View from SPACE: Polypill Improves Adherence and Lowers CVD Risk Factors

May 06, 2014

MELBOURNE, AUSTRALIA — A combined analysis of three studies involving the polypill showed that patients taking only the single tablet were significantly more likely than patients taking multiple cardiovascular drugs to be adherent to therapy at one year and had significantly lower LDL-cholesterol and blood-pressure levels.

Overall, systolic blood pressure was reduced 2.84 mm Hg among those treated with the polypill, and LDL-cholesterol levels were reduced 0.12 mmol/L (4.64 mg/dL). Although these reductions are modest, investigators stress they are still clinically meaningful.

"From our perspective, it is modest, there is no doubt about that," lead investigator Dr Ruth Webster (George Institute for Global Health, Sydney, Australia) told heartwire . "What has to be kept in mind is that our usual-care group was being treated as well. We're not comparing [the polypill] with a placebo, where you might expect a 10- to 15-mm-Hg improvement in blood pressure or larger improvements in cholesterol. This was compared with a treated group."

At a population level, even such small improvements over usual care would translate into significant reductions in cardiovascular morbidity and mortality, say the researchers. Dr Salim Yusuf (McMaster University, Hamilton, ON), who was not involved in the analysis but is a long-time advocate of the polypill strategy to reduce the global burden of cardiovascular disease, said that based on his "back-of-the-envelope calculations," these small improvements in blood pressure and cholesterol would translate into an incremental 9% relative reduction in the risk of cardiovascular disease.

"It's not huge, but it's important," he told heartwire .

The results of the study, known as the Single Pill to Avert Cardiovascular Events (SPACE), were presented this week here at the World Congress of Cardiology 2014 Scientific Sessions .

No SPACE Oddities Here

The SPACE collaboration involved three independent clinical trials conducted in different geographic regions, including the IMPACT trial in New Zealand, the UMPIRE trial in Western Europe and India, and the Kanyini-GAP trial conducted in Australia.

The 3140 patients randomized to the polypill or usual care all had existing cardiovascular disease or were at high risk for cardiovascular disease (>15% risk in the next five years). The patients were obese, 20% were current smokers, and 65% had coronary heart disease. The baseline systolic blood pressure and LDL-cholesterol levels were 139 mm Hg and 92.8 mg/dL, respectively. In the polypill arm, they received aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, and atenolol 50 mg in a single tablet. A second polypill was also available and was similar to the first version with the exception that hydrochlorothiazide 12.5 mg was substituted for atenolol.

At 12 months, 78% of the polypill patients were still taking the medication, compared with 54% in the usual-care arm, a statistically significant difference. This translated into significant reductions in systolic blood pressure and total and LDL cholesterol. Adherence was observed across all the subgroups, although investigators noted better adherence in patients not taking the drugs at baseline. In this group, there was a fourfold improvement in adherence with the polypill.

"And this is our target population," said Webster. "If you're happy to take all four individual pills and you're taking them, that's fine. You don't have to take the polypill. But if you're struggling to take all the medications, then this could be huge help in bridging the evidence-practice gap."

Outcome Data Are Now Awaited

Dr Sidney Smith (University of North Carolina, Chapel Hill), who chaired the press conference announcing the SPACE results, said it's not uncommon for elderly, sick patients to be taking as many as eight to 12 different pills per day. He sees the polypill as something that can simplify treatment, noting that only a minority of cardiovascular patients or those at high risk for cardiovascular events take all four drugs. He pointed out, however, there is still the need for data showing the four drugs in one pill are as effective as the drugs taken alone.

"The Holy Grail is outcomes," he said. "If we use a single pill, are patients actually going to do better than if they are told to take three or four?" One such study, The International Polycap Study 3 (TIPS-3), a 5500-patient phase 3 trial, is under way, with patients randomized to a polypill as part of a primary-prevention strategy. This study began only in 2012, and results aren't expected for a few years.

Given the epidemic of cardiovascular disease, Yusuf said he believes the polypill is a vehicle to reduce this burden, especially in low-income countries. Bulk government purchasing could reduce the cost to just a few rupees per day in India, he noted, while a combination tablet would also make distribution and storage easier in hard-to-access communities.

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