Hypertension Management

Last updated: 06 May 2025

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Evaluation

If the patient is found to have chronically elevated blood pressure, then they should undergo further assessment to determine secondary causes, target organ damage, CVD risk factors, or concomitant disorders that will affect the prognosis. Individuals at increased risk for CVD events include those with established CVD, HMOD, DM, familial hypercholesterolemia or moderate or severe CKD.

The following are identifiable secondary causes of hypertension:

  • Chronic kidney disease
  • Chronic steroid therapy and Cushing syndrome
  • Coarctation of the aorta
  • Obesity
  • Takayasu arteritis
  • Pheochromocytoma
  • Primary aldosteronism
  • Renovascular disease
  • Obstructive sleep apnea
  • Thyroid and parathyroid disorders
  • Congenital adrenal hyperplasia
  • Alcohol- or drug-induced: Prescription, over-the-counter medications, herbal supplements, use of illicit drugs, etc.

The following are CVD risk factors:

  • Increased age
  • Male sex
  • Smoking
  • Unhealthy diet or physical inactivity
  • Low educational or socioeconomic status
  • Diabetes mellitus
  • Overweight or obesity
  • Dyslipidemia
  • Hyperuricemia
  • Metabolic syndrome
  • Obstructive sleep apnea
  • Chronic kidney disease
  • Psychosocial stress
  • Family history of premature CVD (<55 years for male relative or <65 years for female relative)
  • Abdominal obesity (waist circumference [Asian]: Men ≥90 cm; women ≥80 cm)
  • Early-onset menopause

The following are signs or conditions that may point to target organ damage:

  • Heart: Left ventricular hypertrophy, angina or prior myocardial infarction, prior coronary revascularization, heart failure
  • Brain: Stroke or transient ischemic attack (TIA), dementia
  • Kidney: Chronic kidney disease
  • Vascular: Peripheral arterial disease
  • Eyes: Retinopathy



Risk Stratification
 

All patients should be classified not only in relation to stages of hypertension but also in terms of total cardiovascular risk resulting from the coexistence of different risk factors, organ damage, and related diseases. Decisions on the management of hypertension and subsequent follow-up should be based on blood pressure levels along with other cardiovascular risk factors and target organ damage.     

Systolic blood pressure is better in quantifying prognosis than diastolic blood pressure in patients >50 years old. Although in younger patients without comorbidities, diastolic blood pressure is a more important cardiovascular risk factor. Pulse pressure is also a good predictor of cardiovascular events, especially in elderly patients.  

To estimate the 10-year risk of ASCVD, the ACC/AHA pooled cohort equations (http://tools.acc.org/ASCVD-Risk-Estimator/) or the Systemic COronary Risk Evaluation (SCORE) system may be used. Atherosclerotic CVD was defined as first coronary heart disease death, fatal or nonfatal stroke, or nonfatal myocardial infarction. Hypertensive patients who are not at high or very high risk due to established CVD, CKD, or long-lasting or complicated diabetes, severe HMOD, familial hypercholesterolemia or a markedly elevated single risk factor are recommended to have cardiovascular risk assessment with the SCORE2 and SCORE2-OP system. Patients with elevated blood pressure and a SCORE2 or SCORE2-OP CVD risk of ≥10% are considered at increased risk for CVD. Consider using SCORE2-Diabetes in estimating CVD risk in type 2 DM patients with elevated blood pressure, particularly if <60 years old.

CVD risk modifiers for up-classification of risk in individuals with elevated blood pressure and 10-year CVD risk of 5-<10% include:

  • Sex specific risk modifiers: Gestational diabetes, gestational hypertension, preeclampsia, preterm delivery, ≥1 stillbirths, recurrent miscarriages
  • Shared risk modifiers: High-risk ethnicity (eg South Asian), family history of premature-onset ASCVD, socioeconomic deprivation, autoimmune inflammatory diseases, HIV, severe mental illness

Consider the following risk tool tests to improve risk stratification in individuals with elevated blood pressure and 10-year CVD risk of 5-<10%:

  • Coronary artery calcium (CAC) score
  • Cardiac biomarkers: High-sensitivity cardiac troponin or N-terminal pro-brain natriuretic peptide (NT-proBNP)
  • Carotid or femoral artery ultrasound to detect plaque
  • Pulse wave velocity to detect arterial stiffness

 

RISK STRATIFICATION TO QUANTIFY PROGNOSIS
 





Blood Pressure (mmHg)
 Hypertension Disease Stage 
Stage 1  Stage 2   Stage 3
No Other Risk Factors 1-2 Risk Factors ≥3 Risk Factors TOD, CKD Grade 3
or DM without TOD
Established CVD,
CKD Grade ≥4
or DM with TOD
SBP 130-139 or DBP 85-89 Low risk
Low risk Low to Moderate risk Moderate to High risk Very high risk
SBP 140-159 or DBP 90-99 Low risk Moderate risk Moderate to High risk High risk Very high risk
SBP 160-179 or DBP 100-109 Moderate risk Moderate to High risk High risk High risk Very high risk
SBP ≥ 180 or DBP ≥ 110 High risk High risk High risk Very high risk Very high risk
SBP: Systolic Blood Pressure; DBP Diastolic Blood Pressure; CKD: Chronic Kidney Disease; DM: Diabetes Mellitus; CVD: Cardiovascular Disease; TOD: Target Organ Damage
Reference: 2023 European Society of Hypertension (ESH) Guidelines for the management of arterial hypertension.

