NSAIDs on CV conditions

Mechanisms and Efficacy

Hasom (Rachel) Lee, Rong Shan Liu, Stephanie Li, Joshua-Ryan Wye-Yan Heung

PHM142 Fall 2015Coordinator: Dr. Jeffrey HendersonInstructor: Dr. David Hampson

What are NSAID’s?

Non-Steroidal Anti-Inflammatory Drugs

Common over the counter drug

Analgesic (painkiller), antipyretic (lower fevers), anti-inflammatory properties

http://www.mcbuzz.com/2011/seo-101-how-to-choose-keywords-a-lesson-from-bayer-aspirin/http://dccrossfit.com/2014/07/ibuprofen/http://www.cvs.com/shop/health-medicine/pain-fever/non-aspirin-pain-relief/aleve-all-day-strong-naproxen-sodium-tablets-220-mg-skuid-367001

NSAID

Traditional Uses

Osteoarthritis

Low back pain

Headache

Rheumatoid Arthritis

Mild pain relief

http://www.heartmdinstitute.com/health-topics/alternative-medicine/grounding-earthing/106-grounding-healthy-heart http://robertsontrainingsystems.com/blog/should-we-train-people-in-pain/

Aspirin for Cardiovascular Therapy

Anti-thrombotic drugs that prevent cardiovascular events

Dose: 75-325mg/day

Most common: 81mg/day

Adverse Reactions:

GI damage (major bleeding)

Associated with higher doses

Economic implications

http://samadimd.com/health-politics/aspirin-now-recommended-for-patients-at-high-risk-for-heart-disease

Mechanism of NSAIDs

Phospholipid

Arachidonic Acid

Prostaglandin H2

PGE2TXA2

COX (PGH synthase)

NSAID

NSAID Mechanism

Platelet Phase- Normal State

platelet

endothelium

Factor VIII and von Willebrand Factor (vWF)

Platelet Phase - Adhesion

platelet

exposed collagen

Platelet Phase - Activation

Activated platelet releases:

Fibrinogen (forms a mesh around the platelet as the scaffold for platelet binding)

ADP (binds to P2Y, increase in intracellular [Ca2+])

COX-1 synthesizes TXA2 (binds to thromboxane-prostanoid receptor)

Result:

Platelet shape change (disc to round with extensions)

Maturation of GPIIa/IIIa (fibrinogen receptor)

Net Result: platelet plug formation

COX-1 and COX-2

Clinical Evidence: Aspirin Therapy in the Secondary Prevention of Cardiovascular Disease

Study design: Meta-analysis

Number of studies included: 16 secondary prevention studies

Population: 17 000 individuals at high average risk

Results:

Decreased in risk of recurrent major coronary events: 20%

Decreased in risk of recurrent stroke: 19%

Adverse Effects to Consider in Aspirin Therapy● Aspirin therapy may not be right for you; always

consult a doctor first

● Possible adverse effects:

- Damage to the protective mucous layer in the GI tract

- Lead to increased risk of GI ulcers and bleeding

- How?

- No formation of prostaglandins

- Prostaglandins modulate many aspects of mucosal defense

inhibition inhibition

Comparison of NSAIDs (Aspirin) and Warfarin

Anticoagulant, extrinsic pathway, vitamin k antagonist

Indirectly targets clotting factor II, VII, IX, X

By competitively inhibiting vitamin K epoxide reductase and Vitamin K quinone reductase -> decrease in active vitamin KH2

Adverse effects : hemorrhage, necrosis of soft tissue, teratogenicity (birth defects)

Reverse adverse effects: stop giving warfarin, give vitamin K and prothrombin

Do not consume with NSAIDs

No magic bullet, different drugs for different patients

Why We (Future Pharmacists) Care? Many NSAIDS - such as aspirin - are over-the-

counter drugs

Help prevent people from purchasing aspirin to treat CV events unless a doctor have recommended it to them

Helps reduce the chance of adverse effects

Summary

NSAIDs: Non-Steroidal Anti-Inflammatory Drugs

NSAIDs exert their anti-inflammatory and anti-thrombotic effect through COX inhibition

Aspirin acetylates Ser 530 on COX. This covalent modification permanently blocks the enzyme.

Clinical evidence that support the use of daily aspirin associated with secondary prevention cardiovascular

Adverse effects of aspirin therapy: mucosal injury and bleeding

References

Antithrombotic Trialists' (ATT) Collaboration. (2009). Aspirin in the primary and secondary prevention of

vascular disease:collaborative meta-analysis of individual participant data from randomized trials. Lancet.

373: 1849-1860.

Casado-Arroyo, R., Sostres, C., & Lanas, A. (2013). Optimizing the use of aspirin for cardiovascular

prevention. Drugs. 73(8): 803-14.

Dorsam RT, Kunapuli SP. (2004). Central role of the P2Y12 receptor in platelet activation. J Clin Invest.

113(3):340-345.

Flower RJ. (2003). The development of COX2 inhibitors. Nat Rev Drug Discov. 2(3):179-191.

Gasparyan, A. Y., Watson, T., & Lip, G. Y. H. (2008). The role of aspirin in cardiovascular prevention. Journal of

the American College of Cardiology. 51(19): 1829-1843.

Iwamoto J, Yoshifumi S, Honda A, & Matsuzaki Y. (2013). Clinical features of gastroduodenal injury associated

with long-term low-dose aspirin therapy. World J Gastroenterol.19(11): 1673–1682.

Mayhew, M.S. (2010). Aspirin for preventing cardiovascular damage. Journal for Nurse Practitioners. 6(2):

147-148.

Sadler JE. (1998) Biochemistry and genetics of von willebrand factor. Annu Rev Biochem. 67:395-424.

(1994). Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in

Atrial Fibrillation II Study. Lancet. 343: 687-91.