polypill (Polycap)
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Introduction
Different versions of a polypill show benefit in various clinical trials
Indications
- primary prevention for everyone 55 years of age or older[1]
Computer modelling suggests Polypill would
- reduce heart disease by 88%
- reduce stroke by 80%
- 1/3 of people > 55 would benefit
- average live expectancy free of heart disease & stroke would increase by 11 years
Adverse effects
- largely due to aspirin (8-15%)
Clinical trials
ClinicalTrials.gov number, NCT02278471.[5]
- combination of:
- a statin
- 3 antihypertensive agents (each at 1/2 standard dose)
- low dose aspirin
- folic acid included in an early version
- later version contains beta-blocker or thiazide diuretic
- atorvastatin, amlodipine, losartan, & hydrochlorothiazide
- may improve blood pressure & LDL cholesterol levels in socioeconomically disadvantaged adults[5]
revival of the polypill in an industry-sponspored study[4]
- prevention of primary & secondary cardiovascular disease
- hydrochlorothiazide, aspirin, atorvastatin, & enalapril
- cardiovascular events 5.9% vs 8.8% within 5 years[4]
The Indian Polycap Study
- Polycap consists of:
- HCTZ 12.5 mg
- atenolol 50 mg
- ramipril 5 mg
- simvastatin 20 mg
- aspirin 100 mg
- study characteristics:
- double-blind trial in 50 centres in India
- 2053 individuals without cardiovascular disease
- aged 45-80 years
- one cardiovascular risk factor
- results:
- Polycap reduced systolic blood pressure by 7.4 mm Hg & diastolic blood pressure by 5.6 mm Hg
- Polycap reduced LDL cholesterol by 0.70 mmol/L (27 mg/dL) , The UMPIRE Randomized Clinical Trial
- patients with cardiovascular disease or cardiovascular risk factors
- aspirin, simvastatin, lisinopril, & either atenolol or HCTZ
- improved medical compliance (86% vs 65%)
- marginal benefit in systolic blood pressure (3 mm Hg)
- marginal benefit in LDL cholesterol (4 mg/dL)
- too few cardiovascular events to compare groups
South Asian & Southeast Asian countries (NCT01646437)[7]
- study characteristics:
- the polypill
- simvastatin 40 mg
- atenolol 100 mg
- HCTZ 25 mg
- ramipril 10 mg
- +/- aspirin 75 mg
- results
- lowered LDL cholesterol by 19 mg/dL & systolic blood pressure by 5.8 mm Hg
- cardiovascular events non-signigicantly lower vs placebo (4.4% vs 5.5) (without aspirin, aspirin alone vs placebo 4.4% vs 5.5% no different)
- polypill + apsirin (4.1% vs 5.8%; RR=0.69) significant
- study characteristics
- females >= 55 years, males >= 50 years
- no known cardiovascular disease
- intermediate cardiovascular risk
- 5 year study
- the polypill
- simvastatin 40 mg
- atenolol 100 mg
- HCTZ 25 mg
- ramipril 10 mg
- results: improved functional decline, but not cognitive decline
Meta-analysis of randomized controlled trials[8]
- 10 year estimated cardiovascular risk 18%
- polypills: least 2 antihypertensives plus a statin (with or without aspirin)
- reductions in cardiovascular events with polypills with & without aspirin, with greater reductions for polypills including aspirin.[8]
FOCUS (Fixed-dose Combination Drug for Secondary Cardiovascular Prevention) Project
- polypill inproved medication compliance for secondary prevention of cardiovascular disease; improvement small[3]
NCT02596126 Secondary Prevention of Cardiovascular Disease[9]
- fixed-dose combination pills containing aspirin, a statin, ACE inhibitor
- improved outcomes in older patients with recent myocardial infarction[9]
More general terms
Components
- HMG CoA reductase inhibitor (statin)
- beta adrenergic receptor antagonist (beta-blocker)
- thiazide diuretic
- angiotensin-converting enzyme (ACE) inhibitor
- folic acid; folate; vitamin B9
- aspirin (Ecotrin, Empirin, Bayer aspirin, Vazalore, ASA)
References
- ↑ 1.0 1.1 Journal Watch 23(16):127, 2003 Wald NJ & Law MR, A strategy to reduce cardiovascular disease by more than 80%. BMJ 326:1419 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/12829553 <Internet> http://bmj.com/cgi/content/full/326/7404/1419
Law MR et al Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 326:1423 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/12829554 <Internet> http://bmj.com/cgi/content/full/326/7404/1423 Law MR et al Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ 326:1427 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/12829555 <Internet> http://bmj.com/cgi/content/full/326/7404/1427
Rodgers A et al A cure for cardiovascular disease? Combination treatment has enormous potential, especially in developing countries. BMJ 326:1407 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/12829526 <Internet> http://bmj.com/cgi/content/full/326/7404/1407 - ↑ Thom S et al Effects of a Fixed-Dose Combination Strategy on Adherence and Risk Factors in Patients With or at High Risk of CVD. The UMPIRE Randomized Clinical Trial. JAMA. 2013;310(9):918-929. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24002278 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1734704
Gaziano JM Progress With the Polypill? JAMA. 2013;310(9):910-911 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24002274 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1734680 - ↑ 3.0 3.1 Castellano JM et al. A polypill strategy to improve adherence: Results from FOCUS (Fixed-dose Combination Drug for Secondary Cardiovascular Prevention) Project. J Am Coll Cardiol 2014 Sep 1 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25193393
- ↑ 4.0 4.1 4.2 Roshandel G, Khoshnia M, Poustchi H et al Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial Lancet. vol 394, ISSUE 10199, P672-683, August 24, 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31448738 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31791-X/fulltext
- ↑ 5.0 5.1 5.2 Munoz D, Uzoije ), Reynolds C et al Polypill for Cardiovascular Disease Prevention in an Underserved Population. N Engl J Med 2019; 381:1114-1123. Sept 19, 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31532959 https://www.nejm.org/doi/full/10.1056/NEJMoa1815359
- ↑ Joyner MJ, Paneth N. Cardiovascular Disease Prevention at a Crossroads:Precision Medicine or Polypill? JAMA. Published online November 25, 2019. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31764938 https://jamanetwork.com/journals/jama/fullarticle/2756239
- ↑ 7.0 7.1 Yusuf S et al. Polypill with or without aspirin in persons without cardiovascular disease. N Engl J Med 2020 Nov 13; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/33186492 https://www.nejm.org/doi/10.1056/NEJMoa2028220
- ↑ 8.0 8.1 8.2 Joseph P, Roshandel G, Gao P et al. Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: An individual participant data meta-analysis. Lancet 2021 Aug 27; PMID: https://www.ncbi.nlm.nih.gov/pubmed/34469765 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01827-4/fulltext
- ↑ 9.0 9.1 9.2 Castellano JM et al. Polypill strategy in secondary cardiovascular prevention. N Engl J Med 2022 Aug 26; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36018037 https://www.nejm.org/doi/10.1056/NEJMoa2208275
Wang TJ. The polypill at 20 - What have we learned? N Engl J Med 2022 Aug 26; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/36018010 https://www.nejm.org/doi/10.1056/NEJMe2210020 - ↑ 10.0 10.1 Bosch JJ, O'Donnell MJ, Gao P et al Effects of a Polypill, Aspirin, and the Combination of Both on Cognitive and Functional Outcomes. A Randomized Clinical Trial. JAMA Neurol. Published online January 30, 2023. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36716007 https://jamanetwork.com/journals/jamaneurology/article-abstract/2800416