Hypertension has a major associated risk for organ damage and mortality, which 
is further heightened in patients with prior cardiovascular (CV) events, 
comorbid diabetes mellitus, microalbuminuria and renal impairment. Given that 
most patients with hypertension require at least two antihypertensives to 
achieve blood pressure (BP) goals, identifying the most appropriate combination 
regimen based on individual risk factors and comorbidities is important for risk 
management. Single-pill combinations (SPCs) containing two or more 
antihypertensive agents with complementary mechanisms of action offer potential 
advantages over free-drug combinations, including simplification of treatment 
regimens, convenience and reduced costs. The improved adherence and convenience 
resulting from SPC use is recognised in updated hypertension guidelines. Despite 
a wide choice of SPCs for hypertension treatment, clinical evidence from direct 
head-to-head comparisons to guide selection for individual patients is lacking. 
However, in patients with evidence of renal disease or at greater risk of 
developing renal disease, such as those with diabetes mellitus, microalbuminura 
and high-normal BP or overt hypertension, guidelines recommend renin-angiotensin 
system (RAS) blocker-based combination therapy due to superior renoprotective 
effects compared with other antihypertensive classes. Furthermore, RAS 
inhibitors attenuate the oedema and renal hyperfiltration associated with 
calcium channel blocker (CCB) monotherapy, making them a good choice for 
combination therapy. The occurrence of angiotensin-converting enzyme (ACE) 
inhibitor-induced cough supports the use of angiotensin II receptor blockers 
(ARBs) for RAS blockade rather than ACE inhibitors. In this regard, ARB-based 
SPCs are available in combination with the diuretic, hydrochlorothiazide (HCTZ) 
or the calcium CCB, amlodipine. Telmisartan, a long-acting ARB with preferential 
pharmacodynamic profile compared with several other ARBs, and the only ARB with 
an indication for the prevention of CV disease progression, is available in two 
SPC formulations, telmisartan/HCTZ and telmisartan/amlodipine. Clinical studies 
suggest that in CV high-risk patients and those with evidence of renal disease, 
the use of an ARB/CCB combination may be preferred to ARB/HCTZ combinations due 
to superior renoprotective and CV benefits and reduced metabolic side effects in 
patients with concomitant metabolic disorders. However, selection of the most 
appropriate antihypertensive combination should be dependent on careful review 
of the individual patient and appropriate consideration of drug pharmacology.