Hypertension guidelines

Acronyms

AAFP - American Academy of Family Physicians
AAP - American Academy of Pediatrics
ACC - American College of Cardiology
ACE - Angiotensin converting enzyme
ACP - American College of Physicians
ADA - American Diabetes Association
AF - Atrial fibrillation
AHA - American Heart Association
ARB - Angiotensin II receptor blocker
BP - Blood pressure
CAD - Coronary artery disease
CKD - Chronic kidney disease
CVD - Cardiovascular disease
DBP - Diastolic blood pressure
DM - Diabetes mellitus
HFpEF - Heart failure with preserved ejection fraction (diastolic heart failure)
HFrEF - Heart failure with reduced ejection fraction
HTN - Hypertension
JNC 8 - Eighth Joint National Committee
KDIGO - Kidney Disease: Improving Global Outcomes
RCT - Randomized controlled trial
SBP - Systolic blood pressure

AHA/ACC 2017/2023 HYPERTENSION GUIDELINES

^✝If either measure, SBP or DBP, is elevated, criteria is met
AHA/ACC Blood Pressure Categories
Category	SBP (mmHg)	DBP (mmHg)
Normal	< 120	< 80
Elevated	120 - 129	< 80
Stage 1 hypertension^✝	130 - 139	80 - 89
Stage 2 hypertension^✝	≥ 140	≥ 90

References [7,9]
AHA/ACC BP Treatment Recommendations
Patients with any of the following: CVD, HFrEF, CKD, DM, 10-year risk of CVD ≥ 10% Treat with medications if average SBP ≥ 130 mmHg or average DBP ≥ 80 mmHg Use ACC/AHA risk estimator to estimate 10-year risk
Patients with HFpEF Treat with medication if average SBP ≥ 130 mmHg
All other patients Treat with medication if average SBP ≥ 140 mmHg or average DBP ≥ 90 mmHg

Reference [7,9]
AHA/ACC Medication Recommendations
Nonblack patients without comorbidities Use one of the first-line therapies below Two first-line agents are recommended in stage 2 hypertension for patients with an average BP ≥ 20/10 mmHg above their BP goal First-line therapy includes the following: Thiazide diuretics ACE inhibitors Angiotensin receptor blockers (ARB) Calcium channel blockers
Black patients without comorbidities Thiazide diuretic or calcium channel blocker is preferred STUDY A randomized trial found that combination therapy that included amlodipine was superior to an ACE/HCTZ combination for lowering blood pressure in black patients. See amlodipine study below.
Diabetes Patients without albuminuria: Any first-line agent Patients with albuminuria: ACE inhibitor or ARB
Chronic cardiovascular disease (CVD) First-line: ACE/ARB or beta blocker for compelling indication (e.g., recent MI, angina) Other: dihydropyridine calcium channel blocker, long-acting thiazide diuretic, and/or mineralocorticoid receptor antagonist
Chronic kidney disease (CKD) Treatment with an ACE inhibitor is reasonable to slow disease progression ARB may be used if ACE inhibitor is not tolerated
Heart failure preserved ejection fraction (HFpEF) Diuretics should be used first-line in patients with volume overload ACE inhibitor / ARB and/or beta blockers can be used for further blood pressure lowering
Atrial fibrillation (AF) ARBs may help prevent AF recurrence
Patients with thoracic aortic disease (e.g. aneurysms) Beta blockers are preferred
Women who are pregnant or planning to become pregnant Use methyldopa, nifedipine, and/or labetalol

JNC 8 GUIDELINES

JNC 8 Blood Pressure Goals
Adults without diabetes or chronic kidney disease Adults < 60 years old SBP < 140 mmHg and DBP < 90 mmHg Adults ≥ 60 years old SBP < 150 mmHg and DBP < 90 mmHg
Adults with diabetes or chronic kidney disease SBP < 140 mmHg and DBP < 90 mmHg

