Drugs

Treating a usually asymptomatic disease associated with a high risk of cardiovascular and renal complications is obviously a challenge. Although since the 1980s the awareness of the risks of hypertension has markedly increased, the percentage of patients whose blood pressure is controlled at <= 140/90 has remained unchanged (NHanes). This is even more sobering if one realizes that more recent studies in large populations have shown that further blood pressure reduction (e.g. levels below 130/80) are required to preserve renal function in certain high risk groups.

 

General principles for hypertensive pharmacotherapy

• Thiazide diuretics are still considered first line therapy for uncomplicated hypertension unless there is a specific indication to use another class (such as diabetes, proteinuria and heart failure where a start with ACE Inhibitors/Angiotensin Receptor Blockers is indicated)
• If thiazide monotherapy does not achieve blood pressure target, one of the following classes may either be added or substituted: ACE Inhibitors - Angiotensin Receptor Blockers, Ca-channel blockers, or beta blockers.
• Angiotensin receptor Blockers have similar indications as ACE Inhibitors, incluidng some benefit in patients with heart failure, albeit with a better adverse side effect profile (dry cough) compared to ACE Inhibitors
• Beta blockers should nolonger be considered first line treatment for uncomplicated hypertension in the absence of a specific indication for their use (e.g. post myocardial infarction , heart failure or atrial fibrillation)
• Dihydropyridin calcium channel blockers (felodipin, amlodipin) are effective and usually well tolerated in lowering blood pressure and are of particular benefit in preventing stroke in elderly patients with predominantly systolic hypertension. Dialtiazem and verapamil also have effects on the myocardium as well as blood vessels, and are preferrable in patients with angina, or supraventricular tachycardia.
• Loop diuretics are usually reserved for fluid control in patients with heart failure or chronic renal insufficiency and are usually given in combination with drugs from other classes
• Alpha blockers are safe and effective agents for lowering blood pressure, especially in the elderly, at the same time having a benficial effect on benign prostate hyperplasia. Their long term impact on cardiovascular outcome however, has not been studied. Alpha blockers should not be used as monotherapy, as the risk of congestive heart failure is increased.
• Methyldopa is one of the classes that I think is highly underestimated and has a good place in treating bloodpressure in the elderly. Also during pregnancy this is known to be a safe agent.
• Clonidine is a rarely used drug in New zealand, but is widely prescribed overseas. As a centrally acting alpha-2 agonist, it is a potent antihypertensive. there are significant side effects however, and its use should be limited to severely therapy resistant hypertension.
• Minoxidil is a potent vasodilator which may have a role when other classes have failed (usually when triple or quadruple therapy fails). It can be used in combination with a beta blocker and/or a diuretic.
• Hydralazine is also a vasodilator and can be used in moderate hypertension, but its side effects make it usually unsuitable as monotherapy. Hydralazine is however safe during pregnancy.
• Spironolacton is a nonselective aldosterone antagonist. it inhibits not only the aldosteron action but also otherwise interferes with hormone system, causing for example gynaecomastia. A newer compound in this class, eplerone, is reported to have this side effect to a lesser extent. These agents are known to reduce significantly cardiovascular morbidity and mortality in post myocardial infarction patients.
• A new class, not yet available in New Zealand, is aliskiren, a direct renin inhibitor. This agent can be used either as monotherapy, or in combination with other antihypertensives. It lowers blood pressure by inhibiting renin, as opposed to current indirect blockers of the renin-angiotensin-aldosterone system like ACE Inhibitors and Angiotensin Receptor Blockers.