Resistant hypertension poses a significant challenge, especially in patients with chronic kidney disease (CKD). The AMBER trial emerges as a beacon of hope, evaluating the role of the potassium binder patiromer in enabling the use of spironolactone in this difficult-to-treat population. This groundbreaking trial highlights how clinicians can balance the benefits of spironolactone with the risks of hyperkalemia.
Study Overview
The AMBER trial was a phase 2, randomized, double-blind, placebo-controlled study conducted in 2019. It investigated the efficacy of patiromer in allowing patients with resistant hypertension and CKD to persist with spironolactone treatment.
- Objective: To evaluate the use of patiromer to enable the persistent use of spironolactone by mitigating hyperkalemia in this population.
- Participants: The trial enrolled 295 patients, all aged 18 years or older, with:
- Resistant hypertension on at least three BP medications (one being a diuretic).
- Uncontrolled hypertension (HTN), eGFR of 25–45 mL/min/1.73m², and serum potassium levels of 4.3–5.1 mEq/L.
- Exclusion Criteria: Patients with untreated non-CKD hypertension, inability to measure BP, recent renal or cardiovascular events (<3 months), renal transplants, or active cancer (<12 months).
Intervention
- Patiromer Group (n=147): Received patiromer 8.4 g once daily.
- Placebo Group (n=148): Received a placebo.
Patients were monitored for 12 weeks to assess whether patiromer enabled sustained use of spironolactone.
Key Findings
Primary Outcome
The trial demonstrated a significant improvement in the persistence of spironolactone therapy:
- 86% of patients in the patiromer group remained on spironolactone at 12 weeks.
- 66% of patients in the placebo group remained on spironolactone.
- Between-group difference: 19.5% (95% CI 10–29, p < 0.0001).
Secondary Outcomes
- Adverse events were slightly more common in the patiromer group (56%) compared to the placebo group (53%). These were mostly mild or moderately severe.
Conclusion
The AMBER trial provides compelling evidence that patiromer enables persistent spironolactone use in patients with resistant hypertension and CKD by mitigating hyperkalemia. This finding is particularly relevant because spironolactone has proven efficacy in lowering blood pressure in resistant hypertension but is often underutilized due to the risk of hyperkalemia.
The trial’s results highlight the importance of addressing hyperkalemia to ensure patients receive the full benefit of spironolactone therapy. For clinicians treating resistant hypertension in CKD patients, patiromer may serve as a valuable tool to improve outcomes.
Clinical Implications
- Resistant Hypertension Management: The trial reinforces the role of spironolactone as a potent antihypertensive agent and shows how patiromer can support its safe use.
- Personalized Care: Patients with CKD and high potassium levels can benefit from a targeted approach to enable treatment while minimizing risks.
References
Agarwal R et al. “The AMBER Trial: Patiromer vs Placebo to Enable Spironolactone in Resistant Hypertension.” The Lancet. 2019;394:1540–1550.