21st European Meeting on Hypertension and Cardiovascular Prevention

New-onset atrial fibrillation (AF) is a common complication among patients at high vascular risk due to coronary artery disease, cerebrovascular disease, peripheral artery disease (PAD), or complicated diabetes, according to findings from a large clinical trial program. Paolo Verdecchia, MD, Ospedale di Assisi, Assisi, Italy, presented findings the findings of the study.

The Ongoing Telmisartan Alone and In Combination with Ramipril Global Endpoint Trial and Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease(ONTARGET/TRANSCEND; NCT00153101) trials evaluated the effects of angiotensin receptor blockade in patients with a history of myocardial infarction (MI), stroke, PAD, or complicated diabetes (Yusuf S. N Engl J Med 2008; TRANSCEND Investigators. Lancet 2008). The current study evaluated the incidence of new-onset AF in high-risk vascular patients enrolled in the ONTARGET/TRANSCEND trials (n = 30,424).

Over 4.7 years of follow-up, 2,092 patients (6.9%) developed new-onset AF. The overall rate was 1.5% per year, although the annual rate was higher in men than in women (1.66% vs 1.33%) and in older (>65 years) than in younger patients (2.00% vs 0.99%). There were no differences in the risk of new-onset AF among patients treated with ramipril, telmistartan, or combination ramipril/telmisartan.

New-onset AF was associated with several well-known risk factors, including hypertension, creatinine level, left ventricular hypertrophy, and body mass index (BMI). In a novel finding, hip circumference also emerged as a marker of AF risk. Hip circumference alone was stronger than waist circumference or hip-to-waist ratio in predicting the onset of AF.

Patients received several therapies in addition to the ONTARGET/TRANSCENT study drugs. Patients who developed AF were more likely than other patients to be treated with digoxin (14.9% vs 1.7%; p <0.01), beta blockers (66.9% vs 58.4%; p <0.01), statins (74.3% vs 71.6%; p <0.05), and vitamin K antagonists (48.7% vs 5.2%; p <0.01). In contrast, patients with AF were less likely than others to be treated with clopidogrel (9.4% vs 11.5%; p <0.05) or aspirin (54.8% vs 75.7%; p <0.01).

Despite the use of modern cardiovascular (CV) therapies, patients with AF were at increased risk of developing other severe complications over a short period of time. Compared with patients who maintained sinus rhythm, patients with AF were more likely to reach the primary composite endpoint of CV death, non-fatal MI, non-fatal stroke, or heart failure hospitalization (HR, 1.28; 95% CI, 1.14 to 1.43; p <0.01). AF also increased the risk of CV mortality (HR, 1.45; 95% CI, 1.26 to 1.68; p <0.01), stroke (HR, 1.25; 95% CI, 1.02 to 1.53; p <0.05), and especially congestive heart failure (HR, 3.19; 95% CI 2.71 to 3.74; p <0.01). Conversely, AF was associated with a decreased risk of MI (HR, 0.70; 95% CI, 0.55 to 0.90; p <0.01), perhaps due to higher warfarin use in this patient group.

In summary, new-onset AF was a common finding in patients with high-risk vascular disease in the ONTARGET/TRANSCEND trials. Moreover, new-onset AF appeared to increase the risk of other CV complications, including mortality, over a short period of time, suggesting the need for more aggressive surveillance and treatment in these patients.

Further Reading:

TRANSCEND Investigators. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet2008;372:1174-1183.

Yusuf S, Teo KK, Pogue J, et al for the ONTARGET investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-1559.