Chronic hypertension medical therapy

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2017 ACC/AHA Hypertension Guidelines

Patient Information

Overview

Definition

Classification

Pathophysiology

Causes

Differentiating Hypertension from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Blood Pressure Measurement

Physical Examination

Laboratory Findings

Electrocardiogram

ETT

Echocardiography

CT

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Treatment

Lifestyle Modification

Medical Therapy

Practice Guidelines

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [5]; Associate Editor(s)-In-Chief: Yazan Daaboul; Serge Korjian; Ryan Norman; Arzu Kalayci, M.D. [6]


Overview

To review the 2017 AHA/ACC guidelines on HTN, click here.

Blood Pressure Goals

Further information: Chronic hypertension medical therapy blood pressure goals of treatment

Recommendations for treatment goals from recent clinical practice guidelines are tabulated below. However, treated based on underlying risk rather than a blood pressure target may be more effective[1]. The logic supporting a target of 130/80 mm Hg has been disputed[2] and the Cochrane Collaboration found insufficient evidence to determine a treatment goal for adults[3] or adults over 65 years of age[4].

If the goal is 130/80, proper measurement includes (distilled from Table 8 of the ACC/AHA guidelines[5], executive summary[6]):

  • having the patient sit quietly for 5 minutes before a reading is taken
  • supporting the limb used to measure BP
  • ensuring the BP cuff is at heart level
  • using the correct cuff size
  • for auscultatory readings, deflating the cuff slowly
  • the timing of BP measurements in relation to ingestion of the patient’s medication should be standardized
  • a single reading is inadequate for clinical decision-making. An average of 2 to 3 BP measurements obtained on 2 to 3 separate occasions will minimize random error and provide a more accurate basis for estimation of BP.

If the above measurement methods are not use, a preliminary study from Kaiser Northern California suggests a target of 140 mm Hg[7].

AHA[5] vs Roerecke[8] estimates of relationship between routine, auscultated BP measurement and gold standard ambulatory measurement.
Clinic (routine)

AHA, 2017[5]

Clinic (routine)

Roerecke, 2018[8]

Clinic (automated)

Roerecke, 2018[8]

Home (self)

AHA, 2017

Daytime, ambulatory † Nighttime ambulatory

AHA, 2017[5]

24 hour ambulatory[8]

AHA, 2017[5][5] †

120/80 125/82 120/80 120/80 120/80 100/65 115/75
130/80 145/85 130/80 130/80 130/80 110/65 125/75
140/90 150/90 135/85 135/85 135/85 120/70 130/80
160/100 160/95 145/90 145/90 145/90 140/85 145/90
Notes:

† Benegas found that the 24-hour ambulatory systolic pressure may better predict mortality than the daytime systolic blood pressure.[9] The article by Benegas was subsequently retracted[10].


Practice guidelines comparison[6][11][12]
Goal < 60 years old Goal >= 60 years old High risk
JNC-8, 2014[12] 140/90 150/90*
ACP/AAFP, 2017[11] Not applicable 150 or 140 if high risk
HEDIS and MIPS QI Measures < 140/90
Kaiser, 2019[13] 140/90 Kaiser states "In adults with ASCVD, CKD, age > 75 years, or 10-year ASCVD risk > 10%, consider treating to a goal SBP of < 130 mm Hg"

This is consistent with more agressive treatment in the SPRINT trial[14].

AHA/ACC/others, 2017[6] < 130/80†
* Treat to 140/90 if age >=60 with DMII or CKD.

† Treat if > 140/90 or 130/80 if high risk which is defined as existing cardiovascular disease, 10-year cardiovascular risk ≥10%, diabetes, or CKD.

Newer randomized controlled trials have identified conflicting benefits to more intensive therapy.

