CardioExchange Archive

Time Window for TPA in Stroke Extended to 4.5 Hours: A new pooled analysis in the Lancet provides evidence that rt-PA may be beneficial when given up to 4.5 hours after stroke onset. Kennedy Lees and colleagues added data from 2 recent trials (ECASS III and EPITHET) to 6 earlier trials to re-examine the effect of time to treatment. As in previous analyses, earlier time to treatment was associated with better outcomes. No benefits were observed when rt-PA was given after 4.5 hours. In an accompanying comment, Jeffrey Saver and Steven Levine write that the findings “mandate a renewed commitment by clinicians and policy makers to foster very early intervention. We need to increase the proportion of patients arriving at hospital in the first, golden hour after ischaemia onset…. In thrombolytic stroke therapy, sooner is better than later, much better.”

Routine Genotyping for Dual-Antiplatelet Therapy? Should genotyping be used routinely to guide dual-antiplatelet therapy (DAPT)? Two perspectives in the Journal of the American College of Cardiology provide starkly contrasting views of the issue. Samir Damani and Eric Topol, writing in a Viewpoint, note that genetic variations affecting clopidogrel responsiveness are quite common, and are “the root cause of adverse cardiovascular events during clopidogrel treatment.” Although the worth of genotyping has not been proven in large clinical trials, “we cannot afford to wait years for results from these trials that to date have yet to be initiated. In the interim, we should implement all potential interventions to help prevent the catastrophic outcomes of stent thrombosis and death in the tens of thousands of patients currently at risk.”

In an accompanying commentary, Paul Gurbel and colleagues also note the absence of clinical trials, and offer a number of reasons why the available data suggest that routine genotyping is not ready for prime time. They write that “the safety and efficacy of altering therapy in response to genotypic or phenotypic testing are entirely unknown,” and conclude that “ultimately, prospective randomized clinical trials will be needed to test specific personalized antiplatelet algorithms to provide the evidence base necessary for widespread adoption into clinical practice.”

Meta-Analysis Finds Fibrates May Have Benefits: Jun and colleagues analyzed data from 18 placebo-controlled trials of fibrates with 45,058 participants. In their paper in the Lancet, they report that fibrate use was associated with a small but marginally significant 10% reduction in major cardiovascular events (p=0.048) and a slightly larger and highly significant 13% reduction in coronary events (p<0.0001). No benefits were observed for the endpoints of stroke, all-cause mortality, cardiovascular mortality, or sudden death.

“The magnitude of the proportional risk reduction is more modest than that achieved with other vascular preventive therapies targeting lipids, blood pressure, and coagulation, and the clinical relevance of the effect reported here will be debated,” the authors wrote in their conclusion. “As for other drug classes, the real clinical value will depend on both the size of the proportional risk reduction and the absolute level of risk of the population treated.”

Big Drop in CHD Mortality in Ontario: Analyzing data from Ontario, Canada, Wijeysundera and colleagues found that between 1994 and 2005, the age-adjusted CHD mortality rate in the province declined from 191 to 125 deaths per 100,000 inhabitants — a 35% drop. The authors calculated that about half of the reduction was achieved through improvements in medical and surgical treatments. The other half of the mortality reduction was associated with changes in risk factors, despite the increase in obesity and diabetes during the period. The paper is published in JAMA.

Working 9 to 5 Is Good for the Heart:
Dolly Parton may have complained about it, but it turns out that working 9 to 5 is actually good for the heart. More precisely, working overtime is not good for the heart, according to a new report published online in the European Heart Journal. Virtanen and colleagues analyzed data from the Whitehall II study, which has been following more than 10,000 U.K. civil servants since 1985. They found that people who worked 3 to 4 hours of overtime (beyond a 7-8-hour workday) had a 60% increased risk of coronary heart disease.

AHA Scientific Statement on Air Pollution: The American Heart Association has strengthened its position on air pollution. In an update to a 2004 scientific statement, the new statement, “Particulate Matter Air Pollution and Cardiovascular Disease,” finds greater evidence linking air pollution to CV disease and reaches several new conclusions, including:

Even brief exposure over hours or weeks to PM (particulate matter <2.5 µm in diameter) can trigger CV events.
Long-term exposure increases this risk and can reduce life expectancy “by several months to a few years.”
Reducing PM levels can cut CV mortality in as soon as a few years.
New evidence strengthens the “biological plausibility to these findings.”
PM exposure “is deemed a modifiable factor that contributes to cardiovascular morbidity and mortality.”

Bran Linked to Reduced Mortality Risk in Diabetic Women: Among 7,822 diabetic women in the Nurses’ Health Study, those in the highest fifth for whole grain and bran consumption had a 16%-31% lower risk of all-cause mortality, compared with those in the lowest fifth. The benefits of bran remained significant after adjustment for lifestyle and dietary risk factors. In their paper in Circulation, Lu Qi and colleagues write that their “findings suggest that low whole-grain intake may be considered an important modifiable risk factor for decreasing mortality and cardiovascular risk in diabetic patients.”

