Dataset Information

Effect of Doxycycline on Aneurysm Growth Among Patients With Small Infrarenal Abdominal Aortic Aneurysms: A Randomized Clinical Trial.

ABSTRACT: Importance:Abdominal aortic aneurysms affect more than 3% of US older adults. Objective:To test whether doxycycline reduces the growth of abdominal aortic aneurysm over 2 years as measured by maximum transverse diameter. Design, Setting, and Participants:Parallel, 2-group, randomized clinical trial that was conducted at 22 US clinical centers between May 2013 and January 2017, and enrolled patients 50 years or older with small (3.5-5.0 cm for men, 3.5-4.5 cm for women) infrarenal aneurysms. The final date of follow-up was July 31, 2018. Interventions:Patients were randomized to receive twice daily for 2 years doxycycline 100 mg orally (as capsules) (n?=?133) or placebo (n?=?128). Main Outcomes and Measures:The primary outcome was change in abdominal aortic aneurysm maximum transverse diameter measured from CT images at baseline and follow-up at 2 years. Patients were assigned ranks based on the maximum transverse diameter (measured or imputed) of the aorta and also if they underwent aneurysm repair or died. The ranks were converted to scores having a normal distribution to facilitate the primary analysis ("normal scores"). Results:Of 261 patients randomized, no follow-up CT scans were obtained on 7 (3%), leaving a final analysis set of 129 patients assigned to doxycycline and 125 to placebo (mean [SD] age, 71.0 years [7.4 years], 35 women [14%]). The outcome normal scores used in the primary analysis were based on maximum transverse diameter (measured or imputed) in 113 patients (88%) in the doxycycline group and 112 patients (90%) in the placebo group; aneurysm repair in 13 (10%) and 9 (7%), and death in 3 (2%) and 4 (3%), respectively. The primary outcome, normal scores reflecting change in aortic diameter, did not differ significantly between the 2 groups, mean change in normal scores, 0.0262 vs -0.0258 (1-sided P?=?.71). Mean (SD) baseline maximum transverse diameter was 4.3 cm (0.4 cm) for doxycycline and 4.3 cm (0.4 cm) for placebo. At the 2-year follow-up, the change in measured maximum transverse diameter was 0.36 cm (95% CI, 0.31 to 0.40 cm) for 96 patients in the doxycycline group vs 0.36 cm (95% CI, 0.30 to 0.41 cm) for 101 patients in the placebo group (difference, 0.0; 95% CI, -0.07 to 0.07 cm; 2-sided P?=?.93). No patients were withdrawn from the study because of adverse effects. Joint pain occurred in 84 of 129 patients (65%) with doxycycline and 79 of 125 (63%) with placebo. Conclusions and Relevance:Among patients with small infrarenal abdominal aortic aneurysms, doxycycline compared with placebo did not significantly reduce aneurysm growth at 2 years. These findings do not support the use of doxycycline for reducing the growth of small abdominal aortic aneurysms. Trial Registration:ClinicalTrials.gov Identifier: NCT01756833.

SUBMITTER: Baxter BT

PROVIDER: S-EPMC7251450 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Doxycycline on Aneurysm Growth Among Patients With Small Infrarenal Abdominal Aortic Aneurysms: A Randomized Clinical Trial.

Baxter B Timothy BT Matsumura Jon J Curci John A JA McBride Ruth R Larson LuAnn L Blackwelder William W Lam Diana D Wijesinha Marniker M Terrin Michael M

JAMA 20200501 20

<h4>Importance</h4>Abdominal aortic aneurysms affect more than 3% of US older adults.<h4>Objective</h4>To test whether doxycycline reduces the growth of abdominal aortic aneurysm over 2 years as measured by maximum transverse diameter.<h4>Design, setting, and participants</h4>Parallel, 2-group, randomized clinical trial that was conducted at 22 US clinical centers between May 2013 and January 2017, and enrolled patients 50 years or older with small (3.5-5.0 cm for men, 3.5-4.5 cm for women) infr ...[more]

