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Drug Treatment for Hypertension

Essentials

  • Most patients will require a combination of drugs in order to achieve the treatment goal.
  • If blood pressure (BP) is significantly elevated (> 160/100 mmHg, home measurements > 145/90), pharmacotherapy should be started using a drug combination http://www.dynamed.com/management/hypertension-medication-selection-and-management#TOPIC_LYM_QZG_5GB.
  • One drug will lower BP by an average of 9/6 mmHg. A combination of two drugs lowers BP more effectively than doubling the dose of one drug.
  • Lowering BP with drugs by 10/5 mmHg in patients with hypertension will reduce the incidence of stroke by 30-40% and that of severe coronary artery disease events by 16%, and reduce the risk of heart failure by about 40% in 5 years.
  • The average reduction in blood pressure is similar with equivalent doses of ACE inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), beta-blockers, diuretics and calcium-channel blockers, and they are all well tolerated at low doses. Treatment with these agents decreases the incidence of cardiovascular events Different Antihypertensive Agents as First Line Therapies.
    • Adverse effects, particularly those of diuretics, beta-blockers and calcium-channel blockers, are more likely with higher doses.
  • BP can be lowered with aldosterone antagonists, the alpha blocker prazosin and the centrally acting clonidine and moxonidine which inhibit the function of the sympathetic nervous system; however, there is no scientific evidence on their effect on cardiovascular events in patients with hypertension. The prognostic benefit of using spironolactone has been shown in patients with heart failure.

Examples of recommended antihypertensive drugs in different conditions and special circumstances. Source: Finnish Current Care Guideline; Hypertension, 2020 (modified)

ConditionRecommended antihypertensive drugs
No target organ damage
Uncomplicated hypertensionAce inhibitor, ARB, calcium-channel blocker, diuretic
Target organ damage or cardiovascular disease
LVHACE inhibitor, ARB, calcium-channel blocker, diuretic
Microalbuminuria or proteinuriaACE inhibitor, ARB
Renal damage without albuminuria http://www.dynamed.com/management/hypertension-medication-selection-and-management#CHRONIC_KIDNEY_DISEASEACE inhibitor, ARB; calcium-channel blocker, diuretic (furosemide if eGFR < 30 ml/min/1.73 m2 )
History of strokeACE inhibitor, ARB, calcium-channel blocker, diuretic
History of MI http://www.dynamed.com/management/hypertension-medication-selection-and-management#EVIDENCE__CORONARY_ARTERY_DISEASE_Beta-blocker (for the first year), ACE inhibitor (ARB if ACE inhibitor unsuitable)
Symptomatic coronary artery disease http://www.dynamed.com/management/hypertension-medication-selection-and-management#EVIDENCE__CORONARY_ARTERY_DISEASE_Beta-blocker, calcium-channel blocker
Heart failure http://www.dynamed.com/management/hypertension-medication-selection-and-management#EVIDENCE__HEART_FAILURE_ACE inhibitor, ARB, diuretic, beta-blocker, aldosterone antagonist
Atrial fibrillation
  • -Paroxysmal
ARB, ACE inhibitor, beta-blocker
  • Permanent
Beta-blocker, verapamil (note, these two agents should not be combined)
Peripheral artery diseaseACE inhibitor, ARB, calcium-channel blocker
Special situations
Diabetes http://www.dynamed.com/management/hypertension-medication-selection-and-management#DIABETESACE inhibitor, ARB, calcium-channel blocker, diuretic
Gestational hypertensionBeta-blocker, combination of alpha and beta blocker (labetalol), calcium-channel blocker with dihydropyridine structure (nifedipine)
AsthmaCalcium-channel blocker, ARB, diuretic

ACE inhibitors (ACEIs)Reversal of Left Ventricular Hypertrophy in Essential Hypertension, Blood Pressure Lowering Efficacy of ACE Inhibitors, Antihypertensive Agents for Preventing Diabetic Kidney Disease, ACE Inhibitors and Angiotensin Receptor Blockers for Progression of Non-Diabetic Renal Disease, First-Line Renin Angiotensin System Inhibitors Versus other Drug Classes for Hypertension

