Plavix, Heartburn Drugs May Be Risky Combination

Patients with coronary artery stents should discuss the use of these meds with their doctor

Proton-pump inhibitors ( PPIs) are medications used for heartburn. These medications include esomeprazole (Nexium, AstraZeneca), omeprazole, pantoprazole (Protonix, Wyeth), lansoprazole, or rabeprazole (Aciphex, Eisai/Ortho-McNeil-Janssen Pharmaceuticals). Plavix anti-platelet therapy is given to patients to prevent clots especially those who have a history of or tendency for strokes or after getting a stent for coronary artery disease.

So the combination of both Plavix and a PPI up to now has been relatively common.

Recent studies, however, show that one-year risk of cardiovascular events is increased more than 50% in patients taking a proton-pump inhibitor (PPI) on top of clopidogrel, as compared with patients not taking a PPI.

In addition, the risk seems to be a class effect for all the PPI medications, according to this latest retrospective cohort study of more than 16,700 patients who received clopidogrel post-stenting for coronary artery disease. Professional society guidelines recommend the use of PPIs to treat and prevent gastrointestinal ulcers and bleeding in patients on antiplatelet therapy. However, increasing use of PPIs in this setting has raised questions as to whether PPIs may attenuate clopidogrel's antiplatelet response by interfering with CYP2C19-mediated clopidogrel metabolism. This means that the same enzyme in the liver metabolizes both Plavix and PPIs. Therefore, the addition of a PPI can spur a less active form of Plavix to be produced, reducing its beneficial effects.

This new data the results of the Clopidogrel Medco Outcomes study was presented May 6, 2009 as a late-breaking clinical trial during the first day of the Society for Cardiovascular Angiography and Interventions (SCAI) 2009 Scientific Sessions. The study compared major adverse cardiovascular events (MACE).

Higher MACE [major adverse cardiovascular events] occur with PPIs

One study showed that this combination is associated with a 70 percent increased risk of heart attack, a 48 percent increased risk of stroke and a 35 percent increased risk for the need for repeat coronary procedures. The overall incidence of major adverse cardiovascular events was 51 percent higher in those taking Plavix and a PPI than in those taking Plavix alone.

In this latest study, one-year risk of MACE was significantly higher in PPI-treated subjects, at 25.1%, as compared with patients who did not take a PPI, at 17.9%. They also looked at the CV risk associated with individual PPIs, restricting their analysis to PPIs with sufficient patient numbers to detect a difference in risk similar to that seen in the overall population, with adequate statistical power. Don’t be fooled by those who claim rabeprazole is safer than all the other PPIs. Due to low numbers, rabeprazole, taken by just 298 patients, could not be addressed in this analysis, however, each of the PPIs, individually, was associated with a higher risk of major cardiovascular events vs no PPI use, ranging from a 24.3% increased risk with lansoprazole to a 29.2% risk with pantoprazole.

Caveat:
While this particular study is the largest to date to address the question of a PPI-clopidogrel interaction, two other, smaller studies have found disparate results.
Of note, hospitalization rates for upper-GI bleeding were low across all groups of PPI use, in the range of 1.1%. Also of interest, investigators looked at PPI use among patients who were not treated with clopidogrel and found no increased risk of CV events in this group, as compared with patients taking neither a PPI nor clopidogrel.

BOTTOM LINE:
These results provide further support for the hypothesis that PPIs attenuate the effects of clopidogrel. Considering all available evidence, PPI use should be limited to situations clearly indicated in patients on clopidogrel after coronary stenting.

Considering all the available evidence, PPI use should be limited in patients taking clopidogrel, based on the physician's judgment.

Physicians need to do a better job of discriminating between patients who are just at risk of GI symptoms or who may have had previous GI disease and patients who actually have current GI problems. It is the latter group in whom concomitant PIs are likely to be useful. Physicians are urged to take the time to discuss the risks and benefits with patients and to emphasize that patients should not because stop clopidogrel therapy if so prescribed by your doctor.

