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WHAT'S NEW IN COAGULATION: MAY 2010

Can Bariatric Surgery Affect Warfarin Management?

By Julie M. Sease, PharmD,

Approximately 180,000 bariatric surgeries are performed each year in the United States.^[1] A variety of procedures exist, including restrictive (gastric banding, gastroplasty), restrictive with limited digestive capacity (sleeve gastrectomy), restrictive/malabsorptive (gastric bypass), and malabsorptive (biliopancreatic diversion, jejunoileal bypass). Of these procedures, Roux-en-Y gastric bypass is the most commonly performed.^[1] Little information has been published with respect to the effects of bariatric surgery on drug absorption, although theories of how drugs may be affected by bariatric procedures have been proposed. Procedures involving gastric restriction could influence drug absorption in 3 main ways: by decreasing drug disintegration due to decreased gastric mixing; by disrupting drug dissolution and solubility due to increased gastric pH in the newly created stomach; and by decreasing gastric emptying.^[1]

Procedures involving diversion and malabsorption could theoretically impair absorption of drugs with slow dissolution properties (eg, sustained-release or enteric-coated preparations) and of highly lipophilic drugs because they are dependent upon the availability of bile acids to enhance solubility.^[1]

In addition, diversion and malabsorptive procedures reduce the functional gastrointestinal length, although the extent to which this reduction affects drug absorption is unknown. The effects of bypassing certain portions of the small intestine on drug metabolism and efflux within the intestinal wall are also unknown.^[1] The Roux-en-Y gastric bypass procedure is both restrictive and malabsorptive in nature and, therefore, may affect drug absorption in any of the aforementioned ways.

A case report found, using a significantly different surgical procedure, described the effect of malabsorption syndrome following a complete gastrectomy and Roux-en-Y gastric bypass.^[2] The investigators concluded that the patient demonstrated initial warfarin resistance possibly due to impaired absorption resulting from inadequate drug solubility (secondary to the removal of the stomach, which usually provides an acidic environment favorable for warfarin absorption) and a reduced surface area for drug absorption secondary to the gastrectomy and a Roux-en-Y esophagojejunostomy reconstruction.

Patients on warfarin therapy who undergo bariatric surgery should be monitored closely following the procedure. Adjusted doses of warfarin may be required after gastric bypass in order to maintain international normalized ratio within the therapeutic range.

Texas Toddler May Have Died From Overdose Of Heparin.

An overdose of heparin "may have played a role in the death of a Texas toddler Wednesday at the Nebraska Medical Center, hospital officials said." The girl's father "said his daughter received the wrong dose for five hours before the problem was noticed." The hospital "said the following steps were enacted" to prevent future problems with heparin, including the use of "technology that stops heparin infusions programmed to exceed maximum doses," and a "pharmacy staffer will oversee from bedside the start of heparin delivery to a patient."

Parental Stroke Associated With 3-Fold Increased Risk for Stroke in Offspring

By Emma Hitt, PhD

 Parental stroke before the age of 65 years is associated with a 3-fold increased risk for stroke in offspring, according to new data from the Framingham Heart Study.A reliable family history can serve as a 'poor man's genetic risk score' providing a simple, aggregate estimate of an individual's genetic risk.The results are published in the March 23 issue of Circulation.

Data from the Framingham study offspring cohort  analysis included 3443 offspring of the original Framingham cohort who had not had a stroke at baseline and who had parental stroke status verified by the age of 65 years. All offspring attended required examinations and were followed up for up to 8 years.A total of 106 parental strokes were documented by the age of 65 years, and 128 strokes were documented in the offspring. Of the strokes, 74 and 106 among the parents and offspring, respectively, were ischemic.

On multivariate analysis and after adjusting for conventional stroke risk factors, parental stroke was associated with an increased risk for incident stroke of the same type (hazard ratio [HR], 2.79; 95% confidence interval [CI], 1.68 – 4.66; P < .001) and for ischemic stroke (HR, 3.15; 95% CI, 1.69 – 5.88; P < .001).

