Fixed Combination of Candesartan/Amlodipine in the Treatment of Arterial Hypertension

Introduction

The general goal of arterial hypertension therapy is to reduce cardiovascular risk. Besides lowering blood pressure, it is also essential to consider lifestyle or pharmacological modifications of other risk factors. Modifiable factors that increase cardiovascular risk include dyslipidemia, smoking, diabetes mellitus, obesity, and low physical activity.

Treatment of arterial hypertension can start with monotherapy; however, it is effective in only about 30% of patients. For most patients, a combination of two or more antihypertensives is necessary to achieve normal blood pressure levels. Regarding mortality, achieving a diastolic blood pressure value of < 90 mmHg is crucial.

Combination therapy is also suitable as an initial treatment for patients with higher cardiovascular risk. Recommended combinations by professional societies include an ACE inhibitor or an AT₁ receptor antagonist (sartan) with a calcium channel blocker (CCB). An ideal fixed combination involves drugs that affect pathogenic mechanisms at different levels, have a long-term effect, allowing once-daily dosing and improving therapy compliance.

Fixed Combination of Candesartan/Amlodipine

Candesartan is the most commonly used sartan in Europe, and amlodipine is the most widely used calcium channel blocker. The popularity of sartans has been increasing in recent years at the expense of ACE inhibitors because they can be used in the same indication and, unlike ACE inhibitors, do not cause coughing and generally have the fewest side effects among antihypertensives.

The advantage of candesartan is its long-term and steady blood pressure reduction for 24 hours without fluctuations between doses. Amlodipine has a long biological half-life ranging from 35 to 50 hours and a slow onset of action, preventing acute hypotension upon ingestion. Among CCBs, amlodipine's efficacy is supported by numerous studies, and in monotherapy, it is indicated for the treatment of arterial hypertension and myocardial ischemia.

The combination of two different antihypertensive mechanisms brings cardioprotective and renoprotective effects. Candesartan reduces afterload and preload, helps prevent myocardial remodeling, and contributes to left ventricular hypertrophy regression. Amlodipine, within its cardioprotective effects, lowers myocardial oxygen demand, improves heart oxygen supply, increases collateral flow, reduces calcium overload after reperfusion, and similarly to candesartan, helps in left ventricular hypertrophy regression.

In terms of renoprotective effects, amlodipine increases renal perfusion and has natriuretic effects, while candesartan reduces proteinuria, enhances renal perfusion, acts natriuretically, and slows the progression of kidney damage.

The advantage of combination therapy is that candesartan reduces the risk of edema observed with amlodipine. The fixed combination demonstrates organoprotective effects, reduces the occurrence of treatment side effects, and helps increase the success rate of blood pressure control.

Summary and Conclusion

The fixed combination of candesartan/amlodipine represents an ideal fixed combination for blood pressure control in patients with arterial hypertension. The combination of two different antihypertensive mechanisms brings cardioprotective and renoprotective effects. The effects of sartans are comparable to those of ACE inhibitors, but without the unpleasant side effect of coughing.

Candesartan in combination with amlodipine reduces the risk of edema induced by calcium channel blockers. Together, they represent an effective combination of antihypertensives with a good tolerance profile, high compliance, and a low risk of side effects.

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Sources:
1. Vítovec J. Fixed Combination in Hypertension – CARAMLO. XXIII. Annual Congress of the Czech Cardiology Society, May 24–27, 2015, Brno.
2. Špinar J. Metabolically Neutral Combination Therapy of Hypertension 2015. XXIII. Annual Congress of the Czech Cardiology Society, May 24–27, 2015, Brno.