This is the largest study that has evaluated the quality of medication prescribing in patients with CKD in Australian general practice using internationally validated indicators (4). The results of this study indicated possible gaps in the treatment of hypertension and albuminuria in patients with CKD, which are likely to have negative implications for the prevention of CKD progression and development of cardiovascular complications.
Despite guideline recommendations (3), less than 70% of Australian adult patients with CKD stages 3-5 with diabetes and microalbuminuria were receiving an ACEI or ARB. The prescribing percentage was even lower (62.3%) in those patients with macroalbuminuria. Studies from different provinces of Canada (15-17) in CKD reported rates of 74% to 80% for ACEI or ARB prescribing, while the Netherlands study found prescribing in 78% and 82% of non-diabetes and diabetes patients, respectively (4). Similar to our study, the percentages of prescribing of an ACEI or ARB reported by studies in Canada and the Netherlands (4, 15-17) were higher in CKD patients with diabetes compared to those without diabetes.
The prescribing of an ACEI or ARB in patients with CKD with albuminuria was slightly lower (5-10%) in Australian general practice compared to other developed nations (15-18). Furthermore, the proportion of patients who were prescribed at least two RAS blockers concurrently was 7.6%, which is double the proportion (3.7%) reported by the Netherlands study (4) using the same indicator. Studies in the United Kingdom and Canada also reported lower percentages of ACEI and ARB co-prescribing, ranging from 0.7% to 4% (16, 18, 19).
Statins are relatively well-tolerated medications and are beneficial in lowering the risk of developing cardiovascular events in patients with CKD (14, 19). Notwithstanding the Australian Pharmaceutical Benefits Scheme restrictions on the prescribing of statins, the current Kidney Disease: Improving Global Outcomes (KDIGO) and Kidney Health Australia guidelines (3, 14) recommend statin or statin/ezetimibe treatment in adults aged 50 years and over with eGFR <60 mL/min/1.73 m2 but not treated with chronic dialysis or kidney transplantation. In this study, we found that only 46.1% and 40.8% of all patients and patients aged 50 to 65 years, respectively, were receiving statins. A similar study by Smits et al. (4) in the Netherlands reported a higher (74%) rate of statin prescribing in patients with CKD stages 3-5 aged 50 to 65 years. Statin prescribing rates reported in this study were also lower compared with previous studies in the United States (64%) (20) and Canada (64%) (15). The AusHeart study (21) reported that 54% of patients with CKD were receiving lipid-lowering medications in Australian primary care.
NSAIDs should be avoided in patients with advanced CKD (eGFR <30 mL/min/1.73 m2) per practice guidelines (3, 19). They are potentially nephrotoxic medications, which can cause acute kidney injury (AKI) and worsen the progression of CKD (19, 22). In our study, potentially inappropriate prescribing of NSAIDs occurred in 14.3% of these patients. The longitudinal North West Adelaide Health Study in South Australia reported a similar percentage (15.9%) of prescribing of NSAIDs in patients with CKD (23). The Netherlands study (4) which developed the PQIs that we used, reported a lower rate (3%) of NSAID prescribing in patients with eGFR <30 mL/min/1.73 m2. A study in Canada reported that almost 10% of patients were prescribed NSAIDs despite patients’ high risk for renal and cardiovascular complications (24). Another study in the UK on patients with moderate to severe CKD reported 5.7% NSAID use (25). Given that some NSAIDs are also available over the counter, their use is likely to be higher than the estimates reported here using general practice prescription data.
In addition, concurrent use of NSAIDs with other potentially nephrotoxic medications, such as RAS blockers, increases the risk of developing AKI and the progression of CKD (19, 26). In this study, we found that 2.6% of all patients aged 18 to 80 years with CKD were potentially receiving triple therapy (“triple whammy”): a diuretic and an ACEI or ARB plus an NSAID. Smits et al. (4) reported a rate of 4.6% for triple therapy in the Netherlands patients with CKD aged 18 to 80 years.
Patients who were diagnosable with CKD based on laboratory evidence, regardless of whether formally diagnosed and recorded as having CKD by their GP, were included in this study. It is interesting to note that only approximately a quarter of patients had a documented diagnosis of CKD. Details of variation in documenting diagnosable CKD in Australian general practice can be found elsewhere (27). The poor documentation of CKD may indicate a lack of awareness and recognition in diagnosing and managing CKD in Australian general practice. By contrast, the low rate of CKD documentation may also be because of GPs’ caution to avoid unnecessary labelling of older patients with normally declining kidney function with age as having CKD (28). Previous studies in Australian general practice reported even lower levels (8.9% to 18%) of CKD diagnosis documentation (21, 29).
Of those patients with CKD whose blood pressure was monitored in the year 2016, more than one-third had uncontrolled blood pressure (systolic blood pressure above 140 mmHg). This may be due to finding it difficult to control hypertension in this group of patients or a lack of awareness of the need to control hypertension within this target for patients with CKD. Treatment guidelines recommend controlling blood pressure ≤140/90 mmHg to prevent CKD progression and cardiovascular complications (3, 30).
This study also suggests that CKD patients’ SEIFA and rurality may, to some extent, influence the quality of prescribing. Potentially inappropriate medication use, such as simultaneous prescribing of two RAS blockers, prescribing of NSAIDs for CKD patients with eGFR <30 mL/min per 1.73 m2 and triple therapy, were more common in CKD patients living in disadvantaged socioeconomic areas. Similarly, potentially inappropriate prescribing of NSAIDs, metformin and digoxin were more common in CKD patients living in regional and remote areas. In contrast, appropriate prescribing of statins in CKD patients aged 50 to 65 years was higher in patients living in disadvantaged socioeconomic areas, and inappropriate co-prescribing of two RAS blockers was higher in patients living in major cities. A study in France (31) reported that inappropriate prescribing was low in older people living in municipalities with high socioeconomic status and was high in those with low socioeconomic status. A similar study in Ireland (32) also found that inappropriate prescribing was more prevalent in relatively deprived patients aged over 70 years.
Unlike a previous study by Khanam et al (33), using MedicineInsight data, which found higher CoC led to better blood pressure control, in this study there were no significant differences in prescribing quality between patients with higher and lower CoC (Appendix 1).
Strengths and Limitations
This study had a large sample and patient characteristics within the MedicineInsight dataset were similar to the Australian population (5, 7, 8). There are several limitations. For instance, phosphate binders and ESAs are not usually prescribed by GPs (generally prescribed by renal physicians) and thus our data were not complete on the use of these medications. NSAIDs are also available without a prescription, but we could only obtain data on prescribed NSAIDs. Simultaneous prescribing of at least two RAS blockers within the four months might not necessarily indicate concomitant inappropriate use. It might be an overlapping period of switching from one RAS blocker monotherapy to the other. We also did not look at the impact of medication use on patient outcomes.
GPs collected the data for clinical decision making, not for research purposes. The EHRs may not contain all sociodemographic and clinical characteristics. For instance, indigenous status was not recorded for 24.3% of the patients. There is a possibility that aspects of patients’ medical history, prescriptions and laboratory tests were recorded in notes and not included in the research data, which used specified fields and not the body of free-text consultation notes.
In conclusion, we identified the potential for possible improvement in the prescribing of recommended preventive medications and deprescribing of nephrotoxic medication in patients with CKD in Australian primary care. Future studies could target the prescribing of preventive medications, such as an ACEI or ARB and a statin, and deprescribing concurrent NSAIDs and RAS blockers in patients with CKD.