By Märit Jensen, MD, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Clinical Stroke and Imaging Research (CSI) group (@CSI_Lab)

The concept of a polypill, i.e. a single pill combining effective single drugs for prevention of cardiovascular events, is as simple as compelling and has been discussed among researchers in cardiovascular medicine for almost two decades1,2. Usually, the so-called polypill contains aspirin, one or more first line antihypertensive drugs, and a statin, by this combining the effects of lowering of cholesterol, blood-pressure lowering, and of an antiplatelet drug. All these effects are known to reduce adverse cardiovascular events, and the combination of multiple of these drugs in a single pill is proposed to improve patients’ adherence to medication, and to reduce the complexity and costs of prescription. Results of the EU-funded SECURE study3, which was just published and presented at the ESC congress 2022, add novel findings on the effect of a polypill for secondary prevention after myocardial infarction, which also may be of interest for stroke researchers.

In SECURE, patients were randomized within six months of myocardial infarction to secondary prevention using a polypill (including aspirin 100mg, ramipril 2.5, 5, or 10 mg and atorvastatin 20 or 40 mg) or usual care. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, urgent revascularization, or ischemic stroke. A total of 2499 patients were randomized and followed for a median of 36 months. Assignment to the polypill group was associated with a significant reduction in occurrence of the primary endpoint, with a hazard ratio of 0.76 (95% confidence interval 0.60-0.96, p=0.02). Primary outcome events occurred in 118 of 1237 (9.5%) patients in the polypill group and in 156 of 1229 (12.7%) patients assigned to usual care. The most striking effect was observed for cardiovascular death, which occurred in 48 (3.9%) patients in the polypill group and 71 (5.8%) in the usual care group, representing an absolute reduction of 1.9% over a period of three years. Key secondary endpoints were also observed less frequently in the polypill group, while adverse events and all-cause mortality were comparable between groups. As expected, adherence to medication was higher among patients in the polypill group.

Previous polypill trials have mostly focused on the use of a polypill for primary prevention of cardiovascular events, such as the International Polycap Study 3 (TIPS-3)4, or broad inclusion of patients in a pragmatic approach, such as the PolyIran study5. In these studies, the use of a polypill was compared to placebo (TIPS-3), or non-pharmacologic interventions (PolyIran study). In contrast, SECURE tested the polypill approach in a setting of secondary prevention after myocardial infarction, and patients in the usual care group also received antiplatelets and medication for lowering of blood pressure and cholesterol, at the discretion of the treating physicians. The additional benefit of the polypill may be explained by the simplified approach resulting in improved adherence to these effective drugs. SECURE also differs to previous polypill studies by offering different polypills containing different doses of the individual drugs, thus allowing for a personalized adaption of the treatment strategy in case of insufficient risk factor control.

To summarize, the findings from SECURE suggest that a polypill adds to the current strategies of secondary prevention after myocardial infarction. Given these results and given the known problems with adherence to intake of drugs for secondary prevention after stroke, a polypill might also be a powerful tool for the prevention of recurrent strokes and other cardiovascular events in secondary prevention after stroke.


  1. Wang TJ. The Polypill at 20 – What Have We Learned? N Engl J Med 2022.
  2. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003; 326(7404): 1419.
  3. Castellano JM, Pocock SJ, Bhatt DL, et al. Polypill Strategy in Secondary Cardiovascular Prevention. N Engl J Med 2022.
  4. Yusuf S, Joseph P, Dans A, et al. Polypill with or without Aspirin in Persons without Cardiovascular Disease. N Engl J Med 2021; 384(3): 216-28.
  5. Roshandel G, Khoshnia M, Poustchi H, et al. Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial. Lancet 2019; 394(10199): 672-83.

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