scholarly journals Benefits and Risks Associated With Aspirin Use in Patients With Diabetes for the Primary Prevention of Cardiovascular Events and Mortality: A Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hua Ma ◽  
Qing Gu ◽  
Huining Niu ◽  
Xiaohua Li ◽  
Rong Wang

PurposeA meta-analysis was conducted to assess the benefits and risks of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in adults with diabetes.MethodsAn extensive and systematic search was conducted in MEDLINE (via PubMed), Cinahl (via Ebsco), Scopus, and Web of Sciences from 1988 to December 2020. A detailed literature search was conducted using aspirin, cardiovascular disease (CVD), diabetes, and efficacy to identify trials of patients with diabetes who received aspirin for primary prevention of CVD. Demographic details with the primary outcome of events and bleeding outcomes were analyzed. The Cochrane Collaboration’s risk of bias tool was used to assess the methodological quality of the included studies. Random-effects meta-analysis was used to calculate the pooled odds ratio for outcomes of cardiovascular events, death, and adverse events.FindingsA total of 8 studies were included with 32,024 patients with diabetes; 16,001 allocated to aspirin, and 16,023 allocated to the control group. There was no difference between aspirin and control groups with respect to all-cause mortality, cardiovascular mortality, or bleeding events. However, MACE was significantly lower in the aspirin group.ImplicationsAlthough aspirin has no significant risk on primary endpoints of cardiovascular events and bleeding outcomes in patients with diabetes compared to control, major adverse cardiovascular events (MACE) were significantly lower in the aspirin group. Further research on the use of aspirin alone or in combination with other antiplatelet drugs is required in patients with diabetes to supplement currently available research. Systematic Review Registrationidentifier [XU#/IRB/2020/1005].

Author(s):  
Hua Ma ◽  
QIng Gu ◽  
Huining Niu ◽  
Xiaohua Li ◽  
Rong Wang

Background: The use of Aspirin in the primary prevention of cardiovascular disease (CVD) is still a topic of debate, especially in patients with diabetes. The present meta-analysis aims to rule out the efficacy of Aspirin in patients with diabetes and to compare the effectiveness of Aspirin with a placebo (or no treatment) for the primary prevention of CVD and all-cause mortality events in people with diabetes. Materials and Methods: An extensive and systematic search was conducted in Medline (via PubMed), Cinahl (via Ebsco), Scopus, and Web of Sciences from 1988 to December 2020. A detailed literature search was conducted using Aspirin, cardiovascular disease (CVD), diabetes, and efficacy to identify trials of patients with diabetes who received Aspirin for primary prevention of CVD. Demographic details with the primary outcome of events and bleeding outcomes were analyzed. The risk of bias (RoB) in included studies was evaluated using the QUADAS-2 tool. Results: A total of 5 studies out of 13 were included with 23,570 diabetic patients; 11,738 allocated to Aspirin and 11,832 allocated to the placebo group. In patients with diabetes, there was no difference between Aspirin and placebo with respect to the risk of all-cause death with a confidence interval (CI) varying 0.63 to 1.17. In addition, there were no differences in the bleeding outcomes with an odds ratio of 1.4411 (CI 0.47 to 4.34). Conclusion: Aspirin has no significant risk on primary endpoints of cardiovascular events and the bleeding outcomes in diabetic patients compared to placebo. More research on the use of Aspirin alone or in combination with other antiplatelet drugs is required in patients with diabetes to supplement currently available research.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
John A. Cuenca ◽  
Javier Balda ◽  
Ana Palacio ◽  
Larry Young ◽  
Michael H. Pillinger ◽  
...  

