Efficacy and safety of aspirin for cardiovascular risk prevention in younger and older age: an updated systematic review and meta-analysis

Author(s):  
Dario Calderone ◽  
Antonio Greco ◽  
Salvatore Ingala ◽  
Federica Agnello ◽  
Antonio Gabriele Franchina ◽  
...  

Aims - The efficacy and safety of aspirin for primary cardiovascular disease (CVD) prevention is controversial. The aim of this study was to investigate the merits of aspirin in subjects with no overt CVD, with a focus on age as a treatment modifier. Methods and results - Randomized trials comparing aspirin use versus no aspirin use or placebo were included. The primary efficacy outcome was all-cause death. The primary safety outcome was major bleeding. Subgroups analyses were conducted to investigate the consistency of the effect sizes in studies including younger and older individuals, using a cut-off of 65 years. A total of 21 randomized trials including 173,810 individuals at a mean follow-up of 5.3 years were included. Compared with control, aspirin did not reduce significantly the risk of all-cause death (risk ratio 0.96, 95% CI 0.92-1.00, p=0.057). Major adverse cardiovascular events were significantly reduced by 11%, paralleled by significant reductions in myocardial infarction and transient ischemic attack. Major bleeding, intracranial hemorrhage, and gastrointestinal bleeding were significantly increased by aspirin. There was a significant age interaction for death (p for interaction=0.007), with aspirin showing a statistically significant 7% relative benefit on all-cause death in studies including younger patients. Conclusions - The use of aspirin in subjects with no overt cardiovascular disease was associated with a neutral effect on all-cause death and a modest lower risk of major cardiovascular events at the price of an increased risk in major bleeding. The benefit of aspirin might be more pronounced in younger individuals.

2020 ◽  
Vol 12 (549) ◽  
pp. eaay6570 ◽  
Author(s):  
Jonas Bovijn ◽  
Kristi Krebs ◽  
Chia-Yen Chen ◽  
Ruth Boxall ◽  
Jenny C. Censin ◽  
...  

Inhibition of sclerostin is a therapeutic approach to lowering fracture risk in patients with osteoporosis. However, data from phase 3 randomized controlled trials (RCTs) of romosozumab, a first-in-class monoclonal antibody that inhibits sclerostin, suggest an imbalance of serious cardiovascular events, and regulatory agencies have issued marketing authorizations with warnings of cardiovascular disease. Here, we meta-analyze published and unpublished cardiovascular outcome trial data of romosozumab and investigate whether genetic variants that mimic therapeutic inhibition of sclerostin are associated with higher risk of cardiovascular disease. Meta-analysis of up to three RCTs indicated a probable higher risk of cardiovascular events with romosozumab. Scaled to the equivalent dose of romosozumab (210 milligrams per month; 0.09 grams per square centimeter of higher bone mineral density), the SOST genetic variants were associated with lower risk of fracture and osteoporosis (commensurate with the therapeutic effect of romosozumab) and with a higher risk of myocardial infarction and/or coronary revascularization and major adverse cardiovascular events. The same variants were also associated with increased risk of type 2 diabetes mellitus and higher systolic blood pressure and central adiposity. Together, our findings indicate that inhibition of sclerostin may elevate cardiovascular risk, warranting a rigorous evaluation of the cardiovascular safety of romosozumab and other sclerostin inhibitors.


2020 ◽  
Vol 26 (44) ◽  
pp. 5739-5745
Author(s):  
Jieqiong Guan ◽  
Wenjing Song ◽  
Pan He ◽  
Siyu Fan ◽  
Hong Zhi ◽  
...  

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.


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.


2020 ◽  
Vol 11 ◽  
Author(s):  
Ha Young Jang ◽  
Jae Hyun Kim ◽  
Yun-Kyoung Song ◽  
Ju-Young Shin ◽  
Hae-Young Lee ◽  
...  

Aims: Conflicting data exist on whether an association exists between antidepressants and the risk of major adverse cardiovascular events (MACEs) in patients with depression. This may be due to the use of various study designs and residual or unmeasured confounding. We aimed to assess the association between antidepressant use and the risk of MACEs while considering various covariates, including severity of depression and the cardiovascular disease (CVD) risk score.Methods: Patients newly diagnosed with depression with no history of ischemic heart disease and stroke were followed-up from 2009 to 2015. We conducted Cox proportional hazard regression analysis to estimate hazard ratios (HRs) for each antidepressant for MACE risk.Result: We followed-up (median, 4.4 years) 31,830 matched patients with depression (15,915 antidepressant users and 15,915 non-users). In most patients (98.7%), low-dose tricyclic antidepressants (TCAs) were related with a significantly increased risk of MACEs [adjusted HR = 1.20, 95% confidence interval (CI) = 1.03–1.40]. Duration response relationship showed a gradually increasing HR from 1.15 (95% CI = 0.98–1.33; &lt;30 days of use) to 1.84 (95% CI = 1.35–2.51; ≥365 days of use) (p for trend &lt;0.01). High Korean atherosclerotic CVD risk score (≥7.5%) or unfavorable lifestyle factors (smoking, alcohol intake, and exercise) were significantly associated with MACEs.Conclusion: Even at low doses, TCA use was associated with MACEs during primary prevention. Longer duration of TCA use correlated with higher HR. Careful monitoring is needed with TCA use in patients with no known CVD history.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jie Wang ◽  
Yangjing Xue ◽  
Saroj Thapa ◽  
Luping Wang ◽  
Jifei Tang ◽  
...  

