From the Guidelines
The most effective approach to managing resistant hypertension involves a systematic evaluation and optimization of the current antihypertensive regimen, including the addition of a low-dose of spironolactone as a fourth-line agent, as recommended by the 2024 ESC guidelines 1.
Key Considerations
- Confirmation of true resistance by ensuring proper blood pressure measurement technique and medication adherence is crucial.
- Optimizing the current antihypertensive regimen with a three-drug combination that includes a thiazide diuretic, an ACE inhibitor or ARB, and a calcium channel blocker is essential.
- Adding a fourth agent, typically spironolactone, is recommended if blood pressure remains uncontrolled, due to its superior efficacy as a fourth-line agent.
- Other options include beta-blockers, alpha-blockers, or direct vasodilators.
- Addressing secondary causes, such as primary aldosteronism, renal artery stenosis, pheochromocytoma, and obstructive sleep apnea, is crucial.
- Lifestyle modifications, including sodium restriction, regular physical activity, weight loss, limiting alcohol consumption, and following the DASH diet, remain essential.
Recommended Treatment
- The 2024 ESC guidelines recommend the addition of low-dose spironolactone to existing treatment, or the addition of further diuretic therapy if intolerant to spironolactone 1.
- 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.
Lifestyle Modifications
- Sodium restriction (<2.3g/day) is essential, as well as regular physical activity, weight loss if overweight, limiting alcohol consumption, and following the DASH diet.
- These interventions work by targeting different physiological pathways of blood pressure regulation, with spironolactone being particularly effective due to its ability to counteract aldosterone excess often present in resistant hypertension.
From the FDA Drug Label
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC)
The approach to managing resistant hypertension involves:
- Comprehensive cardiovascular risk management
- Lipid control
- Diabetes management
- Antithrombotic therapy
- Smoking cessation
- Exercise
- Limited sodium intake
- Using multiple drugs to achieve blood pressure goals, as many patients may require more than one drug
- Following published guidelines, such as those from the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) 2 3
From the Research
Approach to Managing Resistant Hypertension
The approach to managing resistant hypertension involves a combination of lifestyle adjustments, pharmacologic treatment, and interventional therapies.
- Confirmation of the diagnosis of resistant hypertension is crucial, which includes confirming adherence to therapy and exclusion of secondary causes of hypertension 4, 5, 6.
- Lifestyle modifications such as reduced sodium and alcohol intake, regular physical activity, weight loss, and discontinuation of substances that can interfere with blood pressure control are recommended 5, 6.
- Pharmacologic treatment typically includes a combination of a diuretic, a long-acting calcium channel blocker, an angiotensin-converting enzyme inhibitor, and a mineralocorticoid receptor antagonist where warranted 4, 7, 5, 6.
- Mineralocorticoid receptor antagonists like spironolactone or eplerenone have been shown to be efficacious in patients with resistant hypertension, heart failure, chronic kidney disease, and primary aldosteronism 4, 7, 5.
Evaluation and Treatment
Evaluation of suspected resistant hypertension starts with confirming adherence to the drug regimen and ruling out white coat hypertension with out-of-office blood pressure level measurements 5, 6.
- Obesity, significant alcohol intake, and interfering drugs and other substances can contribute to resistant hypertension 6.
- Resistant hypertension may be due to secondary etiologies such as parenchymal kidney disease, obstructive sleep apnea, or hyperaldosteronism 4, 6, 8.
- Adequate diuretic treatment is a key part of therapy, and patients with resistant hypertension should take a dihydropyridine calcium channel blocker and an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker 4, 6.
- Other drug options include a beta blocker, a long-acting nondihydropyridine calcium channel blocker, or clonidine or guanfacine 6.
Novel Therapies
Novel interventional therapies, including baroreflex activation and renal denervation, have shown promise in lowering blood pressure safely in patients with resistant hypertension 4.
- New approaches under research include selective non-steroidal mineralocorticoid receptor antagonists, selective aldosterone synthase inhibitors, and dual endothelin antagonists 5.