Benefits of Diuretic-Based Low-Cost Antihypertensive Therapy

Abstract

Recent trials demonstrate that blood pressure must be optimally controlled to reduce the risk of cardiovascular mortality and morbidity in the population, and combination treatment is preferable to single medications. Diuretics are a constant component of the antihypertensive regimen to effectively decrease blood pressure, a general practical behaviour that is supported by most large trials, which demonstrate the superiority of diuretics in preventing adverse cardiovascular outcomes (with special evidence for heart failure). Consistent with this strong evidence, the JNC VII (Joint National Committee VII) still indicates diuretics as the first line of antihypertensive therapy. The main argument used against this indication is the metabolic toxicity of diuretics (deterioration of insulin resistance is a common condition among patients with hypertension), which has been repeatedly proven. One factor that might aggravate glucose metabolism during diuretic therapy is the underestimated effect of hypokalaemia, which interferes with glucose-stimulated insulin release. There is evidence that individuals presenting with hypokalaemia after 1 year of treatment (SHEP [Systolic Hypertension in the Elderly Program]) do not experience the reduction in cardiovascular events achieved among those who do not develop hypokalaemia. Among other beneficial effects, correction of hypokalaemia prevents or significantly reduces thiazide-induced hyperglycaemia. Some experiments suggest that thiazide diuretics should be given at low doses, possibly together with K+-saving medications, including ACE inhibitors, angiotensin II type 1 (AT1) receptor antagonists or K+-sparing diuretics. Low doses of anti-aldosterone diuretics have been used successfully in resistant hypertension and have demonstrated effects on blood pressure similar to, or even better than, enalapril or losartan. There are concerns regarding the use of anti-aldosterone diuretics because of the increased rate of hospitalization for hyperkalaemia after the RALES (Randomized ALdactone Evaluation Study). However, this information should be weighted for the assessment of renal function, often deteriorated in heart failure. There are indications that when renal function is still normal, early anti-aldosterone treatment might help to prevent hyperkalaemia. Eventually, economic implications should be considered in the choice of diuretics, taking into account that the (theoretical) single-medication yearly cost of antihypertensive therapy goes from €10 with chlortalidone 12.5mg to about €380 with the most expensive ‘new’ medications. However, financial and social costs related to the prevalence and incidence of arterial hypertension as well as to any other cardiovascular risk factors should take into account the financial and social burden of laboratory examinations, visits, adverse effects, hospitalisations and their frequency, and indirect costs due to temporary loss of work force, which is an issue that should be resolved by ad hoc studies that balance the immediate money saving with the potential increased cost of antihypertensive management.