Tag Archives: ACS

Drug-to-drug interaction. New evidences on Morphine and delayed onset of action of antiplatelet agents.

8 Mag

A recently published article entitled  “Chest pain relief in patients with acute myocardial infarction” (European Heart Journal: Acute Cardiovascular Care April 22, 2015) address in a very well documentrd way the topic about drug-to-drug interactiono between morfine and antiplatelets agents in STEMI patients.

Guido Parodi, a lead interventional cardiologist in Cardiovascular and Thoracic Department of Careggi Hospital in Florence, (Italy) author of the article, highlights the fact that “despite the complete absence of rigorous studies designed to assess the impact of morphine administration in patients with AMI, clinical practice guidelines for the management of patients with STEMI strongly recommend the use of morphine for analgesia.”

As indicated in the article recent literature indicates an increased risk of mortality in STEMI patients treated with Morphine.

The analysis of CRUSADE registry in 2005 has shown how patients treated with morphine had a higher adjusted risk of death than patients not treated with morphine even after using a propensity score matching method. This is a non randomized trial and so influenced from potential bias, and the hypothesis that morphine was administered to higher-risk patients is also to be considered. But an additional potential explanation of morphine’s negative impact on AMI outcome may be related to drug-to-drug interactions.

Biologically a cause effect relation can be explained, because morphine inhibits gastric emptying, delaying absorption and so decreasing peak plasma levels of orally administered drugs in general and antiplatelet agents in this particular case.
This was very well demonstrated in a 2015 study from the same author “Morphine is associated with a delayed activity of oral antiplatelet agents in patients with ST elevation acute myocardial infarction undergoing primary PCI” (Parodi G, Bellandi B, Xanthopoulou I, et al. Circ Cardiovasc Interv Epub ahead of print January 2015) in whom the negative impact of morphine on platelet inhibition was not only limited to patients who vomited (patients with vomiting were excluded), but morphine-treated patients clearly showed higher residual platelet reactivity compared with patients who did not receive morphine.

In ATLANTIC Trial (Montalescot G, van ‘t Hof AW, Lapostolle F, et al.; ATLANTIC Investigators. Prehospital ticagrelor in ST-elevation myocardial infarction. New Engl J Med 2014; 371: 1016–1027), STEMI patients who did not receive morphine had a significant improvement in the ECG-based primary end point (ST-segment resolution), reflecting better myocardial reperfusion,with a significant “p” value for interaction between morphine use and time of ticagrelor administration. Professor Montalescot one of the lead authors of this Trial noted:“Co-administration of morphine in the ambulance may have delayed ticagrelor’s onset of action. To what extent this interaction may have affected our results remains unknown at this stage.”

So what to do with analgesia strategy in STEMI patients?

Given the key importance of platelet inhibition in patients treated by PPCI for STEMI and the absence of data that may support a potential clinical benefit of morphine in patients with acute myocardial infarction, more caution should be used regarding morphine administration in STEMI patients, and a restricted morphine use seems to be reasonably recommended.

Morphine administration has to be reserved, as suggested in the article, just for level of pain ≥ 7 on the base of a numerical rating scale (NRS) related value.

Courtesely from Dott. Guido Parodi

Courtesely from Dott. Guido Parodi

For lower chest pain intensity (NRS ≤ 7) alternative strategies has to be persecuted.
The author indicates paracetamol (1 g) or aspirin (≥300 mg) as alternative of choice to reduce chest pain as well demonstrated in letterature.
It has also to be considered how first line agents, currently indicated from STEMI guidelines, as Beta- blocker and Nitrates are able to reduce AMI-related chest pain until the definitive pain relief effect obtained with myocardial mechanical reperfusion.

Bottom Line

The first impact to reduce chest pain has to be reserved to Nitrates or B-blockers (where all contraindications are excluded).

After this NRS has to be evaluated and the use of Morphine is indicated only for values above 7. For lower values Paracetamol or Aspirin are the agents of choice.



