SGLT2 inhibitors and cardiovascular and renal outcomes: a meta-analysis and trial sequential analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events and renal outcomes in patients with diabetes mellitus (DM). This meta-analysis aimed to provide a thorough evaluation regarding the efficacy and safety of SGLT2 inhibitors. Data search of MEDLINE/PubMed, Embase, and Cochrane Library databases and ClinicalTrials.com from inception through November 26, 2020. We included randomized trials, SGLT2 inhibitors compared with placebo, patients with or without diabetes at recruitment, and reporting the incidence of cardiovascular or renal outcomes. Two authors extracted pertinent data into predefined data collection tables. Ten trials were included (71,553 patients). The mean age was 64.7 ± 8.4 years, with 65.1% male. Follow-up durations range 9-50 months. Inhibition of SGLT2 resulted in lower composite outcome of heart failure (HF) hospitalization or cardiovascular death (RR 0.76, 95% CI 0.73-0.81, P < 0.01) and lower risk of renal outcomes (RR 0.68, 95% CI 0.60-0.77, P < 0.01). Furthermore, SGLT2 inhibitors were associated with lower major adverse cardiovascular events (MACEs), HF hospitalization, cardiovascular mortality, all-cause mortality, myocardial infarction, and serious adverse events, compared with placebo (P < 0.05). Sensitivity analyses revealed lower MACE events also in patients with HF, and a lower HF hospitalization and cardiovascular mortality in non-diabetic patients (P < 0.05). While the amputation risk was comparable between the two groups, the risk of diabetic ketoacidosis was higher in the SGLT2 inhibitor group. Inhibition of SGLT2 in patients with DM and prevalent ASCVD reduces the risk of HF hospitalization, cardiovascular mortality, all-cause mortality, MACE, and renal outcomes without increasing the risk of serious adverse events or amputation.

Meta-analysis of optimal timing of coronary intervention in non-ST-elevation acute coronary syndrome.

OBJECTIVES: We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of early versus delayed invasive management of non-ST-elevation acute coronary syndrome (NSTE-ACS). BACKGROUND: Coronary angiography is recommended for patients with NSTE-ACS, however, the optimal timing for this remains controversial. METHODS: Literature search of Pubmed/MEDLINE, Cochrane Library, and Embase for all RCTs that compared early with delayed invasive approaches in treating NSTE-ACS was conducted by two independent authors. Primary outcome was major adverse cardiovascular events (MACE), while the secondary outcomes included cardiovascular mortality, all-cause mortality, myocardial infarction (MI), and bleeding events. The Mantel-Haenszel random-effects model was used to calculate risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: We included 14 RCTs (9,637 patients, mean age 65.4, 67% males). The early invasive strategy was associated with a lower incidence of MACE compared with the delayed invasive strategy (RR 0.65, 95%CI 0.49-0.87; p = .003). Subgroup analysis according to GRACE score showed a lower incidence of MACE with early invasive strategies in GRACE >140 patients (p for interaction = .002). Furthermore, recurrent ischemia was lower in patients with an early invasive strategy (RR 0.42, 95%CI 0.26-0.69; p < .0005). In contrast, there were no significant differences in all-cause mortality, cardiovascular mortality, MI, or bleeding events between groups (all p > .05). CONCLUSIONS: Among patients with NSTE-ACS, an early invasive strategy was associated with lower incidence of MACE and recurrent ischemia compared with delayed invasive strategy. There were no significant differences in all-cause mortality, cardiovascular mortality, MI, or bleeding events between groups.

Traditional versus distal radial access for coronary angiography: a meta-analysis of randomized controlled trials.

Radial artery occlusion (RAO) is a well known complication that occurs after traditional radial artery (TRA) intervention and limits the radial artery as a future access site, as well as an arterial conduit. Distal radial artery (DRA) access has emerged recently as an alternative approach with a potential lower incidence of RAO. Database search of Pubmed/MEDLINE, Cochrane Library, and EMBASE was conducted by two authors from inception through 1 October 2022. Randomized trials that compared TRA with the DRA approach to perform coronary angiography were included. Two authors extracted pertinent data into predefined data collection tables. The risk ratios and 95% confidence intervals (CIs) were reported. Eleven trials were included (5700 patients) in the study. The mean age was 62.0 ±â€…10.9 years. Compared with DRA, vascular access through the TRA was associated with a higher incidence of RAO (risk ratio 3.05, 95% CI, 1.74-5.35, P < 0.01); however, arterial access by using the TRA was associated with a lower incidence of access failure leading to a crossover compared with the DRA approach (risk ratio 0.35; 95% CI, 0.21-0.57, P < 0.01). The incidence of radial artery spasm and access site-associated hematoma was not significant in the group treated with TRA compared with the DRA approach (P > 0.05). The DRA approach was associated with a lower incidence of RAO compared with the TRA approach but this was at the expense of a higher crossover rate.

