Morning hypertension and antihypertensive therapy

We studied how a difference in plasma half-life of calcium channel blockers (CCBs) affects the elevation of blood pressure in the early morning. In this study, we analyzed the data of outpatients under treatment of essential hypertension with CCB, who measured their blood pressures at home at wake-up time, during the day and before going to bed. In those who received a CCB with short-lasting actions, we changed it to nilvadipine (Nivadil®), a CCB with long-lasting actions to evaluate changes in blood pressure elevation before and after the change. Results are shown below. Blood pressure elevation in the early morning was evaluated by comparing the blood pressure values at wake-up time and those during the day. In the evaluation, we categorized the subjects into the following three groups: short-lasting CCB group; those treated with a CCB with a short plasma half-life or a CCB with a once -daily regimen at longest; long-lasting CCB group; the subjects treated with a CCB with a long plasma half-life or a CCB with a twice-daily regimen at shortest; and non-medication group; those with no serious health risks other than blood pressure and treated only by lifestyle modification. As a result of the evaluation, SBP/DBP in the short-lasting CCB group was 12.7 ± 10.5/7.9 ± 6.5 mmHg, SBP/DBP in the long-lasting CCB group was 7.9 ± 11.6/4.6 ± 5.9 mmHg, and SBP/DBP in the non-medication group was 2.4 ± 6.0/2.8 ± 2.7 mmHg. The blood pressure elevation of SBP and DBP in the short-lasting CCB group was significantly greater than that in the other groups. We also evaluated blood pressure elevation in the early morning by comparing the blood pressure values at wake-up time and those before going to bed. As a result, SBP/DBP in the short-lasting CCB group was 10.8 ± 10.5/7.9 ± 6.3 mmHg, SBP/DBP in the long-lasting CCB group was 8.2 ± 11.4/5.9 ± 5.5 mmHg, and SBP/DBP in the non-medication group was 4.8 ± 4.8/5.6 ± 3.2 mmHg. As can be seen in the differences between the wake-up time and daytime, the blood pressure elevation in the short-lasting CCB group was greater than that in the other two groups. The blood pressure values measured at home before a change into nilvadipine were as follows: SBP/DBP at wake-up time was 148.9/92.2 mmHg, SBP/DBP during the day was 133.4/82.4 mmHg, and SBP/DBP before going to bed was 136.8/82.3 mmHg. Those after the change were as follows: SBP/DBP at wake-up time was 143.7/89.3 mmHg, SBP/DBP during the day was 133.0/81.3 mmHg, and SBP/DBP before going to bed was 135.4/81.2 mmHg. Although no changes were observed in the blood pressures during the day and before going to bed, both SBP and DBP at wake-up time were lowered significantly. The results stated above indicate that blood pressure elevation in the early morning is, in some cases, caused by pharmacokinetics of an antihypertensive drug. We have therefore concluded that it is important to take pharmacokinetics into consideration in selecting an antihypertensive drug and administration method.