JNC 8 Medication Recommendations
Adults without chronic kidney disease Nonblack patients Initiate therapy with one of the following: Thiazide diuretic ACE inhibitor Angiotensin receptor blocker Calcium channel blocker For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with two drugs. When titrating therapy to goal, dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized. If goal is not achieved with medications in the initial therapy group, other medications may be added (e.g., beta blockers, aldosterone antagonists, etc.) Black patients Initiate therapy with one of the following: Thiazide diuretic Calcium channel blocker For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with two drugs. When titrating therapy to goal, dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized. If goal is not achieved with medications in the initial therapy group, other medications may be added (e.g., beta blockers, aldosterone antagonists, etc.) STUDY A randomized trial found that combination therapy that included amlodipine was superior to an ACE/HCTZ combination for lowering blood pressure in black patients. See amlodipine study below.
Adults with chronic kidney disease (diabetic or other) Initiate therapy with one of the following: ACE inhibitor Angiotensin receptor blocker For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with two drugs. When titrating therapy to goal, dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized. If goal is not achieved with medications in the initial therapy group, other medications may be added (e.g., beta blockers, aldosterone antagonists, etc.)

JNC 8 Medication Recommendations

Adults without chronic kidney disease

Nonblack patients

Initiate therapy with one of the following:

For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with two drugs. When titrating therapy to goal, dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized. If goal is not achieved with medications in the initial therapy group, other medications may be added (e.g., beta blockers, aldosterone antagonists, etc.)

Black patients

Initiate therapy with one of the following:

For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with two drugs. When titrating therapy to goal, dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized. If goal is not achieved with medications in the initial therapy group, other medications may be added (e.g., beta blockers, aldosterone antagonists, etc.)
STUDY
A randomized trial found that combination therapy that included amlodipine was superior to an ACE/HCTZ combination for lowering blood pressure in black patients. See amlodipine study below.

Adults with chronic kidney disease (diabetic or other)

Initiate therapy with one of the following:

For patients with higher initial blood pressures (SBP > 160, DBP > 100), therapy may be initiated with two drugs. When titrating therapy to goal, dose of one drug may be maximized before adding another medication, or another medication may be added before previous drug is maximized. If goal is not achieved with medications in the initial therapy group, other medications may be added (e.g., beta blockers, aldosterone antagonists, etc.)

ACP/AAFP 2017 RECOMMENDATIONS FOR ADULTS ≥ 60 YEARS OLD

Reference [3]
ACP/AAFP Recommendations for adults ≥ 60 years old
Adults ≥ 60 years with a history of stroke or TIA or at high risk for CVD Systolic blood pressure goal < 140 mmHg High risk for CVD is generally defined as any of the following: Persons with known vascular disease Most patients with diabetes Older persons with chronic kidney disease (GFR < 45 ml/min) Metabolic syndrome (abdominal obesity, hypertension, diabetes, and dyslipidemia) Older persons
All other adults ≥ 60 years old Systolic blood pressure goal < 150 mmHg
Other The guideline states there is insufficient evidence to make recommendations based on diastolic blood pressure Accurate blood pressure measurement (home and clinic) is important before initiating treatment

