1 INDICATIONS AND USAGE
Azor is indicated for the treatment of hypertension, alone or with other antihypertensive agents, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular (CV) 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. There are no controlled trials demonstrating risk reduction with Azor.
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 Programs 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, sothe 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.
Azormay also be used as initial therapy in patients who are likely to need multiple antihypertensive agents to achieve their blood pressure goals.
Patients with moderate or severe hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. The decision to use a combination as initial therapy should be individualized and should beshaped by considerations such as baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared to monotherapy. Individual blood pressure goals may vary based upon the patients risk.
Data from an 8-week, placebo-controlled, parallel-group factorial study
[
see Clinical Studies (
14.1
)
]provide estimates of the probability of reaching a blood pressure goal with Azor compared to amlodipine or olmesartan medoxomil monotherapy. The figuresbelow provide estimates of the likelihood of achieving the targeted systolic or diastolic blood pressure goals with Azor10/40 mgcompared with amlodipineor olmesartan medoxomilmonotherapy, based upon baseline systolic or diastolic blood pressure.The curve of each treatment group was estimated by logistic regression modeling from all available data of that treatment group. The right tail of each curve is less reliable because of small numbers of subjects with high baseline blood pressures.
Figure 1: Probability of Achieving Systolic Blood
Pressure (SBP) < 140 mmHg at Week 8 With LOCF
Figure 2: Probability of Achieving Diastolic Blood Pressure (DBP) < 90 mmHg at Week 8 With LOCF
Figure 3: Probability of Achieving Systolic Blood Pressure (SBP) < 130 mmHg at Week 8 With LOCF
Figure 4: Probability of Achieving Diastolic Blood Pressure (DBP) < 80 mmHg at Week 8 With LOCF
The figures above provide an approximation of the likelihood of reaching a targeted blood pressure goal (e.g., Week 8 SBP <140 mmHg or <130mmHg or a DBP <90mmHg or <80 mmHg) for the high-dose treatment groups evaluated in the study. Azor 5/20 mg,the lowest dose combination treatment group,increasesthe probability of reaching blood pressure goal compared with the highest dose monotherapies,amlodipine 10 mg and olmesartan medoxomil 40 mg.
For example, a patient with a baseline blood pressure of 160/100 mmHg has about a 48% likelihood of achieving a goal of <140 mmHg (systolic) and a 51% likelihood of achieving a goal of <90 mmHg (diastolic) on monotherapy with olmesartan medoxomil 40 mg, and about a 46% likelihood of achieving a goal of <140mmHg (systolic) and a 60% likelihood of achieving a goal of <90mmHg (diastolic)on monotherapy with amlodipine 10 mg.The likelihood of achieving these same goals increases to 63% (systolic) and 71% (diastolic) on Azor 5/20mg, and to 68% (systolic) and 85% (diastolic)on Azor 10/40mg.
Azor is a combination of amlodipine besylate, a dihydropyridine calcium channel blocker, and olmesartan medoxomil, an angiotensin II receptor blocker, indicated for the treatment of hypertension, alone or with other antihypertensive agents, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions(
1).
Azor may also be used as initial therapy in patients likely to need multiple antihypertensive agents to achieve their blood pressure goals(
1).
Figure 1: Probability of Achieving Systolic Blood Pressure (SBP) < 140 mmHg at Week 8 With LOCF
Figure 2: Probability of Achieving Diastolic Blood Pressure (DBP) < 90 mmHg at Week 8 With LOCF
Figure 3: Probability of Achieving Systolic Blood Pressure (SBP) < 130 mmHg at Week 8 With LOCF
Figure 4: Probability of Achieving Diastolic Blood Pressure (DBP) < 80 mmHg at Week 8 With LOCF