Polycap is a specific five-in-one fixed dose combination polypill created by Cadila Pharmaceuticals Limited of Ahmedabad, India that combines moderate levels of five different medications in a single, one-a-day pill aimed at reducing/preventing heart attacks and strokes. A prominent 2009 study found that this pill's combination of three blood pressure medications, a cholesterol reducer, and aspirin had cut the risk of heart attack and stroke in half, with no more adverse effects than taking the components separately.
Many different fixed dose combination (FDC) polypills have been proposed, and one for reducing cardiovascular risk was especially sought. While there are benefits to reducing the number of pills that patients have to take (alleviating the so-called "pill burden"), FDC polypills (like Polycap) also raise concerns that any particular mass-produced combination of drugs and/or dosages is actually optimal for relatively few patients (i.e., offering many patients too little of the medication they need, or components that they don't need at all, while exposing all to the side effects, etc.). This is often accepted by FDC proponents as a worthwhile tradeoff in exchange for the benefits of reducing pill-burden.
A hypothesis initially proposed by Wald and Law had recommended a six-drug combination to be taken by patients over age 55 at risk of cardiovascular disease events, which would include three half-dose antihypertensives drugs, aspirin, a statin, and folic acid. After further research showed no improvement in clinical outcomes for patients taking folic acid, it was omitted from Cadila Pharmaceuticals' formulation. As tested, "Polycap" combines 100 milligrams of aspirin, with simvastatin (a generic version of Zocor, the cholesterol-lowering statin; 20 mg) and low doses of three blood pressure medications, atenolol (50 mg), ramipril (5 mg) and thiazide (12.5 mg). And despite containing multiple drugs, the pill has a fairly small size which can facilitate swallowing.
The Indian Polycap Study (TIPS)
A study called The Indian Polycap Study (TIPS) was sponsored by Cadila Pharmaceuticals Limited, (where the drug development program was coordinated by JP Parswani, President, and Dr. Arun Maseeh, Vice-President Medical Affairs), and led by Dr. Salim Yusuf of McMaster University in Hamilton, Ontario, and Dr. Prem Pais of St. John's Medical College in Bangalore, India. The results of the randomized, controlled, double-blind study, reported in March 2009 at an American College of Cardiology conference and published online by The Lancet, documented the outcome of 2,000 individuals with an average age of 54 given the medication, all of whom had at least one heart disease risk factor: diabetes, hypercholesterolemia, hypertension, obesity or smoking. The study was registered with ClinicalTrials.gov, number NCT00443794.
During a 12-week treatment period, 400 of the study participants were given Polycap. The remainder were divided into eight groups of 200 who were given either individual components or groups of them. Three of the groups of 200 received only aspirin, simvastatin or thiazide respectively; Three groups received two of the three blood pressure medications; Another received all three blood pressure medications, while the last received all three combined with aspirin.
The individuals who were given Polycap saw their blood pressure drop from six to seven points for both their systolic and diastolic levels. These reductions in blood pressure could cut the risk of heart disease by 62% and of stroke by 48% based on the results of other studies that showed risk reductions from cutting blood pressure levels. The combined pill was almost as effective as the individual pills with no increase in side effects.
Generic versions of the five components cost $17 per month in the United States as of 2009. Estimates are that the combined dose would sell for far less while offering the psychological benefit of reducing the "pill burden" on patients taking multiple medications. Distribution would require approval by the U.S. Food and Drug Administration and other regulatory bodies worldwide. Details of the polycap data were widely reported in the popular media, including USA Today, The Guardian (UK), BBC, CBS Healthwatch, ABC News, India Today.
Polycap PK Study
The Polycap (Cadila) has been found to be safe and effective for reducing multiple cardiovascular risk factors. Bioavailability of each component of PolycapTM and absence of their mutual interaction relative to single component reference formulations have been evaluated by a group of scientists led by Dr. Bhaswat Chakraborty.
Bioavailability of the components of the Polycap (aspirin, ramipril, simvastatin, atenolol and hydrochlorothiazide) when formulated as a single capsule was compared to identical capsules with each of its components administered separately in a five arm, randomized, single-dose, two-period, two-treatment, two-sequence, crossover trial with at least 2 week washout period in a total of 195 healthy humans. Plasma concentrations of each drug and where applicable its active metabolite were measured using validated LC-MS/MS and UPLC. Mean pharmacokinetic parameters and their standard deviations were computed for each analyte. Comparative bioavailability and absence of drug-drug interaction for each component were computed based on a point estimate of test/reference (T/R) ratio of geometric means falling within 80-125% for Cmax, AUC0-t and AUC0-∞.
The ratio of Cmax, AUC0-t and AUC0-∞ for Polycap and reference drugs was within 80-125% for atenolol, hydrochlorothiazide, ramipril, ramiprilat and dose normalized salicylic acid. However, for simvastatin the point estimate of Cmax, AUC0-t and AUC0-∞ for Ln-transformed data were significantly lower (~25%) and for its active metabolite, simvastatin acid, it was significantly higher (~60%). Thus, the increased bioavailability of active simvastatin acid compensated for the loss of bioavailability of simvastatin alone. There was no indication of kinetic drug-drug interaction in any of components.
- Marchione, Marilynn via Associated Press. "Study says one combo pill does work of five", The Record (Bergen County), March 31, 2009. Accessed March 31, 2009.
- Xavier, Denis, et al. "The Need to Test the Theories Behind the Polypill: Rationale Behind the Indian Polycap Study", Nature Clinical Practice Cardiovascular Medicine, 2009; 6(2): 96-97, posted February 12, 2009. Accessed March 31, 2009.
- The Indian POLYCAP Study (TIPS), ClinicalTrials.gov. Accessed April 6, 2009.
- Preservation of Bioavailability of Ingredients and Lack of Drug-drug Interactions in a Novel Five Ingredient Polypill (PolycapTM) in a Five Arm Phase-I Crossover Trial in Healthy Volunteers,by Anil Patel, Tarang Shah, Gaurang Shah, Vijay Jha, Chinmoy Ghosh , Jagruti Desai, Bakulesh Khamar and Bhaswat S Chakraborty, Am. J. Cardiovasc. Drugs, 10: 95-103.
- "Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial", S Yusuf (cochair and principal investigator), P Pais (cochair and principal investigator), D Xavier, A Sigamani, R Gupta, K K Haridas, S S Iyengar, T M Jaison, P Joshi, P Kerkar, V Mohan, S Naik, D Prabhakaran, S Thanikachalam, N Thomas, J Parwani, A Maseeh. http://www.thelancet.com Published online March 30, 2009 doi:10.1016/S0140-6736(09)60611-5
- Christopher P Cannon. Editorial Comment. Can the polypill save the world from heart disease? Published Online March 30, 2009 doi:10.1016/S0140-6736(09)60652-8. http://www.thelancet.com Published online March 30, 2009 doi:10.1016/S0140-6736(09)60652-8
- Preservation of Bioavailability of Ingredients and Lack of Drug-drug Interactions in a Novel Five Ingredient Polypill (PolycapTM) in a Five Arm Phase-I Crossover Trial in Healthy Volunteers,by Anil Patel, Tarang Shah, Gaurang Shah, Vijay Jha, Chinmoy Ghosh, Jagruti Desai, Bakulesh Khamar and Bhaswat S Chakraborty, Am. J. Cardiovasc. Drugs, 10: 95-103.