Reference [8]
2021 KDIGO blood pressure recommendations for CKD patients not on dialysis
Blood pressure measurement Office blood pressure measurement should follow a standardized procedure (see proper BP measurement) Out-of-office BP measurements with ambulatory BP monitoring or home BP monitoring may be used to complement standardized office BP readings for the management of high BP
Lifestyle interventions for lowering BP Target sodium intake should be < 2 g per day (or < 90 mmol of sodium per day, or < 5 g of sodium chloride per day) in patients with high BP and CKD. See sodium and hypertension. Moderate-intensity physical activity for a cumulative duration of at least 150 minutes per week or to a level compatible with the patient's cardiovascular and physical tolerance is recommended
BP goals Target SBP: < 120 mmHg when tolerated
Medication choice See CKD stages and CKD albuminuria categories for definitions Nondiabetics An ACE inhibitor or ARB is recommended in people with high BP, CKD, and severely increased albuminuria (CKD stage G1–G4 \| albuminuria category A3) An ACE inhibitor or ARB is suggested in people with high BP, CKD, and moderately increased albuminuria (CKD stage G1–G4 \| albuminuria category A2) Diabetics An ACE inhibitor or ARB is recommended in people with high BP, CKD, and moderately-to-severely increased albuminuria (CKD stage G1–G4 \| albuminuria category A2 and A3) Medication management Use the highest dose of ACE inhibitor or ARB that is tolerated. Check BP, serum creatinine, and serum potassium within 2 - 4 weeks of initiation, after medication changes, and as indicated. RAAS inhibitor-induced hyperkalemia can often be managed with measures to reduce serum potassium rather than decreasing or stopping the drug. See managing RAAS inhibitor-induced hyperkalemia and treating and preventing hyperkalemia in CKD. Continue ACE inhibitor or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks of initiation or after a dose increase Consider reducing the dose or discontinuing ACE inhibitor or ARB in the setting of either symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment, or to reduce uremic symptoms while treating kidney failure Aldosterone antagonists (spironolactone, eplerenone) are effective for management of refractory hypertension but may cause hyperkalemia or a reversible decline in kidney function, particularly among patients with low eGFR Do not combine ACE inhibitors, ARBS, or renin inhibitors
Kidney transplant recipients BP goals SBP < 130 mmHg and DBP < 80 mmHg Medications A dihydropyridine calcium channel blocker or an ARB should be used as the first-line antihypertensive agent in adult kidney transplant recipients
Children with CKD BP goals 24-hour mean arterial pressure by ambulatory BP monitoring should be lowered to ≤ 50th percentile for age, sex, and height. If ambulatory BP monitoring is unavailable, manual auscultatory office BP with a goal SBP < 90th percentile for age, sex, and height is a reasonable approach. Medications An ACE inhibitor or ARB is the preferred first-line agent. Sexually active females should be warned about the potential for fetal harm.

AAP PEDIATRIC RECOMMENDATIONS

Screening

Screen all children and adolescents ≥ 3 years old annually. Children and adolescents ≥ 3 years with any of the following should be screened at every health encounter: obesity, renal disease, history of aortic arch obstruction or coarctation, diabetes, taking blood pressure-raising medications (e.g., ADHD stimulants).

Diagnosis

AAP blood pressure categories are provided in the table below; the second table gives the upper limits of normal by age and sex.
Hypertension is diagnosed if auscultatory-confirmed blood pressure readings are equal to or greater than the 95th percentile at three different visits. Ambulatory blood pressure monitoring should be performed if office blood pressure measurements are in the elevated category for a year or more, stage 1 hypertension is present over three clinic visits, and/or suspected white coat hypertension. [6]

*See table below for upper limits of normal blood pressure readings by age

Reference [6]
AAP BLOOD PRESSURE CATEGORIES
Children aged 1 - 13 years
Normal BP	< 90th percentile
Elevated BP	≥90th percentile to < 95th percentile OR 120/80 mmHg to < 95th percentile (whichever is lower)
Stage 1 HTN	≥ 95th percentile to < 95th percentile + 12 mmHg, OR 130/80 to 139/89 mmHg (whichever is lower)
Stage 2 HTN	≥ 95th percentile + 12 mmHg, OR ≥ 140/90 mmHg (whichever is lower)
Children aged ≥ 13 years
Normal BP	<120/< 80 mmHg
Elevated BP	120/<80 to 129/<80 mmHg
Stage 1 HTN	130/80 to 139/89 mmHg
Stage 2 HTN	≥140/90 mmHg

Blood pressure readings above these values are considered high

Reference [6]
Upper limits of blood pressure by age
AGE (years)	Boys (SBP/DBP)	Girls (SBP/DBP)
1	98 / 52	98 / 54
2	100 / 55	101 / 58
3	101 / 58	102 / 60
4	102 / 60	103 / 62
5	103 / 63	104 / 64
6	105 / 66	105 / 67
7	106 / 68	106 / 68
8	107 / 69	107 / 69
9	107 / 70	108 / 71
10	108 / 72	109 / 72
11	110 / 74	111 / 74
12	113 / 75	114 / 75
≥ 13	120 / 80	120 / 80