Principles of Therapy

The treatment goals in managing hypertension include choosing an evidence-based therapeutic agent to minimize the long-term risk of CV morbidity and mortality, all-cause mortality and improve quality of life; determining the initial blood pressure threshold requiring treatment and the target blood pressure to achieve and maintain blood pressure goal based on age, risk stratification, and presence and absence of comorbidities (eg diabetes mellitus and CKD); reaching blood pressure target early and maintaining blood pressure with high time-in-target range to ensure treatment benefit and safety; and identifying factors that affect patient’s adherence to treatment. Additionally, to prevent complications through the identification and management of all other identified and reversible risk factors for CVD such as diabetes mellitus or glucose intolerance, lipid disorders, obesity, and smoking. It is also important to and to manage concomitant disorders such as diabetes mellitus, established CVD, or renal disease according to current guideline recommendations. Another goal is to prevent the progression or recurrence of CVD in hypertensive patients with established CVD. 

Target Blood Pressure1  

If the therapy is well tolerated, a treated systolic blood pressure goal of 120-129 mmHg is recommended to reduce CVD risk. If a target systolic blood pressure of 120-129 mmHg is not possible and treatment is poorly tolerated, it is recommended to target a systolic blood pressure level that us as low as reasonably achievable (preferably <140 mmHg). 

A diastolic blood pressure goal of 70-79 mmHg may be considered to reduce CVD risk if the systolic blood pressure is at or below target but diastolic blood pressure is ≥80 mmHg. 

A more lenient blood pressure target (<140/90 mmHg) is considered in the following patients:

  • Age ≥85 years
  • Moderately to severely frail (at any age)
  • With limited lifespan (eg <3 years)
  • With orthostatic hypotension

 
Initiating Treatment1  

Treatment is initiated in patients 18-79 years old with a blood pressure of ≥140/90 mmHg. The decision to initiate therapy is based on the untreated blood pressure level and the presence of target organ damage or concomitant disorders (eg established CVD, HMOD, DM, familial hypercholesterolemia or moderate or severe CKD). A risk-based approach is recommended in the treatment of elevated blood pressure. CVD risk stratification may be done at or after treatment initiation but only when it is feasible and will not delay treatment.  

Primary prevention is recommended for patients without prior history of CVD but with a ≥10% estimated 10-year ASCVD risk and systolic blood pressure of ≥130 mmHg or diastolic blood pressure of ≥80 mmHg, and in patients without prior history of CVD but with a <10% estimated 10-year ASCVD risk and systolic blood pressure of ≥140 mmHg or diastolic blood pressure of ≥90 mmHg. Secondary prevention of recurrent CVD events is recommended in patients with existing clinical CVD and systolic blood pressure of ≥130 mmHg or diastolic blood pressure of ≥80 mmHg.  

Implement lifestyle changes throughout the management. A defined time period of lifestyle changes may be considered in patients with medication intolerance or elevated blood pressure and <10% estimated 10-year ASCVD. Pharmacological treatment is initiated in patients with elevated blood pressure and ≥10% 10-yearASCVD risk (or 5-<10% 10-year ASCVD risk plus risk modifiers or abnormal risk tool tests, or high-risk conditions) if after 3 months of lifestyle changes blood pressure is ≥130/80 mmHg. Medication is started together with lifestyle changes in patients with elevations in systolic blood of >20 mmHg or diastolic blood pressure of >10 mmHg above blood pressure goal, those with target organ damage on screening, and in fit patients 65-80 years old with a systolic blood pressure of 140-159 mmHg if therapy is well tolerated. In patients with a blood pressure of ≥140/90 mmHg regardless of CVD risk, pharmacological therapy is started with lifestyle changes to reduce CVD risk. 

If with high-normal blood pressure, consider initiating drug treatment in very high-risk patients with CVD, especially coronary artery disease. Treatment of elevated blood pressure and hypertension in patients <85 years old and not moderately frail is the same as that for younger individuals provided therapy is well tolerated. Caution is advised when considering treatment in patients with elevated blood pressure and are ≥85 years old, moderately to severely frail or have symptomatic orthostatic hypotension. Start drug treatment promptly in all patients for whom it is necessary to achieve more rapid control of blood pressure.    

