Drug-induced Raynaud phenomenon following initiation of metoprolol succinate

A 69-year-old man with hypertension and hyperlipidemia presented to the emergency department with exertional angina. Coronary artery catheterization demonstrated 80% stenosis in the left anterior descending artery. After stent placement, he was started on acetylsalicylic acid, clopidogrel, and metoprolol succinate 50 mg daily.

Five days later, the patient presented to our cardiology clinic and reported new, intermittent, painful discoloration of his fingers and toes bilaterally, precipitated by cold exposure. He had no history of smoking, Raynaud phenomenon, or similar symptoms. On examination, we saw sharp demarcations of distal pallor and proximal cyanosis on 4 fingers (Figure 1). We saw similar but less prominent findings on his toes. We discontinued metoprolol and counselled him on strategies to prevent Raynaud symptoms, such as avoiding cold exposure and wearing warm gloves. His symptoms resolved within 1 week and have not recurred over the past 18 months.

Figure 1:

Sharp demarcation of distal pallor and proximal cyanosis in 4 fingers, characteristic of Raynaud phenomenon, in a 69-year-old man taking metoprolol.

Raynaud phenomenon has been linked to more than 562 medications, with vasoactive nervous system agents (i.e., migraine therapies and stimulants), cardiovascular drugs, and immunomodulators among the most implicated medications.¹ Nonselective β-blockers are well-known triggers, but even β₁-selective agents like metoprolol can exacerbate Raynaud phenomenon in susceptible patients.¹ The precise pathophysiological mechanisms remain incompletely understood but may involve increased sympathetic activation, endothelial dysfunction, or reduced erythrocyte deformability.² As such, β₁ selectivity alone does not protect against Raynaud phenomenon; ancillary properties such as intrinsic sympathomimetic activity and vasodilation are also important.² A meta-analysis estimated that 7% of patients taking β-adrenoceptor blockers reported peripheral vasoconstriction, compared with 4.6% on placebo, although data were not stratified by β-blocker subtype.² Symptoms often resolve within days to weeks of drug discontinuation or dose reduction.³

In our patient, the close temporal association between starting metoprolol and symptom onset, combined with rapid symptom resolution after stopping the medication, strongly suggested medication-induced Raynaud phenomenon. Clinicians should be aware that β₁-selective blockers can also cause Raynaud phenomenon.