Workup

All children diagnosed with hypertension should have the following studies:

Urinalysis
Basic metabolic profile (BMP)
Lipid panel
Renal ultrasonography if < 6 years of age or abnormal urinalysis or renal function

Secondary hypertension

Signs and symptoms of secondary hypertension are provided in the table below. Patients ≥ 6 years of age do not require an extensive evaluation for secondary hypertension if they have a family history of hypertension, are overweight or obese, and/or do not have findings suggestive of secondary hypertension.

Reference [6]
Signs of secondary hypertension
Renal disease Most common cause of secondary hypertension in children, particularly those < 6 years old
Coarctation of the aorta Right arm SBP that is ≥ 20 mmHg higher than lower extremity SBP Hypertension is common even after successful repair (up to 77% of patients) Masked hypertension is common, and ambulatory blood pressure monitoring should be performed
Obstructive sleep apnea Snoring Adenotonsillar hypertrophy
Medications / Supplements Oral contraceptives Corticosteroids and anabolic steroids Herbal and nutritional supplements Diet products ADHD stimulants
Congenital adrenal hyperplasia Low potassium Acne, hirsutism, and virilization in girls Pseudoprecocious puberty in boys
Hyperaldosteronism Low potassium May be familial
Cushing syndrome Central obesity and enlarged fat pad on upper back (buffalo hump) Hirsutism and acne Moon facies Absent or irregular menses
Hyperthyroidism Tachycardia, anxiety, sweating, heat intolerance
Environmental exposures Lead, cadmium, mercury, phthalates
Neurofibromatosis Cafe-au-lait macules Neurofibromas Lisch nodules of the iris Axillary freckling

Treatment

Treatment goals

SBP and DBP < 90th percentile or < 130/80 mmHg, whichever is lower (see pediatric BP values above)

Medications

Initiate therapy with one of the following:

Sports participation

Children and adolescents with hypertension may participate in competitive sports once hypertensive target organ effects and cardiovascular risk have been assessed

STUDIES | BP GOALS

Overview

The three large trials below compared the effects of intensive BP targets (<120 or <130) to less stringent ones (<140 or < 150) on CVD outcomes in large patient populations.

RCT

SPRINT trial - Intensive (SBP < 120) vs Standard (SBP < 140) Blood Pressure Control for CVD Outcomes, NEJM (2015) [PubMed abstract]

The SPRINT trial enrolled 9361 patients with a SBP ≥ 130 mmHg who were at increased risk of cardiovascular disease

Main inclusion criteria

Age ≥ 50 years
SBP 130 - 180 mmHg
Increased cardiovascular risk defined as ≥ 1 of the following: clinical or subclinical cardiovascular disease (except stroke), chronic kidney disease (CrCl 20 - < 60 ml/min), 10-year heart attack risk of ≥ 15% (Framingham risk calculator), age ≥ 75 years

Main exclusion criteria

Diabetes
History of stroke
Symptomatic heart failure within the past 6 months or EF < 35%

Baseline characteristics

Average age 68 years
Chronic kidney disease - 28%
Average SBP - 140 mmHg
Average DBP - 78 mmHg
Average Framingham 10-year risk - 20%

Randomized treatment groups

Group 1 (4678 patients) - Target SBP < 120 mmHg (Intensive)
Group 2 (4683 patients) - Target SBP < 140 mmHg (Standard)
There was no set treatment algorithm; patients could receive any blood pressure medication(s). Certain medications were encouraged in the study protocol - thiazides as first-line agents, loop diuretics for chronic kidney disease, beta blockers for CAD. Chlorthalidone was recommended as the primary thiazide diuretic. Amlodipine was the recommended calcium channel blocker.