PMID: 32453369

Similar Datasets

Project description:Open repair of abdominal aortic aneurysms (AAAs) is occasionally performed in conjunction with additional procedures; however, how these concomitant procedures affect outcome is unclear. This study determined the frequency of additional procedures during elective open AAA repair and the effect on perioperative outcomes.All elective infrarenal open AAA repairs between January 2003 and November 2014 in the Vascular Study Group of New England (VSGNE) were identified. Patients were grouped by concomitant procedures, which included no concomitant procedure, renal artery bypass, lower extremity bypass, other abdominal procedure, or thromboembolectomy. Analyses were performed using multivariable logistic regression.Of 1314 patients who underwent elective AAA repair, 153 (11.6%) had a concomitant procedure, including renal bypass in 27 (2.1%), lower extremity bypass in 28 (2.1%), other abdominal procedures in 64 (4.9%), and thromboembolectomy in 48 (3.7%). Independent risk factors for 30-day mortality were renal bypass (odds ratio [OR], 7.2; 95% confidence interval [CI], 1.9-27.7), other abdominal procedures (OR, 4.8; 95% CI, 1.6-14.1), and thromboembolectomy (OR, 8.8; 95% CI, 3.1-24.9). Deterioration of renal function was predicted by renal bypass (OR, 5.1; 95% CI, 2.1-12.4) and thromboembolectomy (OR, 3.7; 95% CI, 1.8-7.6). Lower extremity bypass and thromboembolectomy were predictive of postoperative leg ischemia (OR, 8.9; 95% CI, 2.7-29.0; OR, 11.2; 95% CI, 4.4-28.8, respectively), and thromboembolectomy was also predictive of postoperative bowel ischemia (OR, 4.4; 95% CI, 1.6-12.0).Performing additional procedures during infrarenal open AAA repair is associated with increased morbidity and mortality in the postoperative period. Careful deliberation of the operative risks and the necessity of the additional interventions are therefore advised during operative planning. This study also highlights the importance of avoiding perioperative thromboembolic events.

Project description:ImportanceCurrently there is no drug therapy for abdominal aortic aneurysm (AAA).ObjectiveTo test the efficacy of the angiotensin receptor blocker telmisartan in slowing AAA growth in the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial.Design, setting, and participantsA randomized, double-blind, placebo-controlled trial recruited participants between September 6, 2011, and October 5, 2016, to evaluate the efficacy of telmisartan treatment in patients with AAA. Participants with 35- to 49-mm AAAs recruited from Australia, the Netherlands, and the US were randomized 1:1 to receive telmisartan, 40 mg, or identical placebo. Analyses were conducted according to intention-to-treat principles. Final follow-up was conducted on October 11, 2018, and data analysis was performed between June and November 2019.InterventionTelmisartan, 40 mg, or identical placebo.Main outcomes and measuresThe primary outcome of the difference in AAA growth, assessed on core imaging laboratory-read ultrasonographic scanning, was tested with linear mixed-effects models. Other outcomes included effects on blood pressure, computed tomographic (CT)-measured AAA diameter and volume, time to AAA-related events (AAA repair or mortality due to AAA rupture), and health-related quality of life.ResultsOf 300 intended participants, 210 were enrolled and randomized to receive telmisartan (n = 107) or placebo (n = 103). Of patients included in the intention-to-treat analysis (telmisartan: n = 106, placebo: n = 101), 183 were men (88%); mean (SD) age was 73.5 (7.9) years. At 1 year, participants receiving telmisartan had mean lower systolic (8.9; 95% CI, 4.1-13.8 mm Hg; P < .001) and diastolic (7.0; 4.3-9.8 mm Hg; P < .001) blood pressure levels compared with participants receiving placebo. A total of 188 participants (91%) received at least 2 ultrasonographic scans and 133 participants (64%) had at least 2 CT scans. There was no significant difference in ultrasonographic-assessed AAA growth rates among those assigned telmisartan (1.68 mm/y) or placebo (1.78 mm/y): mean difference, -0.11 mm/y (95% CI, -0.60 to 0.38 mm/y; P = .66). Telmisartan had no significant effects on AAA growth assessed by CT-measured AAA diameter (mean difference, -0.01 mm/y; 95% CI, -0.02 to 0.01 mm/y; P = .23) or volume (mean difference, -0.02 cm3/y; 95% CI, -0.04 to 0.00 cm3/y; P = .11), AAA-related events (relative risk, 1.35; 95% CI, 0.54-3.35; P = .52), or health-related quality of life (mean difference in physical component score at 24 months, 0.4; 95% CI, 0.4-0.4; P = .80). Hypotensive symptoms (eg, syncope) were twice as common among participants receiving telmisartan compared with placebo (28 [26%] vs 13 [13%]; P = .02), but overall adverse event rates were otherwise similar for both groups.Conclusions and relevanceThis underpowered study did not show a treatment effect for telmisartan on small AAA growth. Future trials will need to ensure adequate sample size and duration of follow-up.Trial registrationsanzctr.org.au Identifier: ACTRN12611000931976; ClinicalTrials.gov Identifier: NCT01683084.

