J Clin Hypertens (Greenwich). 2012;14:718–726. ©2012 Wiley Periodicals, Inc.

Renin-angiotensin-aldosterone system (RAAS) inhibitors in combination with other antihypertensive drugs (eg, calcium channel blockers [CCBs] and/or diuretics) are a preferred treatment option for managing uncontrolled hypertension in high-risk patients with chronic kidney disease (CKD), diabetes, or heart failure because RAAS inhibitors provide cardiorenal benefits in addition to lowering blood pressure (BP). However, when prescribing antihypertensive therapies to high-risk patients, physicians must be aware of the risks of treatment-related adverse events of hyperkalemia and peripheral edema associated with RAAS inhibitors and CCBs, respectively. This review discusses the use of single-pill combination antihypertensive therapy to optimize BP control in high-risk patients with CKD, diabetes, and/or heart failure and provides strategies for preventing and managing hyperkalemia and peripheral edema in this group. Single-pill combination therapy can utilize different classes of antihypertensive drugs to reduce BP while mitigating the risks of treatment-related adverse events, reducing pill burden, lowering medical cost, and improving patient compliance.