Evaluation
If the patient is found
to have chronically elevated BP, 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, diabetes mellitus, familial
hypercholesterolemia or moderate or severe CKD.
The following are identifiable
secondary causes of hypertension:
- Acromegaly
- CKD
- Chronic steroid therapy and Cushing syndrome
- Coarctation of the aorta
- Congenital adrenal hyperplasia
- Obesity
- Obstructive sleep apnea
- Pheochromocytoma/paraganglioma
- Primary aldosteronism
- Mineralocorticoid excess syndromes other than primary aldosteronism
- Renovascular disease
- Takayasu arteritis
- Thyroid and parathyroid disorders
- 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
- CKD
- 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: CKD
- 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 CV risk factors and target organ damage.
SBP
is better in quantifying prognosis than DBP
in patients >50 years old. Although in younger patients without
comorbidities, DBP is a more important CV
risk factor. Pulse pressure is also a good predictor of CV
events, especially in elderly patients.
The 2025 AHA/ACC high BP
guideline recommends the use of Predicting Risk CVD EVENTs (PREVENTTM)
equations (https://professional.heart.org/en/guidelines-and-statements/prevent-risk-calculator/prevent-calculator)
to estimate the 10-year risk of total CVD (myocardial infarction, stroke, heart
failure) for adults with hypertension without clinical CVD in determining the
BP threshold for treatment initiation. The PREVENTTM equations,
developed for absolute risk assessment of total CVD, provide 10- and 30-year
risk estimates, include eGFR as a predictor, adjust for competing risk of
non-CVD death in adults 30-79 years old, and integrate the social deprivation
index (SDI) within a CV-kidney-metabolic health framework.
The ACC/AHA pooled
cohort equations (PCE) (http://tools.acc.org/ASCVD-Risk-Estimator/) or the
Systemic COronary Risk Evaluation (SCORE) system may also be used to estimate
the 10-year risk of ASCVD. ASCVD 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 CV risk assessment
with the SCORE2 and SCORE2-OP system. Patients with elevated BP 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 diabetes mellitus patients
with elevated BP, particularly if <60
years old.
CVD risk modifiers for up-classification of risk
in individuals with elevated BP 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 BP 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 | |||||
|---|---|---|---|---|---|
| BP (mmHg) |
Hypertension Disease Stage | ||||
| Stage 1 | Stage 2 | Stage 3 | |||
| No Other Risk Factors | 1-2 Risk Factors | ≥3 Risk Factors | Target organ damage, CKD
Grade 3, or diabetes mellitus without target organ damage |
Established CVD, CKD ≥4 or diabetes mellitus w/ target organ damage | |
| 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 |
| 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 BP threshold requiring treatment and the target BP to achieve and maintain BP goal based on age, risk stratification, and
presence and absence of comorbidities (eg diabetes mellitus and CKD); reaching BP target early and maintaining BP with high time-in-target range to ensure
treatment benefit and safety; and identifying factors that affect patient’s
adherence to treatment (eg social
determinants of health [SDOH], low health literacy, stress, anxiety and
depression). 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 BP1
The treatment goal for BP is <130/80 mmHg for all
adults. If the therapy is well tolerated, a treated SBP goal of 120-129 mmHg is recommended to reduce
CVD risk. If a target SBP of 120-129 mmHg is
not possible and treatment is poorly tolerated, it
is recommended to individualize target SBP level with a target as low as
reasonably achievable (preferably <140 mmHg).
A DBP goal of 70-79 mmHg may be
considered to reduce CVD risk if the SBP is
at or below target but DBP is ≥80 mmHg.
A more lenient BP 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 all adults with an average
BP of ≥140/90 mmHg or in adults with hypertension and clinical CVD (coronary
heart disease, heart failure, stroke) if the average SBP is ≥130 mmHg or DBP is
≥80 mmHg. The decision to initiate therapy is based on the untreated BP level and the presence of target organ damage
or concomitant disorders (eg established CVD, HMOD, diabetes
mellitus, familial hypercholesterolemia or moderate or severe CKD). A
risk-based approach is recommended in the treatment of elevated BP. In adults with
hypertension, no clinical CVD but with diabetes, CKD or ≥7.5% 10-year CVD risk
based on PREVENTTM, medications are started if the average SBP is
≥130 mmHg or DBP is ≥80 mmHg to reduce CVD events and mortality. In adults with
hypertension, no clinical CVD and <7.5% 10-year CVD risk based on PREVENTTM,
medications are started if the average SBP ≥130 mmHg or DBP ≥80 mmHg persists
after 3-6 months of lifestyle intervention to prevent target organ damage and
further BP elevation. CVD risk stratification may be done at or after
treatment initiation but only when it is feasible and will not delay treatment.
