Side effects and tolerability of combination blood pressure lowering according to blood pressure levels: an analysis of the perindopril protection against recurrent stroke study and action in diabetes and vascular disease: preterax and diamicron-MR controlled evaluation trials

Atkins, E. R. et al. (2017) Side effects and tolerability of combination blood pressure lowering according to blood pressure levels: an analysis of the perindopril protection against recurrent stroke study and action in diabetes and vascular disease: preterax and diamicron-MR controlled evaluation trials. Journal of Hypertension, 35(6), pp. 1318-1325. (doi: 10.1097/HJH.0000000000001287) (PMID:28169881)

Abstract

Objective: To measure the placebo-controlled effects of combination therapy on hypotension, treatment discontinuation, and major renal outcomes, according to baseline blood pressure. Methods: We conducted an analysis of the action in diabetes and vascular disease: preterax and diamicron-MR controlled evaluation and perindopril protection against recurrent stroke study 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. Results: 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%). Conclusion: 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lees, Professor Kennedy and Woodward, Professor Mark
• Authors: Atkins, E. R., Hirakawa, Y., Salam, A., Woodward, M., Cooper, M., Hamet, P., Harrap, S., Lees, K., Liu, L., Mancia, G., Marre, M., Perkovic, V., Poulter, N., Williams, B., Chalmers, J., and Rodgers, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of Hypertension
• Publisher: Lippincott Williams & Wilkins
• ISSN: 0263-6352
• ISSN (Online): 1473-5598
• Published Online: 06 February 2017