S84 Cardiovascular Disease and Risk Management Diabetes Care Volume 40, Supplement 1, January 2017

patient has hypertension, unless there with the placebo group (3.1%; 1.09 per primary outcome (MI, stroke, or cardiovas-
are contraindications to a particular 100 person-years) (118). cular death) occurred in fewer participants
drug class. While clear benet exists in the treatment group (13.0%) when com-
for ACE inhibitor and ARB therapy in pa- Antihyperglycemic Therapies and pared with the placebo group (14.9%) after
tients with nephropathy or hyperten- Cardiovascular Outcomes a median follow-up of 3.8 years (120).
sion, the benets in patients with Recently published cardiovascular out- Whether other glucagon-like peptide 1 re-
ASCVD in the absence of these condi- come trials have provided additional ceptor agonists will have the same effect
tions are less clear, especially when data on cardiovascular outcomes in in high-risk patients or if this drug class
LDL cholesterol is concomitantly con- patients with type 2 diabetes with car- will have similar effects in lower-risk pa-
trolled (109,110). In patients with prior diovascular disease or at high risk for tients with diabetes remains unknown.
MI, b-blockers should be continued for cardiovascular disease. The BI 10773
at least 2 years after the event (111). (Empagliozin) Cardiovascular Outcome References
Event Trial in Type 2 Diabetes Mellitus 1. Ali MK, Bullard KM, Saaddine JB, Cowie CC,
Patients (EMPA-REG OUTCOME) was a Imperatore G, Gregg EW. Achievement of goals
Diabetes and Heart Failure in U.S. diabetes care, 1999-2010. N Engl J Med
As many as 50% of patients with type 2 randomized, double-blind trial that 2013;368:16131624
diabetes may develop heart failure (112). assessed the effect of empagliozin, a 2. Buse JB, Ginsberg HN, Bakris GL, et al.; American
Data on the effects of glucose-lowering sodiumglucose cotransporter 2 (SGLT2) Heart Association; American Diabetes Association.
agents on heart failure outcomes have inhibitor, versus placebo and standard Primary prevention of cardiovascular diseases in
care on cardiovascular outcomes in pa- people with diabetes mellitus: a scientic state-
demonstrated that thiazolidinediones ment from the American Heart Association and
have a strong and consistent relation- tients with type 2 diabetes and existing the American Diabetes Association. Diabetes Care
ship with heart failure (113115). There- cardiovascular disease. Study partici- 2007;30:162172
fore, thiazolidinedione use should be pants had a mean age of 63 years, 57% 3. Gaede P, Lund-Andersen H, Parving H-H,
had diabetes for more than 10 years, and Pedersen O. Effect of a multifactorial interven-
avoided in patients with symptomatic tion on mortality in type 2 diabetes. N Engl J
heart failure. 99% had established cardiovascular dis-
Med 2008;358:580591
Recent studies have also examined ease. EMPA-REG OUTCOME showed that 4. Centers for Disease Control and Prevention
the relationship between dipeptidyl over a median follow-up of 3.1 years, (CDC), National Center for Health Statistics,
peptidase 4 (DPP-4) inhibitors and heart treatment reduced the composite out- Division of Health Care Statistics. Crude and
come of MI, stroke, and cardiovascular age-adjusted hospital discharge rates for major
failure and have had mixed results. The cardiovascular disease as rst-listed diagnosis
Saxagliptin Assessment of Vascular Out- death by 14% (absolute rate 10.5% vs.
per 1,000 diabetic population, United States,
12.1% in the placebo group) and cardio- 19882006 [Internet]. Available from http://
comes Recorded in Patients with Diabetes
vascular death by 38% (absolute rate www.cdc.gov/diabetes/statistics/cvdhosp/cvd/
MellitusThrombolysis in Myocardial In-
3.7% vs. 5.9%) (119). The FDA recently g3.htm. Accessed 27 August 2015
farction 53 (SAVOR-TIMI 53) study showed 5. de Boer I, Bangalore S, Benetos A, et al. Diabetes
added a new indication for empagliozin,
that patients treated with saxagliptin and hypertension: a position statement of the
to reduce the risk of cardiovascular death American Diabetes Association. Diabetes Care.