  • Parodi G. Chest pain relief in patients with acute myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2015 Apr 22. pii: 2048872615584078. [Epub ahead of print] Review.PMID:25904757

  • Meine TJ, Roe MT, Chen AY, et al. Association of intravenous morphine use and outcomes in acute coronary syndromes: Results from the CRUSADE Quality Improvement Initiative. Am Heart J 2005; 149: 1043–1049.

  • Parodi G,Valenti R, Bellandi B, et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation
    myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol 2013; 61: 1601–1606
  • Parodi G, Bellandi B, Valenti R, et al. Comparison of double (360 mg) ticagrelor loading dose with standard (60 mg) prasugrel loading dose in STEMI patients: The Rapid Activity of Platelet Inhibitor Drugs (RAPID) primary PCI 2 study.
    Am Heart J 2014; 167: 909–914.
  • Nimmo WS, Heading RC, Wilson J, et al. Inhibition of gastric emptying and drug absorption by narcotic analgesics. Br J Clin Pharmacol 1975; 2: 509–513.
  • Parodi G, Xanthopoulou I, Bellandi B, et al. Ticagrelor crushed tablets administration in STEMI patients: The MOJITO study. J Am Coll Cardiol 2015; 65: 511–512.
  • Montalescot G, van ‘t Hof AW, Lapostolle F, et al.; ATLANTIC Investigators. Prehospital ticagrelor in ST-elevation myocardial infarction. New Engl J Med 2014; 371: 1016–1027
  • Duggan ST and Scott LJ. Intravenous paracetamol (acetaminophen). Drugs 2009; 69: 101–113.
  • Zijlstra F, Ernst N, de Boer MJ, et al. Influence of prehospital administration of aspirin and heparin on initial patency of
    the infarct-related artery in patients with acute ST elevation myocardial infarction. J Am Coll Cardiol 2002; 39: 1733–1737
  • Yusuf S, Sleigh P, Rossi P, et al. Reduction in infarct size and chest pain by early intravenous beta blockade in suspected
    acute myocardial infarction. Circulation 1983; 67: 132–141.
  • Kim YI and Williams JF Jr. Large dose sublingual nitroglycerin in acute myocardial infarction: Relief of chest pain and reduction of Q wave evolution. Am J Cardiol 1982; 49: 842–848.

2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes

8 Ott

2014 AHA:ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes were published on September 23.

The new terminology, from Non STE Miocardial Infarction to Non STE Acute coronary Syndromes, establishes a  pathophysiological continuum between unstable angina and Non STE Acute coronary Syndromes, and make those two identities indistinguishable and considered together in this 2014 Guideline.

The need of High Sensitive Troponin and the importance of risk stratification are just few of the many changes made in this 2014 update

You con find this and all the newst guidelines on MEDEST Guidelines section

Sono state pubblicate il 23 di Settembre le 2014 AHA:ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes

Trovate queste e tutte le nuove linee guida su MEDEST nella sezione dedicata

Linee Guida


2014 AHA:ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes

New Non-ST-Elevation ACS Guidelines: New Title, New Approach


Morphine and antiplatelet therapies in acute myocardial infarction: a possible interaction

20 Set

We publish this contribute from Dott. Guido Parodi.

Guido is a good friend of MEDEST and an exceptional interventional cardiologist working at Careggi Hospital in Florence.

The passion for medical research made Guido one of the lead investigators in many studies about antiplatelets therapies in acute coronary syndromes.

His enthusiastic way to work and to talk about the things he does is contagious. So we had this wonderful connection from the first time we met many years ago.

In this post he talks about a brilliant intuition he had, on the possible drug-to-drug interaction between morphine and antiplatelets agents.

So let’s go to the post.


Antiplatelet agents are the mainstay of pharmacological treatment in patients presenting with an acute coronary syndrome, including STEMI. Currently, new strategies are under investigation to improve antithrombotic treatment in patients with ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI). Prasugrel and Ticagrelor, the newer, potent, fast and effective platelet P2Y12 receptor inhibitors, are recommended for STEMI patients in the European Guidelines (1) with the highest level of recommendation (I) and evidence (A).