Randomized controlled trials of lower treatment goals
Patients BP target in intervention group Final BP in intervention group Primary outcome (composite)
(Hazard ratio)
Baseline blood pressure Estimated cardiac risk
(calculated with pooled cohort equation) 		Outcome rate in the control group
ACCORD, 2010[15] 140/76 All patients were diabetic
9% for anglo women and 23% for anglo men 		2.1% per year SBP 120 vs 140 119/64 0.88 (95% CI: 0.73 to 1.06)
SPRINT, 2015[14] 140/78 No diabetics
16% for anglo women and 23% for anglo men (20% overall) 		2.2% per year SBP 120 vs 140 121/67 0.75 (95% CI: 0.64 to 0.89)
HOPE-3, 2016[16] 138/82 16% for anglo women and 23% for anglo men 1.7% per year* No target BP.
Intervention group all received candesartan 16 mg per day plus hydrochlorothiazide 12.5 mg per day 		128/76 0.93 (95% CI: 0.79 to 1.10)
Notes: 
* 1.7% is the sum of the two co-primary outcomes. The HOPE-3 also reported 4.4% over 5.6 years.
  • In the ACCORD (Action to Control Cardiovascular Risk in Diabetes) randomized controlled trial patients with average blood pressure of 140/76 mm Hg and diabetes did not benefit from targeting a systolic blood pressure of less than 120 mm Hg (average 119/64 mm Hg), as compared with less than 140 mm Hg.[15]
    • Assuming the average patient in this trial was a nonsmoker and was diabetic, the estimated 10-year cardiovascular risk is 9% for anglo women and 23% for anglo men.
  • In the SPRINT randomized control trial, patients with an average blood pressure of 140/78 mm Hg and at high risk for CVD but who do not have a history of stroke or diabetes, intensive BP control (target SBP <120 mm Hg) that lowered systolic blood pressure to an average of 121/67 mm Hg improved CV outcomes and overall survival compared to standard therapy, while modestly increasing the risk of some serious adverse events[14].
    • Assuming the average patient in this trial was not diabetic, 50% were smokers (per their publication)), 33% were women, and LDL was 113 (per their publication Friedrwald estimate is 191 - 53 - 125/5)) the estimated 10-year cardiovascular risk is 12% for anglo women and 20% for anglo men.
    • The number needed to treat (NNT), is about 200 (185) for the primary outcome (1.65% vs 2.19%) by dropping the systolic pressure by 15 mm Hg.
  • In the HOPE-3 trial randomized controlled trial, patients with an average blood pressure of 138/82 mm HG and with intermediate risk who did not have cardiovascular disease lowering systolic blood pressure to an average of 128 mm Hg was insignificantly beneficial. [16]
    • Assuming the average patients in this trial was a nonsmoker and not diabetic, the estimated 10-year cardiovascular risk is 10% for anglo women and 19% for anglo men.
    • Benefit was found in a subgroup analysis of patients with systolic blood pressure above 144 mm Hg (mean 154 mm Hg).

Debate exists on how low should physicians target blood pressure in their patients especially in light of studies that have shown a J or U-shaped curve phenomenon associated with hypertension treatment where low and very high blood pressure values are associated with increased risk of cardiovascular events.[17] A less strict target in diabetic and elderly patients is in the new ADA and ESH/ESC 2013 clinical practice guidelines respectively. This rationale is supported by the fact that lower SBP targets in diabetic patients have not been shown to generate better outcomes.[18] Similarly, treatment of stage 1 hypertension in elderly patients and targeting SBP values to <140 mmHg have not been well substantiated and may sometimes carry more risk than benefit.[19]

Practice Guidelines

American College of Cardiology / American Heart Association

The ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA 2017 clinical practice guidelines[5], executive summary[6], and underlying systematic review[6] by the ACC/AHA taskforce recommend a treatment goal for everyone is <130/80 mm Hg:

Definition Treatment
Elevated blood pressure Systolic BP, 120–129 mm Hg
- and -
Diastolic BP, <80 mm Hg
 Lifestyle
Stage 1 hypertension Systolic BP, 130–139 mm Hg
- or -
Diastolic BP, 80–89 mm Hg
 Lifestyle and
Medications if high risk*
Stage 2 hypertension
 Systolic BP, ≥140 mm Hg
- or -
Diastolic BP, ≥90 mm Hg 		Lifestyle and
Medications
* High risk defined as existing cardiovascular disease or 10-year cardiovascular risk ≥10% (calculator and alternative calculator with facts box)

American College of Physicians / American Academy of Family Physicians

For patients aged 60 or more, the American College of Physicians and American Academy of Family Physicians clinical practice guideline[11] and underlying systematic review[20] from 2017 recommend:

  • " initiate treatment in adults aged 60 years or older with systolic blood pressure persistently at or above 150 mm Hg to achieve a target systolic blood pressure of less than 150 mm Hg"
  • "consider initiating or intensifying pharmacologic treatment in adults aged 60 years or older with a history of stroke or transient ischemic attack to achieve a target systolic blood pressure of less than 140 mm Hg"
  • "consider initiating or intensifying pharmacologic treatment in some adults aged 60 years or older at high cardiovascular risk, based on individualized assessment, to achieve a target systolic blood pressure of less than 140 mm Hg"

Eighth Joint National Committee (JNC 8)

JNC 8 recommendations in 2014 for BP goals:[12]

  • Strong evidence for BP goal less than 150/90 mm Hg for patients above age 60.
  • Strong evidence exists for a diastolic goal of less than 90 mm Hg for hypertensive patients between ages 30 - 59.
  • There is insufficient evidence for patients below age 60 for a systolic goal, or in those below age 30 for a diastolic goal, so the panel recommended a BP of less than 140/90 mm Hg for those groups based on expert opinion.

Kaiser Guidelines

The Kaiser Permanente hypertension protocol [21] and San Francisco safety net clinics [22] Kaiser Permanente approached chronic disease with a model using “...implementation, dissemination, and performance feedback approaches...” with a goal of exceeding 85% control of hypertension in their patient population2. The strategies proposed were 1) hypertension registry 2) standardization of blood pressure measurements 3) internal treatment algorithm 4) multidisciplinary approach [21].