Similar findings were observed in the offspring regardless of parental sex. (N Engl J Med. 2009;360:1718-1728).

FDA Finds USP's New Heparin Is 10% Less Effective Than Older Version.

The FDA says laboratory tests have confirmed that heparin manufactured under the new United States Pharmacopeia (USP) monograph is 10% less effective than the blood thinner manufactured under the old one. Still, the "altered drug potency has not changed the recommended dosing or drug label for heparin, though the FDA advised healthcare professionals to exercise judgment in determining proper patient dosing." But the FDA noted on its website that some populations "should be considered for individualized dosing regiments," including pediatric "patients requiring extracorporeal membrane oxygenation," patients "requiring cardiopulmonary bypass," and patients "with potentially fatal thromboses." The FDA also "has advised clinicians that the two cannot necessarily be used interchangeably and advised healthcare givers to separate their supplies while the old drug is still on the shelves."

Prasugrel: Different Mortality Trends in STEMI and Non-STEMI Patients in TRITON

By Sue Hughes

 Further information on deaths in the TRITON trial comparing the antiplatelet agents prasugrel (Effient, Eli Lilly/Daiichi Sankyo) and clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) in ACS patients scheduled for PCI show that prasugrel was associated with opposite mortality trends in the STEMI and non-STEMI populations.The mortality data from TRITON was particularly important, given the controversy that has surrounded the MI end point. "As the definition of MI used in this trial has been queried, the only hard outcome data we have is mortality, and the fact that this is going the wrong way in the population that makes up three-quarters of the patients treated.

The benefits of prasugrel appear to be overestimated and the risks underestimated in TRITON. This important point seems to be reflected in the use of prasugrel in clinical practice. Most clinicians are using this drug selectively and limiting its use to a few weeks. Even though not informed by evidence, I cannot disagree with this strategy to optimize the benefit/risk balance of prasugrel."

References

1. Serebruany VL. Mortality in the TRITON trial: Update from the FDA prasugrel action package. Am J Cardiol 2010; DOI:10.1016/j.amjcard.2009.12.052. Available at: www.AJConline.org.

Clopidogrel Without PCI Curbs Mortality in MI With Heart Failure

 Clopidogrel seems to improve survival in patients with acute myocardial infarction (MI) and heart failure who don't undergo percutaneous coronary intervention (PCI), Danish researchers report in the Journal of the American College of Cardiology published online on March 30th. The team used propensity score matching to select patients with and without heart failure who did or did not receive clopidogrel.The matched cohort with heart failure consisted of 5050 patients overall, with a mean follow-up of 1.5 years. The group without heart failure included 6092 patients followed for a mean of 2.1 years.

Patients with heart failure had a mortality rate of 28.1% with clopidogrel versus 32.2% without it (hazard ratio, 0.86).Patients without heart failure, however, had a mortality rate of roughly 9.5% regardless of whether or not they received clopidogrel.

The researchers conclude that clopidogrel is underused, and "increased awareness of the benefit of clopidogrel in such high-risk patients can have considerable clinical impact."

J Am Coll Cardiol 2010;55:1300-1307.

Investigative Agent Curbs Platelet Hyperreactivity in Diabetics

By David Douglas

Platelet hyperreactivity in type 2 diabetes is resistant to aspirin, but it can be suppressed by a nitric oxide (NO)-donating agent known as NCX 4016, according to Italian researchers.Acute, transient hyperglycemia, like the post-prandial hyperglycemia typical of patients with type 2 diabetes mellitus, induces a strong activation of circulating platelets in diabetic patients and... pretreatment with aspirin, the standard antiplatelet treatment prescribed in these patients, is not able to prevent it.

