Portal de Periódicos da CAPES

Heart failure event definitions in drug trials in patients with type 2 diabetes

2016; Elsevier BV; Volume: 4; Issue: 4 Linguagem: Inglês

10.1016/s2213-8587(16)00049-8

2213-8595

Abhinav Sharma, Deepak L. Bhatt, Gonzalo Calvo, Nancy J. Brown, Faı̈ez Zannad, Robert J. Mentz,

Cardiovascular Function and Risk Factors

In 2008, the US Food and Drug Administration (FDA) issued guidance for industry mandating that drug companies show that new drugs for the treatment of type 2 diabetes do not increase the risk of cardiovascular disease; 1 FDAGuidance for industry: diabetes mellitus—evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. US Food and Drug Administration, Silver Spring, MDDec, 2008http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071627.pdf Google Scholar however, this guidance focuses on cardiovascular death, myocardial infarction, and stroke, but not on heart failure. 2 McMurray JJV Gerstein HC Holman RR Pfeller MA Heart failure: a cardiovascular outcome in diabetes that can no longer be ignored. Lancet Diabetes Endocrinol. 2014; 2: 843-851 Summary Full Text Full Text PDF PubMed Scopus (258) Google Scholar Type 2 diabetes is independently associated with an increased risk of admission to hospital with heart failure. 3 Cavender MA Steg PG Smith SC et al. Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years from the Reduction of Atherothrombosis for Continued Health (REACH) Registry. Circulation. 2015; 132: 923-931 Crossref PubMed Scopus (331) Google Scholar Furthermore, heart failure caused by antidiabetic drugs has re-emerged as a concern because of the increased risk of admission to hospital with heart failure associated with the DPP-4 inhibitor saxagliptin. 4 Scirica BM Bhatt DL Braunwald E et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013; 369: 1317-1326 Crossref PubMed Scopus (2729) Google Scholar , 5 Scirica BM Braunwald E Raz I et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014; 130: 1579-1588 Crossref PubMed Scopus (533) Google Scholar , 6 Scirica BM Bhatt DL Braunwald E et al. The design and rationale of the saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction (SAVOR-TIMI) 53 study. Am Heart J. 2011; 162: 818-825 Summary Full Text Full Text PDF PubMed Scopus (94) Google Scholar Udell and colleagues 7 Udell JA Cavender MA Bhatt DL Chatterjee S Farkouh ME Scirica BM Glucose-lowering drugs or strategies and cardiovascular outcomes in patients with or at risk for type 2 diabetes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2015; 3: 356-366 Summary Full Text Full Text PDF PubMed Scopus (202) Google Scholar showed that glucose-lowering strategies might increase the risk of heart failure. 7 Udell JA Cavender MA Bhatt DL Chatterjee S Farkouh ME Scirica BM Glucose-lowering drugs or strategies and cardiovascular outcomes in patients with or at risk for type 2 diabetes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2015; 3: 356-366 Summary Full Text Full Text PDF PubMed Scopus (202) Google Scholar The American College of Cardiology and American Heart Association 8 Hicks KA Tcheng JE Bozkurt B et al. 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials. J Am Coll Cardiol. 2015; 66: 403-469 Summary Full Text Full Text PDF PubMed Scopus (355) Google Scholar define a heart failure event as worsening signs and symptoms of heart failure, signifying failure of the primary therapeutic management strategy, and resulting in escalation of therapy as an outpatient or requiring hospital admission. 8 Hicks KA Tcheng JE Bozkurt B et al. 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials. J Am Coll Cardiol. 2015; 66: 403-469 Summary Full Text Full Text PDF PubMed Scopus (355) Google Scholar However, specific definitions of heart failure events used in clinical trials of antidiabetic drugs have not been systematically assessed. In view of recent clinical trial results, we propose an update to existing criteria for heart failure events. This Comment is based on discussions among scientists, clinical trialists, industry sponsors, and regulatory representatives, which took place at the 11th Global Cardiovascular Clinical Trialists Forum (Washington DC, USA; Dec 5–7, 2014).