  • An ACE inhibitor http://www.dynamed.com/management/hypertension-medication-selection-and-management#ANGIOTENSIN_CONVERTING_ENZYME__ACE__INHIBITORS_DC is the most appropriate initial drug in many patient groups. They are very effective when the plasma renin concentration is high, for example during long-term diuretic use. A concomitant calcium-channel blocker or diuretic significantly enhances the efficacy of an ACE inhibitor.
  • Contraindicated during pregnancy
  • Slow down the progression of renal disease causing albuminuria
  • The antihypertensive medication of patients with diabetes or renal disease should always include an ACE inhibitor or ARB.
  • In patients with renal failure or renovascular hypertension, use of ACE inhibitors and ARBs requires close monitoring of creatinine and potassium levels.
  • An ACE inhibitor should be prescribed for all patients with coronary artery disease and hypertension.
  • ACE inhibitors and ARBs may prevent atrial fibrillation in patients with hypertension more effectively than other antihypertensive drugs.

Drugs and dosage

Adverse effects

Precautions

  • Plasma potassium and creatinine should be checked one month after treatment onset. If the patient has renal artery stenosis or a risk thereof, symptoms of peripheral atherosclerosis, or renal insufficiency, the first check should be done already one week after treatment onset.
  • Creatinine may increase less than 30 % from the initial level. Potassium and creatinine should be monitored and, as necessary, the dosage should be decreased or the use of the drug completely stopped. Especially concurrent hyperkalaemia Hyperkalaemia is alarming.
  • A stable level is usually achieved within 4 weeks.
  • Further measures depend on the patient's other conditions, see

Angiotensin-receptor blockers (ARBs) Blood Pressure Lowering Efficacy of Angiotensin Receptor Blockers for Primary Hypertension, First-Line Renin Angiotensin System Inhibitors Versus other Drug Classes for Hypertension

Diuretics Blood Pressure Lowering Efficacy of Loop Diuretics for Primary Hypertension, Diuretics as Second-Line Therapy for Primary Hypertension

Drugs and dosage

  • Hydrochlorothiazide 12.5-25 mg once daily. The starting dose for elderly patients is 12.5 mg/day.
  • Amilorideis a potassium-sparing diuretic. A combination preparation of amiloride-hydrochlorothiazide can be used, provided that the creatinine level is normal and there is no risk of hyperkalaemia. Hypokalaemia must be avoided, particularly if the patient has a heart disease or uses digitalis.
  • Indapamide (modified release) 1.5 mg daily is an alternative to hydrochlorothiazide. However, no marked benefits are achieved with indapamide as compared with low doses of thiazides, and indapamide may cause severe electrolyte imbalances in some patients.
  • Furosemide should only be used in renal failure (plasma creatinine > 150 µmol/l)

Adverse effects (at fairly high doses)

  • Hypokalaemia, hyponatraemia
  • Hypomagnesaemia
  • Hyperuricaemia
  • Hyperglycaemia
  • Triglyceride concentration will increase and that of HDL-cholesterol decrease. In practice, the effects on lipids are minor.
  • Increased insulin resistance in some patients

Precautions

  • Plasma potassium and sodium should be checked 1-2 months after treatment onset. If the concentrations are normal, future monitoring typically every 1-2 years in association with follow-up visits, as considered appropriate on a case by case basis, is sufficient.

