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In this meta-analysis, rosiglitazone, a peroxisome-proliferator–activated receptor agonist used for glucose control in type 2 diabetes, was found to be associated with an increased risk of myocardial infarction and death from cardiovascular causes. These findings raise safety concerns, but further analyses of patient-level data are needed to draw definitive conclusions. Rosiglitazone (Avandia) is widely used to treat patients with type 2 diabetes mellitus. In this meta-analysis of 42 trials, rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes. Thiazolidinedione drugs are widely used to lower blood glucose levels in patients with type 2 diabetes mellitus. In the United States, three such agents have been introduced: troglitazone, which was removed from the market because of hepatotoxicity, and two currently available agents, rosiglitazone (Avandia, GlaxoSmithKline) and pioglitazone (Actos, Takeda). The thiazolidinediones are agonists for peroxisome-proliferator–activated receptor γ (PPAR-γ). PPAR-γ receptors are ligand-activated nuclear transcription factors that modulate gene expression, lowering blood glucose primarily by increasing insulin sensitivity in peripheral tissues. 1 , 2 Rosiglitazone was introduced in 1999 and is widely used as monotherapy or in fixed-dose combinations with either metformin (Avandamet, . . .

Five-year data showed that among patients with type 2 diabetes and a BMI of 27 to 43, bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing or resolving hyperglycemia, even among those with a BMI of less than 35. Observational studies 1 – 6 and randomized, controlled trials, which have generally been short-term studies, 7 – 19 have shown that bariatric surgery, when used specifically to treat diabetes, significantly improves glycemic control and reduces cardiovascular risk factors. In the Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial, we reported that, at 1 year and 3 years after randomization, both gastric bypass and sleeve gastrectomy were superior to intensive medical therapy alone in achieving excellent glycemic control (i.e., glycated hemoglobin ≤6.0%), reducing cardiovascular risk, improving quality of life, and decreasing medication use. 8 – 10 The current article provides results of the final, 5-year . . .

At 3 years of follow-up, among obese patients with uncontrolled type 2 diabetes who were randomly assigned to receive intensive medical therapy with or without bariatric surgery, significantly more patients in the surgery groups achieved glycemic control. Bariatric surgery has recently emerged as a potentially useful treatment for type 2 diabetes mellitus. 1 Observational studies 2 – 5 and randomized, controlled trials 6 – 10 have shown that procedures including Roux-en-Y gastric bypass, sleeve gastrectomy, gastric banding, and biliopancreatic diversion significantly improve glycemic control and favorably affect cardiovascular risk factors. In the Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial, we found that 1 year after randomization, gastric bypass and sleeve gastrectomy were superior to intensive medical therapy alone in achieving glycemic control and reducing cardiovascular risk factors while decreasing dependency on pharmacotherapy for diabetes management. 7 Although bariatric surgery yields . . .

This randomized trial involving patients with osteoarthritis or rheumatoid arthritis who were at increased cardiovascular risk showed the noninferiority of celecoxib to naproxen or ibuprofen with respect to cardiovascular safety. Nonsteroidal antiinflammatory drugs (NSAIDs) were introduced in the 1960s and became the most widely prescribed class of drugs in the world, with more than 100 million prescriptions issued annually in the United States alone. 1 NSAIDs inhibit cyclooxygenase (COX), which reduces pain and inflammation through the inhibition of prostaglandins. However, the COX enzyme is also present in gastric mucosa, where it stimulates gastroprotective prostaglandins. The identification of two isoforms, COX-1 and COX-2, and the recognition that antiinflammatory and analgesic effects are mediated through COX-2 inhibition — whereas the gastrointestinal toxic effects are linked to COX-1 inhibition — resulted in the development . . .

ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication. We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006). Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data elements, the potential for ClinicalTrials.gov to address selective publication of clinical trials will be limited. Please see later in the article for the Editors' Summary.

In this trial, intravascular ultrasonography was used to compare the effects of atorvastatin versus rosuvastatin on regression of coronary atherosclerosis. Both statins led to regression in two thirds of patients, with no significant difference between their effects. Randomized clinical trials have consistently shown that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) reduce cardiovascular event rates. 1 – 9 The favorable effects of statins extend across a range of levels of low-density lipoprotein (LDL) cholesterol, with no apparent lower threshold for a benefit. 3 , 9 , 10 In parallel, imaging trials have shown that intensive statin regimens slow the progression of coronary atherosclerosis and may even result in disease regression in some patients. 11 , 12 Accordingly, guidelines for cardiovascular disease prevention have increasingly emphasized that lowering LDL cholesterol levels with statins is the primary goal of lipid-modulating therapy. 13 , 14 Available statins differ considerably . . .

Atherosclerotic plaque results from a complex interplay between lipid deposition, inflammatory changes, cell migration and arterial wall injury. Over the past two decades, clinical trials utilizing invasive arterial imaging modalities, such as intravascular ultrasonography, have shown that reducing levels of atherogenic lipoproteins, mainly serum LDL-cholesterol (LDL-C), to very low levels can safely reduce overall atherosclerotic plaque burden and favourably modify plaque composition. Classically, this outcome has been achieved with intensive statin therapy. Since 2016, newer and potent lipid-lowering strategies, such as proprotein convertase subtilisin–kexin type 9 inhibition, have shown incremental effects on plaque regression and risk of clinical events. Despite maximal reduction in plasma LDL-C levels, considerable residual cardiovascular risk remains in some patients. Therefore, there is a need to study therapeutic approaches that address residual risk beyond LDL-C reduction to promote plaque stabilization or regression. Contemporary imaging modalities, such as coronary computed tomography angiography, enable non-invasive assessment of the overall atherosclerotic plaque burden as well as of certain local plaque characteristics. This technology could allow further study of plaque stabilization and regression using novel therapeutic approaches. Non-invasive plaque assessment might also offer the potential to guide personalized management strategies if validated for this purpose.In this Review, Sarraju and Nissen summarize the clinical trial evidence for coronary atherosclerotic plaque stabilization and regression with plasma LDL-cholesterol-lowering therapy and other treatments. Invasive and non-invasive imaging modalities used to assess plaque burden and composition are discussed.

