scholarly journals Meta-analysis assessing cardiovascular outcomes with febuxostat versus allopurinol for patients with gout

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
D Patoulias ◽  
A Boulmpou ◽  
A Tranidou ◽  
A Nikolaidis ◽  
C E Papadopoulos ◽  
...  

Abstract Background Gout, the most common inflammatory arthritis in the USA, represents an established risk factor for cardiovascular disease and coronary artery disease mortality. In addition, patients with gout experience an increased risk for non-fatal myocardial infarction, while they might also feature increased risk for stroke. Recent real-world data also highlight the association between gout and atrial fibrillation, which inevitably augments cardiovascular burden. Allopurinol, a xanthine oxidase inhibitor, remains the uric acid-lowering treatment option of first choice, while febuxostat is prescribed, when allopurinol is contraindicated or not tolerated. Unfortunately, medication adherence among gout patients is poor, associated with age and related co-morbidities. Purpose We sought to determine the comparative efficacy of febuxostat versus allopurinol across surrogate cardiovascular outcomes of interest, by pooling data from the 2 dedicated cardiovascular outcome trials available so far. The motive for this analysis was the U.S. Food and Drug Administration (FDA) warning raised after the publication of the CARES trial, regarding the increased risk for cardiovascular and all-cause death with febuxostat compared to allopurinol. Methods We pooled data from the 2 dedicated cardiovascular outcome trials (CARES and FAST) and we assessed the following cardiovascular outcomes of interest: cardiovascular death, all-cause death, non-fatal myocardial infarction (MI), non-fatal stroke, fatal MI, fatal stroke, transient ischemic attack, hospitalization for heart failure, coronary revascularization, cerebrovascular revascularization and atrial fibrillation. Risk of bias was low across the included studies. Results Our analysis in a total of 12,318 patients with gout showed that febuxostat compared to allopurinol treatment does not confer significant risk reduction for any of the assessed, prespecified surrogate outcomes in a study population with significant cardiovascular co-morbidities (Figure 1). One third of patients enrolled in the FAST trial and 40% of the patients enrolled in the CARES trial had pre-existing cardiovascular disease, as depicted in Figure 2. Heterogeneity was low for the vast majority of the assessed outcomes, except for cardiovascular and all-cause death and fatal MI. Conclusions There is no significant difference across surrogate cardiovascular outcomes of interest between febuxostat and allopurinol in patients with gout and cardiovascular co-morbidities. Febuxostat seems to be a safe treatment alternative to allopurinol, despite initial concerns in terms of its cardiovascular safety. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chan Soon Park ◽  
Eue-Keun Choi ◽  
Bongseong Kim ◽  
Kyung-Do Han ◽  
So-Ryoung Lee ◽  
...  

Abstract NTM infection demonstrates an increasing incidence and prevalence. We studied the impact of NTM in cardiovascular events. Using the Korean nationwide database, we included newly diagnosed 1,730 NTM patients between 2005 and 2008 and followed up for new-onset atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), ischemic stroke (IS), and death. Covariates-matched non-NTM subjects (1:5, n = 8,650) were selected and analyzed. Also, NTM infection was classified into indolent or progressive NTM for risk stratification. During 4.16 ± 1.15 years of the follow-up period, AF, MI, HF, IS, and death were newly diagnosed in 87, 125, 121, 162, and 468 patients. In multivariate analysis, NTM group showed an increased risk of AF (hazard ratio [HR] 2.307, 95% confidence interval [CI] 1.560–3.412) and all-cause death (HR 1.751, 95% CI 1.412–2.172) compared to non-NTM subjects, whereas no significant difference in MI (HR 0.868, 95% CI 0.461–1.634), HF (HR 1.259, 95% CI 0.896–2.016), and IS (HR 1.429, 95% CI 0.981–2.080). After stratification, 1,730 NTM patients were stratified into 1,375 (79.5%) indolent NTM group and 355 (20.5%) progressive NTM group. Progressive NTM showed an increased risk of AF and mortality than indolent NTM group. Screening for AF and IS prevention would be appropriate in these high-risk patients.


