What are the recommendations for managing cardiovascular risk in patients taking Rinvoq (upadacitinib)?

From the Guidelines

For managing cardiovascular risk in patients taking Rinvoq (upadacitinib), healthcare providers should prioritize lifestyle modifications and pharmacological interventions based on the latest guidelines, such as the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. The management of cardiovascular risk in patients taking Rinvoq should focus on reducing the risk of major adverse cardiovascular events (MACE) by implementing evidence-based strategies.

Key Recommendations:

• Adopting a healthy and balanced diet, such as the Mediterranean or DASH diets, is recommended to help reduce blood pressure (BP) and cardiovascular disease (CVD) risk 1.
• Restricting free sugar consumption and discouraging the consumption of sugar-sweetened beverages is also recommended 1.
• Stopping tobacco smoking and referring patients to smoking cessation programs is crucial, as tobacco use strongly and independently causes CVD, CVD events, and all-cause mortality 1.
• Among all BP-lowering drugs, ACE inhibitors, ARBs, dihydropyridine CCBs, and diuretics have demonstrated the most effective reduction of BP and CVD events, and are therefore recommended as first-line treatments to lower BP 1.
• For patients with multiple cardiovascular risk factors, consider using the lowest effective dose of Rinvoq (15 mg daily rather than 30 mg) when possible, and monitor lipid profiles regularly, as Rinvoq can cause dose-dependent increases in total cholesterol, LDL, and HDL levels.
• Blood pressure should be checked routinely, and any hypertension should be managed according to standard guidelines, with a target BP of <130/80 mm Hg 1.
• If a patient develops a cardiovascular event while on Rinvoq, temporarily discontinuing the medication may be necessary until the event is stabilized. These recommendations are based on the latest clinical trial data and guidelines, which emphasize the importance of lifestyle modifications and evidence-based pharmacological interventions in reducing cardiovascular risk in patients taking Rinvoq.

From the FDA Drug Label

Thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis, have occurred in patients treated for inflammatory conditions with JAK inhibitors, including RINVOQ. Many of these adverse events were serious and some resulted in death In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers. Major Adverse Cardiovascular Events Inform patients that RINVOQ/RINVOQ LQ may increase their risk of major adverse cardiovascular events (MACE) including myocardial infarction, stroke, and cardiovascular death Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5. 4)].

Cardiovascular Risk Management:

• Avoid RINVOQ/RINVOQ LQ in patients that may be at increased risk of thrombosis.
• Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events.
• If symptoms of thrombosis occur, patients should discontinue RINVOQ/RINVOQ LQ and be evaluated promptly and treated appropriately.
• Patients should be managed according to clinical guidelines for the management of hyperlipidemia.
• Assess lipid parameters approximately 12 weeks after initiation of treatment, and thereafter according to the clinical guidelines for hyperlipidemia. 2

From the Research

Cardiovascular Risk with Rinvoq Treatment

The management of cardiovascular risk in patients taking Rinvoq (upadacitinib) is a critical consideration due to the potential for serious heart-related events.

• The US Food and Drug Administration (FDA) issued a drug safety communication and required revisions to the Boxed Warning for Rinvoq to include information about the risk of serious heart-related events, cancer, blood clots, and death 3.
• A study analyzing adverse event reports found that higher proportions of tofacitinib/XR AEs were related to cardiovascular events (14.1%) compared to baricitinib and upadacitinib 3.
• Another study assessing the safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs found that one case of major adverse cardiovascular event was reported in patients receiving upadacitinib during the placebo-controlled phase of the study 4.
• A post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme found that major adverse cardiovascular events were more frequent in higher-risk cohorts, but were generally similar across treatment groups, including upadacitinib and adalimumab 5.

Recommendations for Managing Cardiovascular Risk

• Patients with higher cardiovascular risk, such as those aged ≥50 years with ≥1 cardiovascular risk factor, should be closely monitored for major adverse cardiovascular events, malignancy, and venous thromboembolism 5.
• The use of upadacitinib in patients with potentially dangerous cardiac arrhythmias should be exercised with caution, and clinical examination and thorough medical history review should be conducted to identify individuals at risk before initiating treatment 6.
• Patients with previous cardiac history should be monitored closely and treated aggressively with standard medical therapy if they develop symptoms suggestive of heart failure 7.