1Recommendations may vary between countries. Please refer to available guidelines from local health authorities  

Treatment Regimen  

Assessment of blood pressure and adjustment of the treatment regimen is continuous until the blood pressure goal is reached. Different initial strategies may be considered based on individual circumstances and the preferences of the physician and the patient.  

Although most patients will need >1 drug to achieve blood pressure control, it is reasonable to start with a single antihypertensive agent (monotherapy) in low-risk patients with low baseline blood pressure that is close to the recommended goal, high-risk patients with high-normal blood pressure, frail or old patients who need gentle blood pressure reduction, or those who have a history or are at risk of hypotension or drug-associated side effects. Dosage titration and sequential addition of other agents may be done to achieve the target blood pressure.   

Two first-line agents from separate drug classes, either separately or in a fixed-dose or single-pill combination (combination therapy) are recommended in patients with an average blood pressure of >20/10 mmHg above their target. It has been shown in the general population of individuals with hypertension that combination therapy at a low dose is more effective than monotherapy at a maximal dose. If the target blood pressure cannot be achieved using 2 drugs, an increase in treatment to 3-drug combination therapy (preferably in a single-pill combination) may be done.  

Initial doses of drugs should be at least half the maximum dose so only one dose adjustment is needed to be done thereafter. In general, an effective regimen is expected to be reached within 6-8 weeks, regardless of whether 1, 2, or 3 drugs were employed. Consider stepping down the therapy if the patient's blood pressure remains controlled after 1-2 years of therapy and is without symptoms related to hypertension or target organ damage.

Prior to starting or intensifying blood pressure-lowering treatment to test patient for orthostatic hypotension (≥20 systolic blood pressure and/or ≥10 diastolic blood pressure mmHg drops at 1 and/or 3 minutes after standing following a 5-minute period of lying or sitting position). In patients with orthostatic hypotension, it is recommended to switch to an alternative blood pressure-lowering drug and to not de-intensify treatment. It is recommended to maintain the treatment lifelong, even beyond 85 years of age, if well tolerated. 

Referral to a hypertension specialist may be necessary when blood pressure goals cannot be achieved despite the above strategies or when managing complicated patients for whom additional consultation is warranted.  

Choice of Antihypertensive Agents  

The choice of antihypertensive agents is influenced by the patient’s age, ethnicity or race, previous history with antihypertensive medications (as it is important to monitor for adverse reactions to avoid patient’s noncompliance with medications), presence of other medical conditions (eg coronary diseases, diabetes mellitus, renal disease, pregnancy), the possibility of drug interactions with drugs used for other conditions, patient preference, medication costs or affordability (although this should not predominate efficacy and tolerability), and availability of the drugs. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) should be included in the antihypertensive agents of patients with CKD to improve renal outcomes.

Long-acting dihydropyridine calcium antagonists or renin-angiotensin system inhibitors are considered in patients ≥85 years old and/or with moderate to severe frailty (at any age), followed by a low-dose diuretic if necessary and if tolerated, but preferably not a beta-blocker (except for compelling indications) or an alpha-blocker. Calcium antagonists or thiazide-like diuretics should be included in the antihypertensive agents of black individuals.

Long-acting drugs or preparations providing 24 hours of efficacy that can be given once daily are preferred. This improves compliance and minimizes blood pressure variability. Additionally, once-daily drugs can be taken at any time during the day (either morning or evening). When >1 drug is needed, the use of a combination product (≥2 appropriate medications in a single tablet) can simplify the regimen and improve the adherence of patients. A new therapeutic approach to improve blood pressure control is the use of a quadpill which contains quarter doses of 4 drugs.  


Hypertension_ManagementHypertension_Management



Coronavirus Disease 2019 (COVID-19) Infection and Hypertension

Evidence demonstrates that the risk for severe COVID-19 is increased in the presence of hypertension. Hence, it is important to advise hypertensive patients to continue home blood pressure monitoring and if required, telehealth services (eg phone or video consultation) may be used to access healthcare providers during the COVID-19 pandemic.  

Antihypertensive therapy should follow current guideline recommendations. The risk of COVID-19 infection or the risk of developing severe COVID-19 complications is not increased with prior or current treatment with ACE inhibitors or with ARBs, thus treatment should be continued as prescribed. Treatment may be withdrawn temporarily in patients who develop hypotension or acute kidney injury from severe COVID-19 infection. Parenteral antihypertensive medications are necessary for patients previously treated for hypertension who developed persistent severe hypertension requiring invasive ventilation.  

It is essential to monitor for arrhythmias in hypertensive patients with cardiac disease and for hypokalemia in those with severe COVID-19 infection.  

