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Randomized Controlled Trial
. 2021 Aug 17;42(31):2995-3007.
doi: 10.1093/eurheartj/ehab225.

Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants

Jackie Bosch  1   2 , Eva M Lonn  1   3 , Hyejung Jung  1 , Jun Zhu  4 , Lisheng Liu  4 , Patricio Lopez-Jaramillo  5 , Prem Pais  6 , Denis Xavier  6   7 , Rafael Diaz  8 , Gilles Dagenais  9 , Antonio Dans  10 , Alvaro Avezum  11 , Leopoldo S Piegas  12 , Alexander Parkhomenko  13 , Kati Keltai  14 , Matyas Keltai  14 , Karen Sliwa  15 , Claus Held  16 , Ronald J G Peters  17 , Basil S Lewis  18 , Petr Jansky  19 , Khalid Yusoff  20   21 , Kamlesh Khunti  22 , William D Toff  23   24 , Christopher M Reid  25   26 , John Varigos  25 , Philip Joseph  1   2 , Lawrence A Leiter  27 , Salim Yusuf  1   2
Affiliations
Randomized Controlled Trial

Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants

Jackie Bosch et al. Eur Heart J. .

Abstract

Aims: Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated.

Methods and results: After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64-0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68-1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69-0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69-0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years.

Conclusion: The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect.

Trial registration number: NCT00468923.

Keywords: Cardiovascular disease; Statins; Primary prevention.

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Figures

None
Benefits of primary prevention may be greater than demonstrated from in trial data.
Figure 1
Figure 1
Participant disposition in HOPE-3. Cand, candesartan; HCTZ, hydrochlorothiazide.
Figure 2
Figure 2
Cumulative incidence of MACE-1 according to treatment arm for the entire length of follow-up (8.7 years). (A) Rosuvastatin vs. control. (B) Blood pressure lowering vs. control. (C) Combination therapy vs. control. CI, confidence interval; HR, hazard ratio.
Figure 3
Figure 3
Effect of rosuvastatin on MACE-1 in key subgroups (8.7 years of follow-up). CI, confidence interval; CRP, C-reactive protein; LDL, low-density lipoprotein cholesterol; SBP, systolic blood pressure.
Figure 4
Figure 4
Effect of blood pressure (BP) lowering on MACE-1 in key subgroups (8.7 years of follow-up). CI, confidence interval; CRP, C-reactive protein; DBP, diastolic blood pressure; HCTZ, hydrochlorothiazide; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure.
See this image and copyright information in PMC

Comment in

  • The legacy of HOPE-3.
    Boersma E, Kardys I. Boersma E, et al. Eur Heart J. 2021 Aug 17;42(31):3008-3010. doi: 10.1093/eurheartj/ehab208. Eur Heart J. 2021. PMID: 33956954 No abstract available.

References

    1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jimenez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB, American Heart Association Statistics Committee; Stroke Statistics Subcommittee. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 2016;133:e38–360. - PubMed
    1. Lonn E, Bosch J, Pogue J, Avezum A, Chazova I, Dans A, Diaz R, Fodor GJ, Held C, Jansky P, Keltai M, Keltai K, Kunti K, Kim JH, Leiter L, Lewis B, Liu L, Lopez-Jaramillo P, Pais P, Parkhomenko A, Peters RJ, Piegas LS, Reid CM, Sliwa K, Toff WD, Varigos J, Xavier D, Yusoff K, Zhu J, Dagenais G, Yusuf S, HOPE-3 Investigators. Novel approaches in primary cardiovascular disease prevention: the HOPE-3 trial rationale, design, and participants' baseline characteristics. Can J Cardiol 2016;32:311–318. - PubMed
    1. Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, Pais P, Lopez-Jaramillo P, Leiter LA, Dans A, Avezum A, Piegas LS, Parkhomenko A, Keltai K, Keltai M, Sliwa K, Peters RJ, Held C, Chazova I, Yusoff K, Lewis BS, Jansky P, Khunti K, Toff WD, Reid CM, Varigos J, Sanchez-Vallejo G, McKelvie R, Pogue J, Jung H, Gao P, Diaz R, Lonn E, HOPE-3 Investigators. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med 2016;374:2021–2031. - PubMed
    1. Lonn EM, Bosch J, Lopez-Jaramillo P, Zhu J, Liu L, Pais P, Diaz R, Xavier D, Sliwa K, Dans A, Avezum A, Piegas LS, Keltai K, Keltai M, Chazova I, Peters RJ, Held C, Yusoff K, Lewis BS, Jansky P, Parkhomenko A, Khunti K, Toff WD, Reid CM, Varigos J, Leiter LA, Molina DI, McKelvie R, Pogue J, Wilkinson J, Jung H, Dagenais G, Yusuf S, HOPE-3 Investigators. Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med 2016;374:2009–2020. - PubMed
    1. Khunti K, Kosiborod M, Ray KK. Legacy benefits of blood glucose, blood pressure and lipid control in individuals with diabetes and cardiovascular disease: time to overcome multifactorial therapeutic inertia? Diabetes Obes Metab 2018;20:1337–1341. - PubMed

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