In a March 18th online report in Diabetes Care,  colleagues describe a trial in which they randomized 40 patients to 4 protocols: 800 mg NCX 4016 once daily plus placebo; 100 mg aspirin twice daily plus placebo; NCX 4016 plus aspirin; or placebo only.

In placebo patients, acute hyperglycemia enhanced shear-dependent platelet activation. Although aspirin fully inhibited cyclooxygenase-1, it had no impact on this enhancing action.Both NCX 4016 groups had suppression of platelet activation, even though they had less inhibition of cyclooxygenase-1.Acute, transient hyperglycemic spikes in diabetics are predictive of future cardiovascular events.This study unravels one possible mechanism through which these (spikes) may lead to myocardial infarction or stroke and shows that new antiplatelet agents must be investigated for diabetic patients.

The study was supported in part by NicOx S.A. (Sophia-Antipolis, France), the company that is developing NCX 4016.

Diabetes Care 2010.

Significantly Increased Risk for Arterial Thromboembolic Events With Sunitinib and Sorafenib

Treatment of cancer patients with the targeted agents sunitinib (Sutent, Pfizer) and sorafenib (Nexavar, Bayer and Onyx) is associated with a significant increase in the risk for arterial thromboembolic events, according to a meta-analysis published online March 29 in the Journal of Clinical Oncology.The meta-analysis, which consisted of 10,255 patients with a variety of cancers, found that the incidence of arterial thromboembolic events (ATEs) associated with sunitinib and sorafenib was 1.4% (95% confidence interval [CI], 1.2% - 1.6%), and that the relative risk for ATEs was 3.03% (95% CI, 1.25 - 7.37; P = .015), compared with control patients randomized to placebo.

The overall incidence is very low — less than 5%. The relative risk is higher and is statistically significant, suggesting a 3-fold greater risk for developing ATEs with sorafenib or sunitinib, compared with controls.

Increased Bleeding Also a Risk

In October 2009, as reported by Medscape Oncology, Dr. Choueiri and colleagues published a study showing that the treatment of cancer patients with sunitinib and sorafenib doubled their risk of bleeding.  The risk for bleeding might even be higher in older and frailer cancer patients and in those receiving chemotherapy. He also stated that clinicians had scant awareness of the problem of bleeding with these drugs.

The incidence of ATEs with sunitinib and sorafenib were similar — 1.3% (95% CI, 1.0% - 1.6%) for sunitinib and 1.7% (95% CI, 1.1% - 2.4%) for sorafenib. This difference was not statistically significant (P = .35).

Nor were there significant differences with regard to the type of malignancy or the type of clinical trial, Dr. Choueiri said.

The Good and the Bad of VEGF Inhibition

Speculating on the reasons for the increased incidence of ATEs, Dr. Choueiri told Medscape Oncology that he believes it is because these drugs disrupt the hemostatic balance.

"These drugs inhibit tumor angiogenesis, which has resulted in a major therapeutic advance for many cancers. The [vascular endothelial growth factor] VEGF pathway is vital for tumor angiogenesis, but it also plays an important part in regulating endothelial cells," he said. "Endothelial cells are important in vascular homeostasis for maintaining normal blood viscosity and preventing abnormal bleeding or abnormal clotting. If the balance is tipped toward clotting, arterial thromboembolic events, such as stroke and myocardial infarction, can occur. If it goes the other way, bleeding can occur."VEGF also increases the production of nitric oxide, which has several vascular protective effects, such as antiplatelet activity and the inhibition of leukocyte adhesion.

"If you inhibit VEGF with these drugs, you disrupt, not in a major way but in a statistically significant way as we show in our study, this hemostatic balance and you tip it toward thrombosis or bleeding."

He added that he believes that this is a class effect. "I don't think folks can claim

J Clin Oncol. Published online March 29, 2010. Abstract

Thrombolytic Therapy Appears Safe Even in Stroke Mimics

A new retrospective study suggests prompt treatment with tissue plasminogen activator (tPA) within 3 hours of symptom onset is safe even for patients who ultimately are found not to have had a stroke.Outcomes showed that patients with conditions that simulate acute ischemic stroke, so-called stroke mimics, underwent treatment without any symptomatic intracerebral hemorrhage (ICH), the most feared complication of treatment.