Bad News from Europe; Even Worse News for China: Too many Europeans with coronary disease are not receiving evidence-based treatment, according to a report from the third EUROASPIRE survey. “The majority of coronary patients are not achieving blood pressure, lipid, and diabetes targets as defined in the Prevention Guidelines,” said investigator Dr Kornelia Kotseva, in a press release issued by the ESC in conjunction with EuroPRevent 2010, where the survey was presented. The survey included almost 9000 patients with coronary disease in 22 European countries and found:

56% had BP levels above target
51% had serum cholesterol levels above target
35% had diabetes

The prospects in China may be even worse, according to a new study published in Circulation: Cardiovascular Quality and Outcomes. Andrew Moran and colleagues used a computer model to forecast future rates of cardiovascular disease in China, and found that by 2030 the annual rates for heart disease and stroke could increase by 73%, leading to 7.7 million more CVD deaths between 2010 and 2030. Reductions in smoking and hypertension could help reverse the trend, write the authors.

Large Genetic Study Sheds Light on Triglycerides’ Role in Heart Disease: A large new study appearing in the Lancet provides preliminary evidence that triglycerides may play a causative role in heart disease. Investigators in the Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration studied a promoter polymorphism of a gene (APOA5) tied to triglyceride levels. Performing a Mendelian randomization analysis, the investigators found that subjects with the gene variation had higher levels of triglycerides and an elevated risk for coronary disease.

“Although these genetic findings are consistent with a causative role for triglyceride fats in the development of heart disease, they do not replace the need for large randomised clinical trials of medications that can lower blood triglycerides,” said Dr. Nadeem Sarwar in a press release issued by the Lancet. “Such trials should help establish whether lowering triglyceride levels can reduce the risk of heart disease.”

In an accompanying comment, Guillaume Pare and Sonia Anand compliment the “well executed Mendelian randomization experiment” but note that APOA5 may have “a direct effect on coronary risk above and beyond its effect on triglycerides” and conclude that “the true nature of triglycerides’ effect on coronary risk still needs further clarification.”

Second-Generation DES Superior to First-Generation DES: The industry-funded SPIRIT IV investigators randomized 3687 patients to receive either an everolimus-eluting stent (EES) or a paclitaxel-eluting stent (PES). Unlike many previous DES trials, patients did not undergo routine follow-up angiography, thereby avoiding potential bias created by the “oculostenotic reflex.” At 1 year, the primary endpoint — target-lesion failure (defined as cardiac death, target-vessel MI, or ischemia-driven target-lesion revascularization) — was significantly lower in the EES arm compared to PES (4.2% vs. 6.8%, 95% CI 0.46-0.82, p=001). EES was broadly superior to PES in a number of secondary endpoints, according to the report in the New England Journal of Medicine. In particular, the 1-year rates of MI and stent thrombosis were significantly lower in the EES group. The results of the trial also were consistent across a broad spectrum of subgroups, with the notable exception of diabetics, in whom no significant differences were observed.

In an accompanying editorial, Richard Lange and L. David Hillis (who are also moderators of the Interventional Cardiology group on CardioExchange) ask: “Should we abandon paclitaxel-eluting stents in favor of second-generation everolimus-eluting stents” on the basis of SPIRIT IV? For diabetics, they write, first-generation DES may well suffice. “For patients without diabetes, an analysis of cost-effectiveness would help to determine whether the absolute reduction of 1 to 2 percentage points in myocardial infarction (mostly non–ST-segment elevation) and the absolute reduction of 2 to 3 percentage points in target-lesion revascularization associated with the more costly everolimus-eluting stent (which is approximately $300 more expensive than the paclitaxel-eluting stent) warrant its routine use.”

5-Year Outcomes for Left Main Stenting: The 5-year risk of death and the combined risk of death, Q-wave MI, or stroke were similar in patients with left main coronary disease who were treated with CABG or with a stent. In the Journal of the American College of Cardiology, Duk-Woo Park and colleagues from Korea report the 5-year results from the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry. (The 3-year results were previously published in the New England Journal of Medicine.) However, the risk of target vessel revascularization was higher in the stenting group.

In a press statement issued by the European Society of Cardiology, William Wijns said: “This study should be added to the increasing hypothesis-generating signals emerging from various trials and registries that there may be a place for PCI in the treatment of selected patients with unprotected LMCA. The limitation of the study remains that it is a registry, possibly confounded by selection bias for either therapy. Ultimately only a prospective multi-center randomised trial will provide the definitive answer.”