What is the effect of Tofacitinib (Xeljanz) on the heart?

From the Guidelines

Tofacitinib may increase the risk of major adverse cardiovascular events, including heart attack and stroke, particularly in patients with existing cardiovascular risk factors, as evidenced by the ORAL Surveillance study 1. The risk of cardiovascular events associated with tofacitinib is a significant concern, especially in patients over 50 with at least one cardiovascular risk factor. Key factors that increase the risk of cardiovascular events in patients taking tofacitinib include:

• Age 65 years or older
• Current or previous long-term smoking
• History of cardiovascular disease, such as heart attack or stroke
• History of cancer The mechanism of tofacitinib's increased risk of cardiovascular events is thought to be related to its inhibition of JAK signaling pathways, which may affect lipid metabolism and promote inflammation in blood vessels 1. Patients taking tofacitinib typically experience increases in cholesterol levels, which should be monitored regularly. Those with existing heart disease, high blood pressure, diabetes, or a history of smoking should discuss these risks with their healthcare provider before starting treatment. Regular cardiovascular monitoring is recommended during treatment, and the lowest effective dose should be used for the shortest duration necessary 1. Alternative medications may be considered for patients at high cardiovascular risk. It is essential to weigh the benefits of tofacitinib against the potential risks and to carefully monitor patients for signs of cardiovascular events. The European Medicines Agency recommends cautious use of JAK inhibitors, including tofacitinib, in patients at risk for adverse cardiovascular outcomes 1.

From the FDA Drug Label

1. Increased risk of death in people 50 years of age and older who have at least 1 heart disease (cardiovascular) risk factor and are taking XELJANZ 5 mg twice daily or XELJANZ 10 mg twice daily.
2. Increased risk of major cardiovascular events such as heart attack, stroke or death in people 50 years of age and older who have at least 1 heart disease (cardiovascular) risk factor and are taking XELJANZ 5 mg twice daily or XELJANZ 10 mg twice daily, especially if you are a current or past smoker

Tofacitinib (Xeljanz) may increase the risk of major cardiovascular events, including:

• Heart attack
• Stroke
• Death This risk is higher in people 50 years of age and older with at least one heart disease risk factor, especially if they are current or past smokers. 2

From the Research

Effect of Tofacitinib on the Heart

The effect of Tofacitinib (Xeljanz) on the heart is a topic of interest in various studies. Here are some key findings:

• Tofacitinib is associated with an increased risk of thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE) 3, 4.
• A study found that the incidence rates of DVT, PE, and arterial thromboembolism (ATE) were similar across tofacitinib doses and generally consistent with observational data and published incidence rates of other treatments 3.
• Another study found that tofacitinib was not shown to beilo-9c with an increased risk of major adverse cardiovascular events (MACE) or all-cause mortality compared to placebo, but a trend toward an increased risk of venous thromboembolism (VTE) events was observed 5.
• A post hoc analysis found that the risk of MACE was higher with tofacitinib versus tumour necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis and a history of atherosclerotic cardiovascular disease (ASCVD) 6.
• A systematic review and meta-analysis found that both 5mg and 10mg tofacitinib twice daily were safe to use, with similar risks of adverse drug events, serious adverse events, and adverse events leading to drug discontinuation 7.

Incidence Rates of Thromboembolic Events

The incidence rates of thromboembolic events with tofacitinib are as follows:

• DVT: 0.17 (0.09-0.27) and 0.15 (0.09-0.22) per 100 patient-years for 5mg and 10mg tofacitinib, respectively 3.
• PE: 0.12 (0.06-0.22) and 0.13 (0.08-0.21) per 100 patient-years for 5mg and 10mg tofacitinib, respectively 3.
• ATE: 0.32 (0.22-0.46) and 0.38 (0.28-0.49) per 100 patient-years for 5mg and 10mg tofacitinib, respectively 3.

Comparison with Other Treatments

Tofacitinib has been compared to other treatments, including TNFi, in terms of its effect on the heart:

• A study found that tofacitinib was associated with a higher risk of MACE compared to TNFi in patients with rheumatoid arthritis and a history of ASCVD 6.
• Another study found that tofacitinib was not shown to be with an increased risk of MACE or all-cause mortality compared to placebo 5.