Men With Angina Face Significantly Poorer Outcomes

They face a doubled risk of heart attack, death from ischemic heart disease, all-cause mortality

09 aug 2009-- In patients newly diagnosed with angina, five-year outcomes are significantly worse among men than among women, according to a study published online Aug. 6 in BMJ.

Brian S. Buckley, Ph.D., from the National University of Ireland in Galway, and colleagues studied 1,785 patients (mean age, 62.3 years) who were diagnosed with angina between January 1998 and December 2001.

The researchers found that men had a significantly increased risk of acute myocardial infarction, death from ischemic heart disease, and all-cause mortality (hazard ratios, 2.01, 2.80, and 1.82, respectively). They also found that acute myocardial infarction after an angina diagnosis was associated with an increased risk of all-cause mortality, which was not reduced by coronary artery bypass grafting or percutaneous transluminal coronary angioplasty.

"Linked clinical datasets, such as the one described, provide important opportunities to study prognosis after an event quickly and cost effectively," the authors conclude. "Ideally, future studies of prognosis after a first episode of angina should focus on primary care; include patients who have been phenotyped after diagnostic tests such as coronary angiography; be able to look at the effects of different interventions (such as angioplasty without stenting, or with conventional stents or drug-eluting stents, and medical treatments); allow for the frequency and severity of angina symptoms and changes in treatments and risk factor profiles over time."

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ESC: On Second Go-Round, MERLIN Finds Arrhythmia Magic in Ranolazine

VIENNA, Sept. 6 -- The anti-anginal drug ranolazine (Ranexa) may reduce episodes of ventricular tachycardia and supraventricular tachycardia, researchers reported here.
The potential benefit was detected in a pre-specified analysis of Holter monitor data from MERLIN-TIMI 36 -- a failed trial of ranolazine for treatment of acute coronary syndrome.
Yet the analysis showed that ranolazine reduced the number of ventricular tachycardia episodes by 37% (P<0.001) and reduced supraventricular tachycardia by 19% (P<0.001). Benjamin M. Scirica, M.D., M.P.H. of Brigham and Women's Hospital in Boston, reported at the European Society of Cardiology meeting. The study was published online simultaneously in Circulation, Journal of the American Heart Association.
Dr. Scirica said the drug also tended to reduce occurrence of new onset atrial fibrillation by 27%, but that difference was not statistically significant (P=0.08).
When the MERLIN-TIMI 36 data were reported last spring, the drug failed to demonstrate benefit as a treatment for acute coronary syndrome. But because the drug had previously been associated with prolonged QT interval continuous ECG monitoring (Holter or cECG) was conducted on all patients for the first seven days after randomization.
Analysis of those of thousands of hours of ECG data revealed the antiarrhythmic potential, Dr. Scirica said.
Ranolazine is a piperazine derivative that reduces ischemia via inhibition of the inward sodium current during cardiac repolarization, with a consequent reduction in intracellular sodium and calcium overload.
In MERLIN, 6,560 patients with non-ST elevation acute coronary syndrome were randomized to ranolazine or placebo on top of standard therapy. Of those, 6,351 had ECG recordings evaluable for analysis.
The primary endpoints were a set of prespecified clinically significant arrhythmias that were evaluated by a blinded core laboratory. Those arrhythmias included ventricular tachycardia, defined as at least three beats in length, any supraventricular tachycardia greater than 120 beats per minute and lasting at least four beats, new onset atrial fibrillation, an episode of bradycardia of less than 45 beats per minute lasting at least four beats, complete heart block, or ventricular pause greater than 2.5 seconds.
Those arrhythmias were further classified and included ventricular tachycardias, categorized according to current guidelines -- at least four beats, at least eight beats, and sustained for more than 30 seconds -- as well as any supraventricular tachycardia greater than 120 beats per minute and lasting at least four beats, and new onset atrial fibrillation. Also included were episodes of bradycardia of less than 45 beats per minute lasting at least four beats, complete heart block, and ventricular pause greater than 2.5 seconds.
Among the findings:
Fewer patients had an episode of ventricular tachycardia lasting more than eight beats (166 versus 265, P<0.001).
Supraventricular tachycardia occurred in 1,752 patients in the control group versus 1,413 in the active treatment arm (P<0.001).
New onset atrial fibrillation was reported in 55 ranolazine patients versus 75 placebo patients.
Pauses of more than three seconds occurred in 97 ranolazine patients versus 136 placebo patients (P<0.001).
Dr. Scirica concluded that studies are warranted specifically designed to evaluate the potential role of ranolazine as an anti-arrhythmic agent.
The study was funded by CV Therapeutics and Dr. Scirica said he had received modest honoraria from CV Therapeutics. Additional source: European Society of CardiologySource reference: Scirica, BM et al "The effect of ranolazine, a novel anti-anginal agent with electrophysiologic properties, on the incidence of tachyarrhythmias: results from the MERLIN-TIMI 36 randomised controlled trial." Clinical Trial Update II September 5, 2007

