Considerations for Resistant Hypertension

After use of nonpharmacological and multiple blood pressure lowering medications, uncontrolled blood pressure still may be present. Thus, potential for patient to be diagnosed with resistant hypertension.

It is estimated 103 million United States adults have hypertension, according to American Heart Association, and the death rate from hypertension increased by 11% in the US between 2005 and 2015.1

On a worldwide scale, hypertension affects nearly a third of the adult population and is a common cause of cardiovascular related deaths.1 Recent ACC/AHA High Blood Pressure Guidelines have changed the recommendation for stage 1 hypertension to systolic between 130-139 or diastolic between 80-89, previously set at 140/90 mmHg.2 Specific blood pressure goals do exist for select patient populations based on their comorbidities and age.

Treatment of hypertension has many approaches and factors that play a role. Nonpharmacological interventions are just as important as pharmacological interventions.

In some patients, sodium restrictions, increase in exercise, or weight reduction may reduce blood pressure thus not requiring pharmacological treatment. Treatment with blood pressure lowering medications is recommended in patients with stage 2 hypertension and patients with stage 1 hypertension and have clinical ASCVD or estimated 10 year CVD risk of >10%.3 Primarily agents used to treat hypertension include thiazide diuretics, ACE inhibitors, ARBs, and CCBs. Secondary agents include loop diuretics, potassium sparing diuretics, aldosterone antagonists, beta blockers, direct renin inhibitor, alpha-1 blocker, central alpha-2 agonist, and direct vasodilators. 3

In a select patient population, a combination of primary and secondary treatment options may not control high blood pressure. These patients may have a diagnosis of resistant hypertension.

Diagnosis of resistant hypertension is made when patients take 3 antihypertensive medications with collaborating mechanism of actions (diuretic included in therapy) with no achieved control of blood pressure (office systolic/diastolic > 130/90 mm Hg) or when blood pressure control is achieved with more than 4 medications.3,4 It is beneficial to obtain home blood pressure readings to limit white coat effect. Health care providers should also review patient medication compliance to ensure patient is taking medications as prescribed.3

Management of resistant hypertension may include identifying any reversible causes such as obesity, inactivity, excessive alcohol consumption, and/or diet high in sodium.3 Discontinue interacting substances such as Non-Steroidal Anti-inflammatory Drugs, amphetamines, stimulants, oral contraceptives, ephedra, licorice, monoamine oxidase inhibitors etc.3,4

Most patients with resistant hypertension may have a secondary cause of hypertension. Obstructive sleep apnea, chronic kidney disease, and primary hyperaldosteronism are most frequent comorbidities.4

There is limited randomized trial data to guide choice of drug treatment with resistant hypertension. Optimizing dosing regimens, switching diuretics such as hydrochlorothiazide to chlorthalidone, or adding spironolactone, may be potential options. It is recommended to maximize diuretic therapy, add mineralocorticoid receptor antagonist, and/or utilize secondary agents in overall therapy.3,4 Vasodilating beta blockers, such as carvedilol and labetalol, may be considered as fifth-line drug therapy.4 Secondary agents include prazosin, clonidine, methyldopa, minoxidil, and hydralazine. Many patients with secondary causes of hypertension, associated organ damage, requirement of >4 medications for control, and/or proteinuria >1g/day may require referral to a specialist.4

High blood pressure has become a worldwide clinical problem. Nonpharmacological and pharmacological treatment interventions have shown to be beneficial at reducing and controlling blood pressure. In a select patient population, resistant hypertension may occur. Optimizing therapy and utilizing primary and secondary agents along with nonpharmacological interventions remains the current management efforts of this problem.


  • American Heart Association News. More than 100 million Americans have high blood pressure, AHA says. AHA website. Published January 31, 2018. Accessed April 2019.
  • American College of Cardiology. New ACC/AHA High Blood Pressure Guidelines Lower Definition of Hypertension. ACC website. Published November 13 2017. Accessed April 2019.
  • Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of American College of Cardiology. Volume 71, Issue 19, May 2018. DOI: 10.1016/j.jacc.2017.11.006
  • Yaxley JP, Thambar SV. Resistant hypertension: an approach to management in primary care. J Family Med Prim Care. 2015;4(2):193—199. doi:10.4103/2249-4863.154630