Pharmacological therapy

The WHO recommends the use of medications from any of the following 3 drug classes as first-line antihypertensive agents: ACE inhibitors or ARBs, calcium antagonists, and thiazide and thiazide-like diuretics.   

Angiotensin-converting Enzyme (ACE) Inhibitors  

ACE inhibitors work by preventing the conversion of angiotensin I to angiotensin II by inhibiting the angiotensin-converting enzyme. They are suitable for the initiation and maintenance of therapy for hypertension. They have established clinical outcome benefits in patients with chronic heart failure (CHF) and post-myocardial infarction patients with reduced left ventricular ejection fraction and are also effective in reducing left ventricular hypertrophy and preserving kidney function. They are given as first-line agents at maximally tolerated doses to CKD patients with a urinary albumin-to-creatinine ratio of ≥30 mg/g (or equivalent).  

They are well-tolerated, although their most common side effect is dry cough (most common in women and among Asian and African patients) related to the effects of bradykinin or prostaglandin metabolism. There is a risk of hypotension when starting treatment with ACE inhibitors in patients who are already on diuretics, are on a low-salt diet, or are dehydrated. For patients on diuretics, skipping a dose prior to starting an ACE inhibitor may help prevent this sudden drop in blood pressure. They should not be combined with ARBs or direct renin inhibitors. Drug effects do not seem to have dose-dependent effects, except for hyperkalemia which may occur more frequently with high doses, thus allowing patients to initiate treatment using medium or even approved high doses.  

Alpha-Blockers  

Alpha-blockers reduce blood pressure by blocking the arterial alpha-adrenergic receptors and in effect, preventing the vasoconstrictor actions of these receptors. They are less widely used as first-line agents due to the limited evidence for their clinical outcome benefits. They are useful in treating resistant hypertension when used in combination with other agents such as beta-blockers, diuretics, and ACE inhibitors. They are considered a beneficial part of treatment regimens for older hypertensive men with benign prostatic hypertrophy and have favorable effects on blood glucose and lipid levels.  

Angiotensin II Antagonists (also called Angiotensin Receptor Blockers or ARBs)  

ARBs act by blocking the action of angiotensin II on its angiotensin-1 (AT1) receptors, thereby preventing the vasoconstrictor effects of this receptor. They provide the same cardiovascular and renal benefits as ACE inhibitors. They are recommended as first-line agents at maximally tolerated doses to CKD patients with urinary albumin-to-creatinine ratio of ≥30 mg/g. They can also be used to prevent the recurrence of atrial fibrillation. Similarly, they should not be combined with ACE inhibitors or direct renin inhibitors.  

They are well tolerated and do not cause cough and only rarely cause angioedema. The drug effects do not appear to have dose-dependent effects, thereby allowing patients to start with low to maximum approved doses in single-pill combination. For patients on diuretics, skipping a dose of the diuretic prior to starting ARBS may help prevent a sudden drop in blood pressure.  

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

Example drugs: Sacubitril/ Valsartan
 

ARNI is indicated for the treatment of essential hypertension. It acts by inhibiting neprilysin which slows down the degradation of natriuretic peptides, bradykinin, and other peptides leading to high amounts of circulating A-type natriuretic peptide and BNP resulting in diuresis, natriuresis and relaxation and anti-remodeling of the myocardium. However, it should not be used as first-line agent for hypertension treatment due to the risk of excessive blood pressure reduction.  

Beta-Blockers  

Beta-blockers work by acting as competitive antagonists of the effects of catecholamines at beta-adrenergic receptor sites. Beta-blockers have different affinities for beta1- or beta2- blockade but as doses are increased, the activity of beta2 receptors can become apparent in beta1 selective inhibitors. Beta2-blockade can increase bronchial resistance and inhibition of catecholamine-induced glucose metabolism.  

They may be combined with any of the other major drug classes at any step of the hypertension treatment when indicated (eg post-myocardial infarction, heart failure, angina, atrial fibrillation, or young women planning to get pregnant or are pregnant). For patients without conditions warranting beta-blockade, beta-blockers should not be used as initial therapy.  

They are considered the drug of choice in patients with a history of myocardial infarction and heart failure. They are useful in patients with effort angina and tachyarrhythmia and have been shown to reduce cardiovascular morbidity and mortality in post-myocardial infarction patients and the risk of exacerbations and mortality in patients with chronic obstructive lung disease. The specified beta-blockers for heart failure include Bisoprolol, Carvedilol, Metoprolol succinate, and Nebivolol.  

Studies show that Celiprolol, Carvedilol, and Nebivolol (third generation of beta-blockers) can reduce central pulse pressure and aortic stiffness as compared to Metoprolol and Atenolol (second generation of beta-blockers). Nebivolol has lesser effects on insulin sensitivity than Metoprolol.  

