Comparative effectiveness of fourth-line anti-hypertensive agents in resistant hypertension: A systematic review and meta-analysis

Abstract

AimWe assessed the effectiveness of 4 th line mineralocorticoid receptor antagonists in comparison to other 4 th line anti-hypertensive agents in resistant hypertension. Methods and ResultsWe systematically searched Medline, EMBASE and the Cochrane library from database inception until January 2016. We included randomised and non-randomised studies that compared mineralocorticoid receptor antagonists to other 4 th line anti-hypertensive agents in patients with resistant hypertension. The outcome was change in systolic blood pressure, measured in the office, at home or by ambulatory blood pressure monitoring. Secondary outcomes were changes in serum potassium and occurrence of hyperkalaemia. We used random effects models and assessed statistical heterogeneity using the I 2 test and corresponding 95% confidence intervals.From 2,506 records, 5 studies met our inclusion criteria with 755 included patients. Two studies were randomised and three were non-randomised. Comparative fourth line agents included bisoprolol, doxazosin, furosemide and additional blockade of the renin angiotensinaldosterone system. Using data from randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 7.4mmHg (95% CI 3.2 -11.6) more than the active comparator. When limited to non-randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 11.9mmHg (95% CI 9.3 -14.4) more than the active comparator. ConclusionOn the basis of this meta-analysis, mineralocorticoid receptor antagonists reduce blood pressure more effectively than other 4 th line agents in resistant hypertension. Effectiveness stratified by ethnicity and comorbidities, in addition to information on clinical outcomes such as myocardial infarction and stroke now needs to be determined.

Medicine-use evaluation of doxazosin prescribing to inform formulary recommendations

“…[9,10] Doxazosin use as a fourth-line agent in resistant hypertension, where ≥4 antihypertensive agents are required to achieve normotension, is decreasing. [8,11] This has occurred primarily in response to the findings of the PATHWAY-2 (spironolactone v. placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension) randomised controlled trial, which demonstrated the superior efficacy of spironolactone as a fourth-line agent in resistant hypertension when compared with doxazosin and bisoprolol. [12] This finding has been supported by larger meta-analyses and systematic reviews.…”

“…[12] This finding has been supported by larger meta-analyses and systematic reviews. [11,13] The use of doxazosin is restricted in the Western Cape Province's public healthcare sector, where it is only recommended for treating…”

The comparative effectiveness of fourth‐line drugs in resistant hypertension: An application in electronic health record data

“…Other observational studies have compared different fourth‐lineanti‐hypertensivedrugs and found reductions in systolic BP of on average 12mmHg, favouring AA . These previous observational studies were carried out in hospitals; thus, the identification and inclusion processes were not similar to the algorithms we used.…”

“…Other observational studies have compared different fourthlineanti-hypertensivedrugs and found reductions in systolic BP of on average 12mmHg, favouring AA. 32 These previous observational studies were carried out in hospitals; thus, the identification and inclusion processes were not similar to the algorithms we used. Additionally, investigators in both randomized controlled trials and cohort studies using primary data collection have control over the frequency and method of BP measurement, which is not possible in EHR data.…”

Controlling Hypertension: We Have the Tools—We Just Need to Use Them

“…In this role, MRAs have been shown to be superior to other BP drugs as the fourth drug in randomized controlled trials. 8,9 The MRA was found to reduce SBP an average of 7.4 mmHg versus active comparators such as beta-blockers, improving BP in almost all patients, and bringing over half of patients into full control. Most of the evidence regarding MRAs as a class is with spironolactone, usually at doses of 25-50 mg. Spironolactone is a Bfour-dollar^drug in many pharmacies.…”