Project description:Several reports suggest unexpectedly high rates of late abdominal aortic aneurysm (AAA) rupture occur after endovascular AAA repair (EVAR). However, a population-based study examining causes of late death after EVAR vs open surgical repair has not been performed.We performed a retrospective cohort study of patients undergoing infrarenal AAA repair using information from the Medicare inpatient hospital discharge records (MedPAR files), physician claim files (Part B files, 20% sample), and Medicare Denominator Files for the years 2001 to 2004. Using the Social Security Death Index, we identified all "late" deaths, defined as deaths occurring >30 days and after hospital discharge. We used the National Death Index to identify cause of death information; in particular, those deaths that were likely caused by late rupture. We compared causes of late death and survival between EVAR and open repair using Wilcoxon log-rank and rank-sum tests.Between 2001 and 2004, 13,971 patients underwent AAA repair (6119 EVAR, 7852 open repair). After a mean follow-up of 1.6 years in the EVAR cohort and 1.9 years in the open cohort, mortality rates were similar across repair type (15.4% EVAR, 15.9% open repair), with an adjusted odds ratio for death after open repair of 0.98 (95% confidence interval, 0.90-1.07). Of the 2194 documented deaths, 523 occurred before discharge or <or=30 days, and 1671 occurred >30 days and after hospital discharge. Cause of death information for the 1671 late deaths was available from the National Death Index for 1515 (91%). The 15 most common codes for causes of late death were dominated by cardiac disease (atherosclerotic heart disease, acute myocardial infarction) and pulmonary disease (lung cancer, respiratory failure). Causes of late death with specific mention of aneurysm were identified in 37 patients (2.4% of all deaths), but this event was not more common in EVAR or open repair (15 [0.3%] in the EVAR group, 22 [0.3%], in the open repair group; P = .71).Late deaths from aneurysm rupture after EVAR or open repair appear to be relatively infrequent and similarly distributed across procedure type. Our results emphasize that the effectiveness of EVAR is comparable to open AAA repair in preventing aneurysm-related death.

Project description:BACKGROUND:An abdominal aortic aneurysm (AAA) is an abnormal ballooning of the major abdominal artery. Some AAAs present as emergencies and require surgery; others remain asymptomatic. Treatment of asymptomatic AAAs depends on many factors but an important one is size of the aneurysm, as risk of rupture increases with aneurysm size. Large asymptomatic AAAs (> 5.5 cm in diameter) are usually operated on; very small AAAs (< 4.0 cm diameter) are monitored with ultrasonography. The optimal timing of surgery would benefit from further evidence. OBJECTIVES:This review compared long-term survival in patients with AAAs of diameter 4.0 to 5.5 cm who received immediate repair versus routine ultrasound surveillance. SEARCH METHODS:For this update the Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (February 2012) and CENTRAL (2012, Issue 1). Reference lists of relevant articles were checked for additional studies and the searches were supplemented by handsearches of recent conference proceedings and information from experts in the field. SELECTION CRITERIA:Randomised controlled trials in which men and women with asymptomatic AAAs of diameter 4.0 to 5.5 cm were randomly allocated to immediate repair or imaging-based surveillance at least every six months. Outcomes had to include mortality or survival. DATA COLLECTION AND ANALYSIS:Two authors (GF, MAMM) abstracted the data, which were cross-checked by the other authors (DJB, JTP). Due to the small number of trials, formal tests of heterogeneity and sensitivity analyses were not conducted. MAIN RESULTS:Four trials with a combined total of 3314 patients, the UK Small Aneurysm Trial (UKSAT), the Aneurysm Detection and Management (ADAM) trial, the Comparison of Surveillance Versus Aortic Endografting for Small Aneurysm Repair (CAESAR), and the Positive Impact of Endovascular Options for treating Aneurysms Early (PIVOTAL) fulfilled the inclusion criteria. The four trials showed an early survival benefit in the surveillance group (due to 30-day operative mortality with surgery) but no significant differences in long-term survival (adjusted hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.75 to 1.02, mean follow up 10 years (UKSAT); HR 1.21, 95% CI 0.95 to 1.54, mean follow up 4.9 years (ADAM); HR 0.76, 95% CI 0.30 to 1.93, median follow up 32.4 months (CAESAR); HR 1.01, 95% CI 0.49 to 2.07, mean follow up 20 months (PIVOTAL)). The meta analyses of mortality at one year (CAESAR and PIVOTAL only) and six years (UKSAT and ADAM only) revealed a non-significant association (Peto odds ratio at one year 1.15, 95% CI 0.59 to 2.25; Peto odds ratio at six years 1.11, 95% CI 0.91 to 1.34). AUTHORS' CONCLUSIONS:The results from the four trials to date demonstrate no advantage to early repair (via open or endovascular surgery) for small AAA (4.0 to 5.5 cm) and suggest that 'best care' for these patients favours surveillance. Furthermore, the more recent trials focused on the efficacy of endovascular aneurysm repair and still failed to show benefit. Thus, both open and endovascular repair of small AAAs are not supported by currently available evidence.

