Fixed-dose combination antihypertensives and reduction in target organ damage: are they all the same?
Hypertension is a multifactorial disorder leading to pathophysiologic changes in target organs over time through diverse mechanisms. In addition, hypertension frequently resists control with monotherapy, necessitating combination therapy with two or more antihypertensive agents. Many currently available fixed-dose antihypertensive combinations combine drugs with different, but complementary, mechanisms of action to improve overall efficacy and tolerability. In addition, it is possible to select drug combinations whereby one drug offsets the negative effects of the other drug. Fixed-dose antihypertensive combinations may provide significant advantages over high-dose monotherapy, such as improved BP-lowering efficacy, reduced adverse event frequency, improved patient compliance, potentially lower treatment costs, and shorter time to BP control. Combination therapy has been recommended as potential first-line therapy in recent consensus guideline statements, especially for higher-risk patients, such as those with stage 2 hypertension. The combination of a renin-angiotensin-aldosterone system-targeting agent, such as an ACE inhibitor or angiotensin II receptor antagonist (ARB), and a diuretic or calcium channel antagonist appears to provide synergy with regard to BP lowering. In addition, ACE inhibitors and ARBs have demonstrated beneficial effects beyond BP reduction, reducing cardiovascular morbidity and mortality, inhibiting development and progression of type 2 diabetes mellitus and the progression of renal disease. Preliminary studies of fixed-dose combinations have shown reductions in left ventricular hypertrophy and improvements in markers of renal function. Additional studies currently underway will compare the effects of available fixed-dose combinations on cardiovascular morbidity and mortality, and markers of renal dysfunction.
Smith
David H G
DH
Orange County Research Center, Tustin, California, USA. dsmith@integrium.com
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000503:physiopathology / Q000517:prevention & control*; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use; D004338:Drug Combinations; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control; D051437:Renal Insufficiency / Q000503:physiopathology / Q000517:prevention & control
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D004338:Drug Combinations