Will the Polypill Improve Cardiovascular Outcomes? Ongoing Trials Seek an Answer

August 06, 2014

NEW YORK, NY — Multiple clinical trials, both ongoing and planned, are testing a fixed-dose polypill strategy for addressing the global burden of cardiovascular disease, especially in underdeveloped countries, notes a comprehensive review published this week[1]. The trials, it states, have the "potential power to change the face of healthcare across the world."

Studies published or presented at meetings to date, including SPACE and UMPIRE , among others, have shown the polypill—a fixed-dose combination that typically includes aspirin, a statin, and one or more antihypertensive medications—improves adherence and reduces cardiovascular risk factors. But while the safety and efficacy of this approach has been demonstrated, there is still no evidence this strategy will improve clinical outcomes.

"There are impressive, potential benefits that come with the use of a polypill strategy in cardiovascular prevention," write Dr José Castellano (Mount Sinai Medical Center, New York) and colleagues. "Unfortunately, the use of a polypill for cardiovascular prevention is relatively novel, and although data from clinical trials are accumulating, the clinical question that remains to dissipate skepticism is whether the polypill, beyond improving adherence and risk-factor control as surrogate markers, can significantly reduce cardiovascular events."

The upcoming trials

In the article, published in the August 12, 2014 issue of the Journal of the American College of Cardiology, the reviewers note that several planned and ongoing studies are assessing the viability of the polypill for the reduction of cardiovascular outcomes, while others are looking at the effect of the strategy on adherence and other surrogate end points. Such trials include:

  • TIPS-3 : Polypill combination therapy with three antihypertensive medications (atenolol 50 mg, hydrochlorothiazide 12.5 mg, ramipril 5 mg), simvastatin 20 mg, and aspirin 100 mg vs placebo in 5000 subjects without cardiovascular disease and an estimated annual risk of cardiovascular disease of 1% per year. End points include major cardiovascular disease events and measures of cognitive and renal function.

  • HOPE-3 : Combination therapy with rosuvastatin (Crestor, AstraZeneca) 10 mg and a fixed-combination of candesartan 16 mg and hydrochlorothiazide in 12 000 men and women at moderate risk for cardiovascular disease. End points for this trial, as well, include major cardiovascular disease events and measures of cognitive and renal function.

  • HOPE-4 : Community-cluster randomized, controlled trial that will utilize a simplified screening and treatment algorithm with a polypill strategy implemented by nonphysicians. The initial phase of HOPE-4 will measure blood pressure and lipids and will later be extended to 190 communities in eight countries to evaluate cardiovascular events over six years.

  • Poly-Iran : Primary- and secondary-prevention trial testing a fixed-dose combination with two antihypertensive medications, atorvastatin, and aspirin. In total, 3500 patients will receive the polypill plus minimal follow-up care (education on cardiovascular risk reduction, biannual follow-ups, and blood-pressure measurements), 3500 will receive minimal care only, and 24 000 will receive guideline-recommended usual care. The end points of Poly-Iran will include major cardiovascular events.

  • FOCUS : Two-phase study that will first examine factors limiting appropriate use of cardiovascular medications. Phase 2 will test the effects of a polypill on adherence, blood pressure, and lipids at nine months.

One possible role for the polypill might be in lower-middle-income countries (LMICs), given that they account for 80% of all cardiovascular deaths, suggest the reviewers. In these countries, even the cost of generics are a problem, considering that a one-month supply of secondary-prevention medications costs individuals in LMICs disproportionately more of their annual wages than in richer countries.

"At present, there is no consensus regarding for which patient population the polypill should be prescribed," state Castellano and colleagues in reference to the ongoing polypill debates. Such debates includes whether or not the polypill be utilized in secondary prevention only or be extended to primary-prevention patients. Also, it is not known if the benefits would apply beyond LMIC countries, although the researchers suspect it will.

"Available clinical data support the viability of the polypill in cardiovascular disease prevention and management, but with a few reservations," conclude the authors. "Studies are being conducted around the world as investigators unite to determine whether it is a viable solution to an epidemic facing every country, race, and community. Gradually, the role of the polypill in cardiovascular prevention is being defined."

The authors report no conflicts of interest.

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