WARFARIN PLUS ASPIRIN EFFECTIVE AFTER MI

A randomized multicenter trial by Hurlen et al has found that warfarin—given by itself or with aspirin—is more effective than aspirin alone in preventing death or recurrent thromboembolic events following myocardial infarction (MI). However, warfarin use is associated with a higher incidence of bleeding.

A total of 3,630 patients took part in the study. They were randomized to receive 160 mg/d of aspirin (1,206 patients), warfarin at a dose needed to reach an international normalized ratio (INR) of 2.8 to 4.2 (1,216 patients), or 75 mg/d of aspirin plus warfarin at a dose that would produce an INR of 2.0 to 2.5 (1,208 patients).

Clinical examinations were performed six weeks after MI and at the end of the study (mean duration of observation was four years). Patients received monthly questionnaires asking about new thromboembolic events, compliance with therapy, and adverse effects of medication.

During the study, 625 “first events” occurred (see Table 1 for a definition of first events). Compared with aspirin alone, the risk reduction for a first event in patients receiving warfarin plus aspirin was 29%. In those receiving warfarin alone, it was 19%.

The total number of events, including recurrent events, was 741. Twenty-five percent of the patients in the aspirin group suffered one or more events, as did 19% of the warfarin group and 17% in the combined therapy group. The risk reductions for total events associated with warfarin and combined therapy were 19% and 29%, respectively.

By the end of the study, however, 1,058 patients had discontinued therapy—16% of the aspirin group, 31% of the warfarin group, and 40% of the combined therapy group. More patients in both warfarin groups were withdrawn because of bleeding.

Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002;347:969-974.

CPAP VERSUS MANDIBULAR REPOSITIONING
FOR SLEEP APNEA

In patients with sleep apnea/hypopnea syndrome, continuous positive airway pressure (CPAP) appears significantly more effective than the mandibular repositioning splint (MRS), according to Engleman and colleagues. Forty-eight patients were randomized to CPAP or MRS and were asked to use the treatment for two months, after which treatment was switched. Outcomes were measured during the final 10 days of each treatment period.

Measured both objectively by apnea/hypopnea index (AHI) and subjectively by patient ratings, CPAP was more effective than MRS. During home sleep studies, AHI was reduced to five or less per hour in 19% of patients using MRS and in 34% using CPAP, and to 10 or less per hour in 47% of patients using MRS and in 66% using CPAP. In addition, symptom and subjective sleepiness scores were both better with CPAP.

In an analysis of 18 patients with mild sleep apnea/hypopnea syndrome, symptoms and functional outcomes scores all had significantly better ratings with CPAP. The authors therefore recommend CPAP as first-line treatment for symptomatic patients but noted that rapidly evolving technologies may alter their present recommendation.

Engleman HM, McDonald JP, Graham D, et al. Randomized crossover trial of two treatments for sleep apnea/hypopnea syndrome: continuous positive airway pressure and mandibular repositioning splint. Am J Respir Crit Care Med. 2002;166:855-859.

PREDICTING RISK IN PULMONARY EMBOLISM

Elevated levels of cardiac troponin I (cTnI) and cTnT are strong indicators of risk in patients with acute pulmonary embolism, according to a study by Konstantinides et al.

One hundred six patients with confirmed acute pulmonary embolism were included in the study. Levels of cTnI and cTnT were obtained in blood samples at hospital admission and four, eight, and 12 hours later. CTnI was elevated in 41% of patients, and cTnT was elevated in 37% of patients. The highest cTnI and cTnT levels were from samples taken within four hours of hospital admission.

Elevated cTnI and cTnT levels were significantly associated with overall mortality, a complicated clinical course, and recurrent pulmonary embolism during hospitalization. However, troponin measurements were better at ruling out complications than predicting them: The negative predictive values of elevated cTnI and cTnT levels were 92% and 93%, respectively, whereas their positive predictive values were only 37% and 41%, respectively. Evidence of right ventricular dysfunction was present in 18% of patients with normal cTnT levels and in 48% of those with high cTnT levels. Likewise, 10% of patients with normal cTnI levels had right ventricular dysfunction versus 50% of those with high cTnI levels. The present data strongly support the use of troponin testing as part of risk determination in patients with confirmed pulmonary embolism.

