Pharmacological therapy,and Treatment

Pharmacologic Therapy

If lifestyle modifications are insufficient to achieve the goal blood pressure (BP), there are several drug options for the treatment and management of hypertension. Based on the Seventh Report of the Joint National Committee of Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and the 2010 Institute for Clinical Systems Improvement (ICSI) guideline on the diagnosis and treatment of hypertension recommendations, thiazide diuretics are the preferred initial agents in the absence of compelling indications.^[4] However, the updated JNC 8 guidelines no longer recommend only thiazide-type diuretics as the initial therapy in most patients (angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], calcium channel blockers [CCBs], or diuretics are also good choices).

Compelling indications may include high-risk conditions that can be direct sequelae of hypertension (heart failure, ischemic heart disease, chronic kidney disease, recurrent stroke) or that are commonly associated with hypertension (diabetes, high coronary disease risk), as well as drug intolerability or contraindications.^[4] In such compelling cases, another class of drugs should be initiated. An ACE inhibitor, ARB, CCB, and beta-blocker are all acceptable alternative agents. There are several opinions regarding which antihypertensive agents to use initially, because some patients may respond to a therapy that others may not.

The following are drug class recommendations for compelling indications based on various clinical trials :

• Heart failure: diuretic, beta-blocker, ACE inhibitor, ARB, aldosterone antagonist
• Postmyocardial infarction: beta-blocker, ACE inhibitor, aldosterone antagonist
• High coronary disease risk: diuretic, beta-blocker, ACE inhibitor, CCB
• Diabetes: diuretic, beta-blocker, ACE inhibitor, ARB, CCB
• Chronic kidney disease: ACE inhibitor, ARB
• Recurrent stroke prevention: diuretic, ACE inhibitor

Note that different stages of these diseases may alter their treatment management.

Multiple clinical trials suggest that most antihypertensive drugs provide the same degree of cardiovascular protection for the same level of BP control. Well-designed prospective randomized trials, such as the Swedish Trial in Old Patients with Hypertension (STOP-2), the Nordic Diltiazem (NORDIL) trial, and the Intervention as a Goal in Hypertension Treatment (INSIGHT) trial, have shown that older drugs (eg, diuretics, beta-blockers) and newer antihypertensive agents (eg, ACE inhibitors, CCBs) have similar results.

In addition, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study concluded that there were no differences in primary coronary heart disease outcome or mortality for the thiazide-like diuretic chlorthalidone, the ACE inhibitor lisinopril, and the CCB amlodipine. In a systematic review and meta-analysis, investigators also determined that in patients with essential hypertension without preexisting renal disease, no significant difference was found between Ras inhibitors and other antihypertensive agents in preventing renal dysfunction.

A post hoc analysis of data from the randomized ACCOMPLISH trial concluded that benazepril plus amlodipine (B+A) was more effective than benazepril plus hydrochlorothiazide (B+H) in reducing cardiovascular events in adults with high-risk stage 2 hypertension and coronary artery disease (CAD).

In this study, 5314 patients with CAD and 6192 without CAD were given B+A or B+H. Among patients with CAD, the incidence of cardiovascular events was 16% with B+H and 13% with B+A, a hazard reduction of 18% (P = 0.0016).The composite secondary endpoint of cardiovascular mortality, myocardial infarction, and stroke occurred in significantly fewer B+A patients than B+H patients (5.74% vs 8%; P = 0.033). All-cause mortality was 23% lower in the B+A arm (P = 0.042).

Single agent versus multiagent treatment approach

Over 50% of patients with hypertension will require more than one drug for blood pressure control. In stage 1 hypertension, a single agent is generally sufficient to reduce BP, whereas in stage 2, a multidrug approach may be needed. Initiation of 2 antihypertensive agents, either as 2 separate prescriptions or as a fixed-dose combination, should also be considered when BP is more than 20 mm Hg above the systolic goal (or 10 mm Hg above the diastolic goal).

Several situations demand the addition of a second drug, because 2 drugs may be used at lower doses to avoid the adverse effects that may occur with higher doses of a single agent. Diuretics generally potentiate the effects of other antihypertensive drugs by minimizing volume expansion. Specifically, the use of a thiazide diuretic in conjunction with a beta-blocker or an ACE inhibitor has an additive effect, controlling BP in up to 85% of patients.

The ALTITUDE trial was halted because it was shown that aliskiren can cause adverse events—nonfatal stroke, renal complications, hyperkalemia, and hypotension—when used in combination with an ACE inhibitor or an angiotensin receptor blocker (ARB) in patients with type 2 diabetes and renal impairment who are at high risk of cardiovascular and renal events.