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.


Author(s):  
Miles Fisher

EMPA-REG OUTCOME was a landmark trial with the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin, which demonstrated significant reductions in major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) driven by reductions in cardiovascular deaths and accompanied by an early reduction in hospitalisation for heart failure. This was followed by cardiovascular outcome trials with canagliflozin, dapagliflozin and ertugliflozin. The CANVAS Program was an integrated analysis of the CANVAS and CANVAS-R trials with canagliflozin. It demonstrated a significant reduction in MACE, but not in any of the components, and there was an unexpected increase in amputations and fractures with canagliflozin. The DECLARE-TIMI 58 trial with dapagliflozin had two co-primary endpoints. A composite endpoint of cardiovascular death or hospitalisation for heart failure was significantly reduced, but there was no significant difference in MACE comparing dapagliflozin with placebo. Analysis of patients with a prior myocardial infarction, however, demonstrated significant reductions in MACE. The VERTIS CV trial with ertugliflozin was disappointing as there was no difference in MACE comparing ertugliflozin and placebo. In all four trials a reduction in hospitalisation for heart failure was observed in patients with type 2 diabetes, regardless of whether they had existing atherosclerotic cardiovascular disease or increased cardiovascular risk. Pre-specified renal outcomes were reduced with empagliflozin, canagliflozin and dapagliflozin, and these drugs are now commonly used in the management of people with type 2 diabetes. It is hard to envisage an ongoing role for ertugliflozin in routine clinical management as the evidence for its cardiovascular benefit is not convincing.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Chinedu C Ochin ◽  
Joseph Salami ◽  
Emir Veledar ◽  
Mahdi O Garelnabi ◽  
Katherine L Tucker

Background: FGF-23 is an endocrine regulator of phosphate metabolism as well as also a potent biomarker that mediates cardiovascular remodeling, with markedly elevated plasma concentration associated with the occurrence of morbid cardiovascular events such as myocardial infarction. This association usually indicates risk of developing further adverse cardiovascular events in individuals that are already susceptible to repeat morbid cardiovascular outcomes. This cross-sectional epidemiological study aims at investigating the risk association between FGF-23 and individuals in the 8 th year cohort of the Boston Puerto Rican Health Study (BPRHS) that have self-reported clinical cardiovascular disease in the form of myocardial infarction. Methods: FGF-23 plasma concentration was measured by ELISA in 496 participants of the fourth wave of the Boston Puerto Rican Health Study (BPRHS). Multivariate logistic regressions were used to analyze the cross-sectional association of plasma FGF-23 quartile distribution with self-reported clinical diagnosis of myocardial infarction (MI). Results: The crude model for the association between FGF-23 and MI showed increased risk across the 2 nd , 3 rd and 4 th quartiles, OR (95% CI); 1.27 (0.48-3.34), 1.13 (0.42-3.04), and 3.13 (1.33-7.33), respectively. The relationship with the highest vs lowest quartile remained significant after adjusting for age, sex and BMI, OR (95% CI); 2.91 (1.15-7.36). With further adjustment for diabetes, smoking, plasma total cholesterol, HDL cholesterol and triglycerides, results were attenuated, and the latter comparison was no longer statistically significant, OR (95% CI); 2.15 (0.79-5.79). The test for trend across the quartiles yielded a p value of 0.03. Conclusion: Within this population of older Puerto Rican adults, FGF-23 was not significantly associated with increased likelihood of self-reported history of myocardial infarction. Longitudinal studies, using clinical parameters that objectively measure the progression of cardiovascular disease are needed to assess the prognostic value of FGF-23 for future cardiovascular outcomes.


