Heart failure hospitalization with DPP-4 inhibitors: A systematic review and meta-analysis of randomized controlled trials
Background: Heart failure hospitalization (hHF) with dipeptyl-dipeptidase-4 inhibitors (DPP-4Is) remains at the center stage since the publication of Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus – Thrombolysis in Myocardial Infarction (SAVOR-TIMI) in 2013 s...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2019-01-01
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| Series: | Indian Journal of Endocrinology and Metabolism |
| Subjects: | |
| Online Access: | http://www.ijem.in/article.asp?issn=2230-8210;year=2019;volume=23;issue=1;spage=128;epage=133;aulast=Singh |
| _version_ | 1818408701246046208 |
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| author | Awadhesh Kumar Singh Ritu Singh |
| author_facet | Awadhesh Kumar Singh Ritu Singh |
| author_sort | Awadhesh Kumar Singh |
| collection | DOAJ |
| description | Background: Heart failure hospitalization (hHF) with dipeptyl-dipeptidase-4 inhibitors (DPP-4Is) remains at the center stage since the publication of Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus – Thrombolysis in Myocardial Infarction (SAVOR-TIMI) in 2013 showing significant increase with saxagliptin, compared to placebo. This outcome led to additional label of hHF to both saxagliptin and alogliptin in April 2016 and eventual labelling of hHF to all the four approved DPP-4Is in United States in August 2017, by US Food Drug Administration. To note, neither Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), nor Cardiovascular and Renal Microvascular Outcome Study with Linagliptin (CARMELINA), showed any signals of hHF with these two agents. These developments have seriously generated an uncertainty among clinicians with regards to hHF effect of DPP-4Is in type 2 diabetic patients with high risk of cardiovascular (CV) disease. Aims and Objectives: We systematically searched the database of PubMed, Embase, Cochrane Central library, ClinicalTrials.gov, and International conference presentation from the inception up to October 25, 2018 using MeSH and specific key words. We retrieved all those studies that explicitly looked for hHF as a prespecified end point and were conducted for ≥52 weeks. Subsequently, we conducted the meta-analysis using comprehensive meta-analysis software Version 3, using different sensitivity analysis to study the effect of DPP-4Is on hHF in both dedicated CV outcome trials as well as randomized controlled trials. Results: The meta-analysis of four exclusive dedicated CV outcome trials (N = 43,522) did not find significant increase in hHF with DPP-4 inhibitors (Fixed model Relative Risk [RR] 1.06; 95% Confidence Interval [CI], 0.96-1.17; P = 0.25; I2: 53.95%, tau2: 0.012, P = 0.089). Meta-analysis of all randomized controlled trials that explicitly looked for hHF for ≥52 weeks (N = 48,199) also did not show any significant increase in hHF (fixed model peto odds ratio 1.05; 95% CI 0.95–1.15, P = 0.36; I2: 43.74%, tau2: 0.016, P = 0.10). Conclusions: This meta-analysis suggests no significant increase in hHF with DPP-4 inhibitors, although a nonsignificant heterogeneity across the trials might limit this observation. |
| first_indexed | 2024-12-14T09:47:55Z |
| format | Article |
| id | doaj.art-28c196005e054e909e23d5d1629ec520 |
| institution | Directory Open Access Journal |
| issn | 2230-8210 |
| language | English |
| last_indexed | 2024-12-14T09:47:55Z |
| publishDate | 2019-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Indian Journal of Endocrinology and Metabolism |
| spelling | doaj.art-28c196005e054e909e23d5d1629ec5202022-12-21T23:07:35ZengWolters Kluwer Medknow PublicationsIndian Journal of Endocrinology and Metabolism2230-82102019-01-0123112813310.4103/ijem.IJEM_613_18Heart failure hospitalization with DPP-4 inhibitors: A systematic review and meta-analysis of randomized controlled trialsAwadhesh Kumar SinghRitu SinghBackground: Heart failure hospitalization (hHF) with dipeptyl-dipeptidase-4 inhibitors (DPP-4Is) remains at the center stage since the publication of Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus – Thrombolysis in Myocardial Infarction (SAVOR-TIMI) in 2013 showing significant increase with saxagliptin, compared to placebo. This outcome led to additional label of hHF to both saxagliptin and alogliptin in April 2016 and eventual labelling of hHF to all the four approved DPP-4Is in United States in August 2017, by US Food Drug Administration. To note, neither Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), nor Cardiovascular and Renal Microvascular Outcome Study with Linagliptin (CARMELINA), showed any signals of hHF with these two agents. These developments have seriously generated an uncertainty among clinicians with regards to hHF effect of DPP-4Is in type 2 diabetic patients with high risk of cardiovascular (CV) disease. Aims and Objectives: We systematically searched the database of PubMed, Embase, Cochrane Central library, ClinicalTrials.gov, and International conference presentation from the inception up to October 25, 2018 using MeSH and specific key words. We retrieved all those studies that explicitly looked for hHF as a prespecified end point and were conducted for ≥52 weeks. Subsequently, we conducted the meta-analysis using comprehensive meta-analysis software Version 3, using different sensitivity analysis to study the effect of DPP-4Is on hHF in both dedicated CV outcome trials as well as randomized controlled trials. Results: The meta-analysis of four exclusive dedicated CV outcome trials (N = 43,522) did not find significant increase in hHF with DPP-4 inhibitors (Fixed model Relative Risk [RR] 1.06; 95% Confidence Interval [CI], 0.96-1.17; P = 0.25; I2: 53.95%, tau2: 0.012, P = 0.089). Meta-analysis of all randomized controlled trials that explicitly looked for hHF for ≥52 weeks (N = 48,199) also did not show any significant increase in hHF (fixed model peto odds ratio 1.05; 95% CI 0.95–1.15, P = 0.36; I2: 43.74%, tau2: 0.016, P = 0.10). Conclusions: This meta-analysis suggests no significant increase in hHF with DPP-4 inhibitors, although a nonsignificant heterogeneity across the trials might limit this observation.http://www.ijem.in/article.asp?issn=2230-8210;year=2019;volume=23;issue=1;spage=128;epage=133;aulast=Singhcardiovascular outcomesdpp-4 inhibitorsgliptinsheart failureheart failure hospitalization |
| spellingShingle | Awadhesh Kumar Singh Ritu Singh Heart failure hospitalization with DPP-4 inhibitors: A systematic review and meta-analysis of randomized controlled trials Indian Journal of Endocrinology and Metabolism cardiovascular outcomes dpp-4 inhibitors gliptins heart failure heart failure hospitalization |
| title | Heart failure hospitalization with DPP-4 inhibitors: A systematic review and meta-analysis of randomized controlled trials |
| title_full | Heart failure hospitalization with DPP-4 inhibitors: A systematic review and meta-analysis of randomized controlled trials |
| title_fullStr | Heart failure hospitalization with DPP-4 inhibitors: A systematic review and meta-analysis of randomized controlled trials |
| title_full_unstemmed | Heart failure hospitalization with DPP-4 inhibitors: A systematic review and meta-analysis of randomized controlled trials |
| title_short | Heart failure hospitalization with DPP-4 inhibitors: A systematic review and meta-analysis of randomized controlled trials |
| title_sort | heart failure hospitalization with dpp 4 inhibitors a systematic review and meta analysis of randomized controlled trials |
| topic | cardiovascular outcomes dpp-4 inhibitors gliptins heart failure heart failure hospitalization |
| url | http://www.ijem.in/article.asp?issn=2230-8210;year=2019;volume=23;issue=1;spage=128;epage=133;aulast=Singh |
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