Canagliflozin for Primary and Secondary Prevention of Cardiovascular Events: Results From the CANVAS Program (Canagliflozin Cardiovascular Assessment Study)
Kenneth W. Mahaffey,Bruce Neal,Vlado Perkovic,Dick de Zeeuw,Greg Fulcher,Ngozi Erondu,Wayne Shaw,Elisa Fabbrini,Tao Sun,Qiang Li,Mehul Desai,David R. Matthews +11 more
TLDR
Canagliflozin reduced cardiovascular and renal outcomes with no statistical evidence of heterogeneity of the treatment effect across the primary and secondary prevention groups.Abstract:
BACKGROUND : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that significantly reduces the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with type 2 diabetes mellitus and elevated cardiovascular risk. The comparative effects among participants with and without a history of cardiovascular disease (secondary versus primary prevention) were prespecified for evaluation. METHODS : The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) randomly assigned 10 142 participants with type 2 diabetes mellitus to canagliflozin or placebo. The primary prevention cohort comprised individuals ≥50 years of age with ≥2 risk factors for cardiovascular events but with no prior cardiovascular event, and the secondary prevention cohort comprised individuals ≥30 years of age with a prior cardiovascular event. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included heart failure hospitalization and a renal composite (40% reduction in estimated glomerular filtration rate, renal replacement therapy, or renal death). RESULTS : Primary prevention participants (N=3486; 34%) were younger (63 versus 64 years of age), were more often female (45% versus 31%), and had a longer duration of diabetes mellitus (14 versus 13 years) compared with secondary prevention participants (N=6656; 66%). The primary end point event rate was higher in the secondary prevention group compared with the primary prevention group (36.9 versus 15.7/1000 patient-years, P P P =0.02 for superiority) with no statistical evidence of heterogeneity (interaction P value=0.18) between the primary (HR, 0.98; 95% CI, 0.74-1.30) and secondary prevention (HR, 0.82; 95% CI, 0.72-0.95) cohorts. Renal outcomes (HR, 0.59; 95% CI, 0.44-0.79 versus HR, 0.63; 95% CI, 0.39-1.02; interaction P value=0.73) and heart failure hospitalization (HR, 0.68; 95% CI, 0.51-0.90 versus HR, 0.64; 95% CI, 0.35-1.15; interaction P value=0.91) were similarly reduced in the secondary and primary prevention cohorts, respectively. Lower extremity amputations were similarly increased in the secondary and primary prevention cohorts (HR, 2.07; 95% CI, 1.43-3.00 versus HR, 1.52; 95% CI, 0.70-3.29; interaction P value=0.63). CONCLUSIONS : Patients with type 2 diabetes mellitus and prior cardiovascular events had higher rates of cardiovascular outcomes compared with the primary prevention patients. Canagliflozin reduced cardiovascular and renal outcomes with no statistical evidence of heterogeneity of the treatment effect across the primary and secondary prevention groups. Additional studies will provide further insights into the effects of canagliflozin in these patient populations. CLINICAL TRIAL REGISTRATION : URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01032629 and NCT01989754.read more
Citations
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SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.
Thomas A Zelniker,Stephen D. Wiviott,Itamar Raz,KyungAh Im,Erica L. Goodrich,Marc P. Bonaca,Ofri Mosenzon,Eri Toda Kato,Avivit Cahn,Remo H.M. Furtado,Deepak L. Bhatt,Lawrence A. Leiter,Darren K. McGuire,John P.H. Wilding,Marc S. Sabatine +14 more
TL;DR: SGLT2i have moderate benefits on atherosclerotic major adverse cardiovascular events that seem confined to patients with established atheroscerotic cardiovascular disease, however, they have robust benefits on reducing hospitalisation for heart failure and progression of renal disease regardless of existing atherosclerosis or a history of heart failure.
Journal ArticleDOI
Canagliflozin and cardiovascular and renal events in type 2 diabetes.