Calcium-channel blockers Calcium Channel Blockers Versus other Classes of Drugs for Hypertension

  • Calcium-channel blockershttp://www.dynamed.com/management/hypertension-medication-selection-and-management#CALCIUM_CHANNEL_BLOCKERS__CCBS__DC are suitable for elderly, physically active patients.
  • The BP lowering effect is good, particularly in elderly patients.
  • Calcium-channel blockers do not necessitate laboratory tests to monitor the safety of treatment.
  • The treatment of hypertension is usually started with a dihydropyridine-type calcium-channel blocker, unless there are particular grounds for using verapamil or diltiazem.
  • Dihydropyridine-type calcium-channel blockers may ease the limb symptoms of Raynaud's disease Nifedipine for Raynaud's Phenomenon.
  • Diltiazem and verapamil
    • May prevent atrial arrhythmias and slow down the ventricular rate in fast atrial fibrillation.
    • Contraindicated in patients with slow arrhythmias (SSS or second or third degree atrioventricular block), unless the patient has a pacemaker.
    • Use of diltiazem or verapamil may be considered instead of beta-blockers in patients with coronary artery disease if beta-blockers are contraindicated (but not if left ventricular systolic function is impaired).
    • Contraindicated in patients with systolic heart failure
    • Should not be combined with beta-blockers.

Drugs and dosage

Calcium-channel blockers with vascular effects (dihydropyridine derivatives)

Calcium-channel blockers with more cardiac effects

Adverse effects

  • Leg oedema
  • Headache
  • Dizziness
  • Flushing and skin erythema
  • Gingival hyperplasia
  • Constipation
  • Cardiac conduction defects (verapamil and diltiazem)

Beta-blockers (beta blocking agents) Beta-Blockers as Second-Line Therapy for Primary Hypertension, Beta-Blockers Against other Antihypertensive Drugs, Dual Alpha and Beta Blockers for Primary Hypertension, Antihypertensive Drugs and Incident Diabetes

  • Not recommended as the first-line drug in hypertension, as they lower the risk of stroke less than other first-line drugs, particularly in elderly people http://www.dynamed.com/management/hypertension-medication-selection-and-management#COMPARATIVE_EFFICACY__BETA_BLOCKERS_.
  • Beta-blockers are the first-line choice for patients with coronary artery disease or other indications for a beta-blocker, e.g. arrhythmias. They are suitable for young hyperactive patients who exhibit symptoms of stress, such as sweating, emotional tension and palpitations.
  • They improve the prognosis and should be used to treat hypertension in patients with coronary artery disease with heart failure or impaired left ventricular systolic function (EF < 40%).
    • Prognostic benefit has not been shown in cases where more than one year has elapsed since acute coronary syndrome and left ventricular function is normal.
  • Beta-blockers and a combination of beta-blockers and a diuretic, in particular, should be avoided as first-line medication in patients with metabolic syndrome or an increased risk of diabetes.
  • Beta-blockers are not contraindicated in patients with peripheral arterial disease of the limbs; they may be indicated because of concomitant coronary artery disease, heart failure or atrial fibrillation.
  • Carvedilol and labetalol (also blocking alpha-receptors) may cause postural hypotension in older patients.
  • Highly selective beta-blockers have replaced non-selective and less selective beta-blockers. Selective beta-blockers cause less peripheral vascular and bronchial constriction.

Drugs and dosage

  • Highly selective beta-blockers are the best tolerated and do not have an effect on the lipids.
  • Selective beta-blockers have better tolerability and efficacy than the non-selective ones.
  • Alpha- and beta-blocking agents (vasodilating action)

Adverse effects Cardioselective Betablockers in Patients with Reversible Airway Disease

  • Impaired physical performance, fatigue, impotence
  • Bradycardia
  • Worsening of unstable heart failure.
    • However, when combined with an ACE inhibitor and diuretic, beta-blockers (bisoprolol, carvedilol, metoprolol, nebivolol) reduce cardiac mortality and the need for hospitalisation in patients with heart failure. Heart failure is therefore an indication for a beta-blocker. In patients with heart failure, treatment with a beta-blocker should be initiated with a low dose, and the dose should be slowly increased.
  • Conduction defects, sick sinus syndrome
  • Asthma
    • If the patient with asthma or chronic obstructive pulmonary disease tolerates them, beta1-selective blockers can be used in compelling circumstances (e.g. atrial fibrillation, myocardial infarction, systolic heart failure).
  • Sleep disorders
  • Hypoglycaemia in diabetes (symptoms are masked!)