Concomitant H2-receptor-antagonist therapy showed no effects of these other ant heartburn agents on CV events. In an analysis of 9862 patients taking clopidogrel, but not a PPI, 472 received an H2 blocker, while 9390 did not. The incidence of cardiovascular events was 20.3% for patients taking H2 blockers and 17.8% in patient not taking these agents, a statistically nonsignificant difference.

Given the thousands of patients who receive stents each year, coupled with the significant risks demonstrated in this study, it might be better to use alternative medications for GI symptoms in patients with stents when appropriate. These alternative heartburn medications include histamine (H2) blockers (Zantac [ranitidine, Boehringer Ingelheim], Tagamet [cimetidine, GlaxoSmithKline]) or antacids. In those patients when the use of PPIs may still be warranted, based on the patient's medical problems, it should be taken at the direction of the patient's cardiologist, gastroenterologist, or primary physician and closely monitored.

REFERENCES:
• Platelet-function test finds fault with omeprazole/clopidogrel combo, but not with other PPIs
[Acute Coronary Syndromes > Acute coronary syndromes; Apr 10, 2009]
• More data support adverse clopidogrel and proton-pump inhibitor interaction
[Acute Coronary Syndromes > Acute coronary syndromes; Mar 03, 2009]
• Increased risk of reinfarction with clopidogrel and proton-pump inhibitors
[Acute Coronary Syndromes > Acute coronary syndromes; Jan 29, 2009]
• FDA continuing to study effectiveness of clopidogrel
[Acute Coronary Syndromes > Acute coronary syndromes; Jan 26, 2009]
• Omeprazole reduces antiplatelet effect of clopidogrel?
[Clinical cardiology > Clinical cardiology; Jan 14, 2008]

Part II of II: GERD- Heartburn of Pregnancy

Part II of II.

Gastro-esophageal reflux is the phrase used to describe the backward flow or regurgitation of stomach contents passing up into the esophagus. The typical symptom of GERD is a burning discomfort behind the breast bone. Some describe heartburn as indigestion, a "sour" stomach, pain in the upper abdomen or chest, regurgitation of food or bitter liquid into the mouth or excessive production of saliva. GERD is a common condition and symptoms of heartburn are experienced at least once a month by more than 60 million Americans.

For women, the first experience with heartburn is often during pregnancy. Studies suggest that over 50% of pregnant women will experience heartburn during pregnancy. This is due to hormones of pregnancy and pressure from the growing fetus. Symptoms of heartburn resolve in most of these women after delivery of the baby.

What causes GERD?
Acid is produced in the stomach every day. Normally, a small amount of acid passes into the esophagus through a valve between the esophagus and stomach called the lower esophageal sphincter. When the frequency or amount of acid in contact with your esophagus increases, symptoms and damage to your esophagus can occur.

What are the stimuli of heartburn?
Pregnancy
Eating a large, especially fatty meal
Tomato sauces (spaghetti & pizza)
Lying down after a meal
Chocolate, peppermint
Coffee and tea
Smoking
Alcohol and carbonated beverages
Some muscle relaxers and blood pressure medicines
Excess weight
Eat more frequent, but smaller meals

What to avoid?
fatty food, coffee & tea, chocolate, peppermint, alcohol, smoking, carbonated beverages.

What to do?
Maintain a normal weight
Avoid eating 2-3 hrs before bedtime
Elevate the head of the bed 4-6 inches
Don’t lie down after eating

What medications are effective in relieving symptoms?
Antacids
(liquid or tablets):
Tums®, Rolaids®, Mylanta®, Maalox®, Gaviscon®, and many others.

OTC Acid Blockers:
Pepcid AC® , Tagamet HB® , Zantac AC® ., Prilosec OTC®
*Important Note: If you are pregnant or nursing a baby, seek the advice of a doctor before using OTC acid blockers.

Proton Pump Inhibitors:
esomeprazole, Nexium®; or
lansoprazole, Prevacid®; or
pentaprazole, Protonix®; or
rabeprazole, Aciphex®;

Pro-motility Drugs:
cisapride, Propulsid®

Prescription Strength Antacids:
sucralfate, Carafate®

Prescription Strength H2 Blockers:
cimetidine, Tagamet® , ranitidine, Zantac® , famotidine, Pepcid® , nizatadine, Axid®

When should you see a doctor about symptoms of heartburn?