Primary outcome: Composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes

Results

Outcome	Intensive	Standard	Comparisons
Duration: After a median of 3.26 years, the study was stopped early because the intensive group was superior
Average SBP during follow-up	121.5	134.6	N/A
Average number of BP meds	2.8	1.8	N/A
Primary outcome	5.2%	6.8%	HR 0.75, 95%CI [0.64 - 0.89], p<0.001
Myocardial infarction	2.1%	2.5%	HR 0.83, 95%CI [0.64 - 1.09], p=0.19
Acute coronary syndrome	0.9%	0.9%	HR 1.0, 95%CI [0.64 - 1.55], p=0.99
Stroke	1.3%	1.5%	HR 0.89, 95%CI [0.63 - 1.25], p=0.50
Heart failure	1.3%	2.1%	HR 0.62, 95%CI [0.45 - 0.84], p=0.002
Death from cardiovascular cause	0.8%	1.4%	HR 0.57, 95%CI [0.38 - 0.85], p=0.005
Death from any cause	3.3%	4.5%	HR 0.73, 95%CI [0.60 - 0.90], p=0.003
Hypotension	3.4%	2.0%	p<0.001
Syncope	3.5%	2.4%	p=0.003
Electrolyte abnormality	3.8%	2.8%	p=0.006
Acute kidney injury/failure	4.4%	2.6%	p<0.001
Medication types: ACE or ARB: Intensive - 77%, Standard - 55% \| Beta blocker: Intensive - 41%, Standard - 31% \| Diuretic: Intensive - 67%, Standard - 43%

Findings: Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group.

RCT

SPRINT Subgroup Analysis of Participants ≥ 75 Years Old at Randomization, JAMA (2016) [PubMed abstract]

A subgroup analysis of the SPRINT trial looked at the 2636 patients who were ≥ 75 years old at randomization

Outcome	Intensive	Standard	Comparisons
Duration: After a median follow-up of 3.14 years, the study was stopped early because the intensive group was better
Average BP during follow-up	123/62	135/67	N/A
Average number of BP meds	2.6	1.8	N/A
Primary outcome	7.7%	11.2%	HR 0.66, 95%CI [0.51 - 0.85], p=0.001
Myocardial infarction	2.8%	4.0%	HR 0.69, 95%CI [0.45 - 1.05], p=0.09
Acute coronary syndrome	1.3%	1.3%	HR 1.03, 95%CI [0.52 - 2.04], p=0.94
Stroke	2.1%	2.6%	HR 0.72, 95%CI [0.43 - 1.21], p=0.22
Heart failure	2.7%	4.2%	HR 0.62, 95%CI [0.40 - 0.95], p=0.03
Death from cardiovascular cause	1.4%	2.2%	HR 0.60, 95%CI [0.33 - 1.09], p=0.09
Death from any cause	5.5%	8.1%	HR 0.67, 95%CI [0.49 - 0.91], p=0.009
Hypotension event	3.3%	2.0%	HR 1.66, 95%CI [1.03 - 2.73], p=0.039
Syncope	4.3%	3.3%	HR 1.28, 95%CI [0.85 - 1.92], p=0.240
Electrolyte abnormality	4.6%	3.3%	HR 1.44, 95%CI [0.97 - 2.16], p=0.067
Fall with injury	11.6%	14.1%	HR 0.80, 95%CI [0.64 - 0.99], p=0.040
Kidney injury/failure	5.5%	4.2%	HR 1.39, 95%CI [0.97 - 1.99], p=0.072
Medication types: ACE or ARB: Intensive - 71%, Standard - 52% \| Beta blocker: Intensive - 43%, Standard - 34% \| Diuretic: Intensive - 62%, Standard - 42%

Findings: Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.