Background. Febuxostat is approved in the United States for the management of hyperuricemia in patients with gout. In November 2017 the FDA released a warning alert on a possible link between febuxostat and cardiovascular disease (CVD) reported in a single clinical trial. Objective. To conduct a systematic review and meta-analysis and assess the risk of major adverse cardiovascular events (MACE) in patients receiving febuxostat compared to a control group. Methods. We searched the MEDLINE and EMBASE database for studies published up until March 2018. We included randomized clinical trials (RCTs) that compared febuxostat to control groups including placebo and allopurinol. We calculated the pooled relative risk (RR) of MACE and cardiovascular disease (CVD) mortality with the corresponding 95% confidence intervals (CI). Results. Our search yielded 374 potentially relevant studies. Among the 25 RCTs included in the systematic review, 10 qualified for the meta-analysis. Among the 14,402 subjects included, the median age was 54 years (IQR 52-67) and 90% were male (IQR 82-96); 8602 received febuxostat, 5118 allopurinol, and 643 placebo. The pooled RR of MACE for febuxostat was 0.9; 95% CI 0.6-1.5 (p= 0.96) compared to the control. The RR of CV-related death for febuxostat was 1.29; 95% CI 1.01-1.66 (p=0.03). Conclusions. Compared with other SU-lowering treatments, febuxostat does not increase or decrease the risk of cardiovascular disease but may increase the risk of CVD death. More RCTs measuring cardiovascular safety as a primary outcome are needed to adequately evaluate the risk of CVD with febuxostat.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 174-174
Author(s):  
Nina C Raju ◽  
Magda Sobieraj-Teague ◽  
John W Eikelboom

Abstract Abstract 174 Primary prevention with aspirin reduces the risk of non-fatal cardiovascular events but has not been demonstrated to reduce mortality. We performed an updated meta-analysis of randomised controlled trials of aspirin in primary prevention to obtain best estimates of the benefits and harm of aspirin compared with no aspirin with a focus on mortality. Eligible articles were identified by computerized search of MEDLINE, EMBASE, Cochrane library and CINAHL databases, review of bibliographies of relevant publications and a related article search using PubMed. The outcomes of interest included all cause mortality, cardiovascular mortality, the composite of myocardial infarction, stroke or death, and bleeding. 2 reviewers independently extracted study information and data. Data were pooled from individual trials using the DerSimonian-Laird random-effects model and results are presented as relative risk (RR) and 95% confidence intervals (CI). 8 studies comprising a total of 96,726 subjects were included. Aspirin reduced all-cause mortality (RR 0.94; 95%CI 0.88–1.00), the composite of myocardial infarction, stroke or cardiovascular death (RR 0.87; 95%CI 0.82–0.93), and myocardial infarction (RR 0.8; 95%CI 0.66–0.98) but did not significantly reduce cardiovascular mortality (RR 0.94; 95%CI 0.82–1.08) or stroke (RR 0.93; 95%CI 0.81–1.07). Aspirin increased the risk of major bleeding (RR; 1.69 95%CI 1.38–2.08), gastrointestinal bleeding (RR 1.38; 95%CI 1.16–1.65) and hemorrhagic stroke (RR 1.36; 95%CI 1.01–1.84). There was no interaction between subjects with or without diabetes for the outcomes of all cause mortality, cardiovascular mortality, the composite of myocardial infarction, stroke or death. Aspirin therapy in subjects with no prior history of cardiovascular disease reduces the risk of cardiovascular events, myocardial infarction and overall mortality. These benefits are achieved at the expense of increased bleeding. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Author(s):  
Luiz Sergio Fernandes de Carvalho ◽  
Ana Claudia Cavalcante Nogueira ◽  
Riobaldo Marcelo Ribeiro Cintra ◽  
Isabella Bonilha ◽  
Beatriz Luchiari ◽  
...  

