TIPS: Polypill reduced BP, other CVD risk factors in population with average risk factors

Healthy individuals may be able to cut their risk of CVD by 50% to 60% by taking a polypill that combines three BP-lowering drugs at low doses, a statin, and aspirin with no additional adverse events, according to data from the TIPS trial.

The Indian Polycap Study (TIPS) is the first to evaluate the tolerability of the polypill and test whether it leads to meaningful changes in CV risk factors, according to Salim Yusuf, MD, DPhil, of the Population Health Research Institute at McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.

Yusuf and colleagues in India enrolled 2,053 participants for the three-month study, during which they compared the effect of the polypill and eight other pharmacologic therapies on BP, cholesterol levels and heart rate, among other measures. The combination pill (Polycap, Cadila Pharma), which includes thiazide 12.5 mg per day, atenolol 50 mg per day, ramipril 5 mg per day, simvastatin (Zocor, Merck) 20 mg per day and aspirin 100 mg per day, significantly reduced LDL, BP and platelet aggregability among people with average risk factors for CVD (at least one CV risk factor).

Participants were randomized to the combination pill (n=400) group or to one of eight other study arms, each with about 200 individuals. These groups included 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 mean age of the participants was 54 years. One-third had diabetes. Mean baseline BP was 134 mm Hg/85 mm Hg, mean cholesterol was 180 mg/dL, HDL 44 mg/dL, and LDL 117 mg/dL.

Results

The polypill was well tolerated and there was no evidence of problems with increasing number of active components in the pill. Yusuf said the adverse effects of one drug may be counteracted by another.

Compared to groups not receiving BP-lowering agents, the polypill reduced systolic BP by 7.4 mm Hg and diastolic BP by 5.6 mm Hg; this was similar to when three BP- lowering drugs were used, with or without aspirin. BP reductions increased with the number of BP-lowering drugs used (2.2 mm Hg/1.3 mm Hg with one drug, 4.7 mm Hg/3.6 mm Hg with two drugs, and 6.3 mm Hg/4.5 mm Hg with three drugs).

While the effects of the polypill on BP were lower than what was projected by previous investigators, who expected a 20 mm Hg/11 mm Hg reduction, this is likely because most participants in the present study were not hypertensive, according to Yusuf.

Still, BP reductions among this group could theoretically lead to about a 24% risk reduction in CHD and 33% risk reduction in strokes in those with average BP levels, according to Yusuf. The combination pill reduced LDL by 0.70 mmol/L, which was slightly less than that with simvastatin used alone (0.83 mmol/L; P<.04); both of which were greater than groups without simvastatin (P<.001). The reductions in heart rate with the polypill (7 bpm) and other arms using atenolol (7 bpm) were similar; and both were significantly greater than that in arms without atenolol (P<.001).

“We think we have to follow this up with further trials,” Yusuf said. “These are half doses. [What about] full doses, how well will they be tolerated? How much more of a benefit will we get?” – by Judith Rusk

It’s just really preliminary that you can get away with giving a substantial number of drugs in small doses to people. The side effect profiles were very reasonable and the effects appeared to be additive but I think beyond that there’s not a whole lot more we can say at this stage. I would prefer to see this development for therapies for treatment of actual people at risk rather than people who are essentially healthy.

– Steven Nissen, MD

Department Chair, Cardiovascular Medicine,
and Director of the Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic

For more information:

Yusuf S. Impact of combinations of three BP-lowering drugs, a statin and aspirin on CV risk factors in 2,000 individuals without CVD. #413. Presented at: American College of Cardiology's 58th Annual Scientific Sessions; March 29-31, 2009; Orlando, Fla.