RCT

STEP study - Intensive (SBP < 130) vs Standard (SBP < 150) Blood Pressure Control in Older Patients with Hypertension, NEJM (2021) [PubMed abstract]

The STEP study enrolled 8511 Chinese patients 60 - 80 years old with hypertension

Main inclusion criteria

60 - 80 years of age
SBP 140 - 190 mmHg or taking BP meds
Han ethnicity

Main exclusion criteria

History of ischemic or hemorrhagic stroke
MI within 6 months
PCI or CABG within 12 months
NYHA class III - IV heart failure
HgA1C > 8%

Baseline characteristics

Average age 66 years
Average BMI - 26
Average BP - 146/82
Diabetes - 19%
History of CVD - 6.3%
Current smoker - 16%

Randomized treatment groups

Group 1 (4243 patients): SBP target of 110 to <130 mmHg (Intensive group)
Group 2 (4268 patients): SBP target of 130 to <150 mmHg (Standard group)
Treatment was standardized with an algorithm that included olmesartan, amlodipine, and HCTZ
Patients were seen every 3 months, and all were given home BP machines that uploaded readings to a data center. Patients were required to measure their home BP at least once a week.

Primary outcome: Composite of stroke (ischemic or hemorrhagic), acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes

Results

Outcome	Intensive	Standard	Comparisons
Duration: Median of 3.34 years
Average BP during follow-up	127/76	136/79	N/A
Average number of BP meds	1.9	1.5	N/A
Primary outcome	3.5%	4.6%	HR 0.74 95%CI [0.60 - 0.92], p=0.007
Stroke	1.1%	1.7%	HR 0.67 95%CI [0.47 - 0.97]
Acute coronary syndrome	1.3%	1.9%	HR 0.67 95%CI [0.47 - 0.94]
Acute heart failure	0.1%	0.3%	HR 0.27 95%CI [0.08 - 0.98]
Coronary revascularization	0.5%	0.7%	HR 0.69 95%CI [0.40 - 1.18]
Atrial fib	0.6%	0.6%	HR 0.96 95%CI [0.55 - 1.68]
Death from CV cause	0.4%	0.6%	HR 0.72 95%CI [0.39 - 1.32]
Overall mortality	1.6%	1.5%	HR 1.11 95%CI [0.78 - 1.56]
Hypotension	3.4%	2.6%	HR 1.31 95%CI [1.02 - 1.68], p=0.03
Medication types at 42 months: CCB only: Intensive - 10.8%, Standard - 20.5% \| ARB only: Intensive - 7.1%, Standard - 12.7% \| CCB + ARB: Intensive - 41.9%, Standard - 30.4% \| ARB+CCB+HCTZ: Intensive - 9.3%, Standard - 3.4% \| Other drugs: Intensive - 27.4%, Standard - 29.3%

Findings: In older patients with hypertension, intensive treatment with a systolic blood pressure target of 110 to less than 130 mmHg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mmHg

RCT
ESPRIT study - Intensive (SBP < 120) vs Standard (SBP < 140) Blood Pressure Control in Patients at High Risk for CVD Events, Lancet (2024) [PubMed abstract]

Design: Randomized open-label trial (N=11,255 | length = median 3.4 years) in Chinese patients at high risk for CVD events
Treatment: Intensive (SBP < 120) BP control vs Standard (SBP < 140) BP control
Primary outcome: Composite of myocardial infarction, revascularization, hospitalization for heart failure, stroke, or death from cardiovascular causes
Results:

Average SBP during follow-up: Intensive - 119.1 mmHg, Standard - 134.8 mmHg
Primary outcome: Intensive - 9.7%, Standard - 11.1% (p=0.028)

Findings: For hypertensive patients at high cardiovascular risk, regardless of the status of diabetes or history of stroke, the treatment strategy of targeting systolic blood pressure of less than 120 mmHg, as compared with that of less than 140 mmHg, prevents major vascular events, with minor excess risk.

Summary

Collectively, these three studies show that lower BP targets (<120-130) reduce the risk of CVD events across large populations. The absolute risk reduction is small (1.1 - 1.6%) but meaningful when considering the number of people with hypertension. Similar studies in diabetics have had conflicting results but generally support a lower target (see blood pressure goals in diabetics). Studies in patients with symptomatic lacunar infarcts and strokes have also been performed. [PMID 23726159, PMID 31355878]

STUDIES | MORNING VS EVENING DOSING

Overview

CVD events are more common in the morning hours when cortisol levels rise, and BP tends to run higher. Most BP meds are dosed once daily, meaning trough levels occur 24 hours after intake. Morning dosing causes trough levels to coincide with the period of greatest CVD risk. Theoretically, bedtime dosing, which reverses the pattern, may help lower CVD risk. Two large studies comparing bedtime to awakening dosing of BP meds are detailed below.