Drug-to-drug interaction: RAPID and ATLANTIC study

In patients with STEMI undergoing PPCI a significant number of drugs are usually administered, thereby raising the potential risk for drug-to-drug interaction. In a recent small randomized study aimed to investigate the onset time of the novel P2Y12 receptor inhibitors (i.e., prasugrel and ticagrelor) in STEMI, a delayed antiplatelet effect due to morphine use in the first hours of STEMI has been hypothesized (2). This study showed that residual platelet reactivity soon after a loading dose of prasugrel and ticagrelor in patients with STEMI is higher than that reported for healthy volunteers or subjects with stable coronary artery disease and the majority of PPCI procedures with stent implantation are performed without proper platelet inhibition. A several hours vulnerable window of suboptimal antithrombotic therapy exists, in which STEMI patients are at high risk of thrombotic events, including stent thrombosis. Moreover, in this study morphine use resulted to be associated with a delayed activity of the new oral antiplatelet agents. There may be a biologically plausible cause-effect-relation in this association, given that morphine inhibits gastric emptying, thereby delaying absorption and possibly resulting in decreased peak plasma levels of orally administered drugs. Recently, an international multicentre randomized study, the ATLANTIC trial (3), showed that the pre-hospital administration of the potent platelet P2Y12-receptor antagonist ticagrelor shortly before PPCI in patients with STEMI appeared to be safe but did not improve reperfusion of the culprit artery. Interestingly, the ATLANTIC trial showed that the primary end point of ST-segment resolution was significantly improved with pre-hospital administration of ticagrelor in patients not receiving morphine (P = 0.005) for interaction supporting the hypothesis of a drug-to-drug interaction between morphine and oral antiplatelet agents.

Bottom line

Given the key importance of platelet inhibition in patients treated by PPCI for STEMI and the absence of data that may support a potential clinical benefit of morphine in patients with acute myocardial infarction, more caution should be used regarding morphine administration in STEMI patients, and a restricted morphine use seems to be reasonably recommended.
Courtesely from Dott. Guido Parodi

Courtesely from Dott. Guido Parodi



ACCOAST Trial failed primary end points. Still lack of evidence on benefits of antiplatelets pretreatment in ACS patients undergoing PCI

22 Gen

ACCOAST: Pretreatment with Prasugrel in Non–ST-Segment Elevation Acute Coronary Syndromes

Among patients with NSTE acute coronary syndromes who were
scheduled to undergo catheterization,
pretreatment with prasugrel did not reduce
the rate of major ischemic events up to 30 days
but increased the rate of major bleeding complications.”
  The New England Journal of Medicine vol. 369 no. 11

Il falllimento di ACCOAST pone nuovi e seri interrogativi su quella che è una pratica largamente diffusa nel trattamento di pazienti con sindrome coronarica acuta. Già in passato avevamo posto il probelma riguardo al pretrattamento con antiaggreganti piastrinici (Clopidogrel), il cui beneficio sulla mortalità era stato messo fortemente in dubbio da una review sistematica pubblicata sul JAMA nel 2012 (Association of Clopidogrel Pretreatment With Mortality, Cardiovascular Events, and Major Bleeding Among Patients Undergoing Percutaneous Coronary Intervention).

Anche il Ticagrelor del resto non sta navigando in acque tranquille (vedi La travagliata storia del Ticagrelor) visti i dubbi che riguardano i trial effettuati e le richieste d’approfondimento della FDA sfociate enll’esecuzione di un nuovo studio “riparatore” i cui risultati non sono ancora disponibili.

Inoltre, come già accennato con Guido Parodi, autore dello studio RAPID (Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID Rapid Activity of Platelet Inhibitor Drugs primary PCI study), gli antiaggreganti piastrinici utilizzati in pretrattamento, poco giustificano il loro impiego, in contesti in cui i tempi tra “first medical contact” e “baoloon” sono brevi, vista la lunga latenza dell’attivita inibitoria piastrinica.

Bottom Line

Alla luce delle evidenze attuali e viste le caratteristiche intrinseche dei farmaci disponibili, l’utilizzo degli antiaggreganti piastrinici nel pretrattamento dei pazienti con SCA che effettuano la PCI non è indicato.



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