Abstract Background: Among individuals with type 2 diabetes mellitus (T2DM), RCTs designed to investigate the cardiovascular effects of achieving HbA1c ≤7.0% by using insulin and sulfonylureas were unable to prevent the incidence of major adverse cardiovascular events (MACE) defined as CV death, non-fatal myocardial infarction, and non-fatal stroke. Intense glucose-lowering with newer antidiabetic therapies (ADTs) including SGLT2i, GLP1-RA, pioglitazone and DPP4i show lower risk of hypoglycemia and could lead to additive effect in preventing MACE. In this context, this study was designed to assess the impact of the HbA1c levels achieved with newer ADTs on the risk of MACE. Methods. We searched MEDLINE/PubMed, Cochrane and ClinicalTrials.gov. RCTs published up to January/2021 reporting the occurrence of MACE and all-cause mortality in individuals with T2DM, including a sample size ≥100 individuals in each study arm and follow-up ≥24 weeks, were selected. Data was extracted by four independent observers following PRISMA guidelines. We performed a systematic review and additive-effects network meta-analysis with random effects and a multivariate meta-regression to assess the impact of achieved HbA1c on incident MACE. Results. A total of 122 RCTs were included with 139 treatment arms, 256,990 individuals, and 689,346 individuals-years who were randomized to an active treatment vs. control group. Therapy with SGLT2i, GLP1-RA, or pioglitazone similarly reduced the risk of MACE compared to placebo (HR 0.88 [95%CI 0.83, 0.94, p<0.001], 0.89 [95% CI 0.85, 0.94, p<0.0001], and 0.86 [95% CI 0.76, 0.98, p=0.025], respectively). The achievement of HbA1c≤7.0% in RCTs with SGLT2i, DPP4i, TZD, or GLP1-RA in the active arm was associated with an adjusted HR of 0.91 (95% CI 0.80, 0.97; p=0.039) compared with HbA1c>7.0%. All-cause mortality was not influenced by HbA1c thresholds.Conclusions: Achieving lower glucose levels with newer ADTs is linearly associated with a reduced risk of MACEs, without affecting all-cause mortality. Targeting HbA1c between 6.5 and 7% with SGLT2i, GLP1A, pioglitazone or DPP4i brings cardiovascular benefits considering the available RCT evidence.Study registration: PROSPERO CRD42020200649


Heart ◽  
2021 ◽  
pp. heartjnl-2020-317883 ◽  
Author(s):  
Pei Qin ◽  
Ming Zhang ◽  
Minghui Han ◽  
Dechen Liu ◽  
Xinping Luo ◽  
...  

ObjectiveWe performed a meta-analysis, including dose–response analysis, to quantitatively determine the association of fried-food consumption and risk of cardiovascular disease and all-cause mortality in the general adult population.MethodsWe searched PubMed, EMBASE and Web of Science for all articles before 11 April 2020. Random-effects models were used to estimate the summary relative risks (RRs) and 95% CIs.ResultsIn comparing the highest with lowest fried-food intake, summary RRs (95% CIs) were 1.28 (1.15 to 1.43; n=17, I2=82.0%) for major cardiovascular events (prospective: 1.24 (1.12 to 1.38), n=13, I2=75.7%; case–control: 1.91 (1.15 to 3.17), n=4, I2=92.1%); 1.22 (1.07 to 1.40; n=11, I2=77.9%) for coronary heart disease (prospective: 1.16 (1.05 to 1.29), n=8, I2=44.6%; case–control: 1.91 (1.05 to 3.47), n=3, I2=93.9%); 1.37 (0.97 to 1.94; n=4, I2=80.7%) for stroke (cohort: 1.21 (0.87 to 1.69), n=3, I2=77.3%; case–control: 2.01 (1.27 to 3.19), n=1); 1.37 (1.07 to 1.75; n=4, I2=80.0%) for heart failure; 1.02 (0.93 to 1.14; n=3, I2=27.3%) for cardiovascular mortality; and 1.03 (95% CI 0.96 to 1.12; n=6, I2=38.0%) for all-cause mortality. The association was linear for major cardiovascular events, coronary heart disease and heart failure.ConclusionsFried-food consumption may increase the risk of cardiovascular disease and presents a linear dose–response relation. However, the high heterogeneity and potential recall and misclassification biases for fried-food consumption from the original studies should be considered.


2019 ◽  
Vol 27 (19) ◽  
pp. 2034-2041 ◽  
Author(s):  
Safi U Khan ◽  
Zain Ul Abideen Asad ◽  
Muhammad U Khan ◽  
Swapna Talluri ◽  
Farman Ali ◽  
...  

