Tag Archives: myocardial infarction

Prevent Atherothrombotic Events? It’s Complicated

When researchers reported earlier this week at the American College of Cardiology’s annual meeting results from the TRA 2P-TIMI 50 trial, which tested a novel anticoagulant drug, vorapaxar, for preventing cardiovascular death, myocardial infarction (MI), and stroke in stable patients with cardiovascular disease, the results showed a questionable balance between benefit and bleeding risk that only looked good if you squinted and confined the analysis to patients with just a history of MI, no history of stroke, a body weight of at least 60 kg, and, ideally, those who were younger than 75 years old. Even within this pared-down universe, experts differed on whether vorapaxar had an unequivocal net benefit after taking into account the bleeding risk it caused.

But if vorapaxar someday gets FDA approval and appears on the U.S. market, physicians will face the tricky calculus of how to use it compared with the other new, potent antithrombotic drugs.

blood clot/courtesy Janice Carr; Public Health Image Library

Looking at vorapaxar’s performance in patients with stable cardiovascular disease, it was hard not to recall last November’s report on the ATLAS ACS 2-TIMI 51 trial, which tested adding a 2.5 mg b.i.d. dosage of another new anticoagulant drug, rivaroxaban, in acute coronary syndrome (ACS) patients also treated with aspirin and clopidogrel. In ATLAS, adding this small dose of rivaroxaban led to benefit and a bleeding risk that was strikingly similar to the pattern seen with vorapaxar in TRA 2P.  Rivaroxaban on top of aspirin and clopidogrel produced an absolute, 1.6% cut in the combined rate of cardiovascular death, MI, or stroke while boosting the rate of major bleeds by an absolute 1.2%, and the rate of intracranial bleeds by 0.2%. The new vorapaxar results showed that in the best-case subgroup, adding the drug to aspirin and clopidogrel cut cardiovascular death, MI, or stroke by an absolute 1.9%, while boosting major bleeds by 1.0% and intracranial hemorrhage by 0.2%.

A big difference in the two analyses was that the benefits and risk seen with 2.5 mg rivaroxaban was in the entire study population of 5,100 patients, with no need to resort to subgroup analyses. The vorapaxar result was in about 9,500 patients, roughly 70% of all patients enrolled in the trial. Another big difference was the major impact of rivaroxaban was on cutting cardiovascular deaths. Vorapaxar’s main effect was to lower nonfatal MIs. It cut cardiovascular deaths too, but not as well as low-dose rivaroxaban.

Many experts whom I spoke with at the meeting seemed confident that low-dose rivaroxaban is on track for FDA approval later this year for treating ACS patients. Whether Merck, the company developing vorapaxar, will seek FDA approval for its drug in stable patients based on the TRA 2P data remains to be seen.

But while rivaroxaban won’t receive labeling for treating non-ACS patients, all that separates an ACS patient and a patient who is stable but with a history of prior MI is time; in fact, just a few weeks or months. The point at which an acute ACS patient becomes a stable, post-MI patient is pretty murky. Would anyone consider treating a stable, post-ACS patient with low-dose rivaroxaban? The labeling probably won’t cover it, but will the temptation be there? And the what-ifs don’t stop there.

Both the low-dose rivaroxaban study and the vorapaxar study used aspirin and clopidogrel as standard, background treatment. But U.S. physicians are increasingly switching from clopidogrel to the newer, more potent antiplatelet drugs already on the market, prasugrel and ticagrelor, several experts told me at ACC. Putting a patient on prasugrel or ticagrelor plus aspirin will likely preclude any thought of also adding rivaroxaban, not to mention vorapaxar. These combinations have not been tested, and given the bleeding risks that these drugs pose individually, the idea of using them in combination is downright scary.

After several years when clopidogrel plus aspirin reigned alone as the top treatment for preventing atherothrombotic events, the last few years brought a flurry of new agents. How these drugs compare and relate to each other, and how they are optimally used alone or in combination, will take several more years to sort out.

—Mitchel Zoler (on Twitter @mitchelzoler)


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Filed under Blognosis, Cardiovascular Medicine, IMNG, Internal Medicine, Internal Medicine News

Dealing With Medical Performance Judgment

Earlier this week, I reported a story that dealt in part with the wide variation among Swedish hospitals in their use of proven treatments for acute myocardial infarction patients. Even though steps such as angiography to assess affected coronary arteries, rapid intervention in blocked coronary arteries, and treatment with drugs like beta blockers and angiotensin converting enzyme inhibitors have been know effective for several years, many of the Swedish hospitals in the study continued to lag in applying these measures to their acute MI patients as recently as 2007, the most recent year examined.

image courtesy The Historical Society of the Courts of the State of New York

And, said U.S. experts, there is nothing unique about Sweden. The same thing happens in the United States, too. And they offered a possible solution: More U.S. hospitals need to participate in organized data collection and feedback programs to help hospitals track the care their patients receive, their patients’ outcomes, and how the outcomes match up against similar hospitals. Feedback like this is considered essential if hospitals want to get better in the care they deliver, the process known as quality improvement.