Data on the association between age-related macular degeneration (AMD) and cardiovascular disease and mortality are conflicting. The purpose of this report is to conduct a systematic review to better understand the role of AMD as a risk factor for CVD events and mortality. We searched Medline (Ovid) and Embase (Ovid) for trials published from 1980 to 2015. We included 20 cohort studies that reported relative risks with 95% confidence intervals for the association of AMD and cardiovascular events and mortality, involving 29,964,334 participants. In a random-effects model, the adjusted RR (95% confidence interval [CI]) associated with AMD was 1.08 (1.00–1.117) for all-cause mortality (8 studies) and 1.18 (0.98–1.43) for cardiovascular disease mortality (5 studies). The pooled RR (95% CI) was 1.17 (0.94–1.45) for coronary heart disease (CHD; 3 studies) and 1.13 (0.93–1.36) for stroke (8 studies). Findings from this systematic review support that AMD is associated with increased risk of all-cause mortality. The evidence that AMD predicts incident CVD events or CVD mortality remains inclusive and warrants further study in the future.


2011 ◽  
Vol 162 (1) ◽  
pp. 115-124.e2 ◽  
Author(s):  
Jeffrey S. Berger ◽  
Anuradha Lala ◽  
Mori J. Krantz ◽  
Gizelle S. Baker ◽  
William R. Hiatt

2021 ◽  
Author(s):  
Yuttana Wonngsalap ◽  
Supakorn Ungsriwong ◽  
Wanalee Kumtepm ◽  
Surasak Saokaew ◽  
Vichai Senthong ◽  
...  

Abstract Purpose To assess the efficacy and safety of prasugrel at low doses compared to clopidogrel by looking at the occurrence of major adverse cardiac events (MACE) and major bleeding in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Methods We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for eligible randomized controlled trials (RCTs) and observational studies assessing efficacy and safety of low-dose prasugrel versus clopidogrel in patients with ACS or undergoing PCI up to May 22, 2020. We did a meta-analysis using a random-effects model to estimate relative risks (RRs). The primary efficacy and safety endpoints were MACE and major bleeding, respectively. Results Six RCTs (n = 6,131) and six observational studies (n = 31,426) were included. There was no MACE reduction in patients receiving low-dose prasugrel compared with those receiving clopidogrel (RR 1.02, 95%CI 0.91 to 1.14), but there was an increased risk of major bleeding (RR 1.35, 95%CI 1.10 to 1.67). Conclusions Low-dose prasugrel yields no increase in efficacy when compared with clopidogrel, but it does expose patients to an increased risk of bleeding. Most studies considered here were conducted in Japan. Studies conducted with non-Asian patients may find that low-dose prasugrel offers a more favorable efficacy and risk profile. Considering the results of this analysis we believe low-dose prasugrel should be prescribed with extreme caution as it may result in bleeding events without any additional benefit over clopidogrel.


2016 ◽  
Vol 106 (1) ◽  
pp. 21-27 ◽  
Author(s):  
S. Upala ◽  
A. Sanguankeo ◽  
V. Jaruvongvanich

Objectives: Gallstone disease shares certain risk factors with cardiovascular disease, particularly metabolic risk factors. Patients with gallstone disease may be at increased risk of cardiovascular disease. Several recent studies exploring the effect of gallstone disease on cardiovascular disease outcomes demonstrated inconsistent results. Design: We conducted a systematic review and meta-analysis of cohort, case–control, and cross-sectional studies that compared the risk of developing cardiovascular disease events in patients with gallstone disease versus non-gallstone disease controls. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate the pooled hazard ratio, odd ratio, and 95% confidence interval. Results: Data were extracted from six studies involving 176,734 cases and 803,714 controls. The pooled hazard ratio of cardiovascular events in patients with gallstone disease was 1.28 (95% confidence interval: 1.23–1.33, I2 = 42%). The pooled odd ratio of cardiovascular events in patients with gallstone disease was 1.82 (95% confidence interval: 1.47–2.24, I2 = 68%). Conclusions: Our study demonstrated a statistically significant increase in the risk of cardiovascular disease among patients with gallstone disease.


ESC CardioMed ◽  
2018 ◽  
pp. 3092-3098
Author(s):  
Natalie Staplin ◽  
Colin Baigent

The term ‘meta-analysis’ refers to a statistical method for combining the results of several (often many) studies or experiments in order to arrive at an overall conclusion about the size and variability of the measure of interest. In the context of cardiovascular disease, such studies are most often randomized trials of therapies for the prevention or treatment of cardiovascular events, such as myocardial infarction or stroke. The specialty has now witnessed several decades of success in identifying effective treatments for cardiovascular diseases, and the technique of meta-analysis of randomized trials has played an important role in this success. Not all meta-analyses are made equal, however, and it is important to be aware of the limitations of the method. This chapter considers how the technique can be best employed to guide treatment decisions, while also highlighting the limitations of meta-analysis when the information available is inadequate or potentially biased.


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