Meta-Analysis Comparing Drug-Coated Balloons and Percutaneous Transluminal Angioplasty for Infrapopliteal Artery Disease.

Limited data is available regarding the safety and effectiveness of drug-coated balloon (DCB) versus conventional percutaneous transluminal balloon angioplasty (PTA) in the treatment of critical limb ischemia because of infrapopliteal peripheral arterial disease. We conducted an updated meta-analysis to assess the safety and efficacy of DCB in the treatment of infrapopliteal disease. A database search of PubMed/MEDLINE, EMBASE, and the Cochrane Library was performed by 2 reviewers from inception through November 15, 2021. Randomized trials that compared DCB with conventional PTA in treating infrapopliteal arterial disease were included. The risk ratios (RRs) and 95% confidence intervals (CIs) were reported. A total of 9 trials were included (1,501 participants) in the study. The mean age was 71.1 ± 10.2 years. Regarding the primary end points, treating infrapopliteal arterial disease with DCB had a lower incidence of re-stenosis (RR 0.48, 95% CI 0.33 to 0.70, p = 0.0001) with no significant difference in all-cause mortality (RR 1.11, 95% CI 0.73 to 1.69, p = 0.61), compared with conventional PTA. With regards to the secondary end points, DCB usage was associated with a significant reduction in clinically driven target lesion revascularization (RR 0.54, 95% CI 0.35 to 0.84, p = 0.006) with no significant difference with regards to major target limb amputation and major adverse cardiovascular events (p ≥0.05). In conclusion, among patients with critical limb ischemia secondary to infrapopliteal artery disease, DCB usage was associated with a significantly lower number of restenosis and clinically driven target lesion revascularization compared with conventional PTA. There was no increase in all-cause mortality or major target limb amputation with the use of DCB.

Efficacy and Safety of the Non-Vitamin K Antagonist Oral Anticoagulant Among Patients With Nonvalvular Atrial Fibrillation and Cancer: A Systematic Review and Network Meta-analysis.

Patients with cancer are at higher risk of atrial fibrillation (AF). Currently there are no definitive data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in cancer patients with AF. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of NOACs compared with warfarin. A search through Pubmed/MEDLINE, Embase, and Cochrane library was done from the databases inception to March 2022. Studies that compared NOACs to warfarin in the setting of AF and cancer were included. The primary outcomes were the incidence of major bleeding and ischemic stroke/systemic embolism (SE). Secondary outcomes were major adverse cardiovascular event (MACE), intracranial bleeding, and Major gastrointestinal bleeding. Risk ratios (RRs) with 95% confidence intervals (CI) were used to report the outcomes. A total of 11 studies were included. We found that NOACs were associated with a lower incidence of major bleeding and combined ischemic stroke/SE in patients with AF and cancer compared with warfarin (RR 0.57; 95% CI 0.44-0.75, P < 0.0001 and RR 0.59; 95% CI 0.47-0.75, P < 0.0001, respectively). Also, there was lower incidence of Intracranial and major gastrointestinal bleeding in patients who received NOACs compared with warfarin (P < 0.0001). Network analyses revealed that apixaban and dabigatran were associated with reduction of major bleeding compared with warfarin. Among patients who diagnosed with AF and cancer, NOACs were associated with lower incidence of major bleeding ischemic stroke/SE compared with warfarin. Furthermore, NOACs were associated with lower gastrointestinal and intracranial bleeding.

Initial optimal medical therapy with or without invasive strategy for stable coronary disease: a meta-analysis and systematic review.

