Salim Yusuf1, Philip Joseph1, Antonio Dans1, Peggy Gao1, Koon Teo1, Denis Xavier1, Patricio López-Jaramillo1, Khalid Yusoff1, Anwar Santoso1, Habib Gamra1, Shamim Talukder1, Courtney Christou1, Preeti Girish1, Karen Yeates1, Freeda Xavier1, Gilles Dagenais1, Catalina Rocha1, Tara McCready1, Jessica Tyrwhitt1, Jackie Bosch1, Prem Pais1. 1. From the Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON (S.Y., P.J., P. Gao, K.T., C.C., T.M., J.T., J.B.), Queen's University, Kingston, ON (K. Yeates), and Université Laval Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, QC (G.D.) - all in Canada; the University of the Philippines, Manila (A.D.); St. John's Medical College, Bangalore, India (D.X., P. Girish, F.X., P.P.); Fundación Oftalmológica de Santander, Universidad de Santander, Bucaramanga, Colombia (P.L.-J., C.R.); Universiti Teknologi MARA Selayang, Selangor, and UCSI University, Cheras, Kuala Lumpur - both in Malaysia (K. Yusoff); Universitas Indonesia, National Cardiovascular Center, Jakarta (A.S.); Fattouma Bourguiba Hospital and University of Monastir, Monastir, Tunisia (H.G.); and Eminence, Dhaka, Bangladesh (S.T.).
Abstract
BACKGROUND: A polypill comprising statins, multiple blood-pressure-lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. METHODS: Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive apolypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed. RESULTS: A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups. CONCLUSIONS: Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437.).
RCT Entities:
BACKGROUND: A polypill comprising statins, multiple blood-pressure-lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. METHODS: Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed. RESULTS: A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups. CONCLUSIONS: Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437.).
Authors: Peter S Sever; Björn Dahlöf; Neil R Poulter; Hans Wedel; Gareth Beevers; Mark Caulfield; Rory Collins; Sverre E Kjeldsen; Arni Kristinsson; Gordon T McInnes; Jesper Mehlsen; Markku Nieminen; Eoin O'Brien; Jan Ostergren Journal: Lancet Date: 2003-04-05 Impact factor: 79.321
Authors: Eva Lonn; Salim Yusuf; Malcolm J Arnold; Patrick Sheridan; Janice Pogue; Mary Micks; Matthew J McQueen; Jeffrey Probstfield; George Fodor; Claes Held; Jacques Genest Journal: N Engl J Med Date: 2006-03-12 Impact factor: 91.245
Authors: Salim Yusuf; Eva Lonn; Prem Pais; Jackie Bosch; Patricio López-Jaramillo; Jun Zhu; Denis Xavier; Alvaro Avezum; Lawrence A Leiter; Leopoldo S Piegas; Alexander Parkhomenko; Matyas Keltai; Katalin Keltai; Karen Sliwa; Irina Chazova; Ron J G Peters; Claes Held; Khalid Yusoff; Basil S Lewis; Petr Jansky; Kamlesh Khunti; William D Toff; Christopher M Reid; John Varigos; Jose L Accini; Robert McKelvie; Janice Pogue; Hyejung Jung; Lisheng Liu; Rafael Diaz; Antonio Dans; Gilles Dagenais Journal: N Engl J Med Date: 2016-04-02 Impact factor: 91.245
Authors: Salim Yusuf; Jackie Bosch; Gilles Dagenais; Jun Zhu; Denis Xavier; Lisheng Liu; Prem Pais; Patricio López-Jaramillo; Lawrence A Leiter; Antonio Dans; Alvaro Avezum; Leopoldo S Piegas; Alexander Parkhomenko; Katalin Keltai; Matyas Keltai; Karen Sliwa; Ron J G Peters; Claes Held; Irina Chazova; Khalid Yusoff; Basil S Lewis; Petr Jansky; Kamlesh Khunti; William D Toff; Christopher M Reid; John Varigos; Gregorio Sanchez-Vallejo; Robert McKelvie; Janice Pogue; Hyejung Jung; Peggy Gao; Rafael Diaz; Eva Lonn Journal: N Engl J Med Date: 2016-04-02 Impact factor: 91.245
Authors: Brian R Lindman; Devraj Sukul; Marc R Dweck; Mahesh V Madhavan; Benoit J Arsenault; Megan Coylewright; W David Merryman; David E Newby; John Lewis; Frank E Harrell; Michael J Mack; Martin B Leon; Catherine M Otto; Philippe Pibarot Journal: J Am Coll Cardiol Date: 2021-12-07 Impact factor: 24.094
Authors: Alan P Jacobsen; Zi Lun Lim; Blair Chang; Kaleb D Lambeth; Thomas M Das; Colin Gorry; Michael McCague; Faisal Sharif; Darren Mylotte; William Wijns; Patrick W J C Serruys; Roger S Blumenthal; Seth S Martin; John W McEvoy Journal: J Am Heart Assoc Date: 2022-04-12 Impact factor: 6.106