Essential hypertension - Approach

Approach

The main goal of treatment is to decrease the risk of mortality and of cardiovascular and renal morbidity.[4][60] [ ] The following recommendations are based on the Eighth Joint National Committee (JNC 8) guidelines. JNC 8 states that blood pressure (BP) goal should be <140/90 mmHg for adults ages 18-59 years, including those with diabetes or chronic kidney disease, and <150/90 mmHg in the general population beginning at age 60 years.[3] In contrast, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a BP target of <130/80 mmHg for adults, regardless of age, with confirmed hypertension and known cardiovascular disease (CVD), or a 10-year atherosclerotic CVD risk (using the atherosclerotic CVD [ASCVD] risk estimator) of 10% or more.[5] American College of Cardiology: ASCVD risk estimator plus external link opens in a new window For adults with confirmed hypertension without additional markers of increased CVD risk, a BP target of <130/80 mmHg may be reasonable.

In the general population aged ≥60 years, the JNC 8 guideline recommends pharmacologic therapy to lower blood pressure when BP ≥150/90 mmHg.[3] However, some panel members recommended retaining the JNC 7 systolic BP goal of <140 mmHg, concluding that there was insufficient evidence to implement the less intensive target in high-risk groups, including black people, those with cardiovascular disease, and those with multiple risk factors.[61] The American College of Physicians and American Academy of Family Physicians joint guideline recommends that treatment is initiated in adults ages ≥60 years with systolic BP persistently ≥150 mmHg to achieve a target systolic blood pressure of <150 mmHg to reduce the risk for mortality, stroke, and cardiac events.[62] The joint guideline recommends considering treating adults ≥60 years old with a history of stroke or transient ischemic attack, or at high cardiovascular risk, to achieve a target systolic blood pressure of <140 mmHg.[62] The European Society of Cardiology/European Society of Hypertension guidelines recommend a desired target systolic BP of 130-139 mmHg for adults aged >65 years.[2] US and European guidelines - classification and management external link opens in a new window

Evolving treatment goals

Blood pressure goals are evolving as more studies are being carried out.[63] The SPRINT trial (Systolic Blood Pressure Intervention Trial) ended early as it found that a lower systolic target of 120 mmHg (as measured by automated office blood pressure [AOBP]) reduced cardiovascular complications and deaths in people ages over 50 years with high blood pressure and at least one additional risk factor for heart disease.[6][64] Patients with diabetes or stroke were excluded from the trial. However, in the HOPE-3 trial, intermediate-risk people without cardiovascular disease did not benefit from BP lowering unless in the highest tertile of starting BP (>143.5 mmHg) (as opposed to higher-risk patients in SPRINT).[65]

Because of differences in the general health of older patients, the decision to treat should be on an individual basis, and BP lowering should be gradual and carefully monitored by the physician.[2][66] The SPRINT trial results showed equal benefit in people ages >75 years, regardless of frailty or walking speed.[67] Patients with orthostasis at enrollment, patients with dementia, and those resident in a nursing home were excluded from the trial. One systematic review found insufficient evidence regarding the benefits of hypertension treatment for frail people >80 years of age taking multiple medications, concluding that treatment should be individualized.[68] Older patients >80 years should not be denied treatment or have treatment withdrawn solely on the basis of age.[2]

Regarding patients with concomitant diabetes mellitus, there is good-quality evidence from the ACCORD trial that very intensive BP lowering (targeting a systolic pressure <120 mmHg, as compared with targeting <140 mmHg) does not lessen risk (composite outcome: nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular cause) and may increase risk of adverse events.[69] The American Diabetes Association recommends that blood pressure targets in people with diabetes and hypertension are individualized by assessing cardiovascular risk, potential adverse effects, and patient preference.[70] Targets for people with diabetes range from <130/80 mmHg for those at higher risk and <140/90 mmHg for those at lower risk; for pregnant patients with diabetes, targets of 120-160/80-105 mmHg are suggested.[70] Lower systolic and diastolic blood pressure targets, such as 130/80 mmHg, may be appropriate for individuals at high risk of cardiovascular disease if they can be achieved without undue treatment burden. The ACC/AHA recommend a blood pressure goal of <130/80 mmHg for patients with diabetes.[5]

