Antihypertensive Drugs

Standard office measurement requires the patient to be seated quietly for five minutes, with no caffeine or exercise within thirty minutes. Two readings taken one to two minutes apart are averaged. Both arms are measured at the first visit; a difference greater than 15 millimeters of mercury between arms warrants vascular evaluation for subclavian stenosis or coarctation.

Out-of-office measurement has become an essential part of diagnosis. Ambulatory blood pressure monitoring provides 24-hour continuous readings and is the most accurate predictor of cardiovascular outcome — more so than office measurement alone. Home blood pressure monitoring using a validated automated device is an accessible alternative. Both methods identify BP phenotypes that office measurement alone cannot distinguish.

Comparing office and out-of-office readings defines four clinically meaningful phenotypes. Recognizing these phenotypes prevents both over-treatment (white coat hypertension) and dangerous under-detection (masked hypertension).

The clinical evaluation of a newly diagnosed hypertensive patient serves to identify secondary causes and confirm the absence of target organ damage that would alter drug selection. The medication history deserves particular attention: nonsteroidal anti-inflammatory drugs, oral contraceptives, decongestants, calcineurin inhibitors, stimulants, and erythropoietin are all common causes of drug-induced blood pressure elevation that can be missed without a systematic review.

Physical examination findings that directly influence pharmacological management include a renal artery bruit (suggesting renovascular hypertension and affecting the safety of renin-angiotensin-aldosterone system inhibitors), fundoscopic changes (grading hypertensive retinopathy and indicating treatment urgency), and signs of hormonal excess such as central adiposity and striae (suggesting Cushing syndrome). Baseline laboratory work — serum creatinine, electrolytes, urinalysis, and lipid panel — establishes kidney function, potassium level (critical for diuretic and renin-angiotensin-aldosterone system inhibitor safety), and cardiovascular risk before drugs are started.

For Stage 1 hypertension (130–139/80–89 millimeters of mercury), pharmacotherapy is indicated when the 10-year cardiovascular risk is at or above 10 percent, or when established cardiovascular disease, chronic kidney disease, or diabetes mellitus is present. In lower-risk patients, lifestyle modification is tried first with reassessment at three to six months.

For Stage 2 hypertension (at or