Healthy individuals may be able to cut their risk of cardiovascular disease by 50 to 60% by taking a single pill that combines three blood pressure lowering drugs at low doses, a statin, and aspirin with no additional side effects, according to research presented at the American College of Cardiology’s 58th annual scientific session, in March, Orlando, USA.
The Indian Polycap Study (TIPS) – the first to evaluate the tolerability of the polypill and test whether it leads to meaningful changes in cardiovascular risk factors – enrolled 2,053 participants. During the three-month study, researchers compared the impact of the polypill and eight other pharmacologic therapies on blood pressure, blood cholesterol levels and heart rate, among other measures. The combination pill (Polycap), which includes low doses of thiazide (12.5mg/day), atenolol (50mg/day), ramipril (5mg/day), simvastatin (20mg/day) and aspirin (100mg/day), significantly reduces LDL cholesterol, blood pressure and platelet aggregability.
“The thought that people might be able to take a single pill to reduce multiple cardiovascular risk factors has generated a lot of excitement; it could revolutionise heart disease prevention as we know it,” said Salim Yusuf, Population Health Research Institute at McMaster University and Hamilton Health Sciences, Hamilton, Canada, cochair and principal investigator of the study. “Before this study, there were no data about whether it was even possible to put five active ingredients into a single pill, in terms of feasibility, the bioavailability of different agents and possible interactions, and we found that it works. And side effects with the polypill were no different than when taking one or two medications.”
Participants were randomised to the Polycap (n=400) group or to one of eight other study arms, each with about 200 individuals, which included aspirin alone, simvastatin alone, hydrochlorthiazide alone, three combinations of the two blood pressure lowering drugs, three blood pressure lowering drugs alone, and an arm with three blood pressure lowering drugs plus aspirin. Patients were recruited from 50 centres in India between March, 2007 and August, 2008. The mean age of the participants was 54 years, one-third had diabetes, mean baseline blood pressure was 134/85mmHg, mean cholesterol was 180mg/dL, HDL 44mg/dL, and LDL 117mg/dL. There were several exclusion criteria. The polycap was well tolerated and there was no evidence of problems with increasing number of active components in the pill.
“The side effects of one drug may be counteracted by beneficial effects of another, so the rate of stopping medications was the same,” Yusuf said. Compared to groups not receiving blood pressure lowering agents, the polycap reduced systolic pressure by 7.4mmHg and diastolic pressure by 5.6mmHg; this was similar to when three blood pressure lowering drugs were used, with or without aspirin. Blood pressure reductions increased with the number of pressure lowering drugs used (2.2/1.3mmHg with one drug, 4.7/3.6mmHg with two drugs, and 6.3/4.5mmHg with three drugs). While the effects of the polypill on blood pressure were lower than what was projected by previous investigators, who expected a 20/11mmHg reduction, this is likely because most participants in the present study were not hypertensive. Still, blood pressure reductions among this group could theoretically lead to about a 24% risk reduction in coronary heart disease and 33% risk reduction in strokes in those with average blood pressure levels, according to Yusuf. Polycap reduced LDL by .70 mmol/L, which was slightly less than that with simvastatin used alone (.83 mmol/L; p<.04); both of which were greater than groups without simvastatin (p<.001). The reductions in heart rate with polycap (7 beats/min) and other arms using atenolol (7 beats/min) were similar; and both were significantly greater than that in arms without atenolol (p<.001).
“This trial is a critical first step to inform the design of larger, more definitive studies, as well as further development of appropriate combinations of blood pressure lowering drugs with statins and aspirin,” said Yusuf, who led the study jointly with Dr Prem Pais, St. John’s Medical College, Bangalore, India.
Complete study findings were published in The Lancet. The study was sponsored by Cadila Pharmaceuticals, India.