Combination with a thiazide diuretic is shown to have dysmetabolic effects and increased incidence of new-onset diabetes among patients and is therefore, not recommended in patients at risk for diabetes.  

Calcium Antagonists  

Calcium antagonists act by blocking the inward flow of calcium ions through the L channels of arterial smooth muscle cells. They are powerful antihypertensive agents, especially when given in combination with ACE inhibitors or ARBs.  

Their main side effect is peripheral edema, most especially at high doses, although a clinical rather than a laboratory approach is most often enough to eliminate renal or hepatic etiology for the edema. This is reduced by combining calcium antagonists with ACE inhibitors or with ARBs.  

Dihydropyridine Calcium Antagonists

Example drugs: Amlodipine, Cilnidipine, Felodipine, Isradipine, Manidipine, Nicardipine, Nifedipine, Nisoldipine  


Dihydropyridine calcium antagonists are usually used for their antihypertensive and anti-anginal effects. They have shown beneficial effects on stroke and cardiovascular outcomes in hypertension trials. Dihydropyridines (but not non-dihydropyridines) can be safely combined with beta-blockers.  

They have greater selectivity for vascular smooth muscle than for myocardium and their main effect is vascular relaxation. They have little or no effect on the sinoatrial or atrioventricular nodes and negative inotropic activity is not typical at therapeutic doses.  

Non-dihydropyridine Calcium Antagonists

Example drugs: Diltiazem, Verapamil  

Non-dihydropyridines are typically used for their antiarrhythmic, anti-anginal, and antihypertensive properties. They tend to have less selective vasodilatory activity than dihydropyridine calcium antagonists and they have a direct effect on the myocardium causing depression of sinoatrial or atrioventricular conduction.  

They are preferred in patients with fast heart rates and as rate controllers for atrial fibrillation patients who cannot tolerate beta-blockers. A randomized controlled trial revealed that Verapamil plus Trandolapril was as clinically effective as Atenolol plus Hydrochlorothiazide in hypertensive patients with coronary artery disease. They are also preferred in patients with proteinuria due to the additional antiproteinuric effect in Diltiazem and Verapamil.  

Direct Renin Inhibitors

Example drug: Aliskiren
 

Direct renin inhibitors are found to be as effective as ARBS and ACE inhibitors without a dose-related increase in side effects in the elderly. Combination with an ACE inhibitor or ARBs is not recommended.  

Currently available data show that Aliskiren, as monotherapy, lowers systolic and diastolic blood pressure in younger and elderly hypertensive patients. It has a greater blood pressure-lowering effect when used in combination with a thiazide diuretic, a renin-angiotensin blocker, or a calcium antagonist. Its prolonged use in combination treatment can have a favorable effect on asymptomatic organ damage. It also appears well tolerated among patients >75 years of age, including those with renal disease (with an estimated glomerular filtration rate [GFR] of ≥30 mL/min/1.73 m2).  

Its main side effect is mild diarrhea.  

Diuretics  

The use of diuretics has been well-established in the treatment of hypertension and are suitable for the initiation and maintenance of therapy. They reduce the risk of fatal and nonfatal stroke and have been shown to reduce cardiovascular morbidity and mortality, and all-cause mortality. It is considered the drug of choice in the elderly with no comorbid conditions.  

When used in combination, they may enhance the efficacy of the concurrently used antihypertensive drug. Combination treatment with potassium-sparing diuretics (eg Amiloride, Triamterene), mineralocorticoid antagonists (eg Spironolactone, Eplerenone), and epithelial sodium transport channel antagonists with other agents are useful in treating hypertension by reducing vascular stiffness and systolic blood pressure.  

Aldosterone Antagonists or Mineralocorticoid Receptor Antagonists

Example drugs: Spironolactone, Eplerenone
 

Aldosterone antagonists or mineralocorticoid receptor antagonists are the preferred therapeutic agents for resistant hypertension and primary aldosteronism. They are used as part of the standard treatment of heart failure. They can be effective in lowering blood pressure when added to a standard 3-drug regimen (ACE inhibitor or ARB/calcium antagonist/diuretic) for treatment-resistant hypertension after excluding secondary hypertension. Aldosterone antagonists are contraindicated in patients with hyperkalemia and severe renal impairment.   

Loop Diuretics

Example drugs: Furosemide, Torasemide, Bumetanide  


Loop diuretics are the preferred agents in patients with symptomatic heart failure and are preferred over thiazide diuretics in patients with chronic kidney disease stage 4 and 5.  

Thiazide and Thiazide-like Diuretics

Example drugs: Chlorthalidone, Hydrochlorothiazide, Indapamide, Metolazone
 

Thiazides and thiazide-like diuretics act by increasing the elimination of sodium by the kidneys and may have some vasodilator effects. They are considered most effective in blood pressure reduction when combined with ACE inhibitors or ARBs. They are also effective when combined with calcium antagonists.  