" Time is brain, he said, and the pressure is on in the emergency department to make a decision on whether or not to treat. "That kind of approach can miss other things and lead you to treating things that are not actually stroke. There's not enough time to determine that this really is a seizure, or really is a migraine, or might be something else," he told Medscape Neurology.

The indication from this retrospective study at least is that that approach is safe even for patients who don’t have stroke, but prospective studies would help to better establish the safety of treating stroke mimics, he added.

Their findings were published online March 24 and will appear in the April 27 issue of Neurology.

Clock Is Ticking

Newer imaging modalities, such as computed tomographic (CT) angiography, magnetic resonance angiography, or transcranial Doppler, can show large artery occlusions, and diffusion-weighted imaging is very sensitive for ischemic stroke, the study authors write, but these techniques are not universally available.

No large study has looked at the outcomes of patients treated with tPA who were ultimately found to have a stroke mimic, such as seizure, complicated migraine, or functional deficits, or those assumed to have an averted stroke, that is, those without an infarct on magnetic resonance imaging (MRI) but who were not found to have another diagnosis. This latter group was called neuroimaging-negative cerebral ischemia (NNCI) in this analysis.

The investigators performed a retrospective review of patients treated with intravenous tPA within 3 hours of symptom onset between June 2004 and October 2008, identified from their stroke registry. They recorded admission National Institutes of Health Stroke Scale (NIHSS) scores, modified Rankin score, length of stay, any incidence of symptomatic ICH, and discharge diagnosis.

In all, 512 patients received tPA during that period of which 21% were found not to have an infarct on imaging.Stroke mimics, those in whom another diagnosis was established, accounted for 14%. Their average age was 55 years, median admission NIHSS score was 7, median discharge NIHSS score was 0, median length of stay was 3 days, and none of these patients had symptomatic ICH after treatment. The most common alternate diagnoses among these patients were seizure, complicated migraine, and conversion disorder.

The remaining 7% fell into the NNCI group. The average age in this group was 61 years, median admission NIHSS score again was 7, median discharge NIHSS score again was 0, median length of stay was identical at 3 days, and, again, none had symptomatic ICH.Their data, and those of others, they conclude, support treatment with tPA in those with suspected acute ischemic stroke, even when alternate diagnoses are being considered.

FDA Approves First Absorbable Fibrin Sealant for Use in Cardiovascular Surgery

 The US Food and Drug Administration (FDA) has approved the first absorbable fibrin sealant patch for use in cardiovascular surgery (TachoSil, Nycomed Austria GmbH) to prevent mild and moderate bleeding from small blood vessels when standard surgical techniques are ineffective or impractical.The ready-to-use biodegradable product consists of a sponge made from equine tendons and coated with a dry layer of the human coagulation factors fibrinogen and thrombin. When applied to a wound, the patch mimics the final steps of the natural blood clotting process, creating a hemostatic fibrin clot within 3 to 5 minutes that dissolves within 4 to 6 months.

FDA's action was based on data from a study (n = 119) showing that use of the fibrin sealant patch was significantly more effective than standard hemostatic fleece for achieving hemostasis in cardiovascular surgery patients with persistent hemorrhage (74.6% vs 33.3%).

Although adverse events reported in the study did not differ significantly between treatment groups, allergic type hypersensitivity reactions may occur if the fibrin sealant patch is applied repeatedly or used in patients with known hypersensitivity to its components. Thromboembolic complications are also possible with intravascular application.

Because the fibrin sealant patch is derived from human and equine products, the potential for transmission of infective agents cannot be totally excluded despite screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps to inactivate/remove viruses.

