Hyperlipidemia of diuretic therapy.
Hyperlipidemia is a widely acknowledged side effect of thiazide diuretic therapy, but it is often dismissed as a short-term effect of high-dose therapy. Large clinical trials usually show no lipid change during late follow-up. These large trials use intention-to-treat analysis which masks the lipid effect. On-treatment analysis regularly reveals the persistence of hyperlipidemia during 4-5 years of treatment. Studies of low-dose thiazide therapy give conflicting results. Meta-analysis of these studies reveals hyperlipidemia of a milder degree than with high-dose thiazide treatment. However, a trade-off of effects is apparent because systolic blood pressure is lowered less well with low doses. Thus, thiazide effects on blood pressure and lipids are dose-dependent. Similar meta-analysis of indapamide 2.5 mg daily shows no adverse lipid effect and a lowering of blood pressure equivalent to 50 mg of hydrochlorothiazide. Regarding clinical events, low-dose thiazide treatment exerts primary prevention of coronary heart disease but provides less benefit against stroke and congestive heart failure than does high-dose therapy. Thus, an evidence-based therapeutic strategy for further reducing cardiovascular risk is as follows: initiate antihypertensive therapy with low-dose diuretics. Add beta-blockers and dihydropyridine-type calcium channel blockers for further antihypertensive effect, if needed. Hypertension resistant to a 3-drug regimen should be treated with high-dose thiazides. Lipids should be monitored at each step and treated with diet and statin drugs to maintain lipid goals. Risk factor control is an old concept that has yet to be effectively implemented.
Ames
R
R
Columbia University, New York, N.Y., USA.
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002561:Cerebrovascular Disorders / Q000517:prevention & control; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000517:prevention & control; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006333:Heart Failure / Q000517:prevention & control; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000139:chemically induced* / Q000178:diet therapy / Q000517:prevention & control; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007190:Indapamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008137:Longitudinal Studies; D015201:Meta-Analysis as Topic; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D013599:Systole
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D000960:Hypolipidemic Agents; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D007190:Indapamide