Mr. Susman is a freelance medical writer based in Florida, USA. He travels worldwide to report from medical conferences, writing regularly for wire services, internet websites, and medical journals such as the Journal of the National Cancer Institute and AIDS.
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PARIS, France – In richer countries of the world, advances in treating and preventing heart disease has resulted in cardiac deaths falling out of the top spot in what causes more deaths – relinquishing that unenviable spot to cancer-related mortality, researchers reported here.
In analyzing data accrued from the worldwide Prospective Urban Rural Epidemiology Study (PURE), Salim Yusuf, MD, DPhil, professor of cardiology at McMaster University, Hamilton, Ontario, Canada, said that 23 percent of the causes of death in the representative high-income countries of the world were associated with coronary artery disease whereas cancer represents 55 percent of the deaths in those counties.
At a press conference at the annual meeting of the European Society of Cardiology, Dr. Yusuf said that in the middle-income countries of the world such at the Philippines, 42 percent of the deaths are attributable to cardiac diseases while 30 percent of deaths are due to cancer.
In low-income countries 43 percent of deaths are attributable to heart disease; 19 percent are due to cancer. In those low-income countries, 9 percent of the people die from infections – compared to about 2 percent of people in high-income countries.
“The differences in cardiovascular disease rates are not primarily due to differences in metabolic risk factors,” Dr. Yusuf said. “But may be due to differences in smoking, diet, air pollution and access to care.”
The PURE study includes 202,000 individuals from 27 countries from 5 continents. The high-income countries are represented by Canada, Sweden, Saudi Arabia and the United Arab Emirates.
Dr. Yusuf said that overall, death rates for cancer were about the same in high, middle and low-income countries, but the major differences seen were in cardiovascular death rates which were 2.5 times higher in low income countries as compared to high income countries. Deaths due to respiratory diseases were also higher in low-income countries as were death rates due to injuries and infections.
He said that most of the attributable causes of heart disease can be placed at the foot of hypertension – more than 20 percent of cardiovascular deaths worldwide are related to high blood pressure, he illustrated. A poor lipid profile was the next most attributable cause of cardiovascular death, amounting to about 9 percent of the attributable fraction. That was followed by household pollution, tobacco use, poor diet and low education as attributable factors, Dr. Yusuf said.
Across the board, he said that cardiovascular death was mostly caused by behavior. In high-income countries, the next problem was metabolic causes. In low-income countries, cardiovascular disease causes included low education, low grip strength and household pollution.
In commenting on the studies, Ivor Benjamin, MD, director of the cardiovascular center at the Medical College of Wisconsin, Milwaukee, and immediate past president of the American Heart Association, said, “In the United States, which of course can be considered one of the those highincome countries, we have actually been witnessing this remarkable improvement in cardiovascular health outcomes thanks to decades of research in both prevention and treatment that have yielded unprecedented returns on that investment.
“When you couple that with the fact that we now have improvements in performing revascularization,” he said. “We have devices, stents, surgery and on and on and on. Even when you get a problem with cardiovascular disease, we can keep you alive longer. As a result of these accomplishments, people have to die from something other than cardiovascular disease, and it now appears that this is cancer.”
Dr. Benjamin said these improvements have occurred of the last 40 to 50 years. “We have been actionable in addressing the causal methods of cardiovascular disease are not necessarily translated in the same way for cancer,” he said. “This study very elegantly that when you look at a cross section of the populations of these countries it clearly shows that the ratio of cardiovascular to cancer is as much as 10 times higher in the low-income countries compared to high-income countries.
But Dr. Benjamin said that if the attributable causes for cardiovascular disease are addressed in the poorer nations than they “could have the same cardiovascular rates as we have. The question is: How do we go about achieving that particularly when we don’t have the resources to make that happen.”
Turning the tables
In another study at the ESC, the world’s largest cardiology convention, researchers were surprised that treatment of patients diagnosed with acute coronary syndrome treatment with prasugrel was significantly more effective in preventing the composite endpoint than ticagrelor – precisely the opposite outcome predicted by the ISAR-REACT 5 hypothesis.
“We assumed that ticagrelor is superior to prasugrel in acute coronary syndrome patients with planned invasive strategy in terms of clinical outcomes,” said Stephanie Schüpke, MD, professor of cardiology at the German Center for Cardiovascular Research, Munich, Germany. It didn’t turn out that way.
In the 12-month trial, 9.3 percent of the patients treated with ticagrelor experienced the composite primary endpoint of death, myocardial infarction or stroke compared with 6.9 percent of patients who were assigned to treatment with prasugrel – translating to a 36 percent increased risk of an event with ticagrelor which was statistically significant (P=0.006).
“We were surprised by the result,” Dr. Schüpke admitted at a press conference, noting that previous studies suggested that ticagrelor would have more benefit. She also noted that the achievement in reducing events with prasugrel was accomplished without a significant increase in bleeding events. In fact, 5.4 percent of the patients on ticagrelor experienced bleeding in the trial compared with 4.8 percent of the patients on prasugrel, she reported.
A total of 4018 patients underwent randomization. A primary-end point event occurred in 184 of 2012 patients in the ticagrelor group and in 137 of 2006 patients in the prasugrel group. Dr. Schüpke said that the difference in outcomes was driven by a reduction in myocardial infarction – 4.8 percent of patients on ticagrelor experienced heart attacks, compared with 3 percent of the prasugrel-treated patients. There were more deaths, strokes and stent thromboses in the ticagrelor patients, but these individual components of the endpoint were not statistically different, she said.
“I could give you a number of reasons why ticagrelor should be superior to prasugrel,” Schüpke said “But since we found just the opposite, I really can’t explain it. We are in the midst of analyzing sub-studies so there will be more data coming.
“A potential mechanism could be that the half-life of the drugs are different,” she said. “It could be something with the fact that ticagrelor is taken twice a day and prasugrel is taken once a day; it could be something to do with the mechanism of action – ticagrelor is a reversible antagonist and prasugrel is an irreversible antagonist. The drugs bind at different sites on receptors. There are also differences in side effect profiles that could lead to differences in discontinuation. There were differences in discontinuation rates – 15 percent discontinued ticagrelor and 12 percent discontinued prasugrel. We did perform an on-treatment analysis but that result was consistent with the intention-to-treat analysis.
“This is really a clear result and the data are quite robust. These results are clinically relevant. Prasugrel showed clear superiority over ticagrelor and importantly did so without an increase in bleeding,” Dr. Schüpke said.
She said that the researchers expected to see an event rate of 10 percent with ticagrelor which turned out to be accurate, but they predicted a 12 percent event rate with prasugrel, but that rate turned out to be halved in the clinical trial among patients on the drug.