RCT
Bedtime vs Awakening Dosing of Blood Pressure Medications , European Heart Journal (2019) [PubMed abstract]

Design: Randomized controlled trial (N=19,084 | length = median 6.3 years) in patients with hypertension being treated with ≥ 1 antihypertensive medication(s)
Treatment: Take all BP medications at bedtime vs Take all BP meds upon awakening
Primary outcome: Composite of myocardial infarction, coronary revascularization, heart failure, ischaemic stroke, haemorrhagic stroke, and CVD death
Results:

Primary outcome: Bedtime to awakening hazard ratio 0.55 (95%CI [0.50–0.61]), p <0.001

Findings: Routine ingestion by hypertensive patients of ≥ 1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ambulatory BP control (significantly enhanced decrease in asleep BP and increased sleeptime relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.

RCT
TIME study - Morning vs Evening Dosing of Blood Pressure Medications, Lancet (2022) [PubMed abstract]

Design: Randomized controlled trial (N=21,104 | length = median 5.2 years) in adults with hypertension taking at least one antihypertensive
Treatment: Take all BP meds in the morning (0600 - 1000 h) vs Take all BP meds in the evening (2000 - 0000 h)
Primary outcome: Composite of vascular death or hospitalization for non-fatal myocardial infarction or non-fatal stroke
Results:

Primary outcome: Morning - 3.7%, Evening - 3.4% (p=0.53)

Findings: Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimizes any undesirable effects.

Summary

The effects of bedtime versus morning dosing were mixed in the two trials above, with one finding a benefit and the other none. Both studies were large and similar in design, making it difficult to favor one over the other. Additional trials evaluating the effects of dose timing are underway. Given the current evidence, patients should be advised to take their medications at a time that optimizes their compliance.

STUDIES | BLACKS

RCT
Amlodipine + Perindopril or HCTZ vs Perindopril + HCTZ for HTN in Blacks, NEJM (2019) [PubMed abstract]

Design: Randomized controlled trial (N=621 | length = 6 months) in black patients with uncontrolled hypertension
Treatment: Amlodipine 10 mg/HCTZ 25 mg vs Amlodipine 10 mg/Perindopril 8 mg vs Perindopril 8 mg/HCTZ 25 mg
Primary outcome: Change in the 24-hour ambulatory systolic blood pressure between baseline and 6 months
Results:

Primary outcome: Amlodipine/HCTZ was 3.14 mmHg lower than Perindopril/HCTZ (p=0.03). Amlodipine/Perindopril was 3.00 mmHg lower than Perindopril/HCTZ (p=0.04). There was no significant difference between Amlodipine/HCTZ and Amlodipine/Perindopril (p=0.92)

Findings: These findings suggest that in black patients in sub-Saharan Africa, amlodipine plus either hydrochlorothiazide or perindopril was more effective than perindopril plus hydrochlorothiazide at lowering blood pressure at 6 months.

BIBLIOGRAPHY

1 - PMID 24352797
2 - PMID 25829340
3 - PMID 28135725 - Pharmacologic Treatment of Hypertension in Adults Aged 60 Years or Older to Higher Versus Lower Blood Pressure Targets: A Clinical Practice Guideline From the American College of Physicians and the American Academy of Family Physicians, Annals of Internal Medicine (2017)
4 - ADA Standards of Medical Care in Diabetes 2016
5 - PMID 27979887 - ADA Standards of Medical Care in Diabetes - 2017: Summary of Revisions
6 - PMID 28827377 - Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents, Pediatrics (2017)
7 - PMID 29133356 - 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension (2017)
8 - PMID 34152826 - Management of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice Guideline, Ann Intern Med (2021)
9 - PMID 37471501 - 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines, Circulation (2023)