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SAN DIEGO – No adverse interaction occurred between the dipeptidyl peptidase–4 inhibitor alogliptin and ACE inhibitors in patients with high cardiovascular risk and type 2 diabetes enrolled in the EXAMINE trial.
This is reassuring news that puts to rest concerns that patients on these two classes of medications might experience an increase in cardiovascular events, Dr. Christopher P. Cannon said at the annual meeting of the American College of Cardiology.
These concerns arose from evidence suggesting the possibility that DPP-4 inhibition in the presence of higher-dose ACE inhibitor therapy might activate the sympathetic nervous system through an increase in substance P, with a resultant elevated risk of serious cardiovascular events.
This hypothesis was tested in a secondary analysis of the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) trial. In EXAMINE, 5,380 patients with type 2 diabetes and a history of an acute coronary syndrome within the previous 90 days were randomized in a double-blind fashion to oral alogliptin (Nesina) or placebo on top of standard guideline-directed medical therapy for type 2 diabetes and cardiovascular risk factors. They were prospectively followed for a median of 18 months and a maximum of 40 months.
The primary results of EXAMINE have been reported previously: Among patients with type 2 diabetes and a recent acute coronary syndrome, major adverse cardiovascular events weren’t increased with agoliptin, compared with placebo (N. Engl. J. Med. 2013;369:1327-35). But because of subsequent theoretical safety questions raised about dual therapy with agoliptin and an ACE inhibitor – and in light of the fact that 3,323 participants in EXAMINE were on background ACE inhibitor therapy – the investigators decided to perform this new secondary analysis, according to Dr. Cannon, professor of medicine at Harvard Medical School, Boston.
The composite primary endpoint comprised of cardiovascular death, nonfatal MI, and nonfatal stroke occurred in 11.4% of subjects on alogliptin plus an ACE inhibitor, compared with 11.8% of those on placebo plus an ACE inhibitor, 11.2% of patients on alogliptin without an ACE inhibitor, and 11.9% of those not on alogliptin or an ACE inhibitor.
The secondary composite endpoint of cardiovascular death or hospitalization for heart failure occurred in 6.8% of patients on alogliptin and an ACE inhibitor, 7.2% of those on placebo plus an ACE inhibitor, 8.5% of subjects on alogliptin but no ACE inhibitor, and 8.0% of those on neither – again, with no significant differences.
The EXAMINE trial was funded by Takeda Pharmaceuticals. Dr. Cannon reported serving as a consultant to that company and numerous other pharmaceutical companies.
SAN DIEGO – No adverse interaction occurred between the dipeptidyl peptidase–4 inhibitor alogliptin and ACE inhibitors in patients with high cardiovascular risk and type 2 diabetes enrolled in the EXAMINE trial.
This is reassuring news that puts to rest concerns that patients on these two classes of medications might experience an increase in cardiovascular events, Dr. Christopher P. Cannon said at the annual meeting of the American College of Cardiology.
These concerns arose from evidence suggesting the possibility that DPP-4 inhibition in the presence of higher-dose ACE inhibitor therapy might activate the sympathetic nervous system through an increase in substance P, with a resultant elevated risk of serious cardiovascular events.
This hypothesis was tested in a secondary analysis of the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) trial. In EXAMINE, 5,380 patients with type 2 diabetes and a history of an acute coronary syndrome within the previous 90 days were randomized in a double-blind fashion to oral alogliptin (Nesina) or placebo on top of standard guideline-directed medical therapy for type 2 diabetes and cardiovascular risk factors. They were prospectively followed for a median of 18 months and a maximum of 40 months.
The primary results of EXAMINE have been reported previously: Among patients with type 2 diabetes and a recent acute coronary syndrome, major adverse cardiovascular events weren’t increased with agoliptin, compared with placebo (N. Engl. J. Med. 2013;369:1327-35). But because of subsequent theoretical safety questions raised about dual therapy with agoliptin and an ACE inhibitor – and in light of the fact that 3,323 participants in EXAMINE were on background ACE inhibitor therapy – the investigators decided to perform this new secondary analysis, according to Dr. Cannon, professor of medicine at Harvard Medical School, Boston.
