2 In ALLHAT, >40% of patients required ≥2 antihypertensive agents after 4 years, regardless of the assigned initial treatment, 2 thereby supporting the concept that combination therapy can take advantage of the complementary mechanisms of action of different drug classes, and that this facilitates attainment of goal BP levels. 1 The requirement for combination therapy was very apparent in the large Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) trial. In 2003, the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommended aggressive treatment of hypertensive patients and stressed the importance of combination therapy, particularly for those at high risk. 1 The gap between public awareness and control to target BP indicates that public health goals for hypertension are not being achieved despite many available treatment options. As recently as the year 2000, only 34% of treated patients with systolic BP (SBP) ≥140 mm Hg or diastolic BP (DBP) ≥90 mm Hg attained target BP. Higher rates of peripheral edema and flushing were associated with high-dose ER felodipine, either alone or in combination.Īntihypertensive therapy, β-adrenergic receptor blockers, calcium channel blockers, hypertension, essential, efficacy, safetyĭespite the known importance of treating high blood pressure (BP) to prevent cardiovascular complications such as stroke and myocardial infarction, most hypertensive patients do not achieve target, optimal risk-lowering BP. The most common adverse events leading to discontinuation were peripheral edema (4%), headache (2%), and fatigue (1%). When compared with the highest doses of the individual agents (ER metoprolol succinate 400 mg ER felodipine 20 mg), the low-dose combination ER metoprolol succinate 25/ER felodipine 2.5 was approximately as effective (differences in DBP <1 mm Hg). 05 for all but ER metoprolol succinate 25/ER felodipine 20). All combinations were more effective than their components ( P <. The decline in the placebo group was 2.1/4.0 mm Hg. Monotherapy with ER metoprolol succinate induced dose-related reductions in sitting systolic/diastolic BP (DBP) (mean 8.1/7.7 to 9.7/11.1 mm Hg) as did ER felodipine (mean 7.7/7.7 to 14.0/11.8) and the combinations reflected additive effects (mean 13.8/11.0 to 19.8/15.2). At baseline, treatment groups were well balanced mean sitting BP was 152.6/99.9 mm Hg.