1. Creating a hypertension patient registry (2000 and 2004)

  • Facilitate provider performance feedback with an accurate capture of all hypertensive patients in one database.
  • Required one hypertension code and at least one antihypertensive medication OR diagnosis of stroke, CKD, CAD, or DM.
  • There was a 60% increase in growth of registry that corresponded with a 30% increase in hypertension control.

2. Simplified intensification of therapy

  • One consistent algorithm was utilized for treatment protocols and laminated cards were given to all physicians as reminders.
  • Thiazide or combination pill (Lisinopril-HCTZ 20-25 ½ pill) as first line, regardless of stage.
  • B-blockers removed from first line options.

3. Standardized blood pressure measurements: staff trained and continuously evaluated through validated peer review and feedback (did they say anything about how long to rest)?

  • Bare arm during measurement
  • Arm supported at heart level
  • Appropriate cuff side
  • No talking during measurement

These techniques accompanied by consistent peer training and feedback led to a reduction in technique errors by 40%.

4. Team-based interdisciplinary BP checks by RNs and pharmacists.

  • BP check visits led by non-physicians facilitated access, more frequent visits, and treatment intensification

Blood pressure control outcomes for Kaiser

A recent Kaiser study has achieved 90% blood pressure control within their Medicare population[23] while the national average remains around 70% in the same population per HEDIS measures by NCQA[24].

Implementation of a modified Kaiser protocol in a vulnerable population led to an increase in the percent of patients with controlled hypertension from a baseline of 68% to 74% over the course of fifteen months.[22].

Clinical outcomes for Kaiser

Regarding efficacy in the real world[25], Kaiser Permanente Northern California has published findings that their decline and cardiovascular mortality exceeds the national decline[26]. An unpublished report states that death from cardiac disease is now less than common death from cancer in Kaiser Permanente Northern California[27].

Kaiser Permanente Southern California has shown that death from heart disease is now less common that death from cancer[28].

A preliminary study from Kaiser Northern California suggests a target of 140 mm Hg[29].

ESH/ESC 2013 Guidelines

ESH/ESC 2013 Guidelines. Approach to medical therapy of hypertension.
ESH/ESC 2013 Guidelines. Approach to medical therapy of hypertension.
ESH/ESC 2013 Guidelines. Approach to medical therapy of hypertension.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adult aged ≥18 years
with hypertension
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Implement lifestyle interventions
(continue throughout management)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Set blood pressure goal
Inititate BP lowering-medication
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
General population
(no diabetes or CKD)
 
 
 
 
 
 
 
 
 
Diabetes
or CKD present
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Age ≥60 years
 
 
 
Age <60 years
 
 
 
All ages
Diabetes present
No CKD
 
 
 
All ages
CKD present with
or without diabetes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood pressure goal
SBP <150 mm Hg
DBP <90 mm Hg
 
 
 
Blood pressure goal
SBP <140 mm Hg
DBP <90 mm Hg
 
 
 
Blood pressure goal
SBP <140 mm Hg
DBP <90 mm Hg
 
 
 
Blood pressure goal
SBP <140 mm Hg
DBP <90 mm Hg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nonblack
 
 
 
Black
 
 
 
 
 
 
All races
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate thiazide-type diuretic
or ACEI or ARB or CCB,
alone or in combination
 
 
 
Initiate thiazide-type diuretic
or CCB, alone or in combination
 
 
 
 
 
 
Initiate ACEI or ARB, alone or in combination with other drug class.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Select a drug treatment titration strategy
A. Maximize 1st medication before adding 2nd
OR
B. Add 2nd medication before reaching maximum dose of 1st medication
OR
C. Start with 2 medication classes separately or as fixed-dose combination
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At goal blood pressure?
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reinforce medication and lifestyle adherence.
For strategies A and B:
Add and titrate thiazide-type diuretic or ACEI or ARB or CCB (use medication class not previously selected and avoid combined use of ACEI & ARB).
For strategy C:
Titrate doses of initial medications to maximum.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At goal blood pressure?
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reinforce medication and lifestyle adherence.
Add and titrate thiazide-type diuretic or ACEI or ARB or CCB (use medication class not previously selected and avoid combined use of ACEI & ARB).
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At goal blood pressure?
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reinforce medication and lifestyle adherence.
Add additional medication class (eg, β-blocker, aldosterone antagonist, or others) and/or refer to physician with expertise in HTN management.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
At goal blood pressure?
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Continue current treatment
and monitoring.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Antihypertensive Agents & Indications

Common Antihypertensive Agents

Several classes of medications are used in the treatment of hypertension namely diuretics, ACE inhibitors, angiotensin receptor blockers, beta-blockers, alpha-blockers, and direct vasodilators. Below is a list of common oral agents used in the treatment of hypertension.

