• Prevention & Screening Clinical Trials

Results of the Indian Polycap Study (TIPS; NCT00443794) indicate that it may be possible for individuals who have average risk factors for cardiovascular disease to significantly reduce their risk for heart disease and stroke through the use of a single pill—the Polycap™—which combines low doses of thiazide (12.5 mg), atenolol (50 mg), ramipril (5 mg), simvastatin (20 mg), and aspirin (100 mg). The results of TIPS were presented by the joint principal investigator of the study, Salim Yusuf, PhD, McMaster University, Hamilton, ON, Canada, at the American College of Cardiology 58^th Annual Scientific Session in Orlando, FL.

The primary objective of TIPS was to determine whether the Polycap™ is equivalent to its individual components in reducing blood pressure (BP) and heart rate (HR), modifying lipids, and suppressing urine thromboxane B2 and whether it has a similar adverse event profile. The secondary objective of TIPS was to determine whether the Polycap™ is superior in reducing BP compared with its components.

The study population comprised 2053 subjects aged 45 to 80 years (mean age 54 years; 44% women) without cardiovascular disease but with at least 1 risk factor. One-third (33.9%) of the subjects had diabetes, mean baseline BP was 134/85 mm Hg, and mean cholesterol was 180 mg/dl (HDL 44 mg/dL and LDL 117 mg/dL).

Subjects were randomly assigned to receive either the Polycap™(n=412) or 1 of 8 other formulations (n≈200 each) for 12 weeks. The 8 other formulations, which used the same doses of agents as Polycap™, were: aspirin alone, thiazide alone, thiazide + either ramipril or atenolol or both, thiazide + ramipril + atenolol + aspirin, ramipril + atenenol, and simvastatin alone.

In the Polycap group, BP reductions (7.4 mm Hg systolic and 5.6 mm Hg diastolic) were comparable with those that were seen in the group that received 3 BP medications (6.9 mm Hg systolic and 5.0 mm Hg diastolic). Aspirin did not interfere with the BP-lowering effects of the Polycap™.

LDL reductions in the group that was randomized to Polycap™ (0.70 mmol/L [23.3%]), however, were significantly lower than those that were seen in the group that received simvastatin alone (0.83 mmol/L [27.7%]; p<0.04), leading the investigators to speculate that the 40 mg dose should be tried instead of the 20 mg dose of simvastatin in order to enhance the benefits. Reductions in LDL for both groups of individuals who received the polycap, however, were significantly (p<0.0001) better than for subjects who did not receive simvastatin.

The reductions in HR with Polycap™ (7.0 beats/min) and other arms using atenolol (7.0 beats/min) were similar, and both were significantly greater than those in subjects who did not receive atenolol (p<0.001). The reduction in thromboxane B2 that was seen with Polycap™ (−322.3) was similar to that seen with aspirin alone (−388.0) or the combination of thiazide, atenolol, and ramipril + aspirin (−389.3; all p<0.001 vs baseline).

Polycap™ was well tolerated, and there was no evidence of increasing rates of adverse effects or discontinuation of study drugs with increasing numbers of active components in the pill.

Based on the results of this study, the investigators estimate that in individuals who are at average risk of cardiovascular disease, the use of Polycap™ could potentially result in a 62% reduction in the relative risk for coronary heart disease and a 48% reduction in the relative risk for stroke. However, they emphasized the need for large, prospective randomized trials to evaluate this hypothesis.

The study was sponsored by Cadila Pharmaceuticals, India, which played no role in data collection, analysis, or interpretation.

Results of the TIPS study were simultaneously published in The Lancet (Online Publication, 30 March 2009).

• © 2009 MD Conference Express