A Proposal to Incorporate Trial Data Into a Hybrid American College of Cardiology/American Heart Association Algorithm for the Allocation of Statin Therapy in Primary Prevention.

I greatly appreciate the interest of Dr. Woronow in my recent study published in the Journal (1). Protamine binds with heparin or low-molecular-weight heparin to form a stable ion pair with no anticoagulant activity. This compound is routinely used during cardiopulmonary bypass surgery and is also administered to reverse the effect of heparin in patients in stable condition after invasive cardiac catheterization (e.g., post-transplant evaluation, fractional flow reserve estimation not requiring percutaneous coronary interventions [PCIs]). Protamine, as mentioned by the author, is not only important to reverse anticoagulation in case of major bleeding after PCI, but it is also crucial in the uncommon event of cardiac or coronary perforation during procedures that require large doses of heparin (2). There are several reasons that protamine cannot be routinely used to avoid bleeding after PCI. First, the allergic reactions to protamine are not uncommon and can lead to serious anaphylaxis. Second, even though protamine has been shown to be safe in small series, case-control, and randomized studies, its usefulness has not been proven in large contemporary randomized trials (3). Third, its safety has been tempered with case reports of ischemic complications in patients treated with protamine (4). Fourth, the use of the radial artery for access has diminished the utility of protamine reversal in favor of radial artery patency requiring anticoagulation with heparin. The role of protamine should be explored further, and larger, randomized trials need to be planned. In the meantime, patient selection for use of protamine is important. Patients with seafood allergies or previous use of protamine should not be given this drug. However, patients at very high risk of bleeding (e.g., elderly women presenting with acute coronary syndrome and who had femoral access for PCI) would be ideal candidates for protamine administration for heparin reversal, especially if there are bleeding events (i.e., hematoma, retroperitoneal bleed). Rebound thrombogenicity and allergic reactions to protamine are valid concerns that need to be addressed. Protamine remains a useful tool in the armamentarium of interventional cardiologists, and its judicious use is recommended.