JNC8: Common oral antihypertensive agents[30]
Class Drug Usual Dose Range (mg/day)
Thiazide Diuretics Chlorothiazide 125-500
Chlorthalidone 12.5-25
Hydrochlorothiazide 12.5-50
Polythiazide 2-4
Indapamide 1.25-2.5
Metolazone 0.5-5
Loop Diuretics Bumetanide 0.5-2
Furosemide 20-80
Torsemide 2.5-10
Potassium-sparing Diuretics Amiloride 5-10
Triamterene 50-100
Aldosterone Receptor Diuretics Spironolactone 25-50
Eplerenone 50-100
Beta-Blockers Atenolol 25-100
Betaxolol 5-20
Bisoprolol 2.5-10
Metoprolol 50-100
Metoprolol extended release 50-100
Nadolol 40-120
Propranolol 40-160
Propranolol long-acting 60-180
Timolol 20-40
Beta-Blockers with intrinsic sympathomimetic activity Acebutolol 200-800
Penbutolol 10-40
Pindolol 10-40
Combined Alpha- and Beta-Blockers Carvedilol 12.5-50
Labetalol 200-800
ACE Inhibitors Benazepril 10-40
Captopril 25-100
Enalapril 5-40
Fosinopril 10-40
Lisinopril 10-40
Moexipril 7.5-30
Perindopril 4-8
Quinapril 10-80
Ramipril 2.5-20
Trandolapril 1-4
Angiotensin Receptor Blockers Candesartan 8-32
Eprosartan 400-800
Irbesartan 150-300
Losartan 25-100
Olmesartan 20-40
Telmisartan 20-80
Valsartan 80-320
Nondihydropyridine Calcium Channel Blockers Diltiazem extended release 120-540
Verapamil immediate release 80-320
Verapamil long acting 120-480
Verapamil 120-360
Dihydropyridine Calcium Channel Blockers Amlodipine 2.5-10
Felodipine 2.5-10
Isradipine 2.5-10
Nicardipine sustained release 60-120
Nifedipine long-acting 30-60
Nisoldipine 10-40
Alpha-1 Blockers Doxazosin 1-16
Prazosin 2-20
Terazosin 1-20
Centrally Acting Drugs Clonidine 0.1-0.8
Methyldopa 250-1000
Reserpine 0.1-0.25
Guanfacine 0.5-2
Direct Vasodilators Hydralazine 25-100
Minoxidil 2.5-80

Choice of Initial Agent

Clinical practice guidelines vary in their recommendations for selection of initial medication[6][11][12][31].

Selecting medication based on patient demographics


Some authors have proposed that either the renin level or the renin level indexed to urinary sodium excretion in 24 hours.[32][33] However, the Veterans Affairs Cooperative trial suggests the initial drug may be better selected based on the patient's age, race, and gender.[34][35] The patient's demographic roughly corresponds with their renin profile, but is more predictive than the renin profile.[35] In the Veterans Affairs Cooperative, among the high renin demographic (young whites), diuretics had similar efficacy to placebo; whereas in the low renin demographic (older blacks), the ace-inhibitors had similar efficacy to placebo in the Veterans Affairs Cooperative Study Group on Antihypertensive Agents (see figure).[34]

Selecting fixed-dose combination pills

Two cohort studies suggest that fixed-dose combination pills enhance adherence when compared to monotherapy[36][37]. The increased adherence may lead to improved clinical outcomes[37]. Therefore, it would not be unreasonable to consider starting combination therapy in order to increase patient compliance, a known barrier to hypertension pharmacotherapy.

Using up to 50 mg per day of hydrochlorothiazed, as recommended by Kaiser, is supported by dose-response studies summarized by the Cochrane Collaboration[38]. Previouslky, hydrochlorothiazide a a dose of 100 mg per day, without postassium sparing therapy, was associated with increased risk of cardiac arrest[39].

JNC7: Compelling Indications and Choice of Antihypertensive Agents[30]

Clinical trials and basis for compelling indications for individual drug classes
Compelling Indication Recommended Drugs Clinical Trial Basis
Heart failure Diuretics, Beta blockers, ACEIs, ARBs, Aldosterone antagonist ACC/AHA Heart Failure Guideline [40]; MERIT-HF [41];COPERNICUS [42]; CIBIS [43]; SOLVD [44]; AIRE [45]; TRACE [46]; ValHEFT [47]; RALES [48]
Post-Myocardial infarction Beta blockers, ACEIs, Aldosterone antagonist ACC/AHA Post-MI Guideline [49]; BHAT [50]; SAVE [51]; CAPRICORN [52]; EPHESUS [53]
High coronary disease risk Diuretics, Beta blockers, ACEIs, CCBs, ALLHAT [54]; HOPE[55]; ANBP2 [56]; LIFE [57]; CONVINCE [58]
Diabetes Diuretics, Beta blockers, ACEIs, ARBs, CCBs NKF-ADA Guideline [59][60];UKPDS [61]; ALLHAT [54]
Chronic kidney disease ACEIs, ARBs NFK Guideline [60]; Captopril Trial [62]; RENAAL [63]; IDNT [64]; REIN [65]; AASK [66]
Recurrent stroke prevention Diuretics, ACEIs PROGRESS [67]