Lab Tests Confirm Reduced Potency of New Heparin Formulation

 Laboratory tests confirm that the new formulations of heparin are roughly 10% less potent than the heparin prepared using old standards.The Food and Drug Administration (FDA) issued the safety communication today and is warning healthcare professionals that both the old and new formulations of heparin will be available for some time. As a result, physicians should consider clinical situations where the reduced potency might require dosage adjustments and more frequent monitoring, such as in patients requiring aggressive anticoagulation, including those undergoing cardiopulmonary bypass.The current FDA-approved labeling for heparin remains unchanged, including the recommended doses.

The heparin reformulation is the result of manufacturing controls occurring in the wake of the 2007 and 2008 contamination that were linked to deaths and allergic reactions and was proposed by the US Pharmacopeia (USP), a nonprofit standards-setting organization..The FDA notes that the new heparin has been available since October 2009 and there will be supplies of both the old and new heparin stocked for use in hospitals and pharmacies for about three years.

There are four companies that market heparin in the US: APP, the largest manufacturer, Hospira, Baxter, and B Braun. Three of the four companies include the letter N on their product to identify the heparin with the new reference standard, while Hospira will identify the changed product with lot numbers that begin with the number "82" or higher.

References

1. Food and Drug Administration. FDA drug safety communication: Update: Follow-up to the public health alert about changes to the heparin sodium USP monograph. April 7, 2010. Available here.

Could Omega-3 Fatty Acids Help in Tackling Clopidogrel Resistance?

A small proof-of-concept study indicates that omega-3 fatty acids could possibly be used as an additional therapy in patients undergoing PCI who are resistant to clopidogrel [1].

In the month-long study, the addition of 1 g of omega-3 fatty acids to dual antiplatelet therapy with aspirin and clopidogrel significantly potentiated the platelet response to clopidogrel after PCI. There needs to be a long-term study to see whether omega-3 fatty acids can diminish clopidogrel resistance and improve clinical outcomes.

Patients who are poor responders to clopidogrel have been shown to have a higher risk of post-PCI ischemic events. Recently triple antiplatelet therapy, with the addition of cilostazol (Pletal, Otsuka America) to aspirin and clopidogrel, has been reported to improve the biologic effects of clopidogrel, but the advantages of this approach must be weighed against the potential increased risk of bleeding. This is also true of newer, more potent antiplatelet agents, which, while more effective, often have an increased risk of bleeding, too, he noted.

It is well-known that omega-3 fatty acids have antithrombotic and antiplatelet effects, he said, "but they have never been tried together with dual antiplatelet therapy, so the idea was to combine these therapies, as we know from many trials that omega-3 fatty acids are safe; there is no increased risk of bleeding with them."

They randomized PCI patients receiving standard dual antiplatelet therapy (75 mg/day of aspirin, 600 mg loading dose of clopidogrel followed by 75 mg/day) to receive either 1 g of omega-3 ethyl esters (n=33) or placebo (n=30) for one month.

Gajos said his team was unable to properly examine the effect of omega-3 fatty acids on aspirin resistance, due to the low number of people in the study who were resistant to aspirin. But up to 25% to 40% of the patients, depending on the type of platelet aggregation test used, were resistant to clopidogrel, he noted.

PRI Reduced by 22% After One Month's Treatment With Omega-3 FAs

Platelet function was measured in two ways, by light-transmission aggregometry and by the vasodilator-stimulated phosphoprotein (VASP) assay, at baseline, 12 hours, three to five days, and 30 days after randomization.

The primary end point of the study was the P2Y12 reactivity index (PRI) 30 days after randomization; secondary end points included PRI at earlier time points and maximal platelet aggregation induced throughout the study.

The PRI was significantly lower, by 22%, after one month of treatment with omega-3 polyunsaturated fatty acids compared with placebo when used in addition to dual antiplatelet therapy (p=0.020). Maximal platelet aggregation induced by 5- and 20-µmol/L adenosine diphosphate was also lower, by 13.2% (p=0.026) and 9.8% (p=0.029), respectively.

