ARBs could reduce effort myocardial ischemia

ARBs could reduce effort myocardial ischemia


By Caroline Price - MedwireNews


13 November 2007


Am J Cardiol 2007; 100: 1517-1521


MedWire News: Treatment with the angiotensin receptor blocker (ARB) losartan decreased electrocardiographic measures of ischemia in patients with stable coronary artery disease (CAD), suggesting a possible role for this class of drugs in effort myocardial ischemia, report US researchers.


"Our results showed that losartan 100 mg is able to decrease transient exercise-induced myocardial ischemia by decreasing time to onset of 1-mm ST segment depression, ST-segment depression at peak exercise, and time to recovery of ST-segment depression and increasing exercise duration and maximal workload," report Giancarlo Longobardi (Scientific Institute of Telese Terme, Italy).


The researchers randomly assigned 28 CAD patients to receive losartan 100 mg or placebo for 28 days, followed by 1 week of placebo in both groups and then cross-over to the alternative regimen for a further 28 days.


All patients had reproducible positive exercise test results at the beginning of the study and were normotensive and in sinus rhythm. None of the patients had evidence of left ventricular hypertrophy or conduction defects, or a history of myocardial infarction.


Patients underwent an exercise stress test at the end of each phase of the study.


The results, published in the American Journal of Cardiology, showed that patients' systolic blood pressure (SBP) levels were significantly decreased with losartan compared with placebo (p<0.05). SBP and rate-pressure product were lower after losartan treatment than after placebo at submaximal exercise (both p<0.005), at 1-mm ST depression (p<0.001 and p<0.02, respectively), and at peak exercise (p<0.001 and p<0.005, respectively).


Patients had significantly delayed time to 1-mm ST-depression onset after losartan treatment compared with placebo treatment (479 vs 475 seconds, p<0.01) as well as decreased ST-segment depression at peak exercise (1.3 vs 1.0, p<0.05) and time to recovery of ST-segment depression (120 vs 177, p<0.01).


Furthermore, losartan treatment significantly increased exercise duration (603 vs 565 seconds, p<0.001) and maximal workload (4208 vs 3742 kg, p<0.001) during exercise stress testing compared with placebo.


The team speculates that the mechanism of action, similar to that of nitrates, is likely related to vasodilation in conductive arteries, with a relative decrease in afterload, and vasodilator effects on epicardial and resistance vessels in the coronary circulation.


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Addition of spironolactone to ARB treatment benefits chronic HF patients

Addition of spironolactone to ARB treatment benefits chronic HF patients

13 August 2007

MedWire News: Patients with chronic mild-to-moderate HF have significantly improved left ventricular (LV) reverse modeling and function if they are treated with spironolactone in addition to an angiotensin II receptor blocker (ARB), study results indicate.

Recent research has suggested a positive effect of the aldosterone receptor blocker spironolactone on patients with severe HF, the researchers say.

John Sanderson (University of Birmingham, UK) and colleagues therefore investigated the effects of combining spironolactone with the ARB candesartan in 51 systolic HF patients with LV ejection fraction (LVEF) lower than 40%.

The participants were randomly assigned to receive candesartan plus spironolactone (combination group) or candesartan plus placebo (control group) for 1 year.

Reverse remodeling was assessed by serial cardiac magnetic resonance imaging and echocardiographic tissue Doppler imaging.

At 1-year, patients receiving candesartan and spironolactone had significant improvements in LVEF compared with the control group (35% vs 26%, p<0.01). They also had significant reductions in LV end-diastolic volume index (121 vs 155 ml/m2, p=0.001), end-systolic volume index (88 vs 120 ml/m2, p=0.0005), and LV mass index (81 vs 93 g/m2, p=0.002) compared with controls.

Patients receiving the combination therapy, but not those receiving candesartan alone, also showed a significant increase in peak basal systolic velocity and strain during the ejection phase, and a decrease in index of filling pressure.

Cycling variation integrated backscatter was also increased in the combination group, compared with the control group, which suggests a reduction in myocardial fibrosis, the team notes.

This study demonstrates a "beneficial role of dual blockade of angiotensin II and aldosterone receptors on the reverse remodeling process in chronic mild-to-moderate systolic HF," Sanderson and co-workers write in the Journal of the American College of Cardiology.

They add: "Further larger clinical studies are needed to determine whether spironolactone in conjunction with an ARB can reduce mortality or hospital stays for congestive HF."

Jay Cohn (University of Minnesota, Minneapolis) commented in a related editorial: "These observations lend credence to the concept that the favorable effect of aldosterone inhibition on cardiovascular outcomes can at least in part be attributed to their properties to inhibit structural remodeling."

LINK:

J Am Coll Cardiol 2007; 50: 591-596