Never On Sunday

Photo by Bruce Jancin

From the annual scientific session of the American College of Cardiology, Atlanta

If you’re going to have a heart attack, it remains an excellent idea to arrange it for a weekday.

The “weekend effect”–worse outcomes for myocardial infarction patients admitted on Saturday or Sunday–remains operative across the U.S. despite numerous advances in acute cardiac care in recent years, according to a large national study.

The problem, according to Dr. Abhishek Deshmukh, appears to be that fewer of these treatment advances are brought to bear urgently on weekends because of diminished staffing and, in some hospitals, restricted cardiac catheterization lab hours.

He analyzed more than 287,000 MIs included in the 2007 National Inpatient Sample database and found the in-hospital mortality rate for patients admitted on weekends was 7.6% as compared to 6.4% for weekday admissions. After adjustment for hospital characteristics and disease severity, MI patients admitted on weekends had a 23% greater risk of in-hospital death. They also had greater average lengths of stay, got fewer revascularization procedures, and waited almost half-a-day longer for them.

Nevertheless, if chest pain arises on a weekend it remains critical to seek immediate medical care. Waiting it out until Monday is a very bad idea, stressed Dr. Deshmukh, an internal medicine resident at the Medical College of Wisconsin, Milwaukee.

—Bruce Jancin

Professional Objectivity

As a medical reporter who has been writing about diabetes for more than 20 years and living with the disease myself since 1973, covering JAMA’s diabetes “theme issue” press briefing on Tuesday was familiar territory.

Four papers were presented. Frans J. Th. Wackers, M.D., Ph.D., of Yale University reported that routine screening for cardiovascular disease in asymptomatic patients with type 2 diabetes did not impact CVD outcomes. Rachel A. Whitmer, Ph.D., of Kaiser Permanente presented her group’s finding that severe hypoglycemia resulting in a trip to the hospital was associated with an increased risk for dementia in older adults with type 2 diabetes. The impact of milder episodes needs to be studied, she said.

Dr. Richard K. Burt, of Northwestern University, then discussed his success in the use of autologous nonmyeloablative hematopoietic stem cell transplantation to reverse type 1 diabetes in newly-diagnosed patients. Might this treatment work in type 1s with longstanding disease, I asked him, given that recent evidence suggests that some of us might still retain some residual beta-cell function? “Hmm…maybe,” he answered. The final talk, by medical student John S. Kaddis, of City of Hope National Medical Center, summarized the current state of research in pancreatic islet cells for the treatment of diabetes, a field that has grown tremendously in the last decade.

I’d had a hypoglycemic reaction on my way to the briefing that morning. This, despite the fact that I had cut back both my breakfast insulin bolus dose and had programmed my pump to deliver just one-third of my normal basal infusion during the three-quarter mile walk from my apartment to the subway. The clammy, shaky, confused feeling began to set in just as I stepped on the train. There were no free seats, so I had to hang on to the pole with one hand while using the other to temporarily suspend my pump, grab a couple of glucose tablets from my pocket, and pop them into my mouth as the train lurched forward. Happily, I made it to the press club in one piece.

By the time the briefing started, my blood glucose level had rebounded to 189 mg/dL (normal is about 70-140). But I didn’t give myself more insulin because I didn’t want to risk overcorrecting and dropping low again during the two-hour briefing. My sugar was up to 214 mg/dL at 12:30 p.m. when I finally gave myself more insulin for lunch. How much damage had been done to my eyes, kidneys, nerves, and heart during that time? I try not to think about it. For people with firsthand knowledge of type 1 diabetes, this roller-coaster scenario is painfully familiar.

I suspect that my approach to covering diabetes as a journalist is similar to that of a physician who must deliver bad (or even good) news to a favorite patient: You put your personal feelings aside in order to do your job. The feelings are still there, but you don’t let them cloud your objectivity. In both cases, the “delivery” is heartfelt while remaining professional. The fact that I was given a very short time window to file all four stories certainly assisted me in that regard. 

–Miriam E. Tucker 

(On Twitter: @MiriamETucker)

A Taste of Reality for Drug Trials?

At the April 1st hearing of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee, the panel was asked to evaluate Bristol-Myers Squibb’s cardiovascular safety data for its candidate diabetes drug saxagliptin. This was the first diabetes drug to be reviewed by the committee since the FDA issued new guidance in December 2008 requiring companies to perform more extensive premarketing evaluations of CVD safety than they have done in the past.

As the panel struggled with the statistical uncertainty arising from the low rate of major adverse cardiac events (MACE) in the phase 2/3 clinical trials—a total of just 40 among 4,607 subjects over a mean of 62 weeks—a larger question emerged: Why was the MACE rate so low? The answer, several panel members noted, is that the study population was relatively low-risk: They had a mean age of 54 years and mean diabetes duration of just 4 years. Exclusion criteria for the trials included significant CV events within the past 6 months and congestive heart failure.

“I’m actually feeling quite comfortable giving this drug to a patient who doesn’t have underlying cardiac disease. I just have no idea what happens when you give this to someone who actually has coronary disease or who has had diabetes for a longer time and actually has these underlying risk factors that tend to predispose someone to having a myocardial infarction,” said Dr. John R. Teerlink, a San Francisco cardiologist who served as a temporary voting member of the panel.

Indeed, as a March 30th New York Times article pointed out, multiple chronic conditions are the rule, not the exception: Two-thirds of people over age 65 have more than one chronic condition, and people with five or more conditions comprise 68% of Medicare spending.

Yet patients with multiple diseases are routinely shut out of drug trials. A 2007 study found that 81% of the randomized trials published in the most prestigious medical journals excluded patients because of coexisting medical problems, Times reporter Siri Carpenter wrote, adding, “Because so little research includes complicated patients, physicians have little scientific evidence on which to base their care.”

At the end of the saxagliptin hearing, the advisory panel voted 10-2 to support the drug’s CV safety data for the patient population studied, but voted unanimously, 12-0, to require BMS to conduct a long-term postmarketing study in higher-risk patients with type 2 diabetes who better represent the range of those that physicians see every day. Might this decision signal the start of more such “real-world” pre-marketing drug studies in the future? If so, it would seem that the aging Baby Boomer generation will be the first to gain.

–Miriam E. Tucker

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

“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