A Meta-Analysis of Randomized Controlled Trials of Aspirin in Primary Prevention of Cardiovascular Disease.

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.

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.


BMC Medicine ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Georg Gelbenegger ◽  
Marek Postula ◽  
Ladislav Pecen ◽  
Sigrun Halvorsen ◽  
Maciej Lesiak ◽  
...  

Abstract Background The role of aspirin in primary prevention of cardiovascular disease (CVD) remains unclear. We aimed to investigate the benefit-risk ratio of aspirin for primary prevention of CVD with a particular focus on subgroups. Methods Randomized controlled trials comparing the effects of aspirin for primary prevention of CVD versus control and including at least 1000 patients were eligible for this meta-analysis. The primary efficacy outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, major adverse cardiovascular events (MACE), myocardial infarction, ischemic stroke, and net clinical benefit. The primary safety outcome was major bleeding. Subgroup analyses involving sex, concomitant statin treatment, diabetes, and smoking were performed. Results Thirteen randomized controlled trials comprising 164,225 patients were included. The risk of all-cause and cardiovascular mortality was similar for aspirin and control groups (RR 0.98; 95% CI, 0.93–1.02; RR 0.99; 95% CI, 0.90–1.08; respectively). Aspirin reduced the relative risk (RRR) of major adverse cardiovascular events (MACE) by 9% (RR 0.91; 95% CI, 0.86–0.95), myocardial infarction by 14% (RR 0.86; 95% CI, 0.77–0.95), and ischemic stroke by 10% (RR 0.90; 95% CI, 0.82–0.99), but was associated with a 46% relative risk increase of major bleeding events (RR 1.46; 95% CI, 1.30–1.64) compared with controls. Aspirin use did not translate into a net clinical benefit adjusted for event-associated mortality risk (mean 0.034%; 95% CI, − 0.18 to 0.25%). There was an interaction for aspirin effect in three patient subgroups: (i) in patients under statin treatment, aspirin was associated with a 12% RRR of MACE (RR 0.88; 95% CI, 0.80–0.96), and this effect was lacking in the no-statin group; (ii) in non-smokers, aspirin was associated with a 10% RRR of MACE (RR 0.90; 95% CI, 0.82–0.99), and this effect was not present in smokers; and (iii) in males, aspirin use resulted in a 11% RRR of MACE (RR 0.89; 95% CI, 0.83–0.95), with a non-significant effect in females. Conclusions Aspirin use does not reduce all-cause or cardiovascular mortality and results in an insufficient benefit-risk ratio for CVD primary prevention. Non-smokers, patients treated with statins, and males had the greatest risk reduction of MACE across subgroups. Systematic review registration PROSPERO CRD42019118474.


2019 ◽  
Vol 48 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Jingjing Jin ◽  
Xiaoyang Guo ◽  
Qiyao Yu

Background: The effects of beta-blockers are uncertain in dialysis patients. Except antihypertension, β-blockers may play a unique cardiovascular protective role in the population. This meta-analysis aimed to explore the effects of β-blockers therapy in adult patients treated with dialysis. Methods: We searched MEDLINE, EMBASE, and the Cochrane library from inception to May 2018 for randomized controlled trials (RCTs) and observational studies about the role of β-blockers on all-cause mortality, cardiovascular mortality, cardiovascular events, or hospitalizations in dialysis population. Results: Three RCTs and 9 observational studies met the predefined inclusion criteria. The RCTs showed significant association between β-blockers and reduced all-cause mortality (n = 363; risk ratio [RR] 0.73; 95% CI 0.54–0.97), cardiovascular mortality (n = 314; RR 0.44; 95% CI 0.29–0.68), cardiovascular events (n = 363; RR 0.52; 95% CI 0.31–0.88), or hospitalizations (n = 314; RR 0.61; 95% CI 0.48–0.78) in dialysis patients. The observational studies showed significant difference in all-cause mortality (n = 35,233; hazard ratio [HR] 0.86; 95% CI 0.80–0.92) between β-blockers and no β-blockers therapy in patients with dialysis, while the studies showed no difference in cardiovascular mortality (n = 19,413; HR 0.79; 95% CI 0.57–1.11), or cardiovascular events (n = 87,060; HR 0.79; 95% CI 0.50–1.26). Conclusions: β-blockers seem to be associated with reduced mortality in patients on dialysis. Both the statistical heterogeneity in observational studies and the small number of participants and studies in RCTs limit the strength of these findings. Video Journal Club “Cappuccino with Claudio Ronco” at  https://www.karger.com/Journal/ArticleNews/496083?sponsor=52


2019 ◽  
Vol 15 (1) ◽  
pp. 9-17
Author(s):  
Conor Judge ◽  
Sarah Ruttledge ◽  
Robert Murphy ◽  
Elaine Loughlin ◽  
Sarah Gorey ◽  
...  