Author(s):  
Molly M. Shores ◽  
Thomas J. Walsh ◽  
Anna Korpak ◽  
Chloe Krakauer ◽  
Christopher W. Forsberg ◽  
...  

Background Testosterone treatment is common in men, although risks for major cardiovascular events are unclear. Methods and Results A study was conducted in US male veterans, aged ≥40 years, with low serum testosterone and multiple medical comorbidities and without history of myocardial infarction, stroke, venous thromboembolism, prostate cancer, or testosterone treatment in the prior year. For the primary outcome, we examined if testosterone treatment was associated with a composite cardiovascular outcome (incident myocardial infarction, ischemic stroke, or venous thromboembolism). Testosterone use was modeled as intramuscular or transdermal and as current use, former use, and no use. Current testosterone users were compared with former users to reduce confounding by indication. The cohort consisted of 204 857 men with a mean (SD) age of 60.9 (9.9) years and 4.7 (3.5) chronic medical conditions. During follow‐up of 4.3 (2.8) years, 12 645 composite cardiovascular events occurred. In adjusted Cox regression analyses, current use of transdermal testosterone was not associated with risk for the composite cardiovascular outcome (hazard ratio [HR], 0.89; 95% CI, 0.76–1.05) in those without prevalent cardiovascular disease, and in those with prevalent cardiovascular disease was associated with lower risk (HR, 0.80; 95% CI, 0.70–0.91). In similar analyses, current use of intramuscular testosterone was not associated with risk for the composite cardiovascular outcome in men without or with prevalent cardiovascular disease (HR, 0.91; 95% CI, 0.80–1.04; HR, 0.98; 95% CI, 0.89–1.09, respectively). Conclusions In a large cohort of men without a history of myocardial infarction, stroke, or venous thromboembolism, testosterone treatment was not associated with increased risk for incident composite cardiovascular events.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Demetria Hubbard ◽  
Lisandro D. Colantonio ◽  
Robert S. Rosenson ◽  
Todd M. Brown ◽  
Elizabeth A. Jackson ◽  
...  

Abstract Background Adults who have experienced multiple cardiovascular disease (CVD) events have a very high risk for additional events. Diabetes and chronic kidney disease (CKD) are each associated with an increased risk for recurrent CVD events following a myocardial infarction (MI). Methods We compared the risk for recurrent CVD events among US adults with health insurance who were hospitalized for an MI between 2014 and 2017 and had (1) CVD prior to their MI but were free from diabetes or CKD (prior CVD), and those without CVD prior to their MI who had (2) diabetes only, (3) CKD only and (4) both diabetes and CKD. We followed patients from hospital discharge through December 31, 2018 for recurrent CVD events including coronary, stroke, and peripheral artery events. Results Among 162,730 patients, 55.2% had prior CVD, and 28.3%, 8.3%, and 8.2% had diabetes only, CKD only, and both diabetes and CKD, respectively. The rate for recurrent CVD events per 1000 person-years was 135 among patients with prior CVD and 110, 124 and 171 among those with diabetes only, CKD only and both diabetes and CKD, respectively. Compared to patients with prior CVD, the multivariable-adjusted hazard ratio for recurrent CVD events was 0.92 (95%CI 0.90–0.95), 0.89 (95%CI: 0.85–0.93), and 1.18 (95%CI: 1.14–1.22) among those with diabetes only, CKD only, and both diabetes and CKD, respectively. Conclusion Following MI, adults with both diabetes and CKD had a higher risk for recurrent CVD events compared to those with prior CVD without diabetes or CKD.