Contraindicated medications

Chronic hypertension is considered an absolute contraindication to the use of the following medications:


Severe uncontrolled arterial hypertension is considered an absolute contraindication to the use of the following medications:

ESH/ESC 2013 Guidelines: Drugs to be Preferred in Specific Conditions [31]

Patient Characteristic Drug
Asymptomatic organ damage
Left Ventricular Hypertrophy ACE inhibitor, calcium antagonist, ARB
Asymptomatic atherosclerosis Calcium antagonist, ACE inhibitor
Microalbuminuria ACE inhibitor, ARB
Renal dysfunction ACE inhibitor, ARB
Clinical CV event
Previous stroke Any agent effectively lowering BP
Previous myocardial infarction BB, ACE inhibitor, ARB
Angina pectoris BB, calcium antagonist
Heart failure Diuretic, BB, ACE inhibitor, ARB, mineralocorticoid receptor antagonists
Aortic aneurysm BB
Atrial fibrillation, prevention Consider ARB, ACE inhibitor, BB or mineralocorticoid receptor antagonist
Atrial fibrillation, ventricular rate control BB, non-dihydropyridine calcium antagonist
ESRD/proteinuria ACE inhibitor, ARB
Peripheral artery disease ACE inhibitor, calcium antagonist
Other
ISH (elderly) Diuretic, calcium antagonist
Metabolic syndrome ACE inhibitor, ARB, calcium antagonist
Diabetes mellitus ACE inhibitor, ARB
Pregnancy Methyldopa, BB, calcium antagonist
Blacks Diuretic, calcium antagonist

Impact of Blood Pressure self-monitoring in Hypertension Control

According to systematic review in 2017 [68], self-monitoring blood pressures alone is not an effective treatment for high blood pressure. However, as an adjunct to interventions such as patient education, medication titration, and lifestyle counselling, self-monitoring blood pressures significantly aids in controlling patient blood pressure. “Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (−3.2 mmHg, [95% CI −4.9, −1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (−1.0 mmHg [−3.3, 1.2]), to a 6.1 mmHg (−9.0, −3.2) reduction when monitoring was combined with intensive support.”

This assessment is supported by another systematic review in 2018 [69], who determined that self-monitoring blood pressures significantly helps control patient blood pressure by aiding in physician anti-hypertensive medication titration. “Compared with usual care, the decrease in clinic measured systolic blood pressure at 12 months in patients in both self-monitoring groups was clinically meaningful. The adjusted mean differences vs usual care: self-monitoring alone −3.5 mm Hg [95% CI −5.8 to −1.2]; and telemonitoring −4.7 mm Hg [–7.0 to −2.4]). If sustained, such reductions in blood pressure could be expected to reduce stroke risk by 20% and coronary heart disease risk by 10%.”

Interdisciplinary Approach to Hypertension Management

Recent literature suggests that an interdisciplinary approach to hypertension provides higher control rates and more comprehensive management of hypertension on a population level. [70] [70] Systems-based interventions such as increasing the role of medical assistants and pharmacists in the management of hypertension has shown the most marked improvements in control. Other interventions include single-pill medical therapy, monitoring visits with medical assistants, creating a hypertension registry, and home blood pressure management. [71] [72] [73] [74]

  • When a team approach is used to manage hypertension, the addition of pharmacists alone were found to have the most substantial effect on hypertension control at the population level. [73]
  • There is conflicting evidence on home-monitoring alone as an effective method for increasing blood pressure control. [75] [68] [76]
  • Interventions such as optimizing single pill combination medications or promoting home blood pressure monitoring have not been shown to provide significant improvements in blood pressure when implemented alone.

Management of Hypertension in Special Populations

Diabetic Patients

  • According to the American Diabetes Association, BP goal for diabetic patients must be < 140/80 mmHg to reduce the progression of target organ damage but that lower systolic blood pressure targets <130 mmHg can be targeted in younger patients.[18] The recent shift in the approach to hypertension in diabetics proposed by the 2013 ADA guidelines as well as the 2013 ESH/ESC guidelines is supported by the fact that no major trials have consistently achieved a blood pressure level below 130/80 mmHg in diabetics nor have the smaller trials shown any major benefit from intensive treatment to reach that threshold. In parallel to the ADA, the 2013 ESH/ESC guidelines only support a lower DBP goal set at 80-85 mmHg.[31]
  • According to the American Diabetes Association, ACEI and ARBs are considered superior agents in diabetic patients for their renal protective effects (delay in both GFR decrease and albuminuria worsening).[77] Although RAAS blockers such as ACEI and ARBs are beneficial their combination can sometimes have significant effects on renal function especially in high risk patients.[78]
  • Thiazide-type diuretics were shown to be beneficial in reducing heart disease in diabetic patients.[79] Despite their side effects of worsening hyperglycemia, thiazide-type diuretics were associated with stable target organ damage compared to other anti-hypertensive agents.[80]
  • According to the LIFE study, beta-blockers are especially beneficial in diabetic patients with ischemic heart disease despite their controversial role as monotherapy.[81] Even though decreased insulin sensitivity is a side effect, beta-blockers are not absolutely contraindicated in diabetes.[82]
  • In the management of hypertension, CCBs are unquestionably useful in the reduction of BP values. However, their role in preventing target organ damage in diabetic patients is inferior to other agents. The ALLHAT study demonstrated that amlodipine, a DHP CCB, was less effective than thiazides in reducing heart failure.[79] Similarly, the ABCD Trial also showed that nisoldipine, a dihydropyridine CCB was less effective than enalapril, an ACEI, in reducing ischemic heart disease.[83]