INTRODUCTION: There is a persistent controversy regarding the benefit and timing of angiography in patients with stable coronary artery disease (CAD). With this meta-analysis of randomized controlled trials (RCTs) the advantages of initial invasive strategy and medical therapy compared with only medical therapy. METHODS: We conducted a literature search of the following databases Pubmed/MEDLINE, Cochrane Library and Embase. Data was collected from all the RCTs that compared early invasive approach with medical therapy alone in treating stable CAD which was conducted by two independent authors. Primary outcomes were all-cause mortality and myocardial infarction (MI), while the secondary outcomes included major adverse cardiovascular events (MACE), cardiovascular mortality, cardiovascular hospitalization, hospitalization due to unstable angina and revascularization events. The Mantel-Haenszel random-effects model was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: We included 15 RCTs (13 916 patients, mean age 63.1, 78.9% men). The early invasive strategy, compared with medical therapy alone, did not reveal a significant reduction in the incidence of all-cause mortality (RR, 0.94; 95% CI, 0.84-1.05, P = 0.30) or MI (RR, 0.93; 95% CI, 0.79-1.10, P = 0.42). Furthermore, the early invasive strategy did not reduce the incidence of cardiovascular mortality, cardiovascular hospitalization or the revascularization rate compared with medical therapy alone (P > 0.05). However, the incidence of MACE and hospitalization due to unstable angina were lower in patients treated with early invasive strategy (RR, 0.79; 95% CI, 0.63-0.99, P = 0.04), and (RR, 0.46; 95% CI, 0.32-0.67, P < 0.0001), respectively. CONCLUSIONS: Early invasive strategy with medical therapy did not reduce the incidence of all-cause mortality and MI when compared with medical therapy alone among patients with stable CAD with significant stenosis. However, there was a significant reduction in the incidence of MACE and hospitalization due to unstable angina in the early invasive group.

Omega-3 supplementation and heart failure: A meta-analysis of 12 trials including 81,364 participants.

Heart failure (HF) remains a leading cause of hospitalization and mortality. Marine omega-3 fatty acid supplements (omega-3 s) have shown efficacy in decreasing sudden cardiac death and improving the left ventricle ejection fraction percent (LVEF%). In this review, we evaluated the effect of marine omega-3 fatty acid supplements (omega-3 s) on HF hospitalization, recurrent HF hospitalization, and cardiovascular mortality in patients with heart failure. We found that omega-3 supplementation did not reduce first HF hospitalization or cardiovascular mortality but did significantly reduce recurrent HF hospitalizations, as compared with placebo.

Targeted Temperature Management in Cardiac Arrest Patients With an Initial Non-Shockable Rhythm: A Systematic Review and Meta-Analysis.

BACKGROUND: Targeted temperature management (TTM) is now recommended for patients presenting with an out-of-hospital cardiac arrest. However, there are limited data that support its use in patients with an initial non-shockable rhythm (NSR). METHODS: A literature search of PubMed/MEDLINE, Cochrane Library, and Embase was conducted by two independent authors for studies that compared TTM along with standard care versus standard care alone in treating cardiac arrest with initial NSR. Outcomes were short-term and long-term survival, and a Cerebral Performance Category (CPC) score of 1 to 2 at the longest follow-up period. The Mantel-Haenszel random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was performed on the randomized controlled trials (RCTs). RESULTS: Thirty studies were included in the final analysis: 25 observational and five RCTs, totalling 10,703 patients, 4,023 of whom received TTM and 6,680 received standard care alone. Compared with standard care, patients who presented with an initial NSR cardiac arrest and received TTM (target of 32°C -34°C) had a significantly higher short-term survival (OR 1.44 95% CI 1.15-1.81; P = 0.002), long-term survival (OR 1.52 95% CI 1.03-2.26; P = 0.04), and CPC score of 1 to 2 (OR 1.63 95% CI 1.22-2.17; P = 0.0010). Sensitivity analyses by including only RCTs showed a trend, although not significant, toward better short-term survival (OR 1.25 95% CI 0.82-1.89; P = 0.30), long-term survival (OR 1.15 95% CI 0.80-1.66; P = 0.46), and neurologic outcomes (OR 1.51 95% CI 0.81-2.80; P = 0.19). However, TSA performed on the RCTs revealed that the results were inconclusive. CONCLUSION: Among patients who survived cardiac arrest with an initial NSR, TTM is associated with a higher rate of survival and favorable neurological outcomes compared with no TTM. However, analyses from the included RCTs did not support this conclusion.

Effect of Vitamin D Supplementation on the Incidence of Diabetes Mellitus.

