Clinical guidelines now recognize the importance of a multifactorial approach to 
managing cardiovascular (CV) risk. This idea was taken a step further with the 
concept of the Polypill™. There are, however, considerable patent, 
pharmacokinetic, pharmacodynamic, registration, and cost implications that will 
need to be overcome before the Polypill™ or other single-pill combinations of CV 
medications become widely available. However, a medication targeting blood 
pressure (BP) and lipids provides much of the proposed benefits of the 
Polypill™. A single-pill combination of the antihypertensive amlodipine besylate 
and the lipid-lowering medication atorvastatin calcium (SPAA) is currently 
available in many parts of the world. This review describes the rationale for 
this combination therapy and the clinical trials that have demonstrated that 
these two agents can be combined without the loss of efficacy for either agent 
or an increase in the incidence of adverse events. The recently completed 
Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk 
(CRUCIAL trial) is discussed in detail. CRUCIAL was a 12-month, international, 
multicenter, prospective, open-label, parallel design, cluster-randomized trial, 
which demonstrated that a proactive intervention strategy based on SPAA in 
addition to usual care (UC) had substantial benefits on estimated CV risk, BP, 
and lipids over continued UC alone. Adherence with antihypertensive and 
lipid-lowering therapies outside of the controlled environment of clinical 
trials is very low (~30%-40% at 12 months). Observational studies have 
demonstrated that improving adherence to lipid-lowering and antihypertensive 
medications may reduce CV events. One means of improving adherence is the use of 
single-pill combinations. Real-world observational studies have demonstrated 
that patients are more adherent to SPAA than co-administered antihypertensive 
and lipid-lowering therapy, and this improved adherence translated to reduced CV 
events. Taken together, these findings suggest that SPAA can play an important 
role in helping physicians improve the management of CV risk in their patients.