Selection of antihypertensive drugs for different types of hypertension in the elderly

Hypertension is clinically common, especially in the elderly, who are characterized by increased systolic blood pressure, increased pulse pressure, abnormal blood pressure fluctuations, abnormal circadian rhythms, increased arterial stiffness, and many comorbidities. So, how to choose antihypertensive drugs for different types of hypertension in the elderly?

1. Antihypertensive drugs for hypertension in the elderly

Commonly used antihypertensive drugs include calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIs), β blockers, diuretics, and single-tablet fixed combination preparations (SPCs).

CCBs include dihydropyridine CCBs such as amlodipine, nifedipine, and felodipine, and non-dihydropyridine CCBs such as verapamil and diltiazem, which can lower blood pressure. Dihydropyridine CCB is especially suitable for patients with simple systolic hypertension (ISH), senile hypertension, hypertension with low renin activity or low sympathetic activity, habitual high salt intake and salt-sensitive hypertension, and patients with stable angina, carotid atherosclerosis, and coronary atherosclerosis. Patients with tachycardia and heart failure should use non-dihydropyridine CCBs with caution.

ACE inhibitors/ARBs such as enalapril, benazepril, losartan and irbesartan can lower blood pressure, protect cardiovascular and kidney, improve glucose metabolism, and are preferred for patients with hypertension combined with cardiac insufficiency after myocardial infarction, left ventricular hypertrophy, coronary heart disease, atrial fibrillation, chronic heart failure, metabolic syndrome, microalbuminuria or proteinuria, and diabetic nephropathy. Contraindicated in patients with bilateral renal artery stenosis.

β receptor blockers can lower blood pressure, inhibit sympathetic nerve activity, slow down heart rate, and inhibit myocardial contractility, especially for patients with hypertension with increased sympathetic nerve activity, tachyarrhythmia, chronic heart failure, coronary heart disease, aortic dissection, and hyperdynamic state. Its antihypertensive effect may be more pronounced during wakefulness. Patients with airway spasmodic disease are contraindicated and can be used with highly selective beta-1 blockers (eg, metoprolol, bisoprolol) if needed.

ARNI, such as sacubitril-valsartan, can lower blood pressure, reduce blood pressure during the day and at night, have excellent protection against target organs such as kidney, heart, and blood vessels, reduce the risk of cardiovascular events, improve metabolic disorders, and better control blood pressure at night, and is more suitable for salt-sensitive hypertension, elderly hypertension, hypertension combined with left ventricular hypertrophy, heart failure, and obesity. Patients with severe hepatic insufficiency (Child-PughC grade), biliary cirrhosis and cholestasis, and a history of angioedema are contraindicated.

Diuretics, such as thiazide diuretics, hydrochlorothiazide, loop diuretics, furosemide, and aldosterone receptor antagonists, can lower blood pressure and have no obvious effect on the physiological rhythm of blood pressure, especially suitable for elderly hypertension, salt-sensitive hypertension, refractory hypertension, hypertension combined with heart failure. Thiazide diuretics are contraindicated in patients with gout. Aldosterone receptor antagonists are contraindicated in patients with renal failure.

α receptor blockers can lower blood pressure, improve glucose and lipid metabolism, protect the kidneys, and can be used for patients with hypertension such as benign prostatic hyperplasia, asthma, diabetes, and hyperlipidemia, and can also be used as an adjuvant drug for refractory hypertension.

Combined antihypertensive therapy is preferred to start with SPC, and ACE inhibitors/ARBs combined with CCBs or thiazide diuretics are preferred.

2. Selection of antihypertensive drugs for different types of hypertension in the elderly

Such as elderly ISH, old Chinese New Year's Eve hypertension.

(1) ISH in the elderly

Antihypertensive drugs are preferentially recommended for elderly patients with ISH, and ACE inhibitors and ARBs [eGFR≥45 ml·min-1·1.73m-2] are recommended when combined drugs are required, and ARB/ACEI+CCB is preferentially recommended. Older people with high salt levels may consider ARB/ACEI + diuretics. When systolic blood pressure cannot be reached, it is increased to ARB/ACEI + CCB + diuretic. It is not recommended to β receptor blockers as the first choice for patients with ISH, except for strong indications such as coronary heart disease and heart failure.

(2) High blood pressure on Chinese New Year's Eve

Long-acting antihypertensive drugs are preferentially recommended, and antihypertensive drugs with a half-life of ≥ 15 h are long-acting preparations, which are recommended once a day, and are not routinely recommended to be taken at night, and monotherapy or combination therapy can be used to continuously and stably control blood pressure for 24 hours.

