Blood pressure and mortality in patients with type 2 diabetes and a recent coronary event in the ELIXA trial

Abstract

Background: The relationship between blood pressure and mortality in type 2 diabetes (T2DM) is controversial, with concern for increased risk associated with excessively lowered blood pressure.

Methods: We evaluated whether prior cardiovascular disease (CVD) altered the relationship between baseline blood pressure and all-cause mortality in 5852 patients with T2DM and a recent acute coronary syndrome (ACS) who participated in the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial. Risk of death was assessed in Cox models adjusted for age, sex, race, heart rate, BMI, smoking, diabetes duration, insulin use, HbA1c, eGFR, brain natriuretic peptide (BNP), urine albumin/creatinine ratio, treatment allocation and prior coronary revascularization.

Results: Although overall there was no significant association between systolic blood pressure (SBP) and mortality (hazard ratio per 10 mmHg lower SBP 1.05 (95% CI 0.99-1.12) P = 0.10), lower SBP was significantly associated with higher risk of death (hazard ratio per 10 mmHg lower SBP 1.13 (95% CI 1.04-1.22) P = 0.002) in 2325 patients with additional CVD (index ACS+ at least one of the following prior to randomization: myocardial infarction other than the index ACS, stroke or heart failure). In 3527 patients with only the index ACS no significant association was observed (hazard ratio per 10 mmHg lower SBP 0.95 (0.86-1.04) P = 0.26; P for interaction 0.005).

Conclusions: The association between blood pressure and mortality was modified by additional CVD history in patients with type 2 diabetes and a recent coronary event. When blood pressures measured after an acute coronary event are used to assess the risk of death in patients with type 2 diabetes, the cardiovascular history needs to be taken into consideration. Trial registration ClinicalTrials.gov number NCT01147250, first posted June 22, 2010.

Keywords: Blood pressure; Coronary artery disease; Diabetes mellitus.

Conflict of interest statement

MOW has served on advisory boards or lectured for MSD, Lilly, Novo Nordisk and Sanofi, and has organized a professional regional meeting sponsored by Lilly, Rubin Medical, Sanofi, Novartis and Novo Nordisk. BC has received consulting fees for Amgen, Biogen, Corvia, Myokardia, and Novartis. RD has received speaker fees from Sanofi, Astra Zeneca and Eli Lilly. HG holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care and reports research grants from Eli Lilly, AstraZeneca, Merck, Novo Nordisk and Sanofi; honoraria for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi; and consulting fees from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Janssen, Sanofi, and Kowa. LK has received speaker´s honorarium (personal fee) from AstraZeneca, Novartis and Boehringer, unrelated to this manuscript. EL has received institutional funding for research grant support from Sanofi and Akebia. APM has received personal fees from Bayer, Fresenius, Novartis for participating in study committees outside the present work. EW has received speaker fees from Orion Pharma, Novartis Healthcare, Boehringer-Ingelheim, Merck. MR has received research funding through Oregon Health & Science University: Eli Lilly, Novo Nordisk, AstraZeneca, and honoraria for consulting: Adocia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Intercept, Novo Nordisk, Sanofi, Theracos. JCT has received research grants from Amarin, Astra-Zeneca, DalCor, Esperion, Ionis, RegenXBio, Sanofi and Servier; honoraria from DalCor, Sanofi and Servier; holds minor equity interest in DalCor; and is an author of a patent on pharmacogenomics-guided CETP inhibition. SDS has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, Respicardia, Sanofi Pasteur, Theracos, and has consulted for Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GSK, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau. MAP receives research support from Novartis, serves as a consultant for AstraZeneca, Corvidia, DalCor, GlaxoSmithKline, Novartis, Novo Nordisk, Pharmascience and Sanofi, and has equity in DalCor.

Figures

Fig. 1

Baseline distributions of systolic (a) and diastolic (b) blood pressures. Grey bars show patients with index acute coronary syndrome (ACS) only (n = 3527). Blue bars show patients with additional cardiovascular disease (CVD) (n = 2325)

Fig. 2

Adjusted mortality rates and baseline blood pressures. Upper row: entire cohort, a systolic blood pressure, b diastolic blood pressure, c pulse pressure. Lower row: stratified by prior cardiovascular disease (CVD), d systolic blood pressure, e diastolic blood pressure, f  pulse pressure. Blue = Additional CVD, black = Index ACS only. P values for interaction: 0.005 (SBP), 0.004 (DBP), 0.12 (PP). Adjustments made for: randomization group, coronary revascularization history, age, sex, self-reported race, heart rate, BMI, smoking status, known duration of diabetes, glycated hemoglobin A1c, use of insulin, eGFR, the logarithm of the urinary albumin to creatinine ratio and the logarithm of the BNP level