Chronic Kidney Disease Patients

  • Based mostly on the results from meta-analyses of patients with proteinuria showing slower rate of CKD progression when SBP was targeted to <130 mmHg, JNC7 and the National Kidney Foundation recommended a set BP goal below 130/80 mmHg for all CKD patients and the use of more than a single agent for therapy. The recommended treatment regimen usually includes an ACEI or ARB in combination with a loop diuretic. [30]
  • In 2012, the KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease recommended that diabetic and non-diabetic patients with CKD without proteinuria or microalbuminuria should be treated if their BP measurements are consistently above 140/90 mmHg. Target of treatment in this group is to maintain blood pressure below 140/90 mmHg. In patients with CKD and microalbuminuria or proteinuria, initiation of therapy should be at BP values >130/80 mmHg with target below 130/80 mmHg. The guidelines also advocated the use ACEIs and ARBs in patients with microalbuminuria or proteinuria. Lifestyle modifications proposed included lowering salt intake to <2g per day of sodium, exercise for at least 30 minutes 5 times per week.
  • In contrast, the 2013 ESH/ESC guidelines updated their old recommendations, changing the blood pressure target to <140/90 mmHg, no different than the general population. They based their recommendations on three trials[84][85][86] conducted in patients with chronic kidney disease without diabetes, that showed no difference in ESRD progression and all-cause mortality between patients randomized to low BP targets (<130 mmHg) to those randomized to a higher target (<140 mmHg). To note, observational follow-up data from 2 of these studies showed a tendency to lower adverse events in the lower target group especially in patients with proteinuria.[19]

Patients with Metabolic Syndrome

  • Metabolic syndrome as a clinical concept is largely debatable, mostly since studies have shown little added benefit of the definition on the predictive power of each of the constitutive individual factors, making recommendations about hypertension treatment in this subpopulation limited.[31]
  • Lifestyle modification plays the most important role in anti-hypertensive therapy in patients with metabolic syndrome.
  • Persistence of high BP > 140/90 mmHg still warrants pharmacologic therapy.
  • Management of dyslipidemia, glucose intolerance, and other concomitant comorbidities is essential for reduction of BP in patients with metabolic syndrome.[82]

Ethnic groups

  • African Americans: Enforcement of DASH diet due to its association with greater reduction of BP than other ethnicities.[87] According to the ALLHAT trial that included 15,000 Blacks, diuretics were more effective for African Americans than other classes of anti-hypertensive agents.[79]
  • Mexican Americans, other Hispanic Americans, Native Americans, and Asian/Pacific Islanders have been recruited in insufficient numbers in research trials to adequately identify special considerations.[82]

Elderly Patients

  • There is particular advantage in weight loss and reduced sodium intake in elderly subjects. Trial of Non-pharmacologic Interventions in the Elderly (TONE) showed that sodium intake of less than 80 mmol per day (2 g of sodium per day or 5 grams of sodium chloride salt) could allow the discontinuation of anti-hypertensive agents in 40% of elderly.[88]
  • The 2013 ESH/ESC guidelines modified the approach adopted in 2007 to treat hypertension regardless of age. The new guidelines advocate holding medical therapy for elderly patients with stage 1 hypertension and initiating treatment only in those with stage 2 hypertension or greater. It is also recommended to target a SBP below 150 mmHg rather than 140mmHg. This rationale follows several studies involving elderly patients not achieving blood pressure measurements below 140mmHg. In patients below 80 years of age, treatment can be targeted below 140 mmHg if goal can be tolerated.[31]
  • The HYpertension in the Very Elderly Trial (HYVET) showed that in patients older than 80 years-old with SBP >160mmHg, a significant reduction in major CV events and all-cause mortality can be seen by aiming at SBP values <150mmHg. [89]
  • The JNC7 guidelines concluded in 2004 that antihypertensive therapy should not be withheld in patients with stage 1 hypertension based on age, even though no RCTs had shown benefits from treatment in this population at the time.

