NICE published a Clinical Guideline for Hypertension in August 2004. This guideline was based on the evidence available at the time and was probably dramatically influenced by the ALLHAT Study1.
This Study was conducted in about 42,000 patients and compared active treatments as follows:
- Thiazide Diuretic (Chlorthalidone)
- ACE Inhibitor (Lisinopril)
- Calcium Channel Blocker (Amlodipine)
- Alpha Blocker (Doxazosin)
Based upon the results of this trial there are two key findings that altered (or should alter) daily practice. Firstly, the Doxazosin arm of this study was stopped early as patients in this group were suffering more outcome events than any other arm. It was therefore decided it was unethical to continue this arm of the study and as a consequence of these steps Doxazosin is a fifth line antihypertensive agent.
The ultimate finding of the study was that there is little to choose between the remaining three arms in terms of clinical efficacy in terms of "hard" outcomes like fatal and non-fatal MI. There were differences in blood pressure control between the groups where the Thiazide Diuretic performed well against the other drugs with amlodipine proving better in diastolic pressure only. While the differences are statistically significant, the clinical differences are negligible (0.8 - 2mmHg difference).
This then leaves the only difference for evaluation between the drug arms to be that of cost. As Thiazide Diuretics as the most cost effective option there simply must be the first line treatment for hypertension.
Second line options are added based upon emerging evidence around the risk of diabetes when Beta Blockers are used in conjunction with Thiazide Diuretics. Angiotensin Converting Enzyme Inhibitors (ACEIs) are preferential in those patients who are at higher risk of developing diabetes.
Action: The NICE Guideline is evidence based and should be followed by all clinicians treating Hypertension in Primary Care. For full details of the algorithm, see the Clinical Guideline Quick Reference.
For each of the NICE recommended drug classes the following drugs are recommended:
- Thiazide Diuretic - Bendroflumethiazide 2.5mg
- Beta Blocker - Atenolol 50mg or Bisoprolol 5mg
- ACE Inhibitor - Ramipril or Perindopril (Titrated to maximum tolerated dose)
- Calcium Channel Blocker - Amlodipine (as Mesilate) or Felodipine
ONLY if ACE Inhibitor is not tolerated
- Angiotensin II Receptor Blockers - Candesartan or Irbesartan or Valsartan
- Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group JAMA 2002;288:2981-2997