Pharmacologic treatment of hypertension

1. When is pharmacologic treatment of hypertension indicated?

When an individual’s blood pressure (BP) does not fall below goal after a suitable period of intensive lifestyle modifications, antihypertensive drug therapy is universally recommended. There is general agreement that antihypertensive drug therapy is one of the major reasons for the decline in stroke and coronary heart disease mortality over the past 50 years. Compared to placebo or no treatment, active drug treatment in clinical trials significantly reduced fatal or nonfatal stroke by ∼35%, myocardial infarction by ∼15% to 25%, heart failure by ∼25%, and all-cause mortality by ∼12%. Most meta-analyses suggest that the cardiovascular protective effects of most antihypertensive drug classes can be most easily attributed to their BP-lowering properties, despite the fact that they do so by different molecular mechanisms. However, a large meta-analysis showed that compared with other antihypertensive drug classes, beta blockers more effectively reduce risk of coronary heart disease events in the first several years after myocardial infarction. In addition, the same meta-analysis suggested that calcium channel blockers (CCBs) have less of a protective effect against heart failure compared with several other antihypertensive drug classes.

Frequently updated guidelines are available from the Canadian Hypertension Education Program. Available at: http://guidelines.hypertension.ca/prevention-treatment/ . Accessed October 10, 2016.

2. What are the current recommended goals for treatment of hypertension?

BP treatment goals are controversial despite the recent publication of a trial intended to bring clarity to the issue. By way of background, although epidemiologic data indicate that a BP <115/75 mm Hg is associated with the lowest risk of cardiovascular morbidity and mortality, several studies have suggested that “lower BP” is not necessarily better to prevent cardiovascular events. The traditional BP target of <140/90 mm Hg for all patients with hypertension was lowered to a target of <130/80 mm Hg in patients with diabetes, people with chronic kidney disease (CKD), or those with established heart disease, but recent guidelines have not suggested special BP goal for these groups. Relatively few outcome-based clinical trials have been performed that randomized subjects with hypertension to different BP targets. One of the exceptions is the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) Trial, which showed no significant benefit in patients with hypertension and diabetes randomly assigned to a systolic BP target of <120 mm Hg except for the secondary endpoint of stroke.

Another prominent trial that randomized patients to different BP goals was the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT enrolled over 9000 hypertensive patients at least 50 years of age and randomized them to intensive BP-lowering (goal systolic BP 120 mm Hg) or less intensive BP-lowering treatment (goal systolic BP 140 mm Hg). SPRINT excluded patients with diabetes or prior stroke. The trial was halted before scheduled completion after the Data Safety Monitoring Board revealed a 25% lower risk of fatal and nonfatal major cardiovascular events and death from any cause in the intensive BP-lowering arm. On the other hand, adverse events were more common with intensive treatment. SPRINT’s generalizability has come into question because of the use of unattended automated office BPs in the trial to measure the achieved BP, which was the primary intervention in the trial. The precise correlation of BP measured this way with BP measured in others ways is unclear, although the findings should be applicable to patients who matched the enrollment criteria and whose BP is measured using a similar method.

In November 2017 the American Heart Association (AHA) and American College of Cardiology published the Clinical Practice Guideline for Hypertension. This redefined hypertension as follows:

• Normal: systolic BP (SBP) <120 mm Hg AND diastolic BP (DBP) <80 mm Hg

• Elevated: SBP 120–129 mm Hg AND DBP <80 mm Hg

• Stage 1 hypertension: SBP 130–139 mm Hg OR DBP 80–89 mm Hg

• Stage 2 hypertension: SBP ≥140 mm Hg OR DBP ≥90 mm Hg

Treatment decisions are based on individual patients’ cardiovascular risk. For patients with diabetes, known cardiovascular disease, or more than a 10% risk of an atherosclerotic event in the next 10 years the guideline recommends treating if the BP >130/80 with a treatment goal of a blood pressure below 130/80.

3. What have we learned about monotherapy for hypertension?

Only a minority of patients with hypertension reach their BP targets using only a single drug, so most patients require multiple drugs. Several influential hypertension treatment guidelines have converged on four drug classes as preferred initial therapy, with some exceptions for patients with certain characteristics. In order of their historical introduction, they are:

• 1.

  Thiazide or thiazide-like diuretics

• 2.

  Calcium channel antagonists

• 3.

  Angiotensin-converting enzyme (ACE) inhibitors

• 4.

  Angiotensin receptor blockers

Most guideline committees agree that if a patient has a condition for which a specific type of antihypertensive drug improves prognosis, that medication can be used as initial therapy to lower BP. A hypertensive survivor of a recent myocardial infarction, for example, would benefit from a β-blocker to reduce the risk of death or recurrent infarction, so a β-blocker would be appropriate initial antihypertensive therapy in such a case. All guideline committees recognize the existence and importance of contraindications (including allergies), even for drugs that might otherwise be first-line choices. Recent guidelines have become more concordant with one another with respect to first-line choices of antihypertensive medications ( Table 69.1 ).

4. Is combination therapy better than monotherapy?

Meta-analyses have suggested that, for most antihypertensive drug classes, combining two different classes of drugs at moderate doses is more likely to lower BP than pushing any one drug to its maximum dose. This also reduces adverse effects. Combining a CCB with an ACE inhibitor, or probably an angiotensin II receptor blocker (ARB), tends to reduce incidence and severity of pedal edema seen with higher-dose CCBs. In the Avoiding Cardiovascular events through COMbination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, patients at high risk for cardiovascular events were randomized to a combination of benazepril and amlodipine or a combination of benazepril and hydrochlorothiazide (HCTZ). The combination of benazepril and amlodipine reduced cardiovascular events more than the combination of benazepril and HCTZ.