Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial

Baron, John A.; Sandler, Robert S.; Bresalier, Robert S.; Lanas, Ángel; Morton, Dion; Riddell, Robert H.; Iverson, Erik; DeMets, David L.

doi:10.1016/s0140-6736(08)61490-7

Cited by 207 publications

(123 citation statements)

References 28 publications

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…About 25% of chronic NSAID users experience side effects such as gastrointestinal bleeding and renal toxicity (18,38), which restrict their use as chemopreventive agents. Selective COX-2 inhibitors have reduced gastrointestinal related adverse events (39) but increased risk of cardiovascular diseases (19,40). Selective COX-2 inhibitors may tip the natural balance between prothrombotic thromboxane A2 and antithrombotic prostacyclin, potentially increasing the possibility of a thrombotic cardiovascular event (41).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cyclooxygenase-2 by tetramethylpyrazine and its effects on A549 cell invasion and metastasis

Xiao

2012

Int J Oncol

View full text Add to dashboard Cite

Abstract. Cyclooxygenase (COX)-2 plays an important role in tumorigenesis and has been implicated to be a critical factor for invasion and metastasis of lung cancer. Tetramethylpyrazine (TMP), an effective component of the traditional Chinese medicine Chuanxiong, has been traditionally used in treating neurovascular and cardiovascular diseases. Recently TMP has been reported to have beneficial effect in cancer patients. However, the function and the mechanism of TMP in lung cancer have not been elucidated to date. In this study, we investigated the in vitro and in vivo effect of TMP in tumorigenesis and whether COX-2 is a molecular target of TMP. We showed that TMP exhibited a dose-and time-dependent inhibition on A549 cell proliferation by suppressing cell cycle progression. In vitro treatment of A549 cells with TMP resulted in a significant inhibition of invasion, associated with reduced activities of COX-2 and MMP-2/TIMP-2. Furthermore, in vivo experiments showed that TMP significantly suppressed metastatic growth of A549 cells and COX-2 expression in metastatic nude mouse model. This preclinical study provides the first evidence for the novel anti-tumor effects of TMP as a COX-2 pathway inhibitor in human adenocarcinoma cell line A549. These studies suggest that TMP may serve as an effective agent for the treatment and chemoprevention of non-small cell lung cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of cyclooxygenase-2 by tetramethylpyrazine and its effects on A549 cell invasion and metastasis

Xiao

2012

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…[16] Remarkably, patients receiving rofecoxib 50 mg showed a five-fold increased risk of myocardial infarction (MI) as compared to the patients receiving naproxen 1000 mg. These observations were confirmed in the APPROVE study [17] designed to evaluate the incidence of adenomatous polyps in patients treated with rofecoxib 25 mg compared to placebo. The results of this study demonstrated a two-fold increase in myocardial infarction risk in patients treated with rofecoxib versus placebo and resulted in the removal of the drug from the market.…”

Section: Nsaidsmentioning

confidence: 67%

“…In contrast to APPROVE [17], APC [18] and PreSAP [19] in colon polyp patients, the analysis of the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) [20] offered the opportunity to assess the effect of a COX-2 inhibitor (celecoxib) versus a traditional NSAID (naproxen) and placebo. While the results of the ADAPT trial was stopped prematurely because of concerns in the aftermath of the publication of the APC trial, ADAPT provides first prospective outcome trial evidence comparing a conventional NSAIDs versus a COX-2 selective agent.…”

Section: Nsaidsmentioning

confidence: 99%

Nonsteroidal Antiinflammatory Drugs, Acetaminophen, and Hypertension

et al. 2012

View full text Add to dashboard Cite

Selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) as well as acetaminophen belong to the most widely prescribed therapeutic agents worldwide. Their efficacy in pain relief notwithstanding, the use of NSAIDs is associated with an increased cardiovascular risk, which can be partly attributed to their blood pressure raising potential. Adequately powered placebo-controlled trials specifically evaluating the cardiovascular safety of NSAIDs vs. selective COX inhibitors are currently underway. This review summarizes the current knowledge on the cardiovascular effects of NSAIDs and acetaminophen, and their potential clinical consequences. 3

show abstract

“…Unfortunately, randomised clinical trials and observational studies have shown an increased risk of myocardial infarction, stroke, hypertension and heart failure during prolonged treatment of patients with highly selective COX-2 inhibitors [9,10]. The mechanisms underlying the cardiotoxicity of Coxibs remain a matter of active debate.…”

Section: Introductionmentioning

confidence: 99%

A novel nitro-oxy substituted analogue of rofecoxib reduces human colon cancer cell growth

et al. 2011

View full text Add to dashboard Cite

Rofecoxib is a specific COX-2 inhibitor able to exert antiproliferative activity against colorectal cancer cells. It was withdrawn from the market after the demonstration of an increased risk of cardiovascular complications after prolonged use. Nevertheless it remains an interesting compound for laboratory research as an experimental COX-2 inhibitor. In the present study the antiproliferative activity of a novel dinitro-oxy-substituted analogue of rofecoxib (NO-rofe), potentially less cardiotoxic, has been investigated in vitro on human colon cancer cells and compared with the action of the parent drug. Due to the fact that COX-2 inhibition is the main characteristic of coxibs we performed all experiments in COX-2-overexpressing (HT-29) and COX-2-negative (SW-480) human colon cancer cells, in order to elucidate whether the observed effects were dependent on COX-2 inhibition. Moreover, experiments were performed in order to evaluate whether COX-2 pharmacological inhibition may affect beta-catenin/E-cadherin signalling pathway.NO-rofe exerted a significant antiproliferative activity on COX-2 positive HT-29 human colon cancer cells, being less effective on the COX-2 negative SW-480 human colon cancer cell line. In particular, the rofecoxib analogue retained similar potencies with respect to COX-2 inhibition but was much more active than rofecoxib in inhibiting the growth of human colon cancer cells in vitro.In addition, this novel compound resulted in the induction of membrane β-catenin/E-cadherin expression, a feature that may significantly contribute to its antiproliferative activity.

show abstract

Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial

Cited by 207 publications

References 28 publications

Inhibition of cyclooxygenase-2 by tetramethylpyrazine and its effects on A549 cell invasion and metastasis

Inhibition of cyclooxygenase-2 by tetramethylpyrazine and its effects on A549 cell invasion and metastasis

Nonsteroidal Antiinflammatory Drugs, Acetaminophen, and Hypertension

A novel nitro-oxy substituted analogue of rofecoxib reduces human colon cancer cell growth

Contact Info

Product

Resources

About