Background The benefits of aspirin for primary prevention of stroke are uncertain. Methods We performed a cumulative meta-analysis of trials investigating aspirin for primary prevention of cardiovascular disease with a focus on stroke. We assessed the effects of aspirin on non-fatal stroke, hemorrhagic stroke, non-fatal myocardial infarction, all-cause mortality, cardiovascular mortality, major gastrointestinal bleeding, and an analysis of net clinical effect, in populations without a history of clinical or subclinical cardiovascular disease. Summary of review results Among 11 trials (157,054 participants), aspirin was not associated with a statistically significant reduction in non-fatal stroke (odds ratio, 0.94; 95% CI, 0.85 to 1.04) but was associated with an increased risk of hemorrhagic stroke (odds ratio, 1.29; 95% CI, 1.06 to 1.56). Aspirin was not associated with a statistically significant reduction in all-cause mortality (odds ratio, 0.97; 95% CI, 0.92 to 1.03) or cardiovascular mortality (odds ratio, 0.94; 95% CI, 0.85 to 1.03). Aspirin was associated with a reduction in non-fatal myocardial infarction (odds ratio, 0.80; 95% CI, 0.69 to 0.94) and an increased risk of major gastrointestinal bleeding (odds ratio, 1.83; 95% CI, 1.43 to 2.35). Using equal weighting for non-fatal events and major bleeding, we observed no net clinical benefit with aspirin use for primary prevention. Conclusion Our meta-analysis reports no benefit of aspirin for primary stroke prevention.


Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2218 ◽  
Author(s):  
Tung Hoang ◽  
Jeongseon Kim

Statins and omega-3 supplementation have been recommended for cardiovascular disease prevention, but comparative effects have not been investigated. This study aimed to summarize current evidence of the effect of statins and omega-3 supplementation on cardiovascular events. A meta-analysis and a network meta-analysis of 63 randomized controlled trials were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) for the effects of specific statins and omega-3 supplementation compared with controls. Overall, the statin group showed significant risk reductions in total cardiovascular disease, coronary heart disease, myocardial infarction, and stroke; however, omega-3 supplementation significantly decreased the risks of coronary heart disease and myocardial infarction only, in the comparison with the control group. In comparison with omega-3 supplementation, pravastatin significantly reduced the risks of total cardiovascular disease (RR = 0.81, 95% CI = 0.72–0.91), coronary heart disease (RR = 0.75, 95% CI = 0.60–0.94), and myocardial infarction (RR = 0.71, 95% CI = 0.55–0.94). Risks of total cardiovascular disease, coronary heart disease, myocardial infarction, and stroke in the atorvastatin group were statistically lower than those in the omega-3 group, with RRs (95% CIs) of 0.80 (0.73–0.88), 0.64 (0.50–0.82), 0.75 (0.60–0.93), and 0.81 (0.66–0.99), respectively. The findings of this study suggest that pravastatin and atorvastatin may be more beneficial than omega-3 supplementation in reducing the risk of total cardiovascular disease, coronary heart disease, and myocardial infarction.


2021 ◽  
Author(s):  
Caiyun Zheng ◽  
Meimei Lin ◽  
Yan Chen ◽  
Haiting Xu ◽  
Lingqun Yan ◽  
...  