CONTEXT: The effect of vitamin D supplementation on the risk of type 2 diabetes mellitus (T2DM) remains controversial because most randomized controlled trials (RCTs) have been small or have reported low doses of vitamin D. OBJECTIVE: To conduct a meta-analysis of RCTs testing vitamin D supplementation in the prevention of T2DM. DATA SOURCES: Database search of PubMed/MEDLINE, EMBASE, and the Cochrane Library was performed by 2 reviewers from inception through September 15, 2019. STUDY SELECTION: We included RCTs that reported the effect of vitamin D supplementation for at least 1 year on T2DM prevention. DATA EXTRACTION: Two independent reviewers extracted the data. The risk ratios (RRs) and 95% confidence intervals (CIs) were reported. Primary outcome of the meta-analysis was the incidence of T2DM. DATA SYNTHESIS: Nine RCTs were included (43 559 participants). The mean age (standard deviation) was 63.5 (6.7) years. The RR for vitamin D compared with placebo was 0.96 (95% CI, 0.90-1.03); P = 0.30. In trials testing moderate to high doses of supplementation (≥1000 IU/day), all conducted among participants with prediabetes, the RR for vitamin D compared with placebo was 0.88 (95% CI, 0.79-0.99). In contrast, the trials testing lower doses, which were conducted in general population samples, showed no risk reduction (RR, 1.02; 95% CI, 0.94-1.10; P, interaction by dose = 0.04). CONCLUSION: In patients with prediabetes, vitamin D supplementation at moderate to high doses (≥1000 IU/day), significantly reduced the incidence risk of T2DM, compared with placebo.

Optimal timing of coronary intervention in patients resuscitated from cardiac arrest without ST-segment elevation myocardial infarction (NSTEMI): A systematic review and meta-analysis.

OBJECTIVE: Performing immediate coronary angiography (CAG) in patients with a cardiac arrest and a non-ST-elevation myocardial infarction (NSTEMI) remains a highly debated topic. We performed a meta-analysis aiming to evaluate the influence of immediate, delayed, and no CAG in patients with cardiac arrest and NSTEMI. METHODS: A comprehensive literature review of Pubmed/MEDLINE, Cochrane Library, and Embase was performed for all studies that compared immediate CAG to delayed or no CAG in the setting of cardiac arrest and NSTEMI. The primary outcome was long-term mortality and secondary outcomes included short-term mortality and a Cerebral Performance Category (CPC) score of 1-2 at the longest follow-up period. A random-effects model was used to report odds ratios (ORs) with Bayesian 95% credible intervals (CrIs), and ORs with 95% confidence intervals (CIs) for both network and direct meta-analyses, respectively. RESULTS: 11 studies were included in the final analysis: 8 observational, 1 post-hoc analysis and 2 randomized trials, totaling 3702 patients. The mean age was 63.8±12.8 years with 78% males. We found that immediate and delayed CAG were associated with lower long-term mortality when compared to no CAG (OR 0.21; 95% CrI 0.05-0.82) and (OR 0.11; 95% CrI 0.03-0.43), as well as lower short-term mortality (OR 0.17; 95% CrI 0.04-0.64) and (OR 0.07; 95% CrI 0.01-0.29), respectively. In addition, immediate and delayed CAG were associated with a significantly higher number of patients with a CPC score of 1-2 (OR 4.15; 95% CrI 1.10-16.10) and (OR 4.67; 95% CrI 1.53-15.12), respectively. There were no significant differences between immediate or delayed CAG regarding long-term mortality, short-term mortality, or favorable CPC score. CONCLUSIONS: Among patients who survived cardiac arrest with an NSTEMI, CAG is associated with a higher rate of survival and favorable neurological outcomes compared with no CAG. There were no differences between immediate and delayed strategies.

Best duration of dual antiplatelet therapy after drug-eluting stent implantation: an updated network meta-analysis of randomized controlled trials.

