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Cumulative in-trial and post-trial effects of blood pressure and lipid lowering: systematic review and meta-analysis

Hirakawa, Yoichiroa,*; Arima, Hisatomia,b,*; Rodgers, Anthonya; Woodward, Marka,c,d; Chalmers, Johna

doi: 10.1097/HJH.0000000000001233

Objective: Persistent long-term benefits after discontinuation of treatment have been suggested for blood pressure-lowering and lipid-lowering treatment. We conducted a systematic review to assess the long-term effects of blood pressure (BP) lowering (BPL) and lipid lowering on all-cause and cardiovascular mortality after discontinuation of randomized treatment.

Methods: We systematically searched Medline, Embase, and the Cochrane Central Register of Controlled Trials. We included large-scale randomized controlled trials of BPL or lipid lowering of at least 1 year with post-trial follow-up. We identified 13 BPL trials with 48 892 participants and 10 lipid-lowering trials with 71 370 participants. Mean in-trial and post-trial follow-up was approximately 4 and 6 years, respectively.

Results: BP and lipid levels tended to come together soon in the post-trial period. There was significant benefit of BPL on all-cause mortality during the in-trial period (relative risk 0.85, 95% confidence interval 0.81–0.89), and significant, but attenuated, benefit during overall follow-up (0.91, 0.87–0.94). Likewise, lipid lowering with statins reduced the risk of all-cause mortality during the in-trial period (0.88, 0.81–0.95), and this effect persisted during overall follow-up (0.92, 0.87–0.97). Similar findings were observed for cardiovascular death. In BPL trials, the cumulative reduction in all-cause mortality was significantly lower in trials with at least 5 years of post-trial follow-up compared with those with less than 5 years, and a similar tendency was observed for lipid-lowering trials.

Conclusion: Benefits of BPL and lipid lowering on all-cause and cardiovascular mortality were persistent, but attenuated, after discontinuation of randomized treatment, indicating the importance of continuing therapy.

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aThe George Institute for Global Health, University of Sydney, Sydney, Australia

bDepartment of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

cThe George Institute for Global Health, University of Oxford, Oxford, UK

dDepartment of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA

Correspondence to Prof John Chalmers, MD, PhD, The George Institute for Global Health, PO Box M201, Missenden Road, Camperdown 2050, NSW, Australia; University of Sydney, Sydney, Australia. Tel: +61 2 9993 4587; fax: +61 2 9993 4588; e-mail:

Abbreviations: 4S, Scandinavian Simvastatin Survival Study; AASK, African-American Study of Kidney Disease and Hypertension; ALERT, Assessment of Lescol in Renal Transplantation; ALLHAT-LLT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Lipid-Lowering Trial; ASCOT-LLA, Anglo-Scandinavian Cardiac Outcomes Trial Lipid-Lowering Arm; CI, confidence interval; HDFP, the Hypertension Detection and Follow-up Program; HOPE, the Heart Outcomes Prevention Evaluation; HPS, Heart Protection Study; HYVET, Hypertension in the Very Elderly Trial; LDLC, LDL cholesterol; LIPID, Long-term Intervention with Pravastatin Ischemic Disease; Post-CABG, Post-Coronary Artery Bypass Graft Trial; PREVEND-IT, Prevention of Renal and Vascular Endstage Disease Intervention Trial; PROSPER, Prospective Study of Pravastatin in the Elderly at Risk; RR, relative risk; SHEP, Systolic Hypertension in the Elderly Program; SOLVED, the Studies of Left Ventricular Dysfunction; SYST-EUR, Systolic Hypertension in Europe; TRACE, Trandolapril Cardiac Evaluation; UKPDS, the United Kingdom Prospective Diabetes Study; WOSCOPS, West of Scotland Coronary Prevention Study

Received 7 June, 2016

Revised 10 October, 2016

Accepted 1 December, 2016

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