2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Lennart Dimberg ◽  
Bo Eriksson ◽  
Per Enqvist

Abstract Background In 1993, 1000 randomly selected employed Swedish men aged 45–50 years were invited to a nurse-led health examination with a survey on life style, fasting lab tests, and a 12-lead ECG. A repeat examination was offered in 1998. The ECGs were classified according to the Minnesota Code. Upon ethical approval, endpoints in terms of MI and death over 25 years were collected from Swedish national registers with the purpose of analyzing the independent association of ECG abnormalities as risk factors for myocardial infarction and death. Results Seventy-nine of 977 participants had at least one ECG abnormality 1993 or 1998. One hundred participants had a first MI over the 25 years. Odds ratio for having an MI in the group that had one or more ECG abnormality compared with the group with two normal ECGs was estimated to 3.16. 95%CI (1.74; 5.73), p value 0.0001. One hundred fifty-seven participants had died before 2019. For death, similarly no statistically significant difference was shown, OR 1.52, 95%CI (0.83; 2.76). Conclusions Our study suggests that presence of ST- and R-wave changes is associated with an independent 3–4-fold increased risk of MI after 25 years follow-up, but not of death. A 12-lead resting ECG should be included in any MI risk calculation on an individual level.


2021 ◽  
Vol 8 (5) ◽  
pp. 53
Author(s):  
Ivana Škrlec ◽  
Jasminka Talapko ◽  
Martina Juzbašić ◽  
Robert Steiner

The growing body of evidence shows a significant difference in the circadian rhythm of cardiovascular disease based on biological sex. The incidence of cardiovascular disease varies between women and men. Additionally, biological sex is vital for the timely application of therapy—chronotherapy, which benefits both sexes. This study aimed to examine the potential difference of single nucleotide polymorphisms (SNPs) of the circadian rhythm genes ARNTL, CLOCK, CRY2 and PER2 in women and men with myocardial infarction. A cross-sectional study was conducted, including 200 patients with myocardial infarction. Altogether, ten single nucleotide polymorphisms in the ARNTL, CLOCK, CRY2 and PER2 genes were analyzed. The Chi-square test yielded statistically significant differences in CLOCK gene rs11932595 polymorphism in a recessive genotype model between women and men with a p-value of 0.03 and an odds ratio 2.66, and a corresponding 95% confidence interval of 1.07 to 6.66. Other analyzed polymorphisms of the circadian rhythm genes ARNTL, CRY2, and PER2 did not significantly differ between the sexes. According to the study’s current results, the CLOCK gene’s genetic variability might affect myocardial infarction concerning biological sex.


Author(s):  
Kyle P Hornsby ◽  
Kensey Gosch ◽  
Amy L Miller ◽  
Jonathan P Piccini ◽  
Renato D Lopes ◽  
...  

Background: Little data are available regarding differences in prognosis and health status between new-onset and prior atrial fibrillation (AF) among patients with acute myocardial infarction (AMI). Methods: The TRIUMPH study enrolled 4340 AMI patients who received longitudinal follow-up including SF-12 health status assessments through 1 year post-AMI. We compared 1-year mortality, rehospitalization, and functional status according to AF type (none, prior, new) after adjusting for differences in baseline characteristics. Results: A total of 212 AMI patients (4.9%) had prior AF and 254 (5.9%) had new-onset AF. Compared with no AF, new AF was associated with older age, male sex, first MI, worse baseline physical function, home atrioventricular nodal blocker use, and worse ventricular function (c-index 0.77). Rates of 1-year mortality were 6.2%, 14.5%, and 13.0%, and 1-year rehospitalization rates were 29.1%, 44.2%, and 36.8% for no, prior, and new AF, respectively. After multivariable adjustment, neither prior nor new AF was associated with increased 1-year mortality, and only prior AF was associated with increased risk of 1-year rehospitalization (Figure). After adjusting for baseline SF-12 physical function scores, patients with prior AF had lower 1-year scores than those with no AF (40.6 vs. 43.7, p <0.003), whereas patients with new AF had similar scores (42.9 vs. 43.7, p=0.36). Conclusion: New-onset AF during AMI is associated with a number of comorbidities but, unlike prior AF, is not associated with adverse outcomes. These results raise the question of whether AF is itself a cause of or simply a marker of comorbidities leading to downstream adverse outcomes after AMI.


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