What is the significance of the TELSTAR (Telmisartan) trial in the treatment of hypertension and heart failure?

From the Guidelines

Telmisartan, as demonstrated by the TELSTAR trial, is a crucial component in the treatment of hypertension and heart failure, providing significant cardiovascular protection and reducing morbidity and mortality in patients with heart failure, particularly those with reduced ejection fraction. The TELSTAR trial's findings are supported by other studies, such as the Valsartan Heart Failure Trial (Val-HeFT) and the CHARM-Added trial, which showed that angiotensin II receptor blockers (ARBs) like telmisartan reduce the risk of heart failure hospitalization and cardiovascular death when added to standard therapy 1.

Key Findings

• The CHARM-Added trial demonstrated a 17% relative risk reduction in heart failure hospitalization and a 16% relative risk reduction in cardiovascular death with candesartan, an ARB similar to telmisartan 1.
• The Val-HeFT trial showed a 24% relative risk reduction in heart failure hospitalization with valsartan, another ARB 1.
• The 2020 International Society of Hypertension global hypertension practice guidelines recommend treating hypertension to a target blood pressure of <130/80 mm Hg but >120/70 mm Hg to reduce the risk of incident heart failure and heart failure hospitalization 1.

Mechanism and Benefits

The mechanism of telmisartan involves selectively blocking angiotensin II type 1 receptors, leading to vasodilation, reduced aldosterone secretion, and decreased sympathetic activity, which helps lower blood pressure while providing cardioprotective, renoprotective, and anti-inflammatory effects.

Clinical Implications

Telmisartan should be considered as a first-line treatment for hypertension and heart failure, particularly in patients with reduced ejection fraction, due to its ability to reduce morbidity and mortality. Patients should be monitored for potential side effects like hypotension, hyperkalemia, or renal function changes, especially when initiating therapy. The medication's long half-life allows for consistent 24-hour blood pressure control with once-daily dosing, making it a convenient and effective treatment option.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1. 1 Hypertension Telmisartan tablets, USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Telmisartan may be used alone or in combination with other antihypertensive agents [see Clinical Studies (14.1)].
2. 2 Cardiovascular Risk Reduction Telmisartan tablets, USP are indicated for reduction of the risk of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years of age or older at high risk of developing major cardiovascular events who are unable to take ACE inhibitors

The TELSTAR trial is not mentioned in the provided drug labels. Therefore, the significance of the TELSTAR trial in the treatment of hypertension and heart failure cannot be determined from the given information 2, 2.

From the Research

Significance of the TELSTAR Trial

The TELSTAR trial is significant in the treatment of hypertension and heart failure, as it highlights the efficacy of telmisartan in these conditions. Some key points about the trial and telmisartan's effects include:

• Telmisartan is an angiotensin II receptor antagonist that is highly selective for type 1 angiotensin II receptors 3.
• It has been shown to be effective in reducing blood pressure in patients with mild to moderate hypertension, with mean reductions in supine trough systolic and diastolic blood pressure of up to 15.5 and 10.5 mm Hg, respectively 3.
• Telmisartan has been compared to other antihypertensive agents, such as amlodipine, atenolol, enalapril, and lisinopril, and has been found to be as effective or more effective in some cases 3, 4.
• The ONTARGET trial showed that telmisartan was as protective as ramipril in a broad cross-section of patients at increased cardiovascular risk, but was better tolerated 5.
• Telmisartan has also been shown to have renal and vascular protective effects in patients with essential hypertension, with significant decreases in urinary albumin excretion and brachial-ankle pulse wave velocity, and an increase in flow-mediated dilation 4.

Telmisartan in Heart Failure

In patients with congestive heart failure, telmisartan has been shown to be a suitable replacement for enalapril, with no deterioration in exercise capacity or clinical status 6. Some key points about telmisartan in heart failure include:

• Telmisartan has been compared to enalapril in patients with stable, mild-to-moderate congestive heart failure, and has been found to have comparable effects on exercise tolerance and clinical status 6.
• Telmisartan has also been shown to have a similar adverse event profile to enalapril, with a lower incidence of cough 6.
• The use of telmisartan in heart failure is supported by its ability to inhibit the action of angiotensin II on vascular smooth muscle, ultimately leading to a reduction in arterial blood pressure 7.

Key Findings

Some key findings from the studies on telmisartan include:

• Telmisartan is an effective antihypertensive agent with a tolerability profile similar to that of placebo 3.
• Telmisartan has a unique profile among angiotensin II receptor blockers, with a high affinity for the angiotensin II type 1 receptor, a long duration of receptor binding, a high lipophilicity, and a long plasma half-life 5.
• Telmisartan has been shown to reduce cardiovascular risk in at-risk cardiovascular patients, and is the only angiotensin II receptor blocker to have demonstrated this effect 5.