Hypertension
Cardiovascular Events During Differing Hypertension Therapies in Patients With Diabetes

https://doi.org/10.1016/j.jacc.2010.02.046Get rights and content
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Objectives

The aim of this study was to determine which combination therapy in patients with hypertension and diabetes most effectively decreases cardiovascular events.

Background

The ACCOMPLISH (Avoiding Cardiovascular Events Through COMbination Therapy in Patients Living With Systolic Hypertension) trial compared the outcomes effects of a renin-angiotensin system blocker, benazepril, combined with amlodipine (B+A) or hydrochlorothiazide (B+H). A separate analysis in diabetic patients was pre-specified.

Methods

A total of 6,946 patients with diabetes were randomized to treatment with B+A or B+H. A subgroup of 2,842 diabetic patients at very high risk (previous cardiovascular or stroke events) was also analyzed, as were 4,559 patients without diabetes. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for angina, resuscitated arrest, and coronary revascularization.

Results

In the full diabetes group, the mean achieved blood pressures in the B+A and B+H groups were 131.5/72.6 and 132.7/73.7 mm Hg; during 30 months, there were 307 (8.8%) and 383 (11.0%) primary events (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.68 to 0.92, p = 0.003). For the diabetic patients at very high risk, there were 195 (13.6%) and 244 (17.3%) primary events (HR: 0.77, 95% CI: 0.64 to 0.93, p = 0.007). In the nondiabetic patients, there were 245 (10.8%) and 296 (12.9%) primary events (HR: 0.82, 95% CI: 0.69 to 0.97, p = 0.020). In the diabetic patients, there were clear coronary benefits with B+A, including both acute clinical events (p = 0.013) and revascularizations (p = 0.024). There were no unexpected adverse events.

Conclusions

In patients with diabetes and hypertension, combining a renin-angiotensin system blocker with amlodipine, compared with hydrochlorothiazide, was superior in reducing cardiovascular events and could influence future management of hypertension in patients with diabetes. (Avoiding Cardiovascular Events Through COMbination Therapy in Patients Living With Systolic Hypertension [ACCOMPLISH]; NCT00170950)

Key Words

amlodipine
coronary events
diabetes
hydrochlorothiazide
hypertension

Abbreviations and Acronyms

ACE
angiotensin-converting enzyme
B+A
benazepril plus amlodipine
B+H
benazepril plus hydrochlorothiazide
HR
hazard ratio
RAS
renin-angiotensin system

Cited by (0)

This study was supported financially by Novartis, who also provided logistical and statistical support and expertise (based on the analysis plans of the academic authors). Dr. Weber receives lecture fees from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Forest Pharmaceuticals, GlaxoSmithKline, Novartis, and Sanofi-Aventis; and consultant fees from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Forest Pharmaceuticals, GlaxoSmithKline, Gilead, Novartis, and Takeda Pharmaceuticals. Dr. Bakris receives consulting fees from Merck, Takeda, Boehringer-Ingelheim, Abbott Laboratories, Walgreen's, BMS/Sanofi, Gilead, Novartis, Forest Pharmaceuticals, GlaxoSmithKline, and Daiichi Sankyo; lecture fees from Novartis and Forest Pharmaceuticals; and grant support from GlaxoSmithKline, Juvenile Diabetes Research Foundation, Forest Labs, and CVRx. Dr. Jamerson receives consulting fees from Novartis, Merck, and Daiichi Sankyo; lecture fees from Novartis, Abbott Laboratories, Bristol-Myers Squibb, GlaxoSmithKline, and Merck; and research support from NIH, NIDDK, NHLBI, Novartis, and King Pharmaceuticals. Dr. Weir serves as scientific advisor for Amgen, Nicox, Novartis, Boehringer Ingelheim, Sanofi, Bristol-Myers Squibb, Daiichi Sankyo, and Johnson & Johnson. Dr. Kjeldsen receives lecture fees from Novartis, AstraZeneca, Bayer, Boehringer-Ingelheim, Menarini, Merck, Sankyo, Sanofi, Servier, and Takeda. Dr. Devereux serves on an advisory board for Merck and has received lecture fees from Merck within the past 2 years; during the same time period, he has served as a consultant for Novartis, Sanofi-Aventis, Novo Nordisk Pharmaceuticals, and Neurosearch. Dr. Velazquez receives consulting and lecture fees from Novartis, Cardio-Kinetix, NovaCardia, and Medtronic Foundation. Dr. Dahlöf receives consulting fees from Novartis, Daiichi Sankyo, and Boehringer Ingelheim and lecture fees from Novartis, Boehringer Ingelheim, Pfizer, and Merck. Roxzana Kelly, Tsushung Hua, and Allen Hester are employed by Novartis Pharmaceuticals. Dr. Pitt receives consulting fees from Novartis, Pfizer, Merck, Takeda, Bayer, Forest Laboratories, Sankyo, Ono, and AstraZeneca; has stock options from Relypsa, BG-Medicine, and Nile Therapeutics; and has received grants from Medtronic, Bayer, Novartis, and Abbott Laboratories.