(a DPP-4 inhibitor) were more likely to
in adults with type 2 diabetes and cardio- In press
be hospitalized for heart failure than
vascular disease. Whether other SGLT2 6. Bobrie G, Gene` s N, Vaur L, et al. Is isolated
were those given placebo (3.5% vs. 2.8%, home hypertension as opposed to isolated
inhibitors will have the same effect in
respectively) (116). Two other recent ofce hypertension a sign of greater cardiovascu-
high-risk patients and whether empaglio-
multicenter, randomized, double-blind, lar risk? Arch Intern Med 2001;161:22052211
zin or other SGLT2 inhibitors will have a 7. Sega R, Facchetti R, Bombelli M, et al. Prog-
noninferiority trials, Examination of Car- similar effect in lower-risk patients with nostic value of ambulatory and home blood
diovascular Outcomes with Alogliptin diabetes remains unknown. pressures compared with ofce blood pressure
versus Standard of Care (EXAMINE) and The Liraglutide Effect and Action in Di- in the general population: follow-up results
Trial Evaluating Cardiovascular Out- abetes: Evaluation of Cardiovascular Out- from the Pressioni Arteriose Monitorate e
comes with Sitagliptin (TECOS), did not Loro Associazioni (PAMELA) study. Circulation
come ResultsdA Long Term Evaluation 2005;111:17771783
show associations between DPP-4 inhib- (LEADER) trial was a randomized, double- 8. Lewington S, Clarke R, Qizilbash N, Peto R,
itor use and heart failure. EXAMINE re- blind trial that assessed the effect of Collins R; Prospective Studies Collaboration.
ported that the hospital admission rate liraglutide, a glucagon-like peptide 1 recep- Age-specic relevance of usual blood pressure
for heart failure was 3.1% for patients to vascular mortality: a meta-analysis of individ-
tor agonist, versus placebo and standard
randomly assigned to alogliptin com- ual data for one million adults in 61 prospective
care on cardiovascular outcomes in patients studies. Lancet 2002;360:19031913
pared with 2.9% for those randomly as- with type 2 diabetes at high risk for cardio- 9. Emdin CA, Rahimi K, Neal B, Callender T,
signed to placebo (hazard ratio 1.07 vascular disease or with cardiovascular dis- Perkovic V, Patel A. Blood pressure lowering in
[95% CI 0.791.46]) (117). Alogliptin had ease. Study participants had a mean age of type 2 diabetes: a systematic review and meta-
no effect on the composite end point of analysis. JAMA 2015;313:603615
64 years and a mean duration of diabetes of 10. Arguedas JA, Leiva V, Wright JM. Blood
cardiovascular death and hospital admis- nearly 13 years. Over 80% of study partici- pressure targets for hypertension in people
sion for heart failure in the post hoc anal- pants had established cardiovascular dis- with diabetes mellitus. Cochrane Database
ysis (hazard ratio 1.00 [95% CI 0.821.21]) ease inclusive of a prior MI, prior stroke Syst Rev 2013;10:CD008277
(117). TECOS showed a nonsignicant dif- or transient ischemic attack, prior revascu- 11. James PA, Oparil S, Carter BL, et al. 2014 evi-
dence-based guideline for the management of high
ference in the rate of heart failure hospi- larization procedure, or $50% stenosis of blood pressure in adults: report from the panel
talization for the sitagliptin group (3.1%; coronary, carotid, or lower-extremity ar- members appointed to the Eighth Joint National
1.07 per 100 person-years) compared teries. LEADER showed that the composite Committee (JNC 8). JAMA 2014;311:507520