Lifestyle modification

The initial approach to a newly diagnosed patient should include a thorough explanation of the risks associated with hypertension and the need for adequate control and adherence to therapy. Initial therapeutic measure should be lifelong lifestyle modification including:[2][5][14][38][71][72]

Sodium reduction (optimal goal ≤1.5 g/day) [ ]
Potassium supplementation (3.5 to 5.0 g/day): preferably by consumption of a potassium-rich diet unless contraindicated in the presence of chronic kidney disease or use of medication that reduces potassium excretion
Dietary Approaches to Stop Hypertension (DASH) diet (8-10 servings of fruit and vegetables daily, whole grains, low sodium, low-fat proteins)
Waist circumference <40 inches (<102 cm) for men and <35 inches (<88 cm) for women; weight loss to a BMI of about 25 kg/m²
Increased physical activity: at least 30 minutes of moderate-intensity dynamic aerobic exercise (walking, jogging, cycling, or swimming) 5 days per week to total 150 minutes per week, as tolerated or recommended by physician
Limited alcohol consumption: ≤2 standard drinks (<20-30 g alcohol) per day in hypertensive men; ≤1 standard drink (<10-20 g alcohol) per day in hypertensive women. Total weekly alcohol consumption should not exceed 140 g for men and 80 g for women.

Advice about lifestyle modification should be given upon diagnosis and should continue concurrently with all other therapeutic measures. Prior to initiation of an exercise program, patients should discuss a plan with their healthcare provider.

Smoking cessation should always be encouraged as well, to promote general vascular health, though smoking cessation has not been associated with decreased BP.

A 3-month trial is recommended in adherent patients willing to make therapeutic lifestyle changes, prior to determining that pharmacologic therapy is necessary. Most patients will require drug therapy to achieve target BP control.

Antihypertensive drugs

The main classes of antihypertensives include:[2][5]

Diuretics:
- Thiazide (or thiazide-like): hydrochlorothiazide, chlorthalidone, indapamide
ACE inhibitors: lisinopril, enalapril, captopril
Angiotensin-II receptor antagonists: candesartan, irbesartan, losartan, valsartan
Calcium-channel blockers: amlodipine, diltiazem
Beta-blockers: metoprolol, bisoprolol, carvedilol.

Beta-blockers are not recommended for first-line treatment of hypertension except in the presence of coronary artery disease, heart failure, or atrial fibrillation.[5] The examples of antihypertensive drugs listed are common examples of drugs in each class only; other drugs are available. Some of these drugs are available in fixed-dose combination formulations. These single pill formulations simplify dosing regimens and improve adherence.[2][73]

Drug therapy for stage 1

The ACC/AHA guidelines define stage 1 hypertension as BP 130-139/80-89 mmHg.[5] The European Society of Cardiology/European Society of Hypertension guidelines define this category of BP as high-normal BP.[2]

For stage 1 hypertension, combination therapy or monotherapy where appropriate can be initiated.[2] [ ] The choice of antihypertensive agent is driven by efficacy, adverse-effect profile, and cost. The ACC/AHA guidelines recommend initiating a single antihypertensive agent for patients with a 10-year atherosclerotic CVD risk ≥10% or known cardiovascular disease, diabetes, or chronic kidney disease.[5] American College of Cardiology: ASCVD risk estimator plus external link opens in a new window European guidelines recommend initiating antihypertensive treatment with a two-drug combination, preferably a single pill combination, with the exception of patients with high-normal BP and a high cardiovascular risk or in frail older patients in whom initiating treatment with monotherapy may be appropriate.[2] In patients with high-normal BP and a high cardiovascular risk only a small reduction in BP may be required to achieve the BP target and in frail older patients baroreflex sensitivity is frequently impaired and the risk of hypotension is greater.[2] Many people with stage 1 hypertension have a constellation of other cardiovascular risk factors such as smoking or mild dyslipidemia that increase the importance of BP lowering.

If BP cannot be controlled with a single agent, a drug from a different class of antihypertensives is added.

Generally, when an ACE inhibitor would usually be chosen but is not tolerated, an angiotensin-II receptor antagonist can be substituted.

Stage 1 hypertension: without CVD-related comorbidity or chronic renal disease, or with diabetes

A choice among four preferred classes of drugs is recommended for initial therapy.[2][5][74]

Thiazide (or thiazide-like) diuretics have been shown to be safe and efficacious first-line therapy.[75] They also decrease renal calcium excretion, so may be a good choice for women with osteoporosis. As with all antihypertensive medications, the initial dose should be the lowest possible, and then titrated for a therapeutic effect, while observing for potential adverse effects.

