Method of treating cardiovascular events using colchicine concurrently with an antiplatelet agent

1. A method of treating and/or reducing the risk of a cardiovascular event in a subject, the method comprising:

administering colchicine, a salt thereof, and/or any combination thereof to a subject at risk of a cardiovascular event or who has had a cardiovascular event;

wherein the cardiovascular event is acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke.

2. The method of claim 1 , wherein the composition is administered once per day.

3. The method claim 1 , wherein about 0.5 to about 0.75 mg of colchicine, a salt thereof, and/or any combination thereof is administered to the subject.

4. The method of claim 3 , wherein about 0.5 to 0.6 mg of colchicine, a salt thereof, and/or any combination thereof is administered to the subject.

5. The method of claim 3 , wherein about 0.6 mg of colchicine, a salt thereof, and/or any combination thereof is administered to the subject.

6. The method of claim 1 , wherein the composition is administered orally, topically, parenterally, ophthalmically, intraventricularly, intracranially, intraperitoneally, buccally, rectally, vaginally, intranasally, or by aerosol administration and/or inhalation spray.

7. The method of claim 1 , wherein the composition is administered in the form of a tablet, capsule, liquid dose, gel, or powder.

8. The method claim 1 , wherein the subject receives concurrent treatment with at least one anticoagulant agent or antithrombotic agent.

9. The method claim 8 , wherein the anticoagulant agent is one or more of novel oral anticoagulants (NOACs), coumarins or vitamin K antagonists, heparin, low molecular weight heparin, a synthetic pentasaccharide inhibitor of factor Xa, a factor Xa inhibitor, a thrombin inhibitor, and an antithrombin protein therapeutic.

10. The method of claim 9 , wherein:

(a) the NOAC is dabigatran, rivaroxaban, apixaban, or a combination thereof;

(b) wherein the coumarin or vitamin K antagonist is one or more of warfarin, acenocoumarol, phenprocoumon, atromentin, brodifacoum, and phenindione;

(c) wherein the factor Xa inhibitor is one or more of rivaroxaban, apixaban, edoxaban, and darexaban; and/or

(d) wherein the thrombin inhibitor is one or more of hirudin, lepirudin, bivalirudin, and ximelagatrain.

11. The method of claim 8 , wherein the antithrombotic agent is an antiplatelet agent or a thrombolytic agent.

12. The method of claim 11 , wherein the antiplatelet agent, the anticoagulant agent, and/or the thrombolytic agent is aspirin.

13. The method of claim 11 , wherein the antiplatelet agent is one or more of an irreversible cyclooxygenase inhibitor, an adenosine diphosphate (ADP) receptor inhibitor, a phosphodiesterase inhibitor, a protease-activated receptor-1 (PAR-1) antagonist, a glycoprotein inhibitor, an adenosine reuptake inhibitor, and a thromboxane inhibitor.

14. The method of claim 13 , wherein:

(a) the irreversible cyclooxygenase inhibitor is aspirin and/or triflusal;

(b) the ADP receptor inhibitor is clopidogrel, prasugrel, ticagrelor, ticlopidine, or a combination thereof;

(c) the phosphodiesterase inhibitor is cilostazol;

(d) the PAR-1 antagonist is vorapaxar;

(e) the glycoprotein inhibitor is abciximab, eptifibatide, tirofiban, or a combination thereof;

(f) the adenosine reuptake inhibitor is dipyridamole; and/or

(g) the thromboxane inhibitor is terutroban.

15. The method of claim 11 , wherein the thrombolytic agent is tissue plasminogen activator (t-PA).

16. The method of claim 15 , wherein the t-PA is alteplase, reteplase, tenecteplase, anistreplase, streptokinase, urokinase, or a combination thereof.

17. The method of claim 1 , further comprising co-administering to the subject a therapeutically effective amount of a second agent for the treatment and/or reduction of risk of the cardiovascular event.

18. The method of claim 17 , wherein the second agent is a statin.

19. The method of claim 18 , wherein the statin is atorvastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, simvastatin, pravastatin, any salt thereof, or any combination thereof.

20. The method of claim 1 , wherein the subject exhibits the symptoms of or is diagnosed with a coronary disease.

21. The method of claim 20 , wherein the coronary disease is a clinically stable coronary disease.

22. The method of claim 1 , wherein the subject has the symptoms of or is diagnosed with atherosclerotic vascular disease.

23. The method of claim 22 , wherein the subject is concurrently administered an agent for the treatment and/or reduction of the risk of an atherosclerotic vascular disease.

24. The method of claim 23 , wherein the atherosclerotic vascular disease is a coronary disease.

25. The method of claim 24 , wherein the coronary disease is a clinically stable coronary disease.

26. The method of claim 23 , wherein the agent is a statin.

27. The method of claim 26 , wherein the statin is atorvastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, simvastatin, pravastatin, a salt thereof, or any combination thereof.

28. The method of claim 1 , wherein the composition of colchicine is administered as an immediate release formulation.

29. The method of claim 1 , wherein the composition is administered for at least two years.

30. A method of treating and/or reducing the risk of acute coronary syndrome, out-of-hospital cardiac arrest, and/or noncardioembolic ischemic stroke in a human subject administered at least one of an antiplatelet agent, an anticoagulant agent, and an thrombolytic agent, the method comprising administering about 0.5 mg to about 0.75 mg of colchicine, a salt thereof, and/or any combination thereof to the subject.

31. A method of treating and/or reducing the risk of a cardiovascular event, which comprises administering about 0.5 mg to about 0.75 mg of colchicine, a salt thereof, and/or any combination thereof to a human subject,

wherein the human subject is concurrently administered an antiplatelet agent, an anticoagulant agent, a thrombolytic agent, or any combination thereof;

wherein the cardiovascular event is acute coronary syndrome, cardiac arrest, or noncardio-embolic ischemic stroke;

wherein acute coronary syndrome is acute myocardial infarction or unstable angina;

wherein cardiac arrest is associated with asystole, ventricular tachycardia, or ventricular fibrillation; and

wherein noncardio-embolic ischemic stroke is not attributable to atrial fibrillation or intracranial hemorrhage.