The findings add to a previous study published in January [2], he says, in which adding omega-3 fatty acids to the treatment of aspirin-resistant patients appeared to improve the response to aspirin and effectively reduce platelet reactivity.

References

1. Gajos G, Rostoff P, Undas A, et al. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention. The OMEGA-PCI (OMEGA-3 fatty acids after PCI to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol 2010; 55:1671-1678.
2. Lev EI, Solodky A, Harel N, et al. Treatment of aspirin-resistant patients with omega-3 fatty acids versus aspirin dose escalation. J Am Coll Cardiol 2010; 55:114-1121. Abstract

Men With Prostate Cancer at Higher Risk for Thromboembolic Disease

All men with prostate cancer have a higher risk for thromboembolic disease, compared with the general population, and the risk for deep vein thrombosis (DVT) and pulmonary embolism (PE) is "especially high" in those undergoing hormonal therapy.These results come from a new analysis of data from the Swedish National Prostate Cancer Register, published online in The Lancet Oncology.

This new study focused on thromboembolic disease, but some of the findings are similar to the group's previous study on cardiovascular disease..For instance, the highest risk for both was seen in men undergoing gonadotrophin-releasing hormone (GnRH) agonist therapy or those who had undergone orchidectomy, whereas men who were treated with antiandrogens were at the lowest risk among those who were treated with hormonal therapies. This ties in with research suggesting that testosterone is important both in the functioning of the heart and in thromboembolism and that suppressing it completely is detrimental to both. With antiandrogens, there is still testosterone circulating, but it is prevented from acting on the prostate by androgen receptor blockade, she added.

However, an accompanying editorial points out that several factors limit the observation that antiandrogens were associated with a more modest increase in the risk of thromboembolism compared with GnRH agonist or orchidectomy. Men with prostate cancer who are being treated with hormonal therapies should be monitored for cardiovascular disease (as suggested by the first study) and also for thromboembolic disease (as suggested by this present study), because they are at increased risk of both.

The accompany editorial concurs. These new data "should increase clinical suspicion for venous thromboembolism in men with prostate cancer," the editorialists write, but the data "do not support withholding GnRH agonists or orchidectomy in clinical situations where they are known to be beneficial."

Highest Risk Is for DVT

The new study analyzed data collected in Sweden from 1997 to 2007 on 76,600 men with prostate cancer. Of these, 30,642 were treated with hormonal therapies, specifically, 9066 with a GNRH agonist, 5340 with orchidectomy, 3391 with antiandrogens, and 1199 with a combination of other drugs. The remaining men received either curative treatment, such as prostatectomy (n = 26,432) or active surveillance (n = 19,526).Thromboembolic disease developed in 1881 of these men: 767 had a DVT, 873 had a PE, and 241 had an arterial embolism (AE).

The increase in risk was seen regardless of the treatment received, but the magnitude of this increased risk varied. The largest absolute risk (more than doubled) was seen for DVT for men receiving endocrine treatment.

Although an increase risk in both DVT and PE was seen with endocrine therapy, "causation cannot be inferred from these observations," the editorialists emphasize.

They point out that men treated with endocrine therapy had a greater proportion of metastatic or otherwise poor-risk disease, and advanced cancer is a known risk factor for venous thromboembolism. This group of patients also included the highest proportion of men older than 75 years, and advanced age is also a known risk factor for venous thromboembolism in patients with cancer, they add.

Nevertheless, these latest data raise the question of whether endocrine therapy increases the risk of venous thromboembolism, they concede. They hope that the new findings will "stimulate further study.

Using Cotrimoxazole To Treat UTIs May Increase Upper-GI Hemorrhage Risk In Patients Taking Warfarin.