TL;DR: The scope of S GLT-2 inhibitor therapy to prevent cardiovascular disease in diabetic patients beyond those with preexisting cardiovascular disease studied in the previous empagliflozin study is expanded, raising the question as to whether SGLT- 2 inhibitor therapy should be considered appropriate for most, if not all, type 2 diabetes patients.
Journal ArticleDOI
SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review
Subodh Verma,John J.V. McMurray +1 more
TL;DR: The role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function is focused on.
Journal ArticleDOI
Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology
Petar M. Seferovic,Mark C. Petrie,Gerasimos Filippatos,Stefan D. Anker,Giuseppe M.C. Rosano,Johann Bauersachs,Walter Paulus,Michel Komajda,Francesco Cosentino,Rudolf A. de Boer,Dimitrios Farmakis,Wolfram Doehner,Ekaterini Lambrinou,Yuri Lopatin,Massimo F Piepoli,Michael J. Theodorakis,Henrik Wiggers,John Lekakis,Alexandre Mebazaa,Mamas A. Mamas,Carsten Tschöpe,Arno W. Hoes,Jelena P. Seferovic,Jennifer Logue,Theresa McDonagh,Jillian P. Riley,Ivan Milinković,Marija Polovina,Dirk J. van Veldhuisen,Mitja Lainscak,Aldo P. Maggioni,Frank Ruschitzka,John J.V. McMurray +32 more
TL;DR: The coexistence of type 2 diabetes mellitus and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent and associated with a higher risk of HF hospitalization, all‐cause and cardiovascular (CV) mortality.
Journal ArticleDOI
Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL 2 Study
Mikhail Kosiborod,Carolyn S.P. Lam,Shun Kohsaka,Dae Jung Kim,Dae Jung Kim,Avraham Karasik,Jonathan E. Shaw,Navdeep Tangri,Su-Yen Goh,Marcus Thuresson,Hungta Chen,Filip Surmont,Niklas Hammar,Niklas Hammar,Peter Fenici +14 more
TL;DR: In this article, a randomized trial demonstrated a lower risk of cardiovascular events with SGLT-2 inhibitors in patients with type 2 diabetes (T2D) at high risk of adverse events.
References
More filters
Journal ArticleDOI
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.
Bernard Zinman,Christoph Wanner,John M. Lachin,David Fitchett,Erich Bluhmki,Stefan Hantel,Michaela Mattheus,Theresa Devins,Odd Erik Johansen,Hans-Juergen Woerle,Uli C. Broedl,Silvio E. Inzucchi +11 more
TL;DR: Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.
Journal ArticleDOI
Canagliflozin and cardiovascular and renal events in type 2 diabetes
Bruce Neal,Vlado Perkovic,Vlado Perkovic,Kenneth W. Mahaffey,Dick de Zeeuw,Greg Fulcher,Ngozi Erondu,Wayne Shaw,Gordon Law,Mehul Desai,David R. Matthews +10 more
TL;DR: Patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal.
Journal ArticleDOI
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Steven P. Marso,Gilbert H. Daniels,Kirstine Brown-Frandsen,Peter Lommer Kristensen,Johannes F.E. Mann,Michael A. Nauck,Steven E. Nissen,Stuart J. Pocock,Neil R Poulter,Lasse Steen Ravn,William M. Steinberg,Mette Stockner,Bernard Zinman,Richard M. Bergenstal,John B. Buse +14 more
TL;DR: In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, orNonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo.
Journal ArticleDOI
Global estimates of diabetes prevalence for 2013 and projections for 2035.
TL;DR: The new estimates of diabetes in adults confirm the large burden of diabetes, especially in developing countries, particularly in low- and middle-income countries.
Journal ArticleDOI
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.
Steven P. Marso,Stephen C. Bain,A. Consoli,Freddy G. Eliaschewitz,Esteban Jódar,Lawrence A. Leiter,Ildiko Lingvay,Julio Rosenstock,Jochen Seufert,Mark Warren,Vincent Woo,O Hansen,Anders G. Holst,Jonas Pettersson,Tina Vilsbøll +14 more
TL;DR: In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, orNonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semag lutide.