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.

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.

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

• ARBshttp://www.dynamed.com/management/hypertension-medication-selection-and-management#ANGIOTENSIN_RECEPTOR_BLOCKERS__ARBS__DC have an effect on the renin-angiotensin-aldosterone system, but in a manner that differs from that of ACE inhibitors.
• They are suitable for patients who develop adverse effects from ACE inhibitors.
• Drugs and dosage
  • Losartan 50-100 mg once daily
  • Valsartan 80-320 mg once daily
  • Candesartan 8-32 mg once daily
  • Eprosartan 600 mg once daily
  • Telmisartan 40-80 mg once daily
  • Olmesartan 10-40 mg once daily
• The effect of an ARB will be significantly increased by the addition of a diuretic.
• ARBs are well tolerated. Adverse effects are mild.
• An alternative for patients in whom ACE inhibitors cause a cough.
• Contraindications are the same as for ACE inhibitors.
• Monitoring of creatinine and electrolytes as for ACE inhibitors

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

• Diureticshttp://www.dynamed.com/management/hypertension-medication-selection-and-management#THIAZIDE_TYPE_DIURETICS_DC are particularly suitable for elderly women (osteoporosis prevention with thiazide diuretics Thiazide Diuretics and Fractures) and for patients with signs of salt and fluid retention or oedema related to heart failure. They can also be used in combination with other antihypertensive drugs.
• They are not the first-line drugs for patients with gout, hyperuricaemia, diabetes or metabolic syndrome.
  • A small dose of a thiazide diuretic is effective in enhancing the effect of an ACEI/ARB.
  • Although thiazides may to slightly impair glucose control, they anyhow improve prognosis and are suitable in drug combinations.
• Potassium-sparing diuretics should be avoided in renal failure due to the risk of hyperkalaemia.

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.

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.

Aldosterone antagonists Spironolactone for Hypertension

• Effective in hyperaldosteronism
• Improve the prognosis of patients with severe heart failure Aldosterone Receptor Antagonists Spironolactone and Eplerenone for Congestive Heart Failure.
• In persistent hypertension, spironolactone (12.5-25 mg/day) may be effective http://www.dynamed.com/management/hypertension-medication-selection-and-management#ALDOSTERONE_ANTAGONISTS, but it should be used cautiously, carefully monitoring plasma potassium and creatinine concentrations, if the patient also uses an ACE inhibitor or an ARB.
• Plasma potassium concentration must be closely monitored.

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).

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

• See Image 1 in the Current Care Guideline.
• Hypertensive crisis: see Hypertension: Investigations, Treatment Initiation and Non-Pharmacological Treatment

Reducing or stopping antihypertensive medication