Alternative first-line choices include ACE inhibitors, angiotensin-II receptor antagonists, or calcium-channel blockers, or a combination of two different drugs from these classes (excluding the combination of ACE inhibitors and angiotensin-II receptor antagonists). [ ] Aliskiren, a direct renin inhibitor, is also available; however, its place in the treatment pathway is not yet clear due to concerns about risks in combination with ACE inhibitors or angiotensin-II receptor antagonists, and in the settings of diabetes or renal impairment;[6] and it it is not considered to be a preferred option.

In the general black population, including those with diabetes, a thiazide (or thiazide-like) diuretic or a calcium-channel blocker is recommended as initial pharmacologic therapy.[2][5] The recommendation is derived from a prespecified subgroup analysis of black patients, 46% of whom had diabetes, in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) trial.[76][77]

In patients with diabetes who have increased albumin excretion, ACE inhibitors or angiotensin-II receptor antagonists are recommended. The ALLHAT study showed that chlorthalidone, amlodipine, or lisinopril were co-equal for mild hypertension in type 2 diabetes.[76] ACE inhibitors are renoprotective, decreasing the progression of proteinuria in patients with diabetes.[78] Sleep-time BP is the most significant independent prognostic marker of cardiovascular events in diabetes.

Comorbid coronary artery disease

Beta-blockers are first-line. Beta-blockers have proven beneficial in patients with chronic stable angina, post-myocardial infarction, or congestive heart failure (CHF), in patients with coronary artery disease (CAD) undergoing surgery, or in patients with hypertrophic obstructive cardiomyopathy.[79][80][81][82][83]

ACE inhibitors have been shown in some trials to decrease cardiovascular events, while other studies have not demonstrated a benefit for ACE inhibitors in the setting of stable CAD with normal left ventricular function.[84][85][86] Beta-blockers, ACE inhibitors, or angiotensin-II receptor antagonists can be used as first-line for compelling indications (e.g., previous myocardial infarction, stable angina).[2][5] Other drugs such as dihydropyridine calcium-channel blockers, thiazide diuretics, and/or mineralocorticoid receptor antagonists are added as required to further control hypertension.

Many patients with CAD also take nitrates, which act as exogenous nitric oxide donor. Modest reductions in systolic BP can be observed, but the Food and Drug Administration has not approved the use of nitrates solely as antihypertensive therapy.[16]

Comorbid heart failure with reduced ejection fraction

In patients with comorbid heart failure with reduced ejection fraction (<40%), an ACE inhibitor (or an angiotensin-II receptor antagonist if not tolerated) plus a beta-blocker with or without an aldosterone antagonist is used.

ACE inhibition has been shown to convey a survival advantage in patients with CHF.[80][87] Angiotensin-II receptor antagonists also decrease morbidity and mortality.[88][89] Compared with ACE inhibitors, angiotensin-II receptor antagonists were equivalent, but not superior, in the treatment of patients with CHF.[90][91]

Beta-blockers have proven mortality benefits in patients with chronic CHF.[81][82]

Aldosterone antagonists should be given to patients with heart failure and ejection fraction under 35% who are taking optimized ACE inhibitor or angiotensin-II receptor antagonist plus beta-blocker treatment, who still require antihypertensive therapy. Blockade of aldosterone has been associated with decreased end-organ fibrosis.[92]

Diuretics (nonaldosterone) confer no mortality benefit for patients with CHF. However, they are frequently used to relieve symptoms of fluid overload.

The combination of hydralazine and a nitrate (e.g., isosorbide dinitrate/hydralazine) has been shown to be of benefit for self-defined African Americans already taking ACE inhibitors, beta-blockers, and aldosterone antagonists, as well as in all patients with CHF who are intolerant of both ACE inhibitors and angiotensin-II receptor antagonists.[93][94]

Nondihydropyridine calcium-channel blockers are not recommended for the treatment of hypertension in adults with heart failure with reduced ejection fraction.[5]

Sacubitril/valsartan and ivabradine are newer drugs also used for chronic heart failure.