If you have any of the following:
Symptoms of heartburn two or more times a week
Don’t get lasting relief on medication you are taking
Difficulty swallowing, especially solids
Choking, wheezing, hoarseness caused by regurgitation of acid into the throat
Signs of bleeding (vomiting dark coffee ground-like material or passage of tarry black bowel movements)
Unexplained weight loss
Reflux symptoms over more than one year

What treatments for heartburn are safe during pregnancy?
During pregnancy, the medical treatment of reflux should be balanced to alleviate the mother’s symptoms of heartburn, while protecting the developing fetus.

Step 1: Modification of diet & lifestyle

Step 2: Antacids are probably safe.

Sodium bicarbonate can cause a condition known as metabolic acidosis and should be avoided during pregnancy. Magnesium containing antacids may interfere with uterine contractions during labor and should be avoided during the last trimester of pregnancy.

Step 3: sucralfate (Carafate®) has a good record for safety and results with pregnant patients. Acid blockers can probably be administered safely, but require a doctor’s supervision.

Step 4: Other medical therapy should only be used when the benefit of the medicine for the mother outweighs the risk of the medicine to the developing fetus.


Please remember, as with all our articles we provide information, not medical advice.

For any treatment of your own medical condition you must visit your local doctor, with or without our article[s]. These articles are not to be taken as individual medical advice.

Is it Heartburn or a Heart Attack?

Part I of II :GERD

The experts say “It doesn’t often begins as a sharp, burning sensation in the chest. Many times it seems either like a pressure or burning or indigestion in the chest.”

Is the pain heartburn, or might it be a heart attack?

It's often difficult for people to tell the difference. Complicating the issue is that some people with diagnosed heart disease will also have heartburn, Those are the patients who want to say, 'Oh, this is just heartburn' and not worry about it. If, however, you have any heart history, a cardiologist should be consulted.

But even people without known heart disease who have heartburn shouldn't always just pop an over-the-counter antacid either. Overreacting in seeking medical help is always better than under-reacting.

In the common variety heartburn, or GERD [ gastro-esophageal reflux disorder] stomach acid moves up into the esophagus and causes irritation. It might require a doctor's intervention, to rule out that what a person is feeling stems from heartburn and not heart problems, which can have similar symptoms.

So what's a person to do?

Pay attention to the pattern of heartburn. If people have heartburn on a regular basis after eating specific foods -- every time they eat a greasy pepperoni pizza or drink a large glass of orange juice, for instance -- the food is generally the origin of the symptoms. If, however, if they start having “heartburn” and have not eaten any of the food or drinks that previously triggered a heartburn episode. That would merit a call for medical help.

Pay attention to when the heartburn occurs. If the heartburn follows consumption of a specific food, it's probably run-of-the-mill heartburn, which when it becomes severe will need prompt medical attention.

See a doctor if heartburn is severe and begins to affect quality of life. A medical visit in such an instance, though, would not be as urgently needed as it would be for those with pain and swallowing problems along with heartburn.

If heartburn is a new experience, have it checked out asap. That needs to be evaluated pretty quickly because people with first-time heartburn and risk factors for heart disease -- including high blood pressure, high cholesterol, diabetes, a family history of heart problems and active cigarette smoking -- should seek prompt medical help.

Other “red flag” reasons to quickly talk to a doctor or go to the emergency room.

• If heartburn accompanies exercise or other exertion.

• If a severe episode of heartburn does not get better with antacids. Garden-variety heartburn should subside fairly quickly. An episode might last up to a few hours, and then disappear in varying lengths of time, depending on the type of remedy used to combat it. "If you take an antacid, their effect is usually immediate," "If you take an H-2 blocker [such as Zantac or Tagamet], it may be 30 minutes.

• If heartburn comes with other symptoms, such as shortness of breath or arm pain.


Please remember, as with all our articles we provide information, not medical advice.

For any treatment of your own medical condition you must visit your local doctor, with or without our article[s]. These articles are not to be taken as individual medical advice.