Diuretics have survived 2 decades of controversy and criticism and remain today an effective therapy that is still recommended for the initial treatment of patients with high blood pressure (BP). First introduced for this indication in 1957, di-uretics became the subject of intense debate in the 1980s and 1990s, when critics questioned whether their metabolic side effects canceled out whatever benefits they could offer.

œYet all this noise was based on circumstantial evidence and opinions, not hard data, according to Vasilios Papademetriou, MD, who retells the history of diuretics in a recent editorial published in the Journal of Clinical Hypertension (2006;8:86-92). He says that even in the midst of the early controversy, clinical trial data were consistently affirming the efficacy and safety of diuretics despite some transient increases in serum cholesterol, hyperuricemia, and some increases in plasma glucose.

The publication of the Multiple Risk Factor Intervention Trial (MRFIT), which found higher mortality rates with more aggressive treatment than with usual care, also raised hackles, even though both treatment groups took diuretics. The investigators warned against jumping to conclusions, but critics pounced anyway, saying that MRFIT had established an association between diuretic therapy and an increased risk of sudden death.

A reanalysis of the MRFIT data could not confirm any such association, but the taint was hard to remove.

Diuretics do have a dose-dependent effect on the development of hypokalemia, which appeared to have been correlated with arrhythmias in some early studies. But again, the association could not be confirmed in numerous subsequent trials.

Quoting the adage, the proof of the pudding is in the eating, Dr Papademetriou deduces that œif diuretic-induced hypokalemia or other possible metabolic effects of diuretics had detrimental consequences on health outcomes, differences would have become manifest in the many comparative trials that have tested the effect of newer agents compared with older ones.

He concludes with an admonition. œWe need to remember that BP reduction and BP control are what prevent cardiovascular complications, adding that œthe continued utilization of diuretics is important if we are to see improvements in the rate of BP control."L.B.