Pregnant Women

  • Distinguishing gestational from pre-gestational hypertension in pregnant women is essential. Hypertension is not considered to be caused by pregnancy when it develops before 20 weeks of gestation.[82]
  • Hypertensive women who plan to become pregnant should be instructed to use safe anti-hypertensive medications, such as methyldopa preferentially because long-term follow up studies are available. [90] Labetolol and nifedipine are also other treatment options that can be considered in pregnancy.[31]
  • Pregnant women with stage 1 hypertension present with low cardiovascular risk and anticipated physiological lowering of blood pressure during pregnancy. Thus healthcare providers might advise mere lifestyle modification as therapy during pregnancy and breast feeding, with caution on excessive weight reduction and with possible restriction of aerobic physical activity.[82]
  • The 2013 ESH/ESC guidelines recommend drug treatment of severe hypertension in pregnancy defined as SBP >160 mmHg or DBP >110 mmHg. They also advocate considering treatment in pregnant women with persistant hypertension ≥150/95 mmHg and in symptomatic patients or patients with target organ damage with BP ≥140/90 mmHg.[31]

Patients with Hypertensive Emergency or Urgency

  • Hypertensive emergency is defined as high blood pressure causing acute target organ damage. Usually BP exceeds 180/20 mmHg, but can sometimes occur at even lower values in patients who do not usually have high blood pressure.
  • Hypertensive urgency is defined as a BP > 180/120 mmHg without target organ damage. Hypertensive urgency may or may not be symptomatic.
  • Triage to differentiate between hypertensive emergency and urgency is crucial for appropriate management. While hypertensive emergencies require intensive care unit (ICU) admission for close monitoring and aggressive parenteral agents, hypertensive urgencies can be managed in the emergency department with outpatient follow-up for optimization of therapy.[82]
  • Treatment is based on titrated intravenous medications that act rapidly but safely especially in avoiding severe hypotension and ischemic organ damage. Nicardipine, sodium nitroprusside, labetalol, furosemide and nitrates are some of the agents used. In certain cases of volume overload-associated hypertensive emergency where diuresis is insufficient, dialysis and ultrafiltration may be of benefit.[31]
  • Generally, JNC 7 outlines the acute management of hypertensive emergencies as reduction of a maximum of 25% of mean arterial BP within the first hour followed by decrease of BP to 160/100 within the next 2 to 6 hours. Normalization of blood pressure should occur at a span of 24-48 hours. Rapid decrease in BP might precipitate ischemia caused by target organ damage.[82]
  • The 2013 ESH/ESC guidelines do not dwell much into the treatment of hypertensive emergencies due to the lack of evidence considering the small number of cases but recommend that treatment be individualized by the physician.[31]
  • Specific clinical situations are considered exceptions to the abovementioned management plan:[82]
    • Ischemic stroke will not require immediate BP lowering to maintain cerebral perfusion.
    • Aortic dissection requires SBP to be lowered immediately to < 100 mmHg if tolerated followed by rapid specific management.

Benchmarks in controlling hypertension

In the US the rate of control is estimated at 43.7% in 2017-2018 using NHANES data.[91]

Higher rates of control are reported by:

  • The National Committee for Quality Assurance (NCQA)'s Healthcare Effectiveness Data and Information Set (HEDIS) for patients other than traditional Medicare[92]
  • The Centers for Medicare and Medicaid Services's resource library Electronic Clinical Quality Improvement (eCQI) for Medicare patients[93]

Barriers to blood pressure control

Health care provider barriers

Therapeutic inertia

Therapeutic inertia may contribute to the finding that in the US 62%, and in Europe 85%, of office visits with a high blood pressure the health care provider does not increase medications[94]. In another study, "Among visits in which a diastolic blood pressure of ≥90 mm Hg and systolic blood pressure of ≥155 mm Hg were recorded, the frequency of increases in antihypertensive medications was 25.6 percent"[95]. Similarly, another study found a rate of 17% of visits with uncontrolled hypertension having a treatment intensification[96].

The impact of intensification and deintensification is complicated[97].

Therapeutic inertia may be less with remote monitoring when patients submitted at least 3 elevated BP readings[98].

Choice of follow-up intervals

Among controlled patients, short follow-up intervals (3 versus 6 months), were found in a randomized controlled trial to not improve control[99].

Among uncontrolled patients

  • Short follow-up intervals (comparing < 2 weeks, 2 weeks to 1 month, and > 1 month), were found to improve speed of normalization of blood pressure and "increased probability of normalization of blood pressure at two years"[100] Another observational study also found benefit in 2 weeks follow-up visits for hypertension as well as diabetes and cholesterol goals[101]. Additional studies have found importance of shorter follow-up[102].
  • Short follow-up intervals, were found in a randomized controlled trial to minimally improve control; however, in this study, there was slight variation in the follow-up times between study groups (34, 32, and 32 days)[103].