Scientists at the Institute for Clinical Evaluative Sciences say that "people taking the blood-thinning drug warfarin should avoid a popular antibiotic that's often used to treat urinary tract infections." In fact, they found that "patients on warfarin who were prescribed cotrimoxazole had an almost four-fold greater risk of an upper-gastrointestinal hemorrhage, compared to those not given the antibiotic."

 Cotrimoxazole is known to inhibit cytochrome P450 isozyme 2C9, which is involved in warfarin metabolism -- this is on top of other known effects of many antibiotics on gut flora, which can reduce vitamin-K synthesis   They found that "those who took the antibiotic ciprofloxacin had a risk that was smaller, but still significant at 1.9 times higher," and "those taking other common antibiotics such as amoxicillin, ampicillin, nitrofurantoin, norfloxacin, and ocular antibiotics, had small or negligible increase in risk." The "'message here is that not all antibiotics are created equal..

        In other words, "patients taking warfarin should avoid using cotrimoxazole when possible,  However, "in rare instances, where the two drugs must be used together, patients should be monitored very closely." According to the paper in the Archives of Internal Medicine, "patients taking warfarin should always check with their doctor or pharmacist before taking another drug, even Tylenol [acetaminophen], because of the many drug interactions that can occur."

of potential interactions between androgen deprivation and blood coagulability."

Still No Answers in Largest Review on Clopidogrel/PPIs

Whether treatment with proton-pump inhibitors (PPIs) adversely affects cardiovascular outcomes in patients receiving clopidogrel is still unclear, say the authors of the largest meta-analysis to date to look at the issue.PPIs attenuate the antiplatelet effects of clopidogrel is not in doubt. But where the uncertainty lies is in the extent to which this interaction affects clinical outcomes.Also, it is probable that specific subgroups of patients might be more likely to experience harm with this combination of drugs, and although these people are probably in the minority, further research is necessary to identify them, say experts.

A separate review including literature on the subject from 1980 to August 2009, as well as presentations from key cardiology meetings, has also just been published [2] and concludes much the same as Kwok and Loke. "Take-home message: There is a mechanistic basis and [there are] pharmacodynamic data supporting an interaction between PPIs and clopidogrel. The clinical significance of this interaction is, however, still a subject of intense debate and ongoing research.

Kwok and Loke's review included 93 278 patients and comprised 20 retrospective studies, two post hoc analyses of randomized-trial participants, and the one prospective randomized controlled trial in this field, COGENT, reported last year. COGENT concluded that the interaction between the PPI omeprazole and clopidogrel does not lead to an increase in adverse cardiac outcome. The studies into three different grades, from relatively lower-quality evidence to higher-quality evidence. As you go further up the ladder and the quality of evidence improves, the risk does not seem as apparent as it does with lower-quality studies.In fact, when they analyzed propensity-matched or randomized trials only, participants showed no statistically significant increase in relative risk associated with MI or acute coronary syndrome (ACS) events with PPIs (relative risk 1.15; 95% CI 0.89–1.48), whereas observational studies generally showed a significant association (adjusted relative risk 1.54; 95% CI 1.23-1.92).

A meta-analysis of 13 of the studies showed no significant association between PPI use and overall mortality, however (relative risk 1.09; 95% CI 0.94–1.26; p=0.23).

In most patients,  this interaction "is probably not of major clinical relevance. But it's still a developing story, and we are awaiting more information on this issue.

SSRIs May Help Protect Cardiovascular Health By Slowing The Clumping Of Blood Platelets.

A widely used type of antidepressant may help protect cardiovascular health by slowing the clumping of blood platelets," according to a study to be presented at the American Physiological Society conference. Investigators "compared 25 depressed patients taking a selective serotonin reuptake inhibitor (SSRI) and 25 healthy people who weren't taking an antidepressant." The researchers found that, "at four weeks, the rate of platelet clumping was 95 percent in the healthy volunteers and 37 percent in the patients taking an SSRI."

Donna Castellone

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Donna Castellone,
MS, MT(ASCP)SH
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