The combined use of aspirin, a statin, and blood pressure–lowering agents (polypill components) and the risk of vascular morbidity and mortality in patients with coronary artery disease

Lafeber M, Spiering W, Van der Graaf Y et al.
Am. Heart J. 2013.166 (2): 282-289.e1

Background

European guidelines for risk factor treatment in patients with established coronary artery disease (CAD) recommend the combined use of antiplatelet therapy, lipid-lowering agents (when LDL-c>2.5 mmol/L), a beta-blocker and additional blood pressure (BP)-lowering drugs if systolic BP>140mmHg [1]. In clinical practice, a large gap exists between indicated therapy and prescribed medication, and ineffective therapies are specifically  common in middle-  and low-income countries [2,3]. Suboptimal adherence to medication by patients further complicates matters [4]. Adherence to medication is inversely related to the number of pills and the number of doses per day [5,6].
A fixed-dose combination pill containing aspirin, a statin and >1 BP-lowering agents could help to optimize the prevention of CV disease. Recent studies investigating such cardiovascular polypills in patients with a low and intermediate risk of CVD showed that they are safe, effective in reducing risk factors and at reducing the risk [7-9].
While waiting for the results of ongoing randomised trials testing the effectiveness, adherence and clinical outcomes of combination pills that should lower LDL-c and BP, this cohort study aimed to evaluate the combined use of aspirin, a statin and >1 BP-lowering agent in patients with CAD in clinical practice. Data of 2706 patients enrolled in the prospective Second Manifestations of ARTerial disease (SMART) cohort [10] were used, with a median follow-up time of 5.0 years.

Main results

• Combination therapy was associated with a lower risk of MI (HR: 0.68, 95%CI: 0.49-0.96), ischemic cerebrovascular accident  (iCVA) (HR:0.37, 95%CI: 0.16-0.84), composite vascular endpoint (HR: 0.66, 95%CI: 0.49-0.88), vascular mortality (HR: 0.53, 95%CI:0.33-0.85) and all-cause mortality (HR: 0.69, 95%CI: 0.49-0.96), as compared to lack of combination therapy.
• Different variations of partial combination therapy  were seen, often despite there being an indication for combination therapy based on the medical history.
• As compared to taking combination therapy of all 3 components, using only 2 components gave a higher risk of MI (HR: 1.42, 95%CI:1.00-2.03). Taking only 1 component also yielded a higher risk of MI (HR: 1.95, 95%CI: 1.09-3.50). Similar outcomes were seen for the composite vascular end point, vascular mortality and all-cause mortality.

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Conclusion

In a population of patients with established vascular disease, the combined use of aspirin, a statin and >1 BP-lowering agent is associated with a lower risk of vascular events and all-cause mortality. Taking only one or two components of combination therapy did not give the same cardiovascular protection. These observations strengthens the hypothesis that combination therapy reduces the risk of CV events. Results of ongoing trials assessing the effectiveness of these polypills to improve CV clinical outcome should however be awaited before implementing this strategy in daily practice.

References

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