Global Pulse

Cardiology Review® OnlineDecember 2008
Volume 25
Issue 12

Candesartan nonsignificantly reduces retinopathy in diabetics, except in mild to moderate cases


A randomized, double-blind, parallel-group, placebo-controlled trial that included 1905 participants did not find that candesartan significantly reduced retinopathy in patients with type 2 diabetes, except in mild to moderate cases. Diabetic eye disease, including retinopathy with macular oedema, remains the leading cause of blindness in people of working age. According to the study, which was published in the October 2008 issue of , nearly 40% of people with type 2 diabetes already have some degree of retinopathy at diagnosis, and another 22% will develop it over 6 years.

The trial compared 2 groups, 1 randomized to candesartan, the other to placebo, examined at 309 centers worldwide and followed up for at least 4 years. Participants were normoalbuminuric, normotensive, or treated hypertensive individuals with type 2 diabetes and mild to moderately severe retinopathy. Patients were assigned to candesartan 16 mg once daily or to placebo. After 1 month, the dose of candesartan was doubled to 32 mg once daily.

Of the patients in the candesartan group, 17% had progression of retinopathy by 3 or more steps on the Early Treatment Diabetic

Retinopathy Study scale compared with 19% in the placebo group. The difference, which amounted to a 13% decrease in progression between the 2 groups, was clinically nonsignificant. “We compared patients on active treatment with candesartan to those on placebo, and found an absolute difference of 2%, which translates to a relative difference of 13%. This is because in clinical trials you usually ask for a 5% significance level; otherwise, it is not considered statistically significant,” said Anne Katrin Sjølie, MD, professor in the Department of Ophthalmology at Odense University Hospital in Denmark, and author of the study.

The trial found, however, that treatment with candesartan in type 2 diabetic patients with mild to moderate retinopathy might induce improvement of retinopathy. In a subgroup analysis, patients with mild retinopathy regressed significantly. Candesartan treatment was associated with a 34% increase in regression of retinopathy.

“When you have a complication with diabetes, it usually becomes worse with time. Part of the cause is that these patients have chronic high glucose levels in their blood and organs. Candesartan has been shown in the kidneys in a few cases to reduce the tendency of worsening, and we wanted to see if it could improve eye complications,” Sjølie said.

Western diet exhibiting negative health impact globally



Western diets may be taking a toll on the cardiac health of consumers around the world, according to the INTERHEART study published online in in October. INTERHEART enrolled 12,461 patients with incident cases of acute myocardial infarction (MI) and 14,637 control subjects who were free of heart disease from 262 centers worldwide to determine the impact of various risk factors on the risk of acute MI. The analysis published in focused on diet, which is major modifiable risk factor for cardiovascular disease, and included 5761 acute MI subjects and 10,646 controls from the INTERHEART study. The study found that an unhealthy diet is responsible for approximately 30% of the acute MI risk worldwide. On the other hand, a “prudent” diet may have a slightly beneficial effect on cardiovascular health globally.

INTERHEART divided global eating patterns into 3 categories: the Western diet, characterized by fried foods, salty snacks, eggs, and meat; the prudent diet, which included lots of fruit and vegetables; and the Oriental diet, which included a high intake of tofu, soy, and other sauces. Although an Oriental diet is often thought to be healthy, it was found to be neutral in terms of health effect, according to Professor Salim Yusuf, DPhil, professor of medicine at McMaster University, and director of the Population Health Research Institute. “This is because the protective aspects are balanced by the harmful aspects. The diet is protective because it is high in fruits and vegetables, but harmful because of its high salt content,” Yusuf said.

The study found that approximately 80% of the global cardiovascular disease burden occurs in low- and middle-income countries. “Nevertheless, it is not easy, but it is possible to adopt the prudent diet in both rich and poor countries,” Yusuf said. “That is in part because the price of food is relative to the local economy, with fruits and vegetables more expensive than potatoes or rice. In addition, in poorer countries, when people grow fruits and vegetables, they often sell them,” he added. On the other hand, in countries like Zimbabwe, when a major economic crisis hits, people begin eating the produce they grow. “However, people in these circumstances are not getting much protein because animal products are expensive. In very poor countries, the challenge is undernutrition, not diet,” Yusuf added.

Prasugrel advantage goes beyond first incident

European Heart Journal

Patients who use prasugrel may have a reduction not only in first coronary-related events, but subsequent events as well, compared with patients who use clopidogrel, according to a follow-on study of the data from the TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38) trial, published in the August 2008 online edition of the .

TRITON-TIMI 38, which was reported at the 2007 Scientific Sessions of the American Heart Association, showed an overall reduction in deaths and initial events (cardiovascular death, myocardial infarction, and stroke) over a median period of therapy of 14.5 months with prasugrel compared with clopidogrel in approximately 13,000 patients. The follow-on study found that among patients who underwent planned percutaneous coronary intervention and suffered an initial nonfatal event, those who were given prasugrel experienced fewer secondary events.

There were 58 subsequent events in patients who took prasugrel versus 115 in the clopidogrel group. There were also 15 cardiovascular deaths in the prasugrel group compared with 42 in the clopidogrel group and 37 MIs with prasugrel compared with 68 with clopidogrel; however, use of prasugrel was associated with more fatal bleeds than clopidogrel. “That was not unexpected because more potent antiplatelet activity was achieved,” said Elliott Antman, MD, professor of medicine at Brigham and Women’s Hospital, Harvard Medical School, and senior investigator of the TIMI study group.

The risk of fatal bleeds associated with prasugrel appeared to be higher in a certain subset of the patient population, Antman said. “Individuals who had a stroke or transient ischemic attack [TIA] had an increased risk of bleeding and appeared to have a greater risk of serious bleeds; this group represents only 4% of the trial population,” he said. “However, some proposals have been discussed as to how one might ameliorate the bleeding, such as use of a more radial approach rather than femoral approach catheterizations, avoiding the use of thienopyridines in patients with prior stroke or TIA, and reducing the maintenance dose of prasugrel in the elderly (over 75 years of age) and those with low body weight (under 60 kg),” he said.

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