@article{22744,
  author = {Marre Michel and Hamet Pavel and Woodward Mark and Salam A. and Poulter Neil and Hirakawa Yoichiro and Atkins E. and Rodgers A and Chalmers J. and Cooper Mark and Harrap Stephen and Lees Kennedy and Liu Lisheng and Mancia Giuseppe and Williams Bryan and Perkovic Vlado},
  title = {Side effects and tolerability of combination blood pressure lowering according to blood pressure levels: an analysis of the PROGRESS and ADVANCE trials.},
  abstract = {<p>
<b>OBJECTIVE: </b>To measure the placebo-controlled effects of combination therapy on hypotension, treatment discontinuation, and major renal outcomes, according to baseline blood pressure.
</p>

<p>
<b>METHODS: </b>We conducted an analysis of the action in diabetes and vascular disease: preterax and diamicron-MR controlled evaluation ADVANCE and perindopril protection against recurrent stroke study PROGRESS trials, including 14 684 participants allocated combination therapy or placebo. The mean age was 65 years, 61% were men, and 64% were receiving background blood pressure lowering (BPL) therapy. Participants were stratified into five subgroups by baseline SBP less than 120, 120-129, 130-139, 140-159, and at least 160 mmHg. Discontinuation of study treatment during the active run-in phase and postrandomization follow-up was assessed for hypotension/dizziness and other causes. Major renal outcomes (sustained doubling in creatinine or renal death) were also assessed.
</p>

<p>
<b>RESULTS: </b>Discontinuation during the 4-6-week active run-in phase due to hypotension/dizziness ranged from 3.6% in those with SBP less than 120 mmHg to 1.3% in those with SBP at least 160 mmHg. Median follow-up in the randomized phase was 5.6 years, and discontinuation for hypotension was higher with combination therapy compared with placebo in the less than 120 mmHg group (4.7 vs. 1.2%). However, for each subgroup with baseline SBP 120-129, 130-139, and 140-159 mmHg, the absolute excess of discontinuation due to hypotension with combination therapy was 0.7%. Total discontinuations were only increased in the less than 120 mmHg group (18.4 vs. 12.5%) and the 120-129-mmHg subgroup (17.6 vs. 14.2%). There were no clear differences across the SBP subgroups for the combined renal outcome (overall, 0.8 vs. 0.6%).
</p>

<p>
<b>CONCLUSION: </b>Compared with those with baseline SBP 140-159 mmHg, side effects of dual combination BPL are essentially the same for people with SBP 130-139 mmHg and only modestly increased among patients with SBP 120-129 mmHg. During long-term therapy, side effects sufficient to stop treatment that are treatment related (i.e. occur in excess of rates seen with placebo) occur at less than 0.5%/year in patients with baseline SBP 120-139 mmHg. These results have important implications in assessing the likely balance of benefits and side effects of BPL with combination therapy among those with SBP 120-139 mmHg.
</p>
},
  year = {2017},
  journal = {J Hypertens},
  volume = {35},
  pages = {1318-1325},
  issn = {1473-5598},
  doi = {10.1097/HJH.0000000000001287},
  language = {eng},
}