JACC has the details. Sitagliptin is a DPP-4 inhibitor used to treat type 2 diabetes. It’s sold in the U.S. as Januvia. Note that the alleged higher risk of heart failure is in patients who had a history of prior heart failure. Research findings like this are not always dependable or reproducible. It bears watching, especially if you’re a heart patient.
Tag Archives: heart failure
The Mediterranean diet preserves heart muscle performance and reduces future heart disease events, according to Greek researchers reporting in the American Journal of Clinical Nutrition, May 19, 2010.
The Mediterranean diet is well-established as an eating pattern that reduces the risk of death or illness related to cardiovascular disease—mostly heart attacks and strokes. Most of the studies in support of the heart-healthy diet looked at development of disease in general populations. The study at hand examined whether the diet had any effect on patients with known heart disease, which has not been studied much.
The study population was 1,000 consecutive patients admitted with heart disease to a Greek hospital between 2006 and 2009. In this context, heart disease refers to a first or recurrent heart attack (70-80% of participants) or unstable angina pectoris. Acute heart attacks and unstable angina are “acute coronary syndromes.” Average age was 64. Sixty percent had a prior diagnosis of cardiovascular disease (coronary heart disease or stroke). Thirty percent had diabetes. At the time of hospitalization, half had diminished function of the main heart pumping chamber (the left ventricle), half had normal pump function. Men totalled 788; women 212.
On the third hospital day, participants were given a 75-item food frequency questionnaire asking about consumption over the prior year. If a potential enrollee died in the first two hospital days, he was not included in the study. A Mediterranean diet score was calculated to determine adherence to the Mediterranean diet. Mediterranean diet items were nonrefined cereals and products, fruits, nuts, vegetables, potatoes, dairy products, fish and seafood, poultry, red meats and meat products, olive oil, and alcohol.
Left ventricle function was determined by echocardiogram (ultrasound) at the time of study entry, at the time of hospital discharge, and three months after discharge. Systolic dysfunction was defined as an ejection fraction of under 40%. [Normal is 65%: when the left ventricle is full of blood, and then squeezes on that blood to pump it into the aorta, 65% of the blood squirts out.]
Participants were then divided into two groups: preserved (normal) systolic left ventricular function, or diminished left ventricular function.
They were followed over the next two years, with attention to cardiovascular disease events (not clearly defined in the article, but I assume including heart attacks, strokes, unstable angina, coronary revascularization, heart failure, arrhythmia, and death from heart disease or stroke.
- Four percent of participants died during the initial hospitalization.
- At the three month follow-up visit, those with greater adherence to the Mediterranean diet (a high Mediterranean diet score) had higher left ventricular performance (P=0.02).
- At the time of hospital admission, higher ejection fractions were associated with greater adherence to the Mediterranean diet (P<0.001).
- Those who developed diminished left ventricular dysfunction had a lower Mediterranean diet score (P<0.001)
- During the hospital stay, those in the highest third of Mediterranean diet score had lower in-hospital deaths (compared with the lower third scores) (P=0.009).
- Among those who survived the initial hospitalization, there was no differences in fatal cardiovascular outcomes based on Mediterranean diet score.
- Food-specific analysis tended to favor better cardiovascular health (at two-year follow-up) for those with higher “vegetable and salad” and nut consumption. No significant effect was found for other components of the Mediterranean diet score.
- Of those in the highest third of Mediterranean adherence, 75% had avoided additional fatal and nonfatal cardiovasclar disease events as measured at two years. Of those in the lowest third of Mediterranean diet score, only 53% avoided additional cardiovascular disease events.
The Authors’ Conclusion
Greater adherence to the Mediterranean diet seems to preserve left ventricular systolic function and is associated with better long-term prognosis of patients who have had an acute coronary syndrome.
I agree with the authors’ conclusion.
We’re assuming these patients didn’t change their way of eating after the initial hospitalization. We don’t know that. No information is given regarding dietary instruction of these patients while they were hospitalized. In the U.S., such instruction is usually given, and it varies quite a bit.
In this study, lower risk of cardiovascular death was linked to the Mediterranean diet only during the initial hospital stay. Most experts on the Mediterranean diet would have predicted lower cardiovascular death rates over the subsequent two years. Mysteriously, the authors don’t bother to discuss this finding.
For those who don’t enjoy red wine or other alcoholic beverages, this study suggests that the Mediterranean diet may be just as heart-healthy without alcohol. A 2009 study by Trichopoulou et al suggests otherwise.
Reference: Chrysohoou, C., et al. The Mediterranean diet contributes to the preservation of left ventricular systolic function and to the long-term favorable prognosis of patients who have had an acute coronary event. American Journal of Clinical Nutrition, May 10, 2010. doi:10.3945/ajcn.2009.28982
MedPageToday reported yesterday on the U.S. Food & Drug Administration’s ruling that the diabetes drug rosiglitazone should be used in new patients only if blood sugars are not controlled with other diabetes drugs, such as pioglitazone.
It sounds as if new users and their doctors may have to jump through some paperwork hoops to get the drug, which is more reason not to prescribe it.
The problem is that scientific studies suggest that rosiglitazone increases the risk of heart attack, heart failure, and death.
A week ago, MedPageToday reported that a British advisory commission recommended the diabetes drug rosiglitazone (Avandia) be withdrawn from the market.
On July 6, I wrote about evidence that rosiglitazone users seem to incur a higher risk of stroke, heart failure, and death.
If I were taking Avandia, I’d be asking my doctor about alternatives.
Sold in the U.S. as Avandia, rosiglitazone is a drug used to control type 2 diabetes either alone or in combination with insulin, metformin, or a sulfonylurea. It has only one competitor in its class: pioglitazone (sold as Actos).