U.S. hospitals that treat acute MI patients have access to a free resource to help, a registry run by the American College of Cardiology and the American Heart Association known as the ACTION Registry — Get With the Guidelines.

But while reporting the story this week, I learned a disturbing statistic that should not bet overlooked. Despite being free, despite being on the U.S. scene for several years, as of now only 557 of the roughly 4,000 U.S. hospitals that provide care for MI patients are members of the ACTION Registry — GWTG. That’s about 14%. The people I interviewed made it clear that ACTION –GWTG is not the only such game in town, so some hospitals may belong to a different registry and quality- improvement program, but most likely the vast majority don’t do this. As a potential MI patient myself, like any other adult, I found it pretty scary that I could well wind up treated in a hospital that does zip to make sure their treatment systems are up to date and that they provide the best type of care out there.

The message I heard earlier this month at the annual meeting of the American College of Cardiology, at a session on quality of care, is that hospitals not on top of performance data collection and the physicians who work there should find this scary, too, because they stand to soon get whacked by a growing demand by payers and regulatory agencies to grow more accountable or get out of the way.

“”The train is very close, and we’re standing on the tracks. Clinicians need to take responsibility for the clinical data and for variations in care and find ways to intervene,” advised UCLA cardiologist Charles R. McKay.

“We will all be judged [by administrative databases of hospital and physician performance] and we better figure out how to deal with it,” advised William S. Weintraub, chairman of cardiology at Christiana  Care in Newark, Del.

—Mitchel Zoler (on Twitter @mitchelzoler)

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Filed under Cardiovascular Medicine, Health Policy, Hospital and Critical Care Medicine, IMNG, Internal Medicine, Internal Medicine News, Practice Trends

Which Would You Rather Risk: Stroke or MI?

It sounds like the ultimate trick question, where the correct answer is, of course, C: none of the above.

image courtesy Flickr user chase baltz

But the choice between stroke, myocardial infarction (MI), or another cardiovascular end point, such as need for revascularization, is something now faced by patients confronted by at least a couple of somewhat different clinical situations where treatment of their vascular disease could be done by either endovascular stenting or open surgery. (Sometimes the third option is medical management and no surgery, but these are cases too advanced for medicine alone to work).

One of these situations is severe carotid artery stenosis (especially when the patient already had a stroke or transient ischemic attack).  Last year, results from CREST, the largest randomized study to compare the two main treatment options for these patients, cartoid artery stenting or open surgery by endarterectomy, showed that overall the two treatments led to similar 4-year outcomes based on the cumulative rate of death, stroke, or MI. But more detailed results, hinted at in last year’s report and then expanded on earlier this month at the International Stroke Conference, showed that the choice is a lot more nuanced, and in many ways boils down to what a patient would rather risk, having a MI or stroke. Carotid-artery stenting produced more strokes, especially in women and older patients (65 or older). Carotid endarterectomy produced more MIs, especially in men.

The gut reaction has generally been to regard strokes as a worse outcome, but now other new data from CREST, also reported at the stroke conference, prove it’s true. Dr. Joshua M. Stolker reported on the health-status outcomes from CREST. In part, this showed that CREST patients who had a stroke following their intervention had significant decrements in seven of eight quality-of-life measures on the Short Form-36, compared to a decrement in just one SF-36 measure among the patients who had a MI. Patients with major strokes had decrements in all eight subdomains, but even patients with minor strokes had significant decrements in three or four subdomains, so even a minor stroke was quantitatively worse for patients, on average, than a MI.

The analysis “confirmed what a lot of us already suspected,” Dr. Stolker said when he gave his report.

The stroke or MI choice seen in CREST was reminiscent of the results seen in 2009 from the SYNTAX trial, the most recent study to compared coronary artery bypass surgery with coronary stenting. Interesting, in SYNTAX the adverse event profile was somewhat flipped. In this case it was the CABG patients who underwent open surgery who had a significantly increased rate of stroke during follow-up compared with stented patients. The excess risk faced by patients treated with the endovascular intervention was an increased rate of a need for revascularization therapy down the road.

As far as I know, no follow-up study examined the health impact of the strokes that occurred in SYNTAX and the impact of revascularization, but it’s hard to imagine that the result would be different from what was found in CREST. A stroke is a stroke, and a nasty outcome for patients regardless of their medical history.