Aldosterone antagonists Spironolactone for Hypertension

Centrally acting sympatholytic agents

  • The use of old sympatholytic agents has declined due to their numerous adverse effects (they are used as alternative medication in cases where other medication is unsuitable).

Drugs

  • Clonidine 75-150 µg three times daily
  • Moxonidine 0.2-0.4 mg once daily, maximum dose 0.4 mg daily + 0.2 mg

Other vasodilating drugs Alpha Blockers for Primary Hypertension

  • The use of these drugs has declined since calcium-channel blockers and ACE inhibitors also have vasodilating effects (they are used as alternative medication in cases where other medication is unsuitable).
  • Prazosin
    • Adverse effects: postural hypotension, oedema, urinary frequency, priapism, palpitations

Combining antihypertensive drugs

Aims

The best combinations

  • ACE inhibitor or ARB and calcium-channel blocker
  • ACE inhibitor or ARB and diuretic (or a salt restriction to less than 5 g/day)
  • ACE inhibitor or ARB combined with a diuretic and calcium-channel blocker, if three drugs are needed
  • In treatment-resistant hypertension, it may be effective to add a mineralocorticoid receptor blocker to the regimen (12.5-25 mg/day of spironolactone).

Possible combinations

  • Calcium-channel blocker and diuretic
  • Beta-blocker and dihydropyridine calcium-channel blocker
  • Beta-blocker and diuretic (or a salt restriction to less than 5 g/day)
    • Should not be used as first-line medication in patients with metabolic syndromeMetabolic Syndrome or increased risk of diabetes.
  • Beta-blocker and ACE inhibitor
    • Not the optimal combination as far as the antihypertensive effect is concerned but may be used if indicated for other reasons (e.g. if coronary artery disease and heart failure are indications for a beta-blocker).
  • Beta-blocker, vasodilating calcium-channel blocker and diuretic

Combinations to be avoided

  • Beta-blocker and verapamil or diltiazem
    • May cause a cardiac conduction disorder, excessive bradycardia, hypotension or heart failure in elderly patients and in patients with impaired myocardial function.
  • Combination of drugs that suppress the renin-angiotensin system (ARBs, ACE inhibitors) should not be used in the treatment of hypertension, because they increase the incidence of adverse effects while not reducing cardiovascular events.

Reducing or stopping antihypertensive medication

Principles

  • May be considered in mild, uncomplicated hypertension if BP has remained below 120/80 mmHgfor at least 12 months with lifestyle modification and medication.
  • After the dose has been reduced, BP should be checked at monthly intervals. After stopping the medication, BP should be checked monthly for 6 months, and thereafter permanently every 3-4 months, as hypertension often recurs over the years.
  • The danger of stopping medication is minimal provided that the follow-up is not neglected. The need to restart treatment usually becomes apparent within 2-3 months, but sometimes only after several years.
  • Permanent lifestyle modifications are essential.

Reasons why the need of medication may decrease or end

  • Retirement or stress reduction
  • Weight loss
  • Positive changes in other factors contributing towards hypertension
  • Indications for starting antihypertensive medication were not clear
  • Ageing and admittance to long-term institutional care often "cure" uncomplicated hypertension. In these cases, diuretics in particular can readily cause orthostatic hypotension and other adverse effects impairing the quality of life.
  • Heart failure following myocardial infarction

References

  • [Hypertension]. A Current Care Guideline. Working group appointed by the Finnish Medical Society Duodecim and the Finnish Hypertension Society. Helsinki: the Finnish Medical Society Duodecim, 2020 (accessed 23.2.2024). Abstract available in English at http://www.kaypahoito.fi/en/ccs00014, full guideline in Finnish at http://www.kaypahoito.fi/hoi04010.

Evidence Summaries ⬆