Konstantinides S, Geibel A, Olschewski M, et al. Importance of cardiac troponins I and T in risk stratification of patients with acute pulmonary embolism. Circulation. 2002;106:1263-1268.

BMI LINKED TO HEART FAILURE RISK

Extreme obesity is a known risk factor for heart failure. However, whether lesser degrees of obesity are also culpable is unclear. Recent research has found that increased body mass index (BMI)—even at levels only slightly above the normal range—is associated with an increased risk of heart failure.

Kenchaiah et al examined the relationship between BMI and heart failure incidence among 5,881 participants with a mean age of 55. Mean follow-up was 14 years. Normal subjects were classified as having a BMI of 18.5 to 24.9; overweight subjects, 25.0 to 29.9; and obese subjects, 30.0 or higher.

Heart failure developed in 496 subjects. The risk of heart failure was increased by 34% in overweight subjects and by 104% in obese subjects. Each rise in BMI of 1.0 above normal was associated with a 6% elevation in risk. Furthermore, the risk presented by increased weight was greater in women than men.

An elevated BMI is a risk factor for many conditions that augment the risk of MI; infarct, in turn, can lead to heart failure. Clinicians should continue to emphasize the importance of maintaining normal BMI and body weight to all patients whose BMI is above the normal range.

Kenchaiah S, Evans JC, Levy D, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347:305-313.

SMOKER’S PARADOX DEBUNKED

Despite some previous studies suggesting that smokers have no increased risk of cardiac events after MI—the so-called smoker’s paradox—a recent study conducted by Rea et al has shown the notion to be false. The investigators found that continued smoking after the infarction was associated with a recurrence of cardiac events.

The study included 2,619 patients who were discharged after a first MI and followed from July 1986 (women) or July 1989 (men) through December 1996. Patients were classified as nonsmokers, former smokers (quit before MI), quitters (quit after MI), or active smokers. The primary outcome was incidence of recurrent cardiac events.

At the time of first MI, 880 patients were nonsmokers, 931 were former smokers, and 808 were active smokers. Of the active smokers, 344 quit smoking during hospitalization and 464 were active smokers at time of discharge. Of these active smokers, 105 quit after discharge.

During three years of follow-up, 433 recurrent cardiac events occurred. The risk for these events was similar in former smokers and nonsmokers. However, compared with nonsmokers, the people who continued to smoke after first MI had a 50% increased risk for recurrent coronary events. Among those who quit after first MI, risk declined with time until, after three years, it had reached that of nonsmokers.

Rea TD, Heckbert SR, Kaplan RC, et al. Smoking status and risk for recurrent coronary events after myocardial infarction. Ann Intern Med. 2002;137:494-500.

THREE DAYS OF AMOXICILLIN AS EFFECTIVE AS FIVE

A three-day course of amoxicillin is as effective as a five-day course in young children with nonsevere pneumonia, according to a recent report. A randomized controlled trial was performed with 2,000 children between the ages of 2 and 59 months who were diagnosed with nonsevere pneumonia. All children received 15 mg/kg of oral amoxicillin three times a day for three days. For the next two days, children received either a placebo or oral amoxicillin.

Children were assessed three, five, and 14 days after enrollment. Patients were judged compliant if they took at least 80% of their medication.There were no differences between groups in the number of patients whose treatment failed after three days or five days, or in the number who had a relapse. Younger age (2 to 11 months), vomiting, duration of illness for three days or more, higher respiratory rate, and nonadherence to the regimen were all associated with treatment failure.

Although treatment was equally effective in both groups, the authors noted that the overall failure rate was high. They speculated that their criteria for failure were too sensitive, and the increasing rate of antimicrobial resistance may have been a factor as well.

Pakistan Multicentre Amoxicillin Short Course Therapy (MASCOT) pneumonia study group. Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial. Lancet. 2002;360:835-841.

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