Project description:Background Intraluminal thrombus (ILT) within abdominal aortic aneurysms (AAAs) may be a potential marker for subsequent aneurysm growth. Purpose To investigate the role of ILT in AAA progression as assessed with CT and MRI. Materials and Methods This was a retrospective study, with patient data included from January 2004 to December 2018 at a Veteran Affairs medical center. Male patients with AAA who underwent contrast material-enhanced CT at baseline and CT or black-blood MRI at follow-up (minimal follow-up duration of 6 months) were included. The maximal AAA diameter was measured with multiplanar reconstruction, and the annual growth rate of aneurysms was calculated. Uni- and multivariable linear regression analyses were used to determine the relationship between demographic and imaging factors and aneurysm growth. Results A total of 225 patients (mean age, 72 years ± 9 [standard deviation]) were followed for a mean of 3.3 years ± 2.5. A total of 207 patients were followed up with CT, and 18 were followed up with MRI. At baseline, the median size of the AAA was 3.8 cm (interquartile range [IQR], 3.3-4.3 cm); 127 of 225 patients (54.7%) had ILT. When compared with AAAs without ILT, AAAs with ILT had larger baseline diameters (median, 4.1 cm [IQR, 3.6-4.8 cm] vs 3.4 cm [IQR, 3.2-3.9 cm]; P < .001) and faster growth rates (median, 2.0 mm/y [IQR, 1.3-3.2 mm/y] vs 1.0 mm/y [IQR, 0.4-1.8 mm/y]; P < .001). Small AAAs (size range, 3-4 cm) with ILT grew 1.9-fold faster than did those without ILT (median, 1.5 mm/y [IQR, 0.9-2.7 mm/y] vs 0.8 mm/y [IQR, 0.3-1.5 mm/y]; P < .001). Medium AAAs (size range, 4-5 cm) with ILT had 1.2-fold faster growth than did those without ILT (median growth, 2.1 mm/y [IQR, 1.4, 3.7 mm/y] vs 1.8 mm/y [IQR, 0.9, 2.0 mm/y]; P = .06). In multivariable analysis, baseline diameter and ILT were independently positively related to aneurysm growth rate (standardized regression coefficient, 0.43 [P < .001] and 0.15 [P = .02], respectively). Conclusion Both maximal cross-sectional aneurysm diameter and the presence of intraluminal thrombus are independent predictors of abdominal aortic aneurysm growth. © RSNA, 2020 Online supplemental material is available for this article.

Dataset Information

Effect of Doxycycline on Aneurysm Growth Among Patients With Small Infrarenal Abdominal Aortic Aneurysms: A Randomized Clinical Trial.

Publications

Effect of Doxycycline on Aneurysm Growth Among Patients With Small Infrarenal Abdominal Aortic Aneurysms: A Randomized Clinical Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets