Slide 1

Dual antiplatelet therapy(DAPT)Dr. Ameel Toma

29/10/2016

DAPTThe use of another antiplatelet drug in addition to aspirin. as clopidgrel ,the commonest or prasugrel or Ticagrelor

DAPTWhy? What are indication? angina ? ACS ? Heart failure? What is the risk?For how long we use them?

Interesting question?When was aspirin first used?

When was aspirin used for treatment of IHD?

Medicines made from willow and other salicylate-rich plants appear in Egyptian pharonic pharmacology papyri [1] from the second millennium BC. Hippocrates referred to their use of salicylic tea to reduce fevers around 400 BC

1853: French chemist Charles Frdric Gerhardt determines the chemical structure of salicyclic acid and chemically synthesises acetylsalicylic acid.1876: The first rigorous clinical trial of salicin finds that it induces remission of fever and joint inflammation in patients with rheumatism (Lancet 1876;1:383).

1897: While working for pharmaceutical company Bayer, German chemist Felix Hoffmann, finds that adding an acetyl group to salicylic acid reduces its irritant properties and Bayer patents the process.

1899: Acetylsalicyclic acid is named Aspirin by Bayer. The letter A stands for acetyl, spir is derived from the plant known as Spiraea ulmaria (meadowsweet), which yields salicin, and in was a common suffix used for drugs at the time of the first stable synthesis of acetylsalicylic acid.

1950: Aspirin enters the Guinness World Records for being the most frequently sold painkiller.Aspirin's popularity declined after the development of acetaminophen/paracetamol in 1956 and ibuprofen in 1962

1971: John Vane, professor of pharmacology at the University of London, publishes research describing aspirins mechanism of action (dose-dependent inhibition of prostaglandin synthesis) (Nature New Biology 1971;231:232). He later wins a Nobel prize (1982) for this work.

1974: Data from the first randomised controlled trial of aspirin in the secondary prevention of death from heart attack show a reduction in total mortality of 12% at 6 months and 25% at 12 months but the results are statistically inconclusive (BMJ 1974;1:436).

By the end of the 1980s, aspirin was widely used as a preventive drug for heart attacks and had regained its former position as the top-selling analgesic in the U.S.

1977 andreas Gruntzig first coronary angioplasty.

After Balloon angioplasty there was risk of acute & late closure. Acute closure: a- elastic recoil- 10 % b- acute thrombosis: intimal tear & dissection.

Late closure: due to restenosis .

Coronary stents were, therefore, developed to overcome these issues,-by scaffolding the balloon-dilated artery- sealing the dissection flaps-and preventing late recoil.

Stent

1986: Sigwart &Puel - first stent implanted in coronary artery.

However, this new technology was not without its drawbacks. These initial stents had high metallic density, resulting in a high incidence of stent thrombosis(ST).were still at a significant risk of in-stent restenosis(ISR) about 20-30 %.

Stent thrombosis, associated with 30 days mortality of 25 %

Stent thrombosis:Aspirin alone is not enough !!???ASA + warfarin --- increase risk of bleeding

Stent thrombosis:The development of new antiplatelet agents led to a breakthrough in the use of coronary stents with the adoption of a dual anti-platelet treatment (DAPT), combining aspirin with a thienopyridine (1996).

1st is TiclopidinClopidogrelPrasugrelTicagrelor

Indication of DAPT:1- PCI

Risk of DAPT:Serious GI bleeding are 2- to 4-fold more common in patients who take 75 to 300 mg/d of aspirin compared with controls.

Need for surgery whether elective or emergency.

Proton Pump Inhibitors and DAPTPPIs should be used in patients with a historyof prior gastrointestinal bleeding treated with DAPT (Class I). In patients with increased risk of gastrointestinalbleeding, including those with advanced age and thosewith concomitant use of warfarin, steroids, or nonsteroidal anti-inflammatory drugs, use of PPIs is reasonable (Class IIa). Routine use of PPIs is not recommended for patients atlow risk of gastrointestinal bleeding (Class III)

How long?Depend on:1- underlying condition( ACS or SIHD).2- Type of Stent( BMS, DES).3-DES(old or new generation).4- Intensification of antiplatelet therapy, withthe addition of a P2Y12 inhibitor to aspirin monotherapy,necessitates a fundamental tradeoff betweendecreasing ischemic risk and increasing bleeding risk.

Therefore, in patients with SIHD treated with DES, the minimum recommendedduration of DAPT has been decreased from 12 to 6 months

Compared with oral anticoagulation therapy alone, theaddition of DAPT to oral anticoagulant therapy results inat least a 2- to 3-fold increase in bleeding complications

Dual Antiplatelet Therapy of Clopidogrel and Aspirin in Secondary Prevention of Ischemic Stroke: Evidence and Indications.Su Y1, Cheng X1, Dong Q1.Author informationAbstractNowadays the dual antiplatelet therapy (DAPT) becomes more widely used in patients with ischemic stroke. Nevertheless, controversies exist for indications of DAPT. In view of evidence-based medicine analysis, patients with high-risk transient ischemic attack and minor stroke, severe symptomatic intracranial artery stenosis, symptomatic intracranial and extracranial artery stenosis causing artery-to-artery embolism, ischemic stroke attributed to aortic arch plaques, high-risk atrial fibrillation not suitable for oral anticoagulants, intracranial and extracranial stent implantation, and ischemic stroke with acute coronary syndrome may gain great benefit from DAPT of clopidogrel and aspirin. In clinical practice, individualized antiplatelet therapy strategies should be taken by weighing risks of ischemia and hemorrhage.

For patients with ischemic stroke or TIA and AF who are unable to take oral anticoagulants, aspirin alone is recommended (Class I; Level of Evidence A). The addition of clopidogrel to aspirin therapy, compared with aspirin therapy alone, might be reasonable (Class Iib)

Platelet Function Testing, Genetic Testing, and Switchingof P2Y12 InhibitorsTo date, no RCT has demonstrated thatroutine platelet function testing or genetic testing toguide P2Y12 inhibitor therapy improves outcome; thus,the routine use of platelet function and genetic testing isnot recommended (Class III: No Benefit).