Side Effect Profile
The side effects associated with antihypertensive agents remain the most important cause of poor patient compliance. It is crucial and almost always possible to find drugs or drug combinations that can be well tolerated by individual patients, and a concerted effort should be made by physicians to find the “right drugs.” It should be remembered that almost all the side effects associated with antihypertensive agents are dose dependent, and utilizing smaller doses of various drugs may alleviate the side effects. Also, various surveys have demonstrated that, for various reasons, patients frequently report side effects to their physicians (particularly impotence) but respond by stopping their medication or taking it irregularly. Patients should be specifically questioned to determine whether their drugs are well tolerated.
Convenience
It has now been clearly demonstrated that antihypertensive agents dosed twice a day are taken less readily than those dosed once a day. Physicians should make a concerted effort to treat hypertensive patients with once-a-day agents. However, it is important to use drugs that have true 24-h efficacy. It has been shown that the risk of nonembolic stroke and of myocardial infarction peaks in the early morning, which coincides with the rapid surge of blood pressure that occurs during arousal (typically between 6 am and noon). It seems likely that adequate blood pressure control during this period is very important. Antihypertensive drugs, taken once daily in the morning, that do not provide 24-h efficacy may leave patients uncontrolled at a time they are most at risk of developing cardiovascular events. The duration of action of a particular antihypertensive drug can be assessed in the clinical setting by measuring blood pressure at trough of the drug. Patients should omit taking their medication on the morning of the clinic visit so that blood pressure is measured at 24-26 h into the dosing interval. If blood pressure is controlled, the drug is working for 24 h; if not, it should be substituted or dosed twice a day.
Difficulty in Achieving blood pressure Control with Monotherapy
Studies have shown that with any class of antihypertensive drug, the response rate ranges between 30 and 60%. The remaining patients will require two or more drugs to achieve blood pressure control. This is not surprising, because hypertension is a multifactorial disease in which multiple systems interact and contribute to the increase in blood pressure. Thus, agents interrupting only one of these systems will fail or will provide inadequate control in a significant proportion of patients. Combining two complementary agents, which interrupt two physiologic pathways, improves the response rates to 75-90%. The remaining patients will require three or more drugs in order to achieve blood pressure control.
Lower blood pressure Goals
Data from the MRFIT study and from the Hypertension Optional Treatment (Hypertension Optimal Treatment) study have demonstrated that lower blood pressures are associated with fewer cardiovascular events. This finding is particularly true in diabetic hypertensive patients. Furthermore, it has been shown in patients with renal insufficiency and proteinuria that the greatest renoprotective effects occur in patients with lower blood pressures. For these reasons, the Joint National Committee has now classified a blood pressure of 140/90 mmHg as high normal and regards a blood pressure of 130/85 mmHg as normal. In patients with coronary artery disease, a blood pressure of 120/80 mmHg should be the goal and 125/75 mmHg in diabetic patients with diabetic nephropathy. Thus, if only 27.5% of hypertensive patients are controlled at a blood pressure of 140/90 mmHg, these numbers are substantially lower at the new blood pressure goals.
Reluctance to Titrate Antihypertensive Medication
In a study performed in 11,613 hypertensive patients in Europe, it was shown that only 37% were adequately controlled by their own physicians’ standards for blood pressure control. Sixty-three percent were being treated and had inadequate control. When the study assessed what action was taken by physicians in response to the inadequate blood pressure control, it was found that in 82% of cases no action was taken. In the remaining 18% the dose was increased, the drug was changed, or a second drug was added. The main reasons physicians gave for their reluctance to change the regimen were their concerns about increased side effects with increased dose; adverse metabolic consequences, higher cost, and patient resistance to polypharmacy and/or higher doses.
This would suggest that the best “shot” at controlling hypertension is the “first shot” because there seems to be resistance by physicians (in many cases for good reason) to titrate medication. In addition, patients are more likely to be compliant with their medication if they achieve adequate control early in the course of treatment (when they perceive that the drug is really working and achieving good blood pressure control).
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