The composite primary endpoint comprised of cardiovascular death, nonfatal MI, and nonfatal stroke occurred in 11.4% of subjects on alogliptin plus an ACE inhibitor, compared with 11.8% of those on placebo plus an ACE inhibitor, 11.2% of patients on alogliptin without an ACE inhibitor, and 11.9% of those not on alogliptin or an ACE inhibitor.
The secondary composite endpoint of cardiovascular death or hospitalization for heart failure occurred in 6.8% of patients on alogliptin and an ACE inhibitor, 7.2% of those on placebo plus an ACE inhibitor, 8.5% of subjects on alogliptin but no ACE inhibitor, and 8.0% of those on neither – again, with no significant differences.
The EXAMINE trial was funded by Takeda Pharmaceuticals. Dr. Cannon reported serving as a consultant to that company and numerous other pharmaceutical companies.
SAN DIEGO – No adverse interaction occurred between the dipeptidyl peptidase–4 inhibitor alogliptin and ACE inhibitors in patients with high cardiovascular risk and type 2 diabetes enrolled in the EXAMINE trial.
This is reassuring news that puts to rest concerns that patients on these two classes of medications might experience an increase in cardiovascular events, Dr. Christopher P. Cannon said at the annual meeting of the American College of Cardiology.
These concerns arose from evidence suggesting the possibility that DPP-4 inhibition in the presence of higher-dose ACE inhibitor therapy might activate the sympathetic nervous system through an increase in substance P, with a resultant elevated risk of serious cardiovascular events.
This hypothesis was tested in a secondary analysis of the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) trial. In EXAMINE, 5,380 patients with type 2 diabetes and a history of an acute coronary syndrome within the previous 90 days were randomized in a double-blind fashion to oral alogliptin (Nesina) or placebo on top of standard guideline-directed medical therapy for type 2 diabetes and cardiovascular risk factors. They were prospectively followed for a median of 18 months and a maximum of 40 months.
The primary results of EXAMINE have been reported previously: Among patients with type 2 diabetes and a recent acute coronary syndrome, major adverse cardiovascular events weren’t increased with agoliptin, compared with placebo (N. Engl. J. Med. 2013;369:1327-35). But because of subsequent theoretical safety questions raised about dual therapy with agoliptin and an ACE inhibitor – and in light of the fact that 3,323 participants in EXAMINE were on background ACE inhibitor therapy – the investigators decided to perform this new secondary analysis, according to Dr. Cannon, professor of medicine at Harvard Medical School, Boston.
The composite primary endpoint comprised of cardiovascular death, nonfatal MI, and nonfatal stroke occurred in 11.4% of subjects on alogliptin plus an ACE inhibitor, compared with 11.8% of those on placebo plus an ACE inhibitor, 11.2% of patients on alogliptin without an ACE inhibitor, and 11.9% of those not on alogliptin or an ACE inhibitor.
The secondary composite endpoint of cardiovascular death or hospitalization for heart failure occurred in 6.8% of patients on alogliptin and an ACE inhibitor, 7.2% of those on placebo plus an ACE inhibitor, 8.5% of subjects on alogliptin but no ACE inhibitor, and 8.0% of those on neither – again, with no significant differences.
The EXAMINE trial was funded by Takeda Pharmaceuticals. Dr. Cannon reported serving as a consultant to that company and numerous other pharmaceutical companies.
AT ACC 15
Key clinical point: Concomitant use of an ACE inhibitor and alogliptin by patients with type 2 diabetes and high cardiovascular risk isn’t associated with an increase in serious cardiovascular events.
Major finding: Patients on alogliptin and an ACE inhibitor had an 11.4% incidence of cardiovascular death or nonfatal MI or stroke during a median 18 months’ follow-up, while those on an ACE inhibitor plus placebo rather than alogliptin had a statistically similar 11.8% rate.
Data source: A secondary analysis of the 5,380-patient, randomized double-blind EXAMINE trial.
Disclosures: The EXAMINE trial was sponsored by Takeda Pharmaceuticals. The presenter serves as a consultant to Takeda and numerous other pharmaceutical companies.
