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polypill (Polycap)

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 1) reduce heart disease by 88% 2) reduce stroke by 80% 3) 1/3 of people > 55 would benefit 4) 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) a statin b) 3 antihypertensive agents (each at 1/2 standard dose) - beta blocker - thiazide diuretic - ACE inhibitor c) low dose aspirin d) folic acid included in an early version e) later version contains beta-blocker or thiazide diuretic f) 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: - primry prevention in 5713 participants - intermediate CV risk but no known CVD - median 4.6 years - 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 TIPS-3 trial [10] - 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]

Interactions

drug interactions

General

pharmacologic combination

References

  1. Journal Watch 23(16):127, 2003 Wald NJ & Law MR, A strategy to reduce cardiovascular disease by more than 80%. BMJ 326:1419 PMID: 12829553 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 PMID: 12829554 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 PMID: 12829555 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 PMID: 12829526 http://bmj.com/cgi/content/full/326/7404/1407
  2. 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. PMID: 24002278 http://jama.jamanetwork.com/article.aspx?articleid=1734704 - Gaziano JM Progress With the Polypill? JAMA. 2013;310(9):910-911 PMID: 24002274 http://jama.jamanetwork.com/article.aspx?articleid=1734680
  3. 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: 25193393
  4. 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: 31448738 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31791-X/fulltext
  5. 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: 31532959 https://www.nejm.org/doi/full/10.1056/NEJMoa1815359
  6. Joyner MJ, Paneth N. Cardiovascular Disease Prevention at a Crossroads:Precision Medicine or Polypill? JAMA. Published online November 25, 2019. PMID: 31764938 https://jamanetwork.com/journals/jama/fullarticle/2756239
  7. Yusuf S et al. Polypill with or without aspirin in persons without cardiovascular disease. N Engl J Med 2020 Nov 13; [e-pub] PMID: 33186492 https://www.nejm.org/doi/10.1056/NEJMoa2028220
  8. 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: 34469765 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01827-4/fulltext
  9. Castellano JM et al. Polypill strategy in secondary cardiovascular prevention. N Engl J Med 2022 Aug 26; [e-pub]. PMID: 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: 36018010 https://www.nejm.org/doi/10.1056/NEJMe2210020
  10. 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: 36716007 https://jamanetwork.com/journals/jamaneurology/article-abstract/2800416

Components

angiotensin-converting enzyme (ACE) inhibitor aspirin (Ecotrin, Empirin, Bayer aspirin, Vazalore, ASA) beta adrenergic receptor antagonist (beta-blocker) folic acid; folate; vitamin B9 HMG CoA reductase inhibitor (statin) thiazide diuretic