Recent evidence points to the effectiveness of spironolactone vs placebo in the treatment of resistant hypertension (RH). However, placebo is rarely a realistic treatment choice in uncontrolled hypertension. Using meta-analysis, we assessed the effectiveness of alternative 4th line anti-hypertensive agents in comparison to 4th line spironolactone/eplenerone in RH.Design and Method:
Pubmed, EMBASE and the Cochrane library were systematically searched for randomised and non-randomised studies that compared any 4th line anti-hypertensive agent to spironolactone/eplenerone in RH. Data extraction and quality appraisal were carried out in duplicate. The outcome was change in systolic BP, measured in the office, at home or by ambulatory blood pressure monitoring (AMBP). A random effects model was used to pool the data. Statistical heterogeneity was assessed using the I2 test. Sensitivity analyses were carried out according to study design and method of BP measurement.Results:
From 2,506 records, we identified 1 RCT and 5 observational studies according to our inclusion criteria with 877 included patients (Table 1). The mean age was 57.3yrs, 29.5% female, 41.4% diabetic, mean eGFR of 83.7 ml/min and mean BMI of 29.8 kg/m2. The baseline systolic BP was 143.1 mmHg. Other 4th line agents included bisoprolol, doxazosin and furosemide. When all the data was pooled, spironolactone reduced systolic BP by -10.19mmHg (95% CI 6.76 – 13.62) (Figure 1) more than the active comparator. When limited to studies that measured 24hr AMBP, spironolactone reduced BP by 9.99mmHg (95% CI 7.14 – 12.84) relative to the comparator. Analysing observational studies only, spironolactone reduced systolic BP by 11.24mmHg (95% CI 8.04 – 14.43).Conclusions:
On the basis of this meta-analysis, spironolactone reduces systolic BP more effectively than other potential 4th line treatment options in RH. The comparative effectiveness of 4th line agents with regard to clinical outcomes such as myocardial infarction and stroke now needs to be determined.