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

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 allcause and cardiovascular mortality were persistent, but attenuated, after discontinuation of randomized treatment, indicating the importance of continuing therapy.