Background: Drug-eluting stent(DES) implantation is the main interventional treatment for coronary artery disease, and dual antiplatelet therapy(DAPT) remains the gold standard strategy to prevent ischemic events. However, the optimal duration of DAPT after DES implantation remains controversial. Therefore, we aimed to evaluate the best duration of DAPT following DES implantation. Method: We searched PubMed, Embase, Cochrane Library, and clinicaltrials.gov for all randomized clinical trials(RCTs) that compared different durations of DAPT after DES implantation. Major adverse cardiac events(MACE) and major bleeding were the primary and secondary outcomes, respectively. Results: We included 16 RCTs (n = 42,993). The mean age of included patients was 63.1 ± 10.1. The primary outcome was statistically significant for lower MACE in patients who received DAPT for 24-48 months (mo) following DES when compared with those who received 3-6 mo of DAPT (odds ratio [OR] 0.75; 95% credible interval [CI] 0.58-0.97). There was nonstatistically significant difference in MACE when comparing those who received 12 mo of DAPT to those taking either 3-6 mo of DAPT (OR 0.86; 95% CI 0.69-1.08) or 24-48 mo of DAPT (OR 0.87; 95% CI 0.72-1.05). In contrast, major bleeding was significantly lower in those who received 3-6 mo of DAPT (OR 0.32; 95% CI 0.17-0.54) and 12 mo of DAPT (OR 0.43; 95% CI 0.27-0.63) than in those who received 24-48 mo of DAPT. Conclusion: In patients who undergo DES implantation, a longer duration of DAPT is associated with lower MACE, despite the increased risk of major bleeding events. Therefore, individualizing the duration of DAPT after DES according to the patient's risk of bleeding and recurrent ischemia is recommended.

Comparison of Coronary Artery Bypass Grafting and Drug-Eluting Stents in Patients with Left Main Coronary Artery Disease and Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment of left main coronary artery disease (LMCAD) in patients with chronic kidney disease (CKD) with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. Therefore, we performed a meta-analysis to evaluate the optimal choice of therapy when treating LMCAD in patients with CKD. METHOD: We performed an electronic database search of Pubmed, Embase, and Cochrane Library for all studies that compared PCI with CABG when treating LMCAD in the setting of CKD. Major adverse cardiac and cerebrovascular events (MACCE) were the primary outcome. Secondary outcomes included myocardial infarction (MI), cerebrovascular events, all-cause mortality, and repeat revascularization. RESULTS: Our analysis included 5 studies (2 randomized controlled trial and 3 retrospective) representing a total of 1212 patients. Mean follow up was 3.4 ±â€¯1.3 years. Our study demonstrated a significant reduction in MACCE for patients treated with CABG compared with PCI (odd ratio [OR] 0.72; 95% confidence interval [CI] 0.55-0.95, P = 0.02, I2 = 0%). We also found a significant reduction in both MI (OR 0.55; 95% CI 0.34-0.87; P = 0.01; I2 = 0%) and repeat revascularization (OR 0.22; 95% CI 0.10-0.51; P < 0.001, I2 = 63%) in the CABG group. However, CABG was associated with increased risks of cerebrovascular disease events compared with PCI (OR 2.04; 95% CI 1.02-4.08; P = 0.04, I2 = 0%). CONCLUSION: In patients with CKD requiring LMCAD intervention, CABG is associated with a lower risk of MACCE, MI, and repeat revascularization, however it was associated with an increased risk of cerebrovascular accidents when compared to patients who received PCI therapy. Further RCTs with sufficient power are required to confirm these findings.

Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis.

Importance: Observational studies have reported an association between low serum vitamin D levels and elevated risk of cardiovascular disease (CVD) events, but such studies cannot prove causation because of possible unmeasured confounding. Objective: We conducted a meta-analysis of randomized clinical trials that tested the association of vitamin D supplementation with reduced CVD events and all-cause mortality. Data Sources: Literature search through PubMed, the Cochrane Library, and Embase was completed by 2 reviewers from each database's inception to December 15, 2018. Study Selection: Inclusion criteria were randomized clinical trials that reported the effect of long-term (≥1 year) vitamin D supplementation on CVD events and all-cause mortality. Studies that did not include cardiovascular outcomes were excluded. Data Extraction and Synthesis: Data were abstracted independently by 2 authors. Random-effects models were used to report the risk ratios (RRs) and 95% CIs. Main Outcomes and Measures: Major adverse cardiovascular events was the primary outcome, and rates of myocardial infarction, stroke or cerebrovascular accident, CVD mortality, and all-cause mortality were the secondary end points. Results: Twenty-one randomized clinical trials were included (including 83 291 patients, of whom 41 669 received vitamin D and 41 622 received placebos). The mean (SD) age of trial participants was 65.8 (8.4) years; 61 943 (74.4%) were female. Only 4 trials had prespecified CVD as a primary end point. Vitamin D supplementation compared with placebo was not associated with reduced major adverse cardiovascular events (RR, 1.00 [95% CI, 0.95-1.06]; P = .85) nor the secondary end points of myocardial infarction (RR, 1.00 [95% CI, 0.93-1.08]; P = .92), stroke (RR, 1.06 [95% CI, 0.98-1.15]; P = .16), CVD mortality (RR, 0.98 [95% CI, 0.90-1.07]; P = .68), or all-cause mortality (RR, 0.97 [95% CI, 0.93-1.02]; P = .23). Results were generally consistent by sex, baseline 25-hydroxyvitamin D level, vitamin D dosage, formulation (daily vs bolus dosing), and presence or absence of concurrent calcium administration. Conclusions and Relevance: In this updated meta-analysis, vitamin D supplementation was not associated with reduced major adverse cardiovascular events, individual CVD end points (myocardial infarction, stroke, CVD mortality), or all-cause mortality. The findings suggest that vitamin D supplementation does not confer cardiovascular protection and is not indicated for this purpose.

