From the Guidelines
Resistant hypertension should be managed with reinforcement of lifestyle measures, especially sodium restriction, and the addition of low-dose spironolactone to existing treatment, as recommended by the 2024 ESC guidelines 1. The management of resistant hypertension requires a comprehensive approach that includes lifestyle modifications and optimization of medication therapy. Resistant hypertension is defined as blood pressure that remains above goal despite using three antihypertensive medications of different classes at optimal doses, including a diuretic.
Key Lifestyle Modifications
- Sodium restriction (<2.3g/day)
- Weight loss
- Regular physical activity
- Limited alcohol consumption
- A DASH diet For medication therapy, the 2024 ESC guidelines recommend the addition of low-dose spironolactone to existing treatment, which is particularly effective in resistant hypertension due to its aldosterone-blocking effects 1.
Alternative Fourth-Line Options
- Eplerenone
- Beta-blockers (such as bisoprolol)
- Alpha-blockers (such as doxazosin)
- Centrally-acting agents
- Further diuretic therapy, including a higher dose thiazide/thiazide-like diuretic, or a loop diuretic It is essential to consider medication adherence issues, secondary causes of hypertension, and interfering substances if hypertension remains resistant despite optimal therapy. The 2020 International Society of Hypertension global hypertension practice guidelines also recommend optimizing the current treatment regimen, including health behavior change and diuretic-based treatment, and adding a low dose of spironolactone as the 4th line agent in those whose serum potassium is <4.5 mmol/L and whose eGFR is >45 ml/min/1.73m2 1.
Specialist Referral
Resistant hypertension should be managed in specialist centers with sufficient expertise and resources necessary to diagnose and treat this condition 1. The 2018 American College of Cardiology/American Heart Association hypertension guideline also emphasizes the importance of accurate office BP measurements, assessment for nonadherence to prescribed antihypertensive medications, and obtaining home or ambulatory BP readings to rule out the white coat effect 1.
Key Takeaways
- Resistant hypertension requires a systematic approach to management
- Lifestyle modifications and optimization of medication therapy are essential
- Spironolactone is a recommended addition to existing treatment
- Specialist referral may be necessary for optimal management
From the FDA Drug Label
Spironolactone tablets are indicated as add-on therapy for the treatment of hypertension, to lower blood pressure in patients who are not adequately controlled on other agents. Many patients will require more than one drug to achieve blood pressure goals. Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits The management of resistant hypertension may involve the use of spironolactone as add-on therapy to lower blood pressure in patients who are not adequately controlled on other agents 2.
- The goal is to achieve blood pressure goals through the use of one or more drugs.
- Blood pressure reduction is largely responsible for the reduction in cardiovascular morbidity and mortality.
- The selection of therapy may be guided by considerations such as the patient's absolute risk, diabetes, or hyperlipidemia.
From the Research
Definition and Diagnosis of Resistant Hypertension
- Resistant hypertension is defined as a blood pressure level that remains above the goal level despite adherence to at least three appropriately dosed antihypertensive drugs of different classes, one of which is a diuretic 3.
- It can also be defined as blood pressure above goal despite confirmed adherence to 3 first-line antihypertensive agents or when blood pressure is controlled with 4 or more medications at maximal or maximally tolerated doses 4.
- Diagnosis requires the exclusion of apparent treatment resistant hypertension, which is most often the result of non-adherence to treatment 5.
Evaluation and Management of Resistant Hypertension
- Evaluation of suspected resistant hypertension starts with confirming adherence to the drug regimen and ruling out white coat hypertension with out-of-office BP level measurements, ideally using 24-hour ambulatory BP monitoring 3.
- Lifestyle modifications, including exercise and dietary sodium restriction, can be useful in management 3.
- Pharmacologic treatment should prioritize optimizing first-line, once daily, longer acting medications followed by the stepwise addition of second-, third-, and fourth-line agents as tolerated 4.
- Combination therapy including a diuretic, a long-acting calcium channel blocker, an angiotensin-converting enzyme inhibitor, a beta blocker, and a mineralocorticoid receptor antagonist where warranted is the classic regimen for patients with treatment-resistant hypertension 6.
Treatment Options for Resistant Hypertension
- Spironolactone is an effective fourth drug for patients with resistant hypertension 3, 6.
- Chlorthalidone has the potential to improve BP control among patients with advanced CKD and treatment-resistant hypertension 7.
- Novel interventional therapies, including baroreflex activation and renal denervation, have shown promise in lowering blood pressure safely 6.
- Several device-based approaches have been tested, with renal denervation being the best supported and only approved interventional device treatment for resistant hypertension 5.
Special Considerations
- Patients with resistant hypertension are at higher risk for adverse cardiovascular events and are more likely to have a potentially treatable secondary cause contributing to their hypertension 4.
- Secondary causes of hypertension, including obstructive sleep apnea, primary aldosteronism, renovascular disease, are common in patients with RHTN and often coexist in the same patient 6.
- Patients with treatment-resistant hypertension in chronic kidney disease may benefit from chlorthalidone, but caution is advised due to potential side effects 7.