Article

Original Article

Clopidogrel with or without Omeprazole in Coronary Artery Disease

 

 

On the basis of data from several studies, clopidogrel has become the second most commonly used prescription drug worldwide.1-9 Gastrointestinal hemorrhage is the most common serious bleeding complication from the use of long-term antiplatelet therapy.10,11 Data from randomized studies support the concept that therapies reducing acidity decrease gastrointestinal complications of antiplatelet therapy involving aspirin, though the data are largely based on endoscopic end points; observational data also support this effect.12-16 Randomized, controlled trials have shown that proton-pump inhibitors (PPIs) reduce the rate of recurrent gastrointestinal bleeding in high-risk patients receiving aspirin.17 Observational studies, however, have suggested that there may be an interaction between clopidogrel and PPIs that, if real, could have significant clinical effects.18,19 These studies have been bolstered by results of ex vivo analyses, many of which have shown inhibition of the antiplatelet effect of clopidogrel by PPIs, omeprazole most consistently.20-22 In addition, genetic polymorphisms have been identified that could affect the response to clopidogrel and, at least theoretically, could increase the likelihood of drug interactions mediated by cytochrome P-450.23-27 A number of other observational studies, however, did not show an interaction between clopidogrel and PPIs.28,29 Given the conflicting data regarding a possible interaction, the optimal care of patients who require concomitant therapy with clopidogrel and PPIs remains uncertain.30-34
We initiated the Clopidogrel and the Optimization of Gastrointestinal Events Trial (COGENT) to assess the efficacy and safety of concomitant administration of clopidogrel and PPIs in patients with coronary artery disease who are receiving clopidogrel plus aspirin.

Methods

Study Conduct

The trial was designed by an academic steering committee (see the Supplementary Appendix, available with the full text of this article at NEJM.org) and the sponsor, Cogentus Pharmaceuticals. The steering committee was responsible for the overall leadership of the trial. A clinical research organization, Parexel, performed the data management and site monitoring. Randomization was performed centrally with the use of an interactive voice-response system before the initiation of study treatment. Parexel generated the randomization sequence. All sites operated under approval from institutional review boards or ethics committees, and all patients gave written informed consent to participate in the trial. The study was conducted according to the study protocol (available at NEJM.org). At the conclusion of the trial, the full database was transferred to an academic principal investigator. The analyses were performed independently of the sponsor, by two academic authors. An academic principal investigator prepared the first draft of the manuscript, which was then reviewed and edited by the academic steering committee and other authors; all the academic authors made the decision to submit the paper for publication. There was no agreement made regarding confidentiality of the data between the sponsor and the academic authors or their institutions. The sponsor did not have the right to approve the final manuscript. The academic principal investigators vouch for the accuracy and integrity of the analyses and interpretation of the data.

 

 

Video

Article

 OMEPRAZOL

 

  https://www.youtube.com/watch?v=ekzHIouo8Q4

http://dspace.unach.edu.ec/handle/123456789/323

 

Adverse effects

Some of the most frequent side effects of omeprazole (experienced by over 1% of those taking the drug) are headache, diarrhea, abdominal pain, nausea, dizziness, trouble awakening and sleep deprivation, although in clinical trials the incidence of these effects with omeprazole was mostly comparable to that found with placebo. Other side effects may include iron and vitamin B12 deficiency, although there is very little evidence to support this.

Proton pump inhibitors may be associated with a greater risk of osteoporosis related fractures and Clostridium difficile-associated diarrhea. By suppressing acid-mediated breakdown of proteins, antacid preparations (such as omeprazole) lead to an elevated risk of developing food and drug allergies. This happens due to undigested proteins then passing into the gastrointestinal tract where sensitisation occurs. It is unclear whether this risk occurs with only long-term use or with short-term use as well.Patients are frequently administered the drugs in intensive care as a protective measure against ulcers, but this use is also associated with a 30% increase in occurrence of pneumonia.The risk of community-acquired pneumonia may also be higher in people taking PPIs.

Since their introduction, proton pump inhibitors (especially omeprazole) have been associated with several cases of acute tubulointerstitial nephritis, an inflammation of the kidneys that often occurs as an adverse drug reaction.

PPI use has also been associated with fundic gland polyposis.

The following adverse reactions have been identified during post-approval use of Prilosec Delayed-Release Capsules.Because these reactions are voluntarily reported from a population of uncertain size, it is not always possible to reliably estimate their actual frequency or establish a causal relationship to drug exposure.

Systemic: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, urticaria, fever; pain; fatigue; malaise;hair loss;

Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure, peripheral edema

Endocrine: Gynecomastia

Gastrointestinal: Pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth, microscopic colitis. During treatment with omeprazole, gastric fundic gland polyps have been noted rarely. These polyps are benign and appear to be reversible when treatment is discontinued. Gastroduodenal carcinoids have been reported in patients with ZE syndrome on long-term treatment with Prilosec. This finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors.

Hepatic: Liver disease including hepatic failure (some fatal), liver necrosis (some fatal), hepatic encephalopathy hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, and elevations of liver function tests [ALT, AST, GGT, alkaline phosphatase, and bilirubin]

Metabolism and Nutritional disorders: Hypoglycemia, hypomagnesemia, hyponatremia, weight gain

Musculoskeletal: Muscle weakness, myalgia, muscle cramps, joint pain, leg pain, bone fracture

Nervous System/Psychiatric: Psychiatric and sleep disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, apathy, somnolence, anxiety, and dream abnormalities; tremors, paresthesia; vertigo

Respiratory: Epistaxis, pharyngeal pain

Skin: Severe generalized skin reactions including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, and erythema multiforme; photosensitivity; urticaria; rash; skin inflammation; pruritus; petechiae; purpura; alopecia; dry skin; hyperhidrosis

Special Senses: Tinnitus, taste perversion

Ocular: Optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, ocular irritation, blurred vision, double vision

Urogenital: Interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, urinary frequency, testicular pain

Hematologic: Agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, leukopenia, leucocytosis

Muscles

SISTEMA MUSCULAR

Musculos del brazo, del antebrazo, del hombro, de la mano, de la pierna, del pie, del cuello, de la espalda, de la cadera, del abdomen, del torax, del hombro.

MUSCULO ESQUELETICO se corresponde con los musculos quew estan en contacto con los huesos(esqueleto), son organos de contraccion voluntaria, cuyas celulas se llaman fibras, son alargadas y multinucleadas.- Las fibras tienen estrias, por lo que se dice que estan compuestos por tejido muscular estriado.-
MUSCULO LISO estos musculos estan presentes en las visceras, por ejemplo en los intestinos,y vasos sanguineos,.- Sus celulas tienen forma de huso, tienen un solo nucleo central, son de contraccion involuntarias, no tienen estrias por eso se llaman lisos
MUSCULo CARDIACO este musculo es propio y exclusivo del corazon.- Es de contraccion involuntaria.- Sus celulas son estriadas con muchos nucleos .

MUSCULOS:

Pectorales
Deltoides
Biceps
Triceps
Abdominales ( pared anterior del abdomen, abdomen transverso y oblicuos interno y externo)
Dorsales (espalda)
Lumbares
Cuadriceps (muslo)
Biceps Femorales (parte posterior del muslo es decir atras)
Gluteo Mayor
Pantorrillas ( M Soleo y Gastrocnemio)
Esternocleidomastoideo (cuello)
Trapecio (espalda y cuello)
Aductores ( parte medial del muslo)
Serrato Anterior (espalda)