They have proven clinical outcome benefits in reducing strokes and major cardiovascular events. Chlorthalidone has a longer duration of action and has been proven to reduce the risk of CVD. It was suggested by some meta-analyses and a large randomized controlled trial comparing first-step agents that diuretics, especially the long-acting thiazide-like agent Chlorthalidone, may provide an optimal choice for the initial treatment of hypertension.  

Their main side effects (metabolic, such as hypokalemia, hyponatremia, hyperuricemia, hyperglycemia) are reduced by lowering the doses or combining them with ACE inhibitors. They are also used in combination with potassium-sparing diuretics to prevent thiazide-induced hypokalemia.  

Other Antihypertensives  

Centrally Acting Agents

Example drugs: Clonidine, Methyldopa
 

Centrally acting agents act by reducing sympathetic outflow from the central nervous system. They are more often used nowadays as part of multiple drug combinations. Methyldopa may be considered for resistant hypertension in combination with other antihypertensive agents. They are considered safe to use during pregnancy.  

Direct Vasodilators

Example drugs: Hydralazine, Minoxidil
 

Direct vasodilators are most effective in reducing blood pressure when combined with diuretics and beta-blockers or sympatholytic agents. They are usually used only as fourth-line or as later additions to treatment regimens.  

Endothelin Receptor Antagonist

Example drug: Aprocitentan  

Endothelin receptor antagonist is indicated for the treatment of hypertension in combination with other antihypertensive medications for blood pressure reduction in adult patients with resistant hypertension. It has a sustained blood pressure-lowering effect in patients with resistant hypertension. The drug is available through a restricted distribution program called the Tryvio REMS for women of child-bearing potential. 

INDICATIONS AND PREFERRED ANTIHYPERTENSIVE TREATMENT

Indication

Preferred Antihypertensives

Angina pectoris

  • Beta-blocker
  • Calcium antagonist

Asymptomatic atherosclerosis

  • ACE inhibitor
  • Calcium antagonist

Atrial fibrillation

Recurrent:

  • Angiotensin II antagonist
  • ACE inhibitor
  • Beta-blocker
  • Aldosterone antagonist

Permanent:

  • Beta-blocker
  • Calcium antagonist (Nondihydropyridine)

Diabetes mellitus*

Combination of ≥2 drugs are typically needed to reach target BP

  • ACE inhibitor
  • Angiotensin II antagonist
  • Calcium antagonist
  • Beta-blocker
  • Thiazide diuretic

Heart failure*

Asymptomatic patients with ventricular dysfunction:

  • ACE inhibitor

Symptomatic ventricular dysfunction or end-stage heart disease:

  • ACE inhibitor
  • Angiotensin II antagonist
  • Angiotensin receptor-neprilysin inhibitor
  • Aldosterone antagonist
  • Beta-blocker
  • Diuretic

Isolated systolic hypertension (ISH) (elderly)

  • Diuretics
  • ACE inhibitor
  • Angiotensin II antagonist
  • Direct renin inhibitor
  • Calcium antagonist

LV hypertrophy

  • Angiotensin II antagonist
  • ACE inhibitor
  • Calcium antagonist
  • Diuretic

Metabolic syndrome

  • ACE inhibitor
  • Angiotensin II antagonist
  • Calcium antagonist

Microalbuminuria

  • ACE inhibitor
  • Angiotensin II antagonist
  • Direct renin inhibitor

Peripheral arterial disease

  • Calcium antagonist
  • Beta-blocker (if with arterial hypertension)
  • ACE inhibitor

Post MI

  • ACE inhibitor
  • Aldosterone antagonist
  • Angiotensin II antagonist
  • Beta-blocker

Post stroke

  • ACE inhibitor
  • Angiotensin II antagonist
  • Calcium antagonist
  • Thiazide-like diuretic

Proteinuria/End-stage renal disease*

  • ACE inhibitor
  • Loop diuretics
  • Angiotensin II antagonist
  • Calcium antagonist

ACE: Angiotensin converting enzyme; ARB: Angiotensin receptor blocker; Ca: Calcium
*Sodium-glucose linked transporter 2 (SGLT2) inhibitors are included in the treatment strategies of hypertensive patients with type 2 diabetes mellitus, heart failure and CKD.


Effective Antihypertensive Combinations
 
Antihypertensive combinations include an ACE inhibitor or angiotensin II antagonist plus a calcium antagonist and/or a diuretic. Combination therapy can be initiated in high-risk patients (eg ASCVD, diabetes mellitus, CKD) with high-normal blood pressure, or in patients with blood pressure of ≥140/90 mmHg. If blood pressure control cannot be achieved with a 2-drug combination after titrating from low to full doses, a 3-drug combination may be used, preferably in a fixed-dose or single-pill combination. A beta-blocker may be added to any treatment step when compelling indication is present (eg atrial fibrillation, angina, heart failure, post-MI, or young women planning to get pregnant or are pregnant).



Resistant Hypertension
 

Resistant hypertension is considered when the target blood pressure is not achieved, and the patient was already treated with ≥3 drugs at optimal doses (including a diuretic) or the blood pressure is <130/80 mmHg but the patient was treated with ≥4 drugs.  

For patients not controlled on 3 drugs, maximizing diuretic therapy and adding an aldosterone antagonist (eg Spironolactone), a beta-blocker, a centrally acting agent, an alpha-blocker, or a direct vasodilator or an endothelin receptor antagonist will often be helpful. If patient is intolerant to Spironolactone, consider additional diuretic therapy (eg Amiloride, Eplerenone, a loop diuretic, or a higher-dose thiazide or thiazide-like diuretic).  Thiazide or thiazide-like diuretics are recommended if eGFR is ≥30 mL/min/1.73 m2; loop diuretics should be used if eGFR is <30 mL/min/1.73 m2.  

If blood pressure is still uncontrolled after 3 drugs at near-max doses, consider inaccurate blood pressure measurements, nonadherence to lifestyle modifications, noncompliance to treatment regimen, drug interactions, white coat hypertension, secondary hypertension, or complications of long-standing hypertension (eg nephrosclerosis).  

Other interventions that can be considered include bedtime dosing in patients with documented high night-time blood pressure for greater morning blood pressure reduction, referral to a hypertension specialist if after 6 months of therapy, blood pressure remains uncontrolled, and renal denervation if eGFR ≥40 mL/min/1.73 m2.  

Nonpharmacological

Lifestyle Modification

Lifestyle modification is considered the cornerstone of hypertension prevention and treatment. The blood pressure lowering effects of lifestyle intervention can be equivalent to drug monotherapy; however, its major drawback is diminishing patient compliance over time.  

It is effective in the prevention or delay of hypertension among non-hypertensive individuals, as well as in the prevention of or delay in the use of drug therapy among those in stage 1 hypertension. It contributes to blood pressure reduction among hypertensive patients already on drug therapy, allowing for the reduction of the doses and the number of antihypertensive agents. It may also contribute to the control of other medical conditions and cardiovascular risk factors. Annual follow-up is recommended to detect and treat hypertension as early as possible.
 
Weight Reduction and Maintenance  

Weight reduction is helpful in treating hypertension, diabetes mellitus, and lipid disorders, especially among overweight or obese patients. A weight loss of ≥5% in overweight or obese patients is considered significant. Maintenance of healthy body weight (BMI of about 23 kg/m2) and waist circumference (<90 cm in men; <80 cm in women) should be encouraged. Patients should be informed that systolic blood pressure is reduced by 1 mmHg with a weight loss of 1 kg from baseline. A multidisciplinary approach that includes regular exercise and physical activity, and an appropriate healthy diet including an increased intake of polyunsaturated fatty acids, decreased total and saturated fat, increased dietary potassium, decreased sodium intake, and moderation in alcohol intake should be promoted.  

Additionally, there is a known relationship between obesity and obstructive sleep apnea (OSA), hence weight loss and exercise are recommended. Continuous positive airway pressure (CPAP) therapy may also be used to reduce obstructive sleep apnea.  

Salt Restriction
 

Higher salt sensitivity, even with mild obesity and higher salt intake, is an Asian characteristic of hypertension. There is evidence that a causal relationship between blood pressure and salt intake exists in which excessive salt intake may contribute to resistant hypertension, and the mechanisms involved are increasing peripheral vascular resistance and extracellular volume.  

A daily intake of 5-6 g of salt is recommended for the general population with an optimal goal of <1.5 g/day. Studies have shown that a salt reduction to about 5 g/day results in a modest (1-2 mmHg) systolic blood pressure-lowering effect among normotensive individuals while the effect is more pronounced (4-5 mmHg) among hypertensive individuals. The effects of salt reduction are seen more among older people, among the black population, and in patients with metabolic syndrome, diabetes mellitus, or CKD.  

Other Dietary Changes  

Advise patients to follow the Mediterranean or Dietary Approaches to Stop Hypertension (DASH) diet and to consume whole grains and proteins from plant sources, soluble fiber, and low-fat dairy products. Advise patients to replace the traditional diet with fresh vegetables and fruits, although consumption of fruits among overweight patients should be done with caution due to the possible high carbohydrate content of some fruits which may promote weight gain. Potassium supplementation (3.5-5 g/day) is recommended except in patients with CKD or patients using drugs that decrease the excretion of potassium. Consumption of sweets, sugar-sweetened beverages, and red meat is discouraged or restricted. 

Regular Exercise  

Regular aerobic and resistance exercises can contribute to both the prevention and management of hypertension and lower the risk of cardiovascular morbidity and mortality. Additionally, it minimizes the need for more intensive medical intervention and enhances treatment endpoints. It is important to start slowly then gradually increase the exercise intensity. A study showed that a decrease in the risk of coronary heart disease is related more to the intensity of physical activity than to the amount of exercise time. Patients may be advised to engage in at least 30 minutes of moderate-intensity dynamic aerobic exercise (eg walking, cycling, jogging, swimming) for 5-7 days weekly or 75 minutes of vigorous intensity aerobic exercise for 3 days weekly together with resistance training 2-3 times per week to lower blood pressure and CVD risk. 

Moderate Alcohol Consumption  

Discourage excessive alcohol consumption since great amounts can raise blood pressure. Advise patients to limit alcohol consumption to about 100 grams per week of pure alcohol or ≤2 drinks per day for men and 1 drink per day for women.

Smoking Cessation  

Since smoking is a major cardiovascular risk factor, patients must be advised to stop this habit. In addition, smoking cessation is a most effective lifestyle measure for preventing CVD, including myocardial infarction, stroke, and peripheral vascular diseases (PVDs).

Patient Education

For patients who have high normal or elevated blood pressure, inform patients that they are at high risk for developing hypertension and that lifestyle modification may reduce this risk. Advise those patients with diabetes mellitus and kidney disease that they are candidates for drug therapy if lifestyle modification fails to decrease their blood pressure to goal. Remind patients that periodic follow-up (eg every 3-6 months) is recommended to detect and treat hypertension as early as possible.

All patients need to be highly motivated to establish and maintain a healthy lifestyle and to take the prescribed antihypertensive medications. Discuss with the patient the medication’s benefits/safety and side effects. If the diagnosis of hypertension is not made, measure the patient’s clinic blood pressure at least annually thereafter. More frequent blood pressure measurements may be needed for patients whose clinic blood pressure is close to 130/80 mmHg. Encourage patients to measure their blood pressure at home. In Asians, strict 24-hour blood pressure control starting with Home Blood Pressure Monitoring is important. 

Patients should be made aware that lowering BP can decrease the risk of death from stroke, coronary events, and heart failure, along with decreasing the progression of renal failure. All causes of mortality can be reduced with effective antihypertensive management.  

Work with the patient to establish the goal of therapy. Notably, stress reduction (eg transcendental meditation) can have modest effects on BP control. The patient’s cultural beliefs may influence their attitude and the physician needs to be sensitive when handling these issues.  

Blood Pressure Measurement and Monitoring  

Before taking the blood pressure measurements, advise patients to avoid exercise, caffeine intake, and smoking at least 30 minutes prior to the measurement. Remove any clothing that can hinder cuff placement. Make sure that all devices to be used are working properly (tubes, cuff, batteries, stethoscope) and that the logbook is within reach. Remind the patient to avoid crossing their legs, talking, and any sudden movements during the measurement.    

Advise patients about the different blood pressure measuring devices. Make sure that the devices to be used are professionally validated and calibrated annually. Devices that measure blood pressure from the brachial artery are preferred to those that read from distal sites (fingers, wrists). Electronic or digital blood pressure devices are preferred to be used; however, patients and caregivers should be well trained in using an aneroid blood pressure device. Advise patients to have their mercurial or aneroid apparatus checked every 1-2 years and every 6 months for electronic devices. Inform patients about appropriate cuff sizes as listed on the table below:

RECOMMENDED CUFF SIZES
Arm Circumference Description Cuff Size
22-26 cm Small adult 12x22 cm
27-34 cm Adult 16x30 cm
35-44 cm Large adult 16x36 cm
45-52 cm Adult thigh 16x42 cm


Instruct patients on how to do self-measurement or monitoring of blood pressure. Advise them to measure at the same time in the morning and evening, find a quiet room with a comfortable chair, rest for at least 5 minutes before taking blood pressure measurement, and sit down with their back supported, feet on the floor, arm supported horizontally, and blood pressure cuff at the level of the heart.  

Additionally, instruct the patient that when using a sphygmomanometer, slowly inflate the cuff while palpating the brachial artery and when the pulse disappears (systolic blood pressure), slowly deflate the cuff, taking note when the pulse reappears (diastolic blood pressure). With the use of a stethoscope, reinflate the cuff 20 mmHg above the previous systolic blood pressure, then deflate the cuff by 1-2 mmHg/sec. Inform the patient that when a tapping sound is heard, this is the systolic blood pressure; when it disappears, it is the diastolic blood pressure. Advise the patient to follow instructions on how to use electronic devices properly as well. Remind the patient to stay still while the apparatus takes the blood pressure reading. Ask the patient to wait for 1-2 minutes, then take another blood pressure measurement. Advise the patient to write the results in the logbook immediately after each reading.

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