Comparison of Risk Factor Reduction and Tolerability of a Full-Dose Polypill (With Potassium) Versus Low-Dose Polypill (Polycap) in Individuals at High Risk of Cardiovascular Diseases The Second Indian Polycap Study (TIPS-2) Investigators
ABSTRACT A daily single capsule (polycap) of 3 blood pressure (BP) lowering drugs (hydrochlorthiazide, 12.5 mg; atenolol, 50 mg; ramipril, 5 mg) at low doses, simvastatin (20 mg), and aspirin (100 mg) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol. We examined the incremental effects of 2 (full dose) plus K(+) supplementation versus single polycap (low dose) on risk factors and tolerability.
After a run-in period, 518 individuals with previous vascular disease or diabetes mellitus from 27 centers in India were randomly assigned to a single-dose polycap or to 2 capsules of the polycap plus K(+) supplementation for 8 weeks. The effects on BP, heart rate (HR), serum lipids, serum and urinary K(+), and tolerability were assessed using an intention-to-treat analysis. The full-dose polycap (plus K(+) supplementation) reduced BP by a further 2.8 mm Hg systolic and 1.7 mm Hg diastolic, compared with that observed with the low-dose polycap (P=0.003; P=0.001), but there were no differences in HR (0.1 bpm). The differences in total and low-density lipoprotein cholesterol between the full-dose and low-dose polycap was 7.2 mg/dL (P=0.014) and 6.6 mg/dL (P=0.006), respectively, but there were no differences in high-density lipoprotein cholesterol or triglycerides. The rates of discontinuation of the study drug after randomization were similar in the 2 groups (6.9% low dose versus 7.8% full dose).
The full-dose polycap (plus K(+) supplementation) reduces BP and low-density lipoprotein cholesterol to a greater extent compared with the low dose, with similar tolerability. Therefore, the full-dose polycap should potentially lead to larger benefits. Clinical Trial Registration- URL: http://www.ctri.nic.in. Unique identifier: CTRI/2010/091/000054.
- Preventive Medicine 10/2012; 55(6). DOI:10.1016/j.ypmed.2012.09.023 · 2.93 Impact Factor
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ABSTRACT: To assess the blood pressure and lipid-lowering efficacy and tolerability of 'polypills' used in cardiovascular disease prevention trials. Systematic review and meta-analysis. Search strategy: The Cochrane Central Register of Controlled Trials, Medline, and PubMed databases were searched for eligible trials. Study inclusion criteria: Randomised controlled trials of at least six weeks duration, which compared a 'polypill' (that included at least one anti-hypertensive and one lipid-lowering medication) with a placebo (or one active component). Outcome measures: Change from baseline in systolic and diastolic blood pressures, and total and LDL-cholesterol; discontinuation of study medication and reported adverse effects. Of 44 potentially eligible studies, six trials (including 2,218 patients without previous cardiovascular disease) fulfilled the inclusion criteria. Compared with placebo, 'polypills' reduced systolic blood pressure by -9.2 mmHg (95% confidence interval (CI): -13.4, -5.0) diastolic blood pressure by -5.0 mmHg (95%CI: -7.4, -2.6), total cholesterol by -1.22 mmol/L (95%CI: -1.60, -0.84) and LDL-cholesterol by -1.02 mmol/L (95%CI: -1.37, -0.67). However, those taking a 'polypill' (vs. placebo or component) were more likely to discontinue medication (20% vs 14%) (Odds ratio: 1.5 (95% CI: 1.2, 1.9)). There was no significant difference in reported adverse effects amongst those on a 'polypill' (36% vs. 28%) (OR: 1.3 (95%CI: 0.7, 2.5)). There was high statistical heterogeneity in comparisons for blood pressure and lipid-lowering but use of random-effects and quality-effects models produced very similar results. Compared with placebo, the 'polypills' reduced blood pressure and lipids. Tolerability was lower amongst those on 'polypills' than those on placebo or one component, but differences were moderate. Effectiveness trials are needed to help clarify the status of 'polypills' in primary care and prevention strategies.PLoS ONE 12/2012; 7(12):e52145. DOI:10.1371/journal.pone.0052145 · 3.53 Impact Factor
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ABSTRACT: Cardiovascular diseases are responsible for a significant proportion of global mortality and morbidity. Modifiable risk factors like hypertension, hyperlipidemia, physical inactivity, unhealthy diet, tobacco use, obesity and inflammatory states contribute to an increased risk of cardiovascular diseases. The mortality risk increases with increase in number of risk factors. So, simultaneous modification of multiple risk factors is expected to reduce mortality due to these disorders more than the reduction of any individual risk factor. Based on the same rationale, the polypill strategy is based on utilizing a once-daily fixed-dose combination pill to reduce multiple cardiovascular risk factors simultaneously. Two cardiovascular epidemiologists, Wald and Law, proposed the strategy in a patent application in 2000. The idea of combining multiple medications to improve efficacy of treatment has been effectively applied in the treatment of many cancers, HIV/AIDS, tuberculosis and malaria. However, such combination strategy has not been tested in preventing a chronic disease. Thus, this idea has generated a lot of interest as well as controversy. In this article, we will review the pharmacokinetics, clinical trials, advantages and limitations of the polypill strategy.Drugs of today (Barcelona, Spain: 1998) 05/2013; 49(5):317-24. DOI:10.1358/dot.2013.49.5.1950148 · 1.00 Impact Factor