Diabetes is a multisystem disorder associated with a nearly twofold excess risk for a broad range of adverse cardiovascular outcomes including coronary heart disease, stroke, and cardiovascular death. Liraglutide is a human glucagon-like peptide receptor analog approved for use in patients with type 2 diabetes mellitus (T2DM). To formally assess the cardiovascular safety of liraglutide, the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial was commenced in 2010. LEADER is a phase 3B, multicenter, international, randomized, double-blind, placebo-controlled clinical trial with long-term follow-up. Patients with T2DM at high risk for cardiovascular disease (CVD) who were either drug naive or treated with oral antihyperglycemic agents or selected insulin regimens (human NPH, long-acting analog, or premixed) alone or in combination with oral antihyperglycemics were eligible for inclusion. Randomized patients are being followed for up to 5 years. The primary end point is the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. LEADER commenced in September 2010, and enrollment concluded in April 2012. There were 9,340 patients enrolled at 410 sites in 32 countries. The mean age of patients was 64.3 ± 7.2 years, 64.3% were men, and mean body mass index was 32.5 ± 6.3 kg/m2. There were 7,592 (81.3%) patients with prior CVD and 1,748 (18.7%) who were high risk but without prior CVD. It is expected that LEADER will provide conclusive data regarding the cardiovascular safety of liraglutide relative to the current standard of usual care for a global population of patients with T2DM.

ObjectiveLipoprotein(a) (Lp(a)) is an important genetically determined risk factor for atherosclerotic vascular disease (ASCVD). With the development of Lp(a)-lowering therapies, this study sought to characterise patterns of Lp(a) levels in a global ASCVD population and identify racial, ethnic, regional and gender differences.MethodsA multicentre cross-sectional epidemiological study to estimate the prevalence of elevated Lp(a) in patients with a history of myocardial infarction, ischaemic stroke or peripheral artery disease conducted at 949 sites in 48 countries in North America, Europe, Asia, South America, South Africa and Australia between April 2019 and July 2021. Low-density lipoprotein cholesterol (LDL-C) and Lp(a) levels were measured either as mass (mg/dL) or molar concentration (nmol/L).ResultsOf 48 135 enrolled patients, 13.9% had prior measurements of Lp(a). Mean age was 62.6 (SD 10.1) years and 25.9% were female. Median Lp(a) was 18.0 mg/dL (IQR 7.9–57.1) or 42.0 nmol/L (IQR 15.0–155.4). Median LDL-C was 77 mg/dL (IQR 58.4–101.0). Lp(a) in women was higher, 22.8 (IQR 9.0–73.0) mg/dL, than in men, 17.0 (IQR 7.1–52.2) mg/dL, p<0.001. Black patients had Lp(a) levels approximately threefold higher than white, Hispanic or Asian patients. Younger patients also had higher levels. 27.9% of patients had Lp(a) levels >50 mg/dL, 20.7% had levels >70 mg/dL, 12.9% were >90 mg/dL and 26.0% of patients exceeded 150 nmol/L.ConclusionsGlobally, Lp(a) is measured in a small minority of patients with ASCVD and is highest in black, younger and female patients. More than 25% of patients had levels exceeding the established threshold for increased cardiovascular risk, approximately 50 mg/dL or 125 nmol/L.Trial registration number

Background The EXAMINE trial tested the efficacy and safety of alogliptin, an inhibitor of dipeptidyl peptidase 4, compared with placebo in 5380 patients with type 2 diabetes and a recent acute coronary syndrome. Because alogliptin is cleared by the kidney, patients were stratified according to screening renal function within two independently randomized strata: (1) estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73m 2 and (2) eGFR < 60 ml/min/1.73m 2 . We aim to assess the efficacy and safety of alogliptin vs. placebo according to the renal function strata. Methods Cox-proportional hazard models with an interaction term by renal function strata were used. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke. Results Patient characteristics were balanced within each renal function strata. In total, 3946 patients were randomized within the eGFR ≥ 60 stratum, and 1434 patients within the eGFR < 60 stratum. The effect of alogliptin was modified by the renal function strata. Primary outcome: eGFR ≥ 60 HR = 0.81, 95%CI, 0.65–0.99, and eGFR < 60 HR = 1.20, 95%CI, 0.95–1.53; interaction p  = 0.014. Cardiovascular death: eGFR ≥ 60 HR = 0.61, 95%CI, 0.42–0.88, and eGFR < 60 HR = 1.16, 95%CI, 0.82–1.65; interaction p  = 0.013. Non-fatal MI: eGFR ≥ 60 HR = 0.86, 95%CI, 0.66–1.13, and eGFR < 60 HR = 1.48, 95%CI, 1.07–2.06; interaction p  = 0.013. Conclusions Alogliptin may benefit patients with eGFR ≥ 60, but may be detrimental to patients with eGFR < 60 ml/min/1.73m 2 . These hypothesis-generating findings require further validation to assess the potential benefit and risk of alogliptin across the renal function spectrum among patients with type 2 diabetes and a recent acute coronary syndrome. Trial registration ClinicalTrials.gov, NCT00968708