Implement lifestyle changes throughout the management.
Medication is started together with lifestyle changes in patients with
elevations in systolic blood of >20 mmHg or DBP
of >10 mmHg above BP goal, those with
target organ damage on screening, and in fit
patients 65-80 years old with a SBP of 140-159 mmHg if therapy is well tolerated. In
patients with a BP of ≥140/90 mmHg regardless
of CVD risk, pharmacological therapy is started with lifestyle changes to
reduce CVD risk.
If with high-normal BP,
consider initiating drug treatment in very high-risk patients with CVD,
especially coronary artery disease. Treatment of elevated BP 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 BP 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 BP.
1Recommendations may vary between
countries. Please refer to available guidelines from local health authorities
Treatment Regimen
Assessment of BP
and adjustment of the treatment regimen is continuous until the BP
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 BP control, it is reasonable to start with a single antihypertensive agent
(monotherapy) in low-risk patients with low baseline BP that is close to the recommended
goal, high-risk patients with high-normal BP, frail or old patients who need gentle BP 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 BP.
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 a
BP ≥140/90 mmHg or an average BP
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 BP
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 BP remains controlled after 1-2 years of
therapy and is without symptoms related to hypertension or target organ damage.
Prior to starting or intensifying BP-lowering
treatment to test patient for orthostatic hypotension (≥20 SBP and/or ≥10 DBP
mmHg drop 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 BP-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 BP 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 BP 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,
reduce time to achieve BP control, and improve
the adherence of patients. A new therapeutic approach to improve BP control is the use of a quadpill which contains quarter
doses of 4 drugs.
Hypertension_ManagementCoronavirus 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 BP 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 recommended in patients
with hypertension and diabetes when CKD is present (eGFR <60 mL/min/1.73 m2
or albuminuria ≥30 mg/g) and should be considered with mild albuminuria (<30
mg/g) to slow diabetic kidney disease progression. They are recommended in
patients with hypertension and CKD to reduce CVD and to slow kidney disease
progression.
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 BP.
Drug effects do not seem to have dose-dependent effects, except for
hyperkalemia which may occur more frequently with high doses; treatment may be
initiated with medium or approved high doses. They should not be combined with
ARBs or direct renin inhibitors.
Alpha-Adrenoreceptor Antagonists
(Alpha-Blockers)
Alpha-blockers reduce BP 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 (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 CV and renal benefits as ACE inhibitors. ARBs
are recommended in patients with hypertension and diabetes when CKD is present
and should be considered with mild albuminuria to slow diabetic kidney disease
progression. They are recommended in patients with hypertension and CKD to
reduce CVD and slow kidney disease progression. They can also be used to
prevent the recurrence of atrial fibrillation.
They are well tolerated and do
not cause cough and only rarely cause angioedema. For patients on diuretics,
skipping a dose of the diuretic prior to starting ARBS may help prevent a
sudden drop in BP. The drug
effects do not appear to have dose-dependent effects; treatment may be
initiated with low to maximum approved doses in single-pill combination. They
should not be combined with ACE inhibitors or direct renin inhibitors.
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 BP 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 CV 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 CV 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 DBP in
younger and elderly hypertensive patients. It has a greater BP-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 CV 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 SBP.
Aldosterone Antagonists or MRAs
Example drugs: Spironolactone, Eplerenone
Aldosterone antagonists or MRAs
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 BP 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 CKD 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 BP 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 CV 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 BP 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.