The role of anticoagulation in venous thromboembolism primary prophylaxis in patients with malignancy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with cancer. As such, we conducted a meta-analysis of randomized controlled trials (RCTs) that evaluated anticoagulants as primary prophylaxis against VTE in cancer patients. METHODS: Pubmed/MEDLINE, Embase, and the Cochrane Library were screened for all RCTs that used anticoagulation therapy in cancer patients for primary prevention of VTE. The primary outcomes were VTE events. Secondary outcomes included all-cause mortality, VTE-related mortality and major bleeding. A random effects model was used to report the risk ratios (RR) with 95% confidence intervals (CIs), and odds ratios (ORs) with Bayesian 95% credible intervals for both direct and network meta-analyses, respectively. RESULTS: Twenty-four RCTs were included totaling 13,338 patients (7197 received anticoagulation and 6141 received placebo). The mean age ranged between 54.6 and 68.1 years, with 50.5% male. Compared with placebo, low-molecular-weight heparin (LMWH) or direct Xa inhibitors were associated with lower VTE events (RR 0.58; 95%CI 0.48-0.69, P < 0.001) and (RR 0.39; 95%CI 0.24-0.63, p < 0.001), respectively. LMWH was associated with decreased VTE and all-cause mortality when compared with placebo (P < 0.05). Regarding safety outcomes, LMWH and direct Xa inhibitors were not associated with increased risks of major bleeding (P > 0.05) when compared with placebo. Results regarding VTE events and major bleeding were consistent in both lung and pancreatic cancers. CONCLUSIONS: Both LMWH and direct Xa inhibitors were associated with a lower VTE events compared with placebo. However, this potentially protective effect must be balanced against the possible increased risk of bleeding for some patients.

Aspirin Efficacy in Primary Prevention: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The role of aspirin as a means of primary prevention remains controversial. AIM: We have conducted a meta-analysis of all randomized controlled trials (RCTs) to evaluate the role of aspirin in primary prevention. METHODS: Literature search was performed via PubMed, Embase, and the Cochrane Library for all related RCTs. All-cause mortality was the primary endpoint. Secondary endpoints included major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiovascular mortality, cerebrovascular events, and bleeding events. We used a random effects model to report the risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Our analysis included 17 RCTs (164,862 patients; 83,309 received aspirin and 81,744 received placebo). Our study did not demonstrate any significant reduction in all-cause mortality for patients treated with aspirin when compared with placebo (RR 0.97; 95% CI 0.93-1.01; P = 0.13). Sensitivity analysis performed by excluding healthy elderly (≥ 65) showed significant reductions in all-cause mortality in the aspirin-treated patients (RR 0.94; 95% CI 0.90-0.99; P = 0.01). There were no significant differences between both groups regarding cardiovascular mortality and cerebrovascular events (P > 0.05). However, aspirin-treated patients significantly reduced MACE and MI events (RR 0.89; 95% CI 0.85-0.93; P < 0.001 and RR 0.88; 95% CI 0.78-0.98; P = 0.02, respectively), respectively. However, aspirin was associated with a significantly higher incidence of bleeding, including major bleeding and intracranial bleeding (P < 0.001). CONCLUSIONS: Aspirin use in primary prevention has resulted in a lower incidence of MACE and MI without significantly effecting cerebrovascular events. However, aspirin was associated with a higher bleeding risk. Use of aspirin as a means of primary prevention should be thoroughly discussed with patients and pursued based on the risk of cardiovascular disease while also considering bleeding risk.