Both drugs in the thiazolidinedione class (aka TZDs or glitazones) increase the risk of heart failure. Prior studies had suggested that rosiglitazone increases the risk of heart attack, heart failure, and death. Research suggested that pioglitazone actually reduces the risk of heart attack, stroke, and death.
A study just published in the Journal of the American Medical Association directly compared clinical use of rosiglitazone and pioglitazone. Investigators looked at Medicare data involving over 227,000 patients, average age 74, average follow-up of 105 days.
Rosiglitazone comes out the loser: users had significantly higher risk of stroke, heart failure, and death. Risk of heart attack trended a bit higher in the rosi users but did not reach statistical significance.
The researchers also calculated the composite risk of suffering either a heart attack, stroke, heart failure, or death: rosiglitazone risk was about 18% higher compared to pioglitazone.
What do these numbers mean from a practical viewpoint? The researchers calculated a “number needed to harm.” Treat 60 patients with rosi and 60 with pio for one year; the rosi group will have one extra event—heart attack, stroke, heart failure, or death—compared with the pio users.
Why put up with that risk? There’s no good reason. Especially when pioglitazone is available.
If you take rosiglitazone, ask your doctor to find an alternative or switch you to pioglitazone. Soon.
Clearly, we don’t know all of the adverse effects of many of the drugs doctors prescribe, whether for diabetes or other illnesses. We balance the good with the bad, and that equation changes over time.
Rosiglitazone’s manufacturer may pull the drug off the market voluntarily. If not, the FDA will do it. Cardiovascular disease—e.g., heart attacks, strokes, heart failure—kills 68% of diabetics. The last thing we need is a drug that increases that risk.
Within a month, you’ll see ads on U.S. television from trial lawyers asking if you or a loved one has been hurt by rosiglitazone. “If so, call this toll-free number now…”
Reference: Graham, D., Ouellet-Hellstrom, R., MaCurdy, T., Ali, F., Sholley, C., Worrall, C., & Kelman, J. (2010). Risk of Acute Myocardial Infarction, Stroke, Heart Failure, and Death in Elderly Medicare Patients Treated With Rosiglitazone or Pioglitazone JAMA: The Journal of the American Medical Association DOI: 10.1001/jama.2010.920
Remember that drug names—both generic and brand—may vary depending on country and manufacturer. In the U.S., rosiglitazone is sold as Avandia; pioglitazone is Actos. This is just a brief overview: consult your physician or pharmacist for full details.
How do they work?
In short, TZDs increase glucose utilization and decrease glucose production, leading to lower blood sugar levels. They sensitize several tissues to the effect of insulin. Insulin, among other actions, helps put circulating blood sugar into our muscles, fat cells, and (to a lesser extent) liver cells. So blood sugar levels fall. Thiazolidinediones (aka TZDs) make these tissues more sensitive to this effect of insulin. Insulin also suppresses glucose production by the liver, an effect enhanced by TZDs. They reduce insulin resistance.
TZDs may also help preserve pancreas beta cell function. Beta cells produce insulin.
They reduce both fasting and after-meal glucose levels. Fasting blood sugar drops and average of 40 mg/dl. Hemoglobin A1c falls by 1 to 1.5% (absolute, not relative).
TZDs tend to improve blood lipids: lower triglycerides, higher HDL cholesterol, decreased small, dense LDL cholesterol. Pioglitazone has the more pronouned effect.
On a cellular level, they activate peroxisome proliferator-activated receptor-gamma, so they are sometimes referred to as PPAR-gamma agonists. Pioglitazone also affects PPAR-alpha.
TZDs can be used alone or in combination with insulin, metformin, and sulfonylureas in people with type 2 diabetes.
Note that onset of action is delayed by several weeks, perhaps as many as 8-12 weeks.
Pioglitazone: Start at 15-30 mg/day by mouth. Maximum dose is 45 mg/day.
Rosiglitizone: Start at 4 mg/day by mouth. After 8-12 weeks, dose may be increased to 8 mg/day.
Weight gain is fairly common, through both fluid retention and increase in fat tissue. Weight gain with pioglitazone, for example, is around 6–12 pounds (3–5 kg). Mild anemia and puffy feet and hands (edema from fluid retention) are also seen. Fluid retention may ultimately cause congestive heart failure. This drug-induced fluid retention does not respond very well to fluid pills (diuretics).
The combination of insulin injections and TZD may increase the risk of heart failure.
Some studies suggest that rosiglitazone increases the risk of heart attacks, heart failure, and death. That’s why the Food and Drug Administration in 2011 drastically curtailed use of the drug. The FDA re-examined the date in 2013 and decided that rosiglitazone didn’t increase cardiovascular risk after all.
Preliminary data suggest a link between bladder cancer and pioglitazone.
TZDs are associated with increased risk for broken bones, perhaps doubling the risk.
Macular edema—manifested by blurry vision—may occur infrequently.
When used as the sole diabetic medication, TZDs do not cause hypglycemia. But when used with insulin injections or insulin secretagogues, low blood sugar can occur.
Don’t use if you . . .
. . . have a significant degree of congestive heart failure or active liver disease. Even a history of heart failure may be a reason to avoid TZDs. TZDs should probably not be used in women with low bone density or anyone else prone to fractures.
Updated December 26, 2013
On April 24, 2009, NutritionData.com published a blog post of mine discussing heart failure. Since diabetes is a cause of heart failure, you may be interested in it. If so, please click here to see the post.
Today, NutritionData published my post on other causes and prevention of heart failure.
Steve Parker, M.D.