Fixed low-dose combination in first-line treatment of hypertension.

Hypertension is poorly controlled in most patients. The control rate, defined as a systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg, is 27% in the USA, despite data documenting the reduction of cardiovascular events by treating diastolic hypertension and isolated systolic hypertension. Control rate is even lower for patients with renal insufficiency and type 2 diabetes mellitus. Thus, monotherapy is unlikely to achieve blood pressure control. Supported by the 6th Joint National Committee Report (JNC VI), interest has been sparked in the use of fixed low-dose combination drugs as first-line treatment of hypertension. The rationale is to enhance hypertension control by using drugs that are additive while avoiding complex regimens that result in non-compliance. When low doses of two drugs are used, adverse drug reactions are fewer compared with the maximal dose of each drug tested separately. Multifactorial trials document the efficacy of hydrochlorothiazide (HCTZ) 6.25 mg in combination with bisoprolol 2.5-10 mg once daily. DBP control rates have been 64-77% and equal to or superior to HCTZ 25 mg once daily, amlodipine 2.5-10 mg once daily, enalapril 5-40 mg once daily or losartan 50-100 mg and losartan 50 mg with 12.5 mg HCTZ once daily. This low-dose combination has a side-effect profile similar to placebo. Erectile dysfunction and hypokalaemia are uncommon. Fixed-dose combination antihypertensive drugs simplify dosing regimens, improve compliance, improve hypertension control, decrease dose-dependent side-effects, and reduce cost as the first-line treatment of hypertension.