Dual
Endothelin Receptor Antagonist
Example
drug: Aprocitentan
Endothelin receptor
antagonist is indicated for the treatment of hypertension in combination with
other antihypertensive medications for BP
reduction in adult patients with resistant hypertension. It has a sustained BP-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 |
|
|
Asymptomatic atherosclerosis |
|
|
Atrial fibrillation |
Recurrent:
Permanent:
|
|
Diabetes mellitus* |
Combination of ≥2 drugs are typically needed to reach target BP
|
Heart failure* |
Asymptomatic patients with ventricular dysfunction:
Symptomatic ventricular dysfunction or end-stage heart disease:
|
|
Isolated systolic hypertension (ISH) (elderly) |
|
|
LV hypertrophy |
|
|
Metabolic syndrome |
|
|
Microalbuminuria |
|
|
Peripheral arterial disease |
|
|
Post MI |
|
|
Post stroke |
|
|
Proteinuria/End-stage renal disease* |
|
*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.
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 BP, or in patients with BP of ≥140/90 mmHg. If BP 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-myocardial
infarction, or
young women planning to get pregnant or are pregnant).
Resistant
Hypertension
Resistant hypertension
is considered when the target BP is not achieved, and the
patient was already treated with ≥3 drugs at optimal doses (including a
diuretic) or the BP 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 a dual 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 or
Chlorthalidone should be used if eGFR is
<30 mL/min/1.73 m2.
If
BP is still uncontrolled
after three
drugs at near-max doses, consider inaccurate BP measurements, nonadherence to lifestyle modifications, non-compliance to
treatment regimen, drug interactions (review
medications for BP-interfering drugs), white
coat hypertension, secondary hypertension, or complications of long-standing
hypertension (eg nephrosclerosis). Regarding
secondary hypertension, screening for primary aldosteronism is recommended in
adults with resistant hypertension, irrespective of the presence of
hypokalemia, to enhance the detection, diagnosis, and specific targeted
treatment.
Other
interventions that can be considered include bedtime dosing in patients with
documented high night-time BP for greater morning BP reduction and renal denervation if eGFR ≥40 mL/min/1.73 m2. Candidates for renal denervation should be
evaluated by an expert multidisciplinary team, with shared decision-making on
the benefits and procedural risks versus continuing medical therapy. Referral
to a hypertension specialist may also be considered if after 6 months of
therapy, BP remains uncontrolled; patient is also referred for the management
of known or suspected secondary cause/s of hypertension.
Nonpharmacological
Lifestyle Modification
Lifestyle modification
is considered the cornerstone of hypertension prevention and treatment. The BP 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 BP 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 CV 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 goal
of ≥5% or ≥3 kg/m2
reduction in BMI 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 SBP 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 and BP.
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 BP 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 BP-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), preferably from dietary sources, is
recommended except in patients with CKD or patients using drugs that decrease the
excretion of potassium. In adults with or
without hypertension, potassium-based salt substitutes may help prevent or
treat elevated BP and hypertension, particularly when most dietary salts come
from food preparation or flavoring at home; in patients with CKD or on
medications that impair potassium excretion, use requires monitoring. 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 CV 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 BP and CVD risk.
Alcohol Consumption
Abstaining from alcohol
consumption is strongly recommended. Discourage excessive alcohol
consumption since great amounts can raise BP. 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 CV 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 BP, 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 BP 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 BP at least
annually thereafter. More frequent BP measurements
may be needed for patients whose clinic BP is close to 130/80
mmHg. Encourage patients to measure their BP at home. In Asians, strict 24-hour BP control starting with
HBPM 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, yoga, breathing control
techniques) can be used to prevent or treat elevated BP and hypertension. The patient’s
cultural beliefs may influence their attitude and the physician needs to be
sensitive when handling these issues.
BP Measurement and
Monitoring
Before taking the BP 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 BP
measuring devices. Make sure that the devices to be used are professionally validated and
calibrated annually. Devices that measure BP from the brachial artery are preferred to those that
read from distal sites (fingers, wrists). Electronic or digital BP devices are
preferred to be used; however, patients and caregivers should be well trained
in using an aneroid BP 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 BP. 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 BP measurement, and sit down with their back supported, feet on the
floor, arm supported horizontally, and BP 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 (SBP), slowly deflate
the cuff, taking note when the pulse reappears (DBP). With the use of a stethoscope, reinflate the cuff 20
mmHg above the previous SBP, then deflate the cuff by 1-2 mmHg/sec. Inform the
patient that when a tapping sound is heard, this is the SBP; when it
disappears, it is the DBP. 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 BP reading. Ask the patient to wait for 1-2 minutes, then take another BP measurement; measure
BP twice a day. Advise the patient to write
the results in the logbook immediately after each reading.
Hypertension_Follow Up