—Mitchel Zoler (on Twitter @mitchelzoler)

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Filed under Cardiovascular Medicine, Hospital and Critical Care Medicine, IMNG, Internal Medicine, Surgery, Thoracic Surgery

Treating Knee Injury Like a Myocardial Infarction

  When a skier skids on an icy patch, torques her knee, and gets a sudden ligament tear, is it the orthopedic equivalent of a myocardial infarction? Can rapid medical treatment in the knee damp down the resulting inflammatory, pathologic cascade and help preserve the knee’s long-term health, the same way that rapid restoration of coronary blood flow limits the extent of a myocardial infarct and long-term loss of cardiac function?

image courtesy Flickir user Dance Party Duo

 It’s an intriguing concept, and forms the rationale behind a new approach to acute management of traumatically injured knees that is starting clinical testing.

 “The early phase of acute joint injury represents a window of opportunity to promote healing and prevent a subsequent cascade of joint destructive processes,” said Duke rheumatologist Virginia Byers Kraus last week at the World Congress on Osteoarthritis in Brussels.

 “We think of osteoarthritis as a slow, chronic disease,” but that’s when it appears years after a traumatic knee injury, she said. “This is a curable type of osteoarthritis because you know when it starts. We should start to treat joint injury emergently, like an acute myocardial infarction.”

 At the Congress, she presented early evidence supporting this approach. A single, knee-joint injection of a potent anti-inflammatory drug, the interleukin 1 receptor antagonist anakinra, produced dramatic improvements in short-term pain and function when administered roughly 2 weeks after traumatic injury in a pilot controlled study with 11 patients. The next step is to look at more patients, and to push the time of treatment even earlier, within a few hours after injury, Dr. Kraus said.

 The time seems ripe for finding new ways to manage knee injuries, as middle-aged and elderly Americans are experiencing an epidemic of knee osteoarthritis that needs the ultimate treatment, total knee replacement. A second report at the Congress documented that the rate of total knee replacement surgeries soared during the decade ending in 2007. The number of knee replacements in Americans aged 45-64 tripled in that period, reaching 221,000 in 2007, with all U.S. knee replacements in 2007 reaching an all-time, 1-year high of 550,000.

 —Mitchel Zoler (on Twitter @mitchelzoler)

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Filed under Emergency Medicine, Family Medicine, IMNG, Internal Medicine, Orthopedic Surgery, Physical Medicine and Rehabilitation, Primary care, Rheumatology, Sports Medicine

Statins Stand Out

From the annual scientific session of the American College of Cardiology in Orlando

Statins are the new aspirin.

Several years ago, aspirin gained the reputation of a wonder drug for its very beneficial cardiovascular-protective effects and cheap cost. It’s time to add statins to this list (unless they’re already there).

Reports at this year’s ACC meeting only helped burnish the already glowing reputation of statins.

I blogged a few days ago about the double scored by rosuvastatin in new results from the JUPITER trial. The dramatic mortality and cardiovascular-event benefit seen in the study with 20 mg/day rosuvastatin (Crestor) treatment was confirmed to be in part a C-reactive protein effect, nailing down the suggestion to use a statin in people with “normal” lipid levels but high CRP.

It was the second observation that many cardiologist found even more intriguing: proof that the same statin regimen also stopped many episodes of pulmonary embolism or deep vein thrombosis with no bleeding risk. While the exact role of statins as antithrombotic drugs still needs clarifying, the finding hinted at a new, unexpected, and apparently very safe way to stop unwanted blood clots from forming.

But there’s more. Results from a pair of Italian studies showed that:

1) Administering a bolus, oral dose of 80 mg atorvastatin (Lipitor) to patients not already on a statin during the day before an elective percutaneous coronary intervention (PCI) cut their myocardial infarction rate while in the hospital by about a third. The finding prompted U.S. cardiologist Dr. Chrisopher Cannon to declare that standard practice should now be to start an intensive statin regimen as soon as patients are hospitalized for acute coronary syndrome or coronary catherization.

2) In a separate study of 350 patients who were already on a statin, adding an 80 mg dose of atorvastatin 12 hours before their PCI procedure and a second, 40 mg dose 2 hours before was safe and halved the rate of in-hospital myocardial infarctions. In the subgroup of patients with non-ST elevation myocardial infarction, this extra statin boost cut in-hospital events by about 80%, reported Prof. Germano Di Sciascio from Policlinic University in Rome.
Prof. Germano Di Sciascio  /photo: Mitchel Zoler

Prof. Germano Di Sciascio /photo: Mitchel Zoler

“We believe a statin load is part of the first-line treatment for patients with acute coronary syndrome,” Prof. Di Sciascio said.  A bolus dose of a statin “should probably be given to myocardial infarction patients the same way as aspirin–at the first medical contact,”  before patients even get to the hospital.

—Mitchel Zoler @mitchelzoler

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Filed under Cardiovascular Medicine, Family Medicine, Hospital and Critical Care Medicine, Internal Medicine, Practice Trends