Background The safety and efficacy of aspirin for the primary prevention of cardiovascular disease in patients with diabetes mellitus remains controversial. Design A meta-analysis to investigate the effects of aspirin for the prevention of cardiovascular disease in diabetes mellitus. Methods Ten randomized controlled trials were selected using MEDLINE, EMBASE and CENTRAL databases until 27 September 2018. Risk ratios (RRs) with 95% confidence intervals (CIs) and risk differences (RDs) reported as incident events per 1000 person-years were calculated. Results In 33,679 patients, aspirin did not significantly reduce the risk of major adverse cardiovascular outcomes (RR 0.93, 95% CI 0.87–1.00, P = 0.06; RD −0.68 incident cases per 1000 person-years (95% CI −1.54, 0.17)), cardiovascular mortality (RR 0.95, 95% CI 0.83–1.09, P = 0.49; RD 0.11 incident cases per 1000 person-years (95% CI −0.80, 1.02)), myocardial infarction (RR 0.91, 95% CI 0.75–1.11, P = 0.36; RD −0.66 incident cases per 1000 person-years (95% CI −2.07, 0.75)), or stroke (RR 0.91, 95% C, 0.76–1.10, P = 0.33; RD −0.55 incident cases per 1000 person-years (95% CI −1.57, 0.47)). There was a significantly higher risk of total bleeding associated with aspirin (RR 1.29, 95% CI 1.07–1.55, P = 0.01; RD 1.49 incident cases per 1000 person-years (95% CI 0.36, 2.61)). Conclusion The use of aspirin for primary prevention of cardiovascular disease in patients with diabetes mellitus increases the risk of total bleeding without reducing the risk of major adverse cardiovascular outcomes.


Diabetes Care ◽  
2013 ◽  
Vol 36 (2) ◽  
pp. 471-479 ◽  
Author(s):  
S. Kodama ◽  
S. Tanaka ◽  
Y. Heianza ◽  
K. Fujihara ◽  
C. Horikawa ◽  
...  

2018 ◽  
Vol 25 (8) ◽  
pp. 844-853 ◽  
Author(s):  
Safi U Khan ◽  
Swapna Talluri ◽  
Haris Riaz ◽  
Hammad Rahman ◽  
Fahad Nasir ◽  
...  

Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception – September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55–0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62–0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49–0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83–0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77–0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA, 50%). Conclusion PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.


BMJ ◽  
2020 ◽  
pp. m3342 ◽  
Author(s):  
Kristian B Filion ◽  
Lisa M Lix ◽  
Oriana HY Yu ◽  
Sophie Dell’Aniello ◽  
Antonios Douros ◽  
...  

Abstract Objective To compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world context of clinical practice. Design Multi-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis. Setting Canadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18. Population 209 867 new users of a SGLT2 inhibitor matched to 209 867 users of a DPP-4 inhibitor on time conditional propensity score and followed for a mean of 0.9 years. Main outcome measures The primary outcome was major adverse cardiovascular events (MACE, a composite of myocardial infarction, ischaemic stroke, or cardiovascular death). Secondary outcomes were the individual components of MACE, heart failure, and all cause mortality. Cox proportional hazards models were used to estimate site specific adjusted hazards ratios and 95% confidence intervals, comparing use of SGLT2 inhibitors with use of DPP-4 inhibitors in an as treated approach. Site specific results were pooled using random effects meta-analysis. Results Compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of MACE (incidence rate per 1000 person years: 11.4 v 16.5; hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), myocardial infarction (5.1 v 6.4; 0.82, 0.70 to 0.96), cardiovascular death (3.9 v 7.7; 0.60, 0.54 to 0.67), heart failure (3.1 v 7.7; 0.43, 0.37 to 0.51), and all cause mortality (8.7 v 17.3; 0.60, 0.54 to 0.67). SGLT2 inhibitors had more modest benefits for ischaemic stroke (2.6 v 3.5; 0.85, 0.72 to 1.01). Similar benefits for MACE were observed with canagliflozin (0.79, 0.66 to 0.94), dapagliflozin (0.73, 0.63 to 0.85), and empagliflozin (0.77, 0.68 to 0.87). Conclusions In this large observational study conducted in a real world clinical practice context, the short term use of SGLT2 inhibitors was associated with a decreased risk of cardiovascular events compared with the use of DPP-4 inhibitors. Trial registration ClinicalTrials.gov NCT03939624 .


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