Comorbid heart failure with preserved ejection fraction

Diuretics should be used to control hypertension in patients with comorbid heart failure with preserved ejection fraction (>45%) who present with symptoms of volume overload.[5] If hypertension persists after the management of volume overload, ACE inhibitors or angiotensin-II receptor antagonists and beta-blockers should be used and titrated to achieve the target BP goal.

Comorbid left ventricular hypertrophy

ACE inhibition has proven beneficial across a myriad of cardiovascular disease states including CHF and left ventricular hypertrophy (LVH).[84][85] An angiotensin-II receptor antagonist is first choice for comorbid LVH. Angiotensin-II receptor antagonists have been shown to decrease morbidity and mortality in patients with hypertension and LVH.[88]

Comorbid renal disease

An ACE inhibitor is first choice for comorbid renal disease (chronic kidney disease stage 3 or higher or stage 1 or 2 with albuminuria [≥300 mg/day or ≥300 mg/g albumin-to-creatinine ratio or equivalent in the first morning void]).[5] If an ACE inhibitor is not tolerated, an angiotensin-II receptor antagonist can be used.

Comorbid atrial fibrillation

First choice is a beta-blocker. Second choice is a nondihydropyridine calcium-channel blocker.

Evidence from post-hoc analyses suggest that angiotensin-II receptor antagonists and ACE inhibitors do not prevent the occurrence[95][96] or the recurrence[97][98] of atrial fibrillation. However, more recent guidelines note that use of ACE inhibitors and angiotensin-II receptor antagonists may be effective in the prevention of atrial fibrillation.[5][99] More investigation is needed.

Comorbid benign prostatic hypertrophy

The ALLHAT study conclusively demonstrated that alpha-blockers should not be a first-line antihypertensive therapy for patients with symptomatic benign prostatic hypertrophy (BPH). In these patients, the preferred first-line antihypertensive options are the same as for most other groups (i.e., thiazide-like diuretics, ACE inhibitors, angiotensin-II receptor antagonists, and calcium-channel blockers), and the alpha-blocker indication is simply to treat the BPH symptoms.

Comorbid Raynaud disease, peripheral vascular disease, or coronary artery spasm

Calcium-channel blockers are first choice. In addition to vascular disease, calcium-channel blockers are also useful for persistent angina or stroke prevention.[100][101]

Stage 2 hypertension

The ACC/AHA guidelines define stage 2 hypertension as BP ≥140/90 mmHg.[5] The European Society of Cardiology guidelines define this category of BP in three grades:[2]

Grade 1 hypertension BP 140-159/90-99 mmHg
Grade 2 hypertension 160-179/100-109 mmHg
Grade 3 hypertension ≥180 mmHg/110 mmHg.

Patients presenting with stage 2 hypertension will require more than one drug for BP control. Therefore, the initiation of two concurrent antihypertensives of different classes is recommended.

The combination of a nondihydropyridine calcium-channel blocker with a beta-blocker should be avoided, because of an increased risk of high-degree atrioventricular block.

Recalcitrant (resistant) hypertension

Recalcitrant (resistant) hypertension is defined as above-goal elevated BP in a patient taking three antihypertensive agents (commonly including a long-acting calcium-channel blocker, an ACE-inhibitor or angiotensin-II receptor antagonist, and a diuretic) at maximally tolerated doses.[59] Managing recalcitrant hypertension requires expertise. Frequently requiring multiple antihypertensive agents, patients must be observed and counseled regarding adverse effects, medication adherence, potential drug-drug interactions, and metabolic abnormalities. Infrequently, patients will require a screen for secondary causes of hypertension.

Representative agents of the main treatment class options, including ACE inhibitors, angiotensin-II receptor antagonists, and calcium-channel blockers, should be maximized. An optimally dosed thiazide-like diuretic, such as chlorthalidone or indapamide, should be used over hydrochlorothiazide.[59] ACE inhibitors, angiotensin-II receptor antagonists, and/or direct renin inhibitors should not be used together due to the risk of acute renal failure.

The fourth-line drug option is generally spironolactone. Eplerenone can be used as an alternative. Spironolactone and eplerenone are contraindicated in patients with hyperkalemia. Caution should be used in patients with renal impairment; either a dose adjustment may be required, or the drug may be contraindicated depending on the severity of renal impairment, indication for use (i.e., hypertension versus heart failure), and local guidance. Concomitant administration with potassium-sparing diuretics is contraindicated.

