The Indian Polycap Study (TIPS) is the first to evaluate the tolerability of the polypill-enrolled 2,053 participants. During the three-month study, researchers compared the impact of the polypill-- one pill that combines three low-dose antihypertensives, a statin and aspirin, with no additional side effects--and eight other pharmacologic therapies on BP, blood cholesterol levels and heart rate, among other measures. The combination pill (Polycap), which includes low doses of thiazide (12.5 mg/day), atenolol (50 mg/day), ramipril (5 mg/day), simvastatin (20 mg/day) and aspirin (100 mg/day), significantly reduces LDL cholesterol, blood pressure (BP) and platelet aggregability.
Participants were randomized to the Polycap (400 patients) group or to one of eight other study arms, each with about 200 individuals, including aspirin alone, simvastatin alone, hydrochlorthiazide alone, three combinations of the two BP lowering drugs, three BP lowering drugs alone, and an arm with three BP lowering drugs plus aspirin. The researchers recruited participants from 50 centers in India between March 5, 2007 and Aug. 5, 2008. The mean age of the participants were between the ages of 45 and 80, one-third had diabetes, mean baseline BP was 134/85 mmHg, mean cholesterol was 180 mg/dl, HDL 44 mg/dl and LDL 117 mg/dl.
In terms of the dose ranging of the ACE inhibitor in the study, Yancey said that its "intuitive to start a low dose, and gradually increase. The biggest challenge of mixing five drugs in one pill is to trying to find the optimal dose to affect the largest population in the best possible way without harm."
To be enrolled in TIPS, the patients only had to have one-risk factor for cardiovascular disease, which could have far-reaching implications for the amount of people who could potentially be prescribed the polypill. "The whole premise of the trial was for primary prevention, and the question that needs to be asked what is the burden of proof in the patient population," Yancey said.
TIPS lead investigator Salim Yusuf, DPhil, of the Population Health Research Institute at McMaster University and Hamilton Health Sciences in Hamilton, Ontario, reported that the polycap was well tolerated, and there was no evidence of problems with increasing number of active components in the pill.
"The reductions in blood pressure that we recorded in this non-hypertensive population with the Polycap could theoretically lead to about a 24 percent risk reduction in cardiovascular heart disease and 33 percent risk reduction in strokes in individuals with average blood pressure levels...On the basis of the more modest lowering of LDL cholesterol that we noted, a 27 percent relative risk reduction in cardiovascular heart disease and an 8 percent risk reduction in stroke can be projected," the authors wrote. The researchers also said that the combined effects of all the components in the Polycap could potentially halve cardiovascular events, in average, middle-aged individuals.
"While we're all intrigued by the possibility of a polypill, this is a feasibility study, and no one is ready to apply the findings in any guidelines or recommendations," Jones said.
While Jones agrees with Yusuf's claim that a mass approach is necessary to combat the global prevalence of coronary artery disease (CAD), it is "not necessarily with pills," he said. "If we're going to use a population approach, we should expend our efforts towards having a healthier food supply and better education about proper eating, and we could achieve the same results. While some think the CAD statistics are too prevalent to reverse the negative trend, I personally believe healthcare spending should be focused in that area."
Jones added that he is not opposed to the idea of dedicating time and effort into developing and testing a polypill in particular for this generation of middle-aged people. "However, for future generations, it might be better to begin with childcare and primordial education about behavioral remedies," he said. But, acknowledged that those efforts "are not going well now."
Yancey also cautioned that the introduction of a polypill could potentially overlook individual patient heterogeneity. "One patient compared to another may have more or less of a given risk factor, requiring a more focused attention on hypertension in some and lipid-lowering efforts in another. It may not be amenable to a combination tablet that is all things to all people," he said.
Gibbons added that while the U.S. is "clearly not doing a very good job as a healthcare system in taking of hypertension, he noted that the stimulus package had $1 billion earmarked for preventive care, "so we are beginning to recognize that prevention has not been adequately supported and reimbursed in our healthcare system."
"The value is in treating the high blood pressure to existing standards, but we do not adequately reimburse the kind of effort that takes, in terms of patient education, physician and nurse follow ups, along with dietitian consultants. Therefore, it doesn't get done," Gibbons said.
"However", he added, "once that at-risk patient ends up in the hospital with heart failure, for example, we realize we have to pay for it. Heart failure is the most expensive DRG, and we are having more and more about the disastrous readmission rates. Now, the system is covering the patient. And, if that patient gets really sick, we implant devices-defibrillators and resynchronization therapies, which costs about $50,000 to the system."
Gibbons concluded that the "real value was treating hypertension in the first place, which our system doesn't support that approach. The polypill is just an option-it's a first step achieving feasibility. But, this approach is too easy. I'd rather see the healthcare system adequately supporting prevention.
However, based on the results of the TIPS study, Yancey said that this polypill population approach is theoretically feasible. However, he added that the homogenous nature of the TIPS patient population, adding that "it should eventually be tested in more diverse patient populations to be confident that the benefits were translatable."
The study, simultaneously published in the Lancet, was sponsored by Cadila Pharmaceuticals in Ahmedabad, India, which manufactures the Polycap.