High Blood Pressure Can Mask Dangerous Chest Pain

MONTREAL, July 11 -- Patients with high blood pressure may be at risk for silent ischemia because they have a decreased perception of the pain that would otherwise signal heart disease, researchers here said.
In a prospective study of 907 men and women suspected of having myocardial ischemia, those with high blood pressure tended to have significantly lower pain scores during exercise (P=0.003) than those with normal pressure, according to Bianca D'Antono, Ph.D., of the Montreal Heart Institute, and colleagues.
The relationship was present whether or not imaging showed an actual deficit in perfusion, the researchers reported in the July issue of Psychophysiology.
Previous studies - using experimental models of pain - have suggested that people with high blood pressure feel less discomfort, but this is one of the first to look at pain in a more natural setting, the researchers said.
From 2000 through 2003, men and women referred to the Montreal Heart Institute for diagnosis of possible myocardial ischemia were asked to take part in the study, which measured their pain both at rest and during exercise stress testing.
Patients' cardiac perfusion was measured using single positron emission tomography (SPECT) at baseline, at rest, and after a stress test. The participants also filled out the short form of the McGill Pain Questionnaire on the rest day and after exercise.
The exercise test itself was conducted on a treadmill using the Bruce protocol and was stopped when a patient reported considerable pain, was out of breath, showed anomalies on an electrocardiogram, or reached 90% of the maximal heart rate expected for the patient's age.
The cohort was divided in two on the basis of median post-exercise systolic blood pressure, with the cut-off for high blood pressure being 170 millimeters of mercury.
In a general linear model of total score on the pain questionnaire, ischemia, post-exercise systolic blood pressure, and exercise duration were significant predictors of pain.
Specifically:
Patients who had ischemia, as determined by SPECT, felt significantly more pain during exercise, at P=0.025.
Patients who exercised longer had significantly less pain, at P<0.001.
Patients with high post-exercise systolic blood pressure had significantly less pain, at P=0.003, regardless of whether they had a perfusion deficit or EEG anomalies.
The patients also evaluated their pain as being more or less widespread. Analysis of those evaluations showed that exercise duration was significantly associated (at P<0.001) with the perception of widespread pain, but blood pressure was not, the researchers said.
They noted that the inverse relationship between blood pressure and pain remained significant after adjustment for a range of possible confounding variables.
The researchers also evaluated exertional chest pain during daily living, using the Canadian Cardiovascular Society grading scale. Again, higher blood pressure was significantly associated at P=0.001 with lower angina, they found.
The latter findings are important, the researchers concluded, because "the clinical problems associated with silent ischemia, such as failure to take medication or seek medical care, are related to the experience of angina in the daily life rather than in the hospital."
The study was supported by the Canadian Institutes for Health Research and the Heart and Stroke Foundation of Quebec. The authors did not report any potential conflicts. Primary source: PsychophysiologySource reference: Ditto B et al. "Chest pain is inversely associated with blood pressure during exercise among individuals being assessed for coronary heart disease." Psychophysiology, 44 (2007), 183-188.