HYPERLIPIDEMIA OF DIURETIC THERAPY

Hyperlipidemia is a widely acknowledged side effect of thiazide diuret ic therapy, but it is often dismissed as a short-term effect of high-d ose therapy. Large clinical trials usually show no lipid change during late follow-up. These large trials use intention-to-treat analysis wh ich masks the lipid effect. On-treatment analysis regularly reveals th e persistence of hyperlipidemia during 4-5 years of treatment. Studies of low-dose thiazide therapy give conflicting results. Metaanalysis o f these studies reveals hyperlipidemia of a milder degree than with hi gh-dose thiazide treatment. However, a trade-off of effects is apparen t because systolic blood pressure is lowered less well with low doses. Thus, thiazide effects on blood pressure and lipids are dose-dependen t. Similar meta-analysis of indapamide 2.5 mg daily shows no adverse l ipid effect and a lowering of blood pressure equivalent to SO mg of hy drochlorothiazide. Regarding clinical events, low-dose thiazide treatm ent exerts primary prevention of coronary heart disease but provides l ess benefit against stroke and congestive heart failure than does high -dose therapy. Thus, an evidence-based therapeutic strategy for furthe r reducing cardiovascular risk is as follows: initiate antihypertensiv e therapy with low-dose diuretics. Add beta-blockers and dihydropyridi ne-type calcium channel blockers for further antihypertensive effect, if needed. Hypertension resistant to a 3-drug regimen should be treate d with high-dose thiazides. Lipids should be monitored at each step an d treated with diet and statin drugs to maintain lipid goals. Risk fac tor control is an old concept that has yet to be effectively implement ed.