information on prescriber and drug dosing.

Conclusions: In patients with CKD and poor BP control, changes in antihypertensive drug prescriptions are common and relate to clinician preferences and patients' tolerability. Sustainable reduction in systolic BP after add-on of a drug class is infrequently achieved.

Keywords: antihypertensive agents; blood pressure; chronic kidney disease; hypertension; renin-angiotensin system.

Figure 1

Rates of add-ons and withdrawals (with 95% confidence intervals) by antihypertensive drug class. Figure displays add-on and withdrawal rates for drug classes with at least 85 events. Rates for drug classes with fewer events, as well as number of events and persons at risk for all drug classes are shown in Supplementary Table 5.

Figure 2

Changes in the number of antihypertensive drugs prescribed during follow-up. In this Sankey plot, bars represent the distribution of the number of antihypertensive drug classes at baseline and at the first 3 change time points. X-axis depicts the median time to each prescription change (in months). Y-axis represents the percentage of patients with a given number of drug classes prescribed. Links from one bar to another are proportional to the flow rate of patients whose number of antihypertensive drug classes changed.

Figure 3

One-year systolic BP trends in patients with and without an add-on of an antihypertensive drug. In patients with add-on of an antihypertensive drug class, time zero corresponds to timing of add-on. In patients without add-on, time zero corresponds to 8.4 months from baseline (median time of the first add-on in patients who had it). Abbreviation: SBP, systolic blood pressure.