Otherwise, a safe fourth- or fifth-line option is a peripheral adrenergic blocker. Hydralazine is a less-preferred option due its twice-daily dose requirement and increased risk of edema with simultaneous calcium-channel blocker treatment. Minoxidil is rarely required in patients with advanced chronic kidney disease and its use requires some expertise in anticipating and managing side-effects of fluid retention. Combined alpha- and beta-blockers (e.g., carvedilol, labetolol) are considerations. Additionally, physicians with expertise in managing difficult-to-control hypertension have had niche success using a combination of a dihydropyridine calcium-channel blocker plus a nondihydropyridine calcium-channel blocker (e.g., amlodipine plus diltiazem). Clonidine is generally avoided because of its side-effect profile.

The most important principles for managing challenging hypertension are:

Promotion of medication adherence using the principle of pill reduction (i.e., use of single pill, fixed-dose combination formulations or avoidance of twice-daily dose regimens when possible)
Maximizing the dose of the diuretic
Use of spironolactone or eplerenone as a fourth drug when possible.[102]

It is also important to question the patient's alcohol use and offer lifestyle counseling.

Referral to a specialist in hypertension should be considered.

Older adults

In very elderly patients, many physicians are reluctant to treat hypertension in accordance with usual BP goals, for a number of reasons, including concerns about fall risk, drug interactions, adverse effects, and lack of benefit in mortality reduction. Previous literature reviews and meta-analysis demonstrated reductions in stroke, heart failure, and cardiovascular events in the very elderly without reaching mortality benefit.[103][104] However, the SPRINT trial found that treating ambulatory adults ages 75 years or older to a systolic BP target of <120 mmHg (as measured by AOBP) resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause, compared with a systolic BP target of <140 mmHg.[67] Patients with orthostasis at enrollment, patients with dementia, and those resident in a nursing home were excluded from the trial.

The 2017 ACC/AHA guidelines recommend a systolic BP goal of <130 mmHg for noninstitutionalized ambulatory community-dwelling adults. For older adults ≥65 years of age with hypertension and a high burden of comorbidity and limited life expectancy, clinical judgment, patient preference, and a team-based approach to assess risk/benefit is reasonable for decisions regarding intensity of BP lowering and choice of antihypertensive drugs.[5]

European guidelines recommend a BP target of <140/90 mmHg in all patients including independent older patients and, if treatment is tolerated, a BP target of ≤130/80 mmHg in most patients.[2]

The JNC 8 guideline recommends initiating pharmacologic therapy for patients aged ≥60 years at systolic BP ≥150 mmHg or diastolic BP ≥90 mmHg, and to treat to a systolic BP goal of <150 mmHg and a diastolic BP goal of <90 mmHg.[3]

Pregnancy

Treatment described in this topic is for nonpregnant patients. Management in pregnancy should be referred to an obstetrician specializing in high-risk patients.

For more information, please see our topic on Gestational hypertension.

Implementation success

High levels of hypertension control in large multi-ethnic populations has been demonstrated using basic principles of implementation science.[105][106][107] Core principles include:

A comprehensive hypertension registry
An evidence-based hypertension treatment algorithm based on single pill combination therapy
Free medical assistant visits for blood pressure measurement with follow-up triage, and
Team-based performance reporting.

The use of 2-drug combination therapy, including single pill combinations, for patients with newly diagnosed hypertension with and without comorbidities is consistent with the evidence-based JNC 8 guideline as well as the 2017 ACC/AHA guidelines and the European guidelines.[2][5]

Given the large number of patients with hypertension and the use of protocol-based hypertension care delivery, team-based care incorporating nurses and clinical pharmacists is a key success factor.[108][109] In team-based care collaboration, generally the role of the clinical pharmacist involves medication choice and delivery, and the role of the nurse is patient education. One randomized controlled trial demonstrated the efficacy of a low cost nurse-led email reminder program across a spectrum of cardiovascular risk factors, including lipid improvement and blood pressure reduction.[110]

The patient should be considered a hypertension team member. The TASMINH4 trial has shown that self-monitoring, with or without telemonitoring, used by general practitioners to titrate antihypertensive medication in patients with poorly controlled blood pressure, leads to significantly lower blood pressure compared with titration guided by clinic readings.[111]

An important goal is to continue to make efforts to improve disparities in blood pressure control among people of different ancestries.[112]

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