Involving self-monitoring and medication self-titration

A randomized controlled trial found "self-monitoring with self-titration of antihypertensive medication compared with usual care resulted in lower systolic blood pressure at 12 months."[104]

Vulnerable populations

Underserved or vulnerable populations face additional socioeconomic barriers to hypertension control including decreased clinic resources, limited access to care, and inconsistent follow-up.

A recent cohort study with a time-series analysis conducted in San Francisco safety net clinics adapted the 2013 Kaiser protocol (details above)[71] to fit the specific needs of safety-net clinics by focusing on 4 specific modifications[22]:

  1. Creating a hypertension patient registry
  2. Simplified intensification of therapy
  3. Standardized BP measurements
  4. Team-based interdisciplinary BP checks by RNs and pharmacists.

Implementation of the modified Kaiser protocol led to an increase in the percent of patients with controlled hypertension from a baseline of 68% to 74% over the course of fifteen months. Overall, the results of this study demonstrated that large-scale hypertension protocols can be successfully applied to high-risk populations[22].

Student-run free clinics

Student-run free clinics provide healthcare to a diverse population of patients including those that are: uninsured, unemployed, homeless, ethnic minority, non-native speakers, or low-income status. Student-run clinics that have published baseline rates of hypertension control show that these clinics are able to exceed national standards in their uninsured populations.

According to HEDIS (2018), the national rate of hypertension control in Medicaid patients is 58.9%[105].

In student-run free clinics:

  • Wahle et al. reported a baseline hypertension control rate of 46.8% (defined by JNC 7 & 8) at Indiana University Student Outreach Clinic[106].
  • Smith et al. reported a baseline hypertension control rate of 59.7% (defined by JNC 7 & 8) at 4 student run health clinics associated with the University of California San Diego[107].
  • Zucker et al. reported a baseline hypertension control rate of 50% (defined by JNC 7) at a Student Family Health Care Center affiliated with the University of Medicine and Dentistry at New Jersey[108].

Despite the challenges associated with running a student-run free clinic, these studies show it is possible to achieve rates of hypertension control comparable to patients insured by Medicaid.

References

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  2. ↑ Wilt TJ, Kansagara D, Qaseem A, Clinical Guidelines Committee of the American College of Physicians (2018). "Hypertension Limbo: Balancing Benefits, Harms, and Patient Preferences Before We Lower the Bar on Blood Pressure". Ann Intern Med. 168 (5): 369–370. doi:10.7326/M17-3293. PMID 29357397.
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  83. ↑ Schrier RW, Estacio RO, Esler A, Mehler P (2002). "Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes". Kidney Int. 61 (3): 1086–97. doi:10.1046/j.1523-1755.2002.00213.x. PMID 11849464.
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  92. ↑ National Committee for Quality Assurance Controlling High Blood Pressure (CBP). Available at https://www.ncqa.org/hedis/measures/controlling-high-blood-pressure/
  93. ↑ Available at https://qpp.cms.gov/resources/resource-library (search for "quality benchmarks")
  94. ↑ Wang YR, Alexander GC, Stafford RS (2007). "Outpatient hypertension treatment, treatment intensification, and control in Western Europe and the United States". Arch Intern Med. 167 (2): 141–7. doi:10.1001/archinte.167.2.141. PMID 17242314.
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  98. ↑ Lee NS, Anastos-Wallen R, Chaiyachati KH, Reitz C, Asch DA, Mehta SJ (2022). "Clinician Decisions After Notification of Elevated Blood Pressure Measurements From Patients in a Remote Monitoring Program". JAMA Netw Open. 5 (1): e2143590. doi:10.1001/jamanetworkopen.2021.43590. PMID 35029664 Check |pmid= value (help).
  99. ↑ Birtwhistle RV, Godwin MS, Delva MD, Casson RI, Lam M, MacDonald SE; et al. (2004). "Randomised equivalence trial comparing three month and six month follow up of patients with hypertension by family practitioners". BMJ. 328 (7433): 204. doi:10.1136/bmj.37967.374063.EE. PMC 318487. PMID 14726370.
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  104. ↑ McManus RJ, Mant J, Haque MS, Bray EP, Bryan S, Greenfield SM; et al. (2014). "Effect of self-monitoring and medication self-titration on systolic blood pressure in hypertensive patients at high risk of cardiovascular disease: the TASMIN-SR randomized clinical trial". JAMA. 312 (8): 799–808. doi:10.1001/jama.2014.10057. PMID 25157723. Review in: Evid Based Med. 2015 Apr;20(2):58 Review in: Ann Intern Med. 2015 Jan 20;162(2):JC7 Review in: Evid Based Nurs. 2015 Jul;18(3):87
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  106. ↑ Wahle, B Meyer K, Faller M, Kochhar K, Sevilla J (2017). "Assessment of Hypertension Management and Outcomes at an Indianapolis Student-Run Free Clinic". J Health Care Poor Underserved. 28 (2): 694–706. doi:10.1353/hpu.2017.0068. PMID 28529218.
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