Abstract BackgroundControlled studies and observational studies have shown that sodium-glucose cotransporter type 2 inhibitors (SGLT-2s) are beneficial to the mortality of patients with heart failure (HF). However, it is unclear whether SGLT-2s can benefit patients with other cardiovascular diseases. Here, we conducted a systematic review and meta-analysis to determine the clinical benefits of SGLT-2s in cardiovascular patients with or without diabetes.MethodsWe searched PubMed, EMBASE, Cochrane Library, Web of Science databases, and ClinicalTrials.gov databases for randomised controlled trials written in English from inception until November 1, 2020. Two reviewers independently identified randomised controlled trials comparing the effects of SGLT-2s in patients with cardiovascular disease with or without diabetes. Primary outcomes were all-cause mortality, cardiovascular mortality, and hospitalisation for heart failure. Secondary outcomes were major adverse events from cardiovascular, metabolic, renal, and infectious diseases. The effects of SGLT-2s were evaluated using RevMan5.3 software. The Cochrane risk of bias tool was used to assess study quality.ResultsWe identified 10 randomised controlled trials (24500 patients in the SGLT-2 group and 17960 patients in the placebo group). Meta-analysis showed that SGLT-2 treatment significantly reduced all-cause mortality, cardiovascular mortality, and hospitalisation for heart failure (HHF) in patients with cardiovascular disease (all-cause mortality relative risk [RR]: 0.86; 95% confidence interval [CI]: 0.80–0.91; P < 0.00001; I2 = 11%; cardiovascular mortality RR: 0.85; 95% CI: 0.79–0.92; P < 0.0001; I2 = 35%; HHF RR: 0.69; 95% CI: 0.64–0.81; P < 0.00001; I2 = 0%). In patients with heart failure, mortality and HHF after SGLT-2 treatment for heart failure with reduced ejection fraction were significantly reduced, whereas heart failure with preserved ejection fraction did not differ compared with placebo treatment. Moreover, SGLT-2s induced a lower incidence of renal damage and myocardial infarction than the placebo group; however, the risk of infection, amputation, volume depletion, and diabetic ketoacidosis was higher. ConclusionsIn this exploratory analysis, SGLT-2s had significant clinical effects in the treatment of patients with cardiovascular disease and had significant benefits in terms of renal function and myocardial infarction, but were associated with increased risk of infection, ketoacidosis, amputation, and volume depletion.


2020 ◽  
Vol 112 (6) ◽  
pp. 1642-1652
Author(s):  
David J A Jenkins ◽  
David Kitts ◽  
Edward L Giovannucci ◽  
Sandhya Sahye-Pudaruth ◽  
Melanie Paquette ◽  
...  

ABSTRACT Background Antioxidants have been promoted for cardiovascular disease (CVD) risk reduction and for the prevention of cancer. Our preliminary analysis suggested that only when selenium was present were antioxidant mixtures associated with reduced all-cause mortality. Objective We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effect of selenium supplementation alone and of antioxidant mixtures with or without selenium on the risk of CVD, cancer, and mortality. Methods We identified studies using the Cochrane Library, Medline, and Embase for potential CVD outcomes, cancer, and all-cause mortality following selenium supplementation alone or after antioxidant supplement mixtures with and without selenium up to June 5, 2020. RCTs of ≥24 wk were included and data were analyzed using random-effects models and classified by the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results The meta-analysis identified 9423 studies, of which 43 were used in the final analysis. Overall, no association of selenium alone or antioxidants was seen with CVD and all-cause mortality. However, a decreased risk with antioxidant mixtures was seen for CVD mortality when selenium was part of the mix (RR: 0.77; 95% CI: 0.62, 0.97; P = 0.02), with no association when selenium was absent. Similarly, when selenium was part of the antioxidant mixture, a decreased risk was seen for all-cause mortality (RR: 0.90; 95% CI: 0.82, 0.98; P = 0.02) as opposed to an increased risk when selenium was absent (RR: 1.09; 95% CI: 1.04, 1.13; P = 0.0002). Conclusion The addition of selenium should be considered for supplements containing antioxidant mixtures if they are to be associated with CVD and all-cause mortality risk reduction. This trial was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42019138268.


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].


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260844
Author(s):  
Karel H. van der Pol ◽  
Kimberley E. Wever ◽  
Mariette Verbakel ◽  
Frank L. J. Visseren ◽  
Jan H. Cornel ◽  
...  

Aims To compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients. Methods and results Pubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT’s a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT’s and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved (<0.36 mmol/l). Conclusions Data from RCT’s and observational studies indicate that allopurinol treatment reduces cardiovascular risk in patients with hyperuricemia. However, the quality of evidence from RCTs is low to moderate. To establish whether allopurinol lowers the risk of cardiovascular events a well-designed and adequately powered randomized, placebo-controlled trial is needed in high-risk patients with hyperuricemia. Systematic review registration PROSPERO registration CRD42018089744


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