According to the Chinese Expert Consensus on the Management of Nocturnal Hypertension (2023), it is recommended to use ARB telmisartan, ACE inhibitor perindopril, CCB amlodipine long half-life antihypertensive drugs or controlled-release preparations such as β receptor blocker metoprolol, CCB nifedipine, and α receptor blocker doxazosin, and sufficient treatment or a combination of two or more drugs to achieve daytime, night and blood pressure control. Due to the short half-life (<8 h) of metoprolol and ARB losartan/valsartan, if the blood pressure control at night is not good after routine morning medication, 2 times/d are often required to maintain 24 h blood pressure control. New antihypertensive drugs such as ARNI sacubitril-valsartan, ARB alisartan cil, and mineralocorticoid hormone antagonist (MRA) Esaxerenone can better control nocturnal hypertension.

Patients with nocturnal hypersympathetic activity may be treated with antagonistic sympathetic antihypertensive drugs, such as β-blockers. Patients with high blood pressure and simple recumbent hypertension can take short- to medium-acting antihypertensive drugs before bedtime if necessary to control nocturnal hypertension.

(3) Early morning hypertension in the elderly

Long-acting antihypertensive drugs can be used in full doses and in combination to reduce early morning blood pressure elevations. Patients with non-dipping type and reverse dipping type can consider using long-acting ARB/ACEI and CCB, which can reduce nocturnal hypertension and promote the recovery of normal circadian rhythm, and give priority to antihypertensive drugs and ARNI with good efficacy in controlling nocturnal hypertension. Antihypertensive drugs that can effectively lower blood pressure at night include long-term half-life ARBs such as alisartan cilexetil and ARNI, which can lower blood pressure for a long time, and also promote the excretion of sodium ions, which is conducive to lowering blood pressure at night. Taking antihypertensive drugs before bedtime is suitable for people with non-dipping and anti-dipping early morning hypertension. People with early-morning hypertension with arytenoid type are recommended to take antihypertensive drugs in the morning, or a combination of early morning drugs in the morning and in the evening.

(4) Hypertension with different comorbidities in the elderly

Such as diabetes, chronic cardiac insufficiency, etc. In combination with coronary artery disease β receptor blockers and ACE inhibitors/ARBs are preferred, and CCBs can be added when poor control is not well controlled. ACE inhibitors/ARBs are preferred in the elderly with hypertension and diabetes mellitus, and CCBs can be added when poor control is performed. ACE inhibitors/ARBs are preferred for atrial fibrillation, and β-blockers and non-dihydropyridine CCBs are available for fast ventricular rate. ACE inhibitors, β-blockers, diuretics, aldosterone receptor antagonists, and ARNIs are preferred for chronic cardiac insufficiency, and ARBs are used when ACE inhibitors cannot be tolerated. CCB is the preferred choice for asthma, chronic obstructive pulmonary disease, and intermittent claudication. ACE inhibitors/ARBs can be used for dyslipidemia. ACE inhibitors/ARBs and β blockers can be used after myocardial infarction.

(5) Refractory hypertension in the elderly

Preference is given to ACE inhibitors, ARBs, and ARNIs in combination with long-acting CCBs and thiazide diuretics, and may also be considered α receptor blockers and β blockers in combination with thiazide diuretics. Patients with refractory hypertension in end-stage renal disease often require loop diuretics.

When the combined antihypertensive of the three antihypertensive drugs is still not ideal at full dose, a fourth drug such as an aldosterone receptor antagonist can be added. ACE inhibitors, ARBs, and ARNIs, combined with long-acting CCBs and thiazide diuretics, are β blockers and α blockers when blood pressure lowering is still not ideal.

(6) Hypertension combined with orthostatic blood pressure variability in the elderly

For orthostatic hypotension (OH), the treatment is mainly to increase blood volume and peripheral vascular resistance, such as midodrine, droxidopa, atomoxetine, pyridostigmine bromide, fludrocortisone, and erythropoietin.

(7) Hypertension in the elderly combined with postprandial hypotension (PPH)

Patients with hypertension and PPH may be treated with non-diuretic antihypertensive drugs. Acarbose can be tried, and patients with diabetes can also try metformin, lisinatide, linagliptin, etc. If PPH is caused by antihypertensive drugs, antihypertensive drugs can be taken between meals.

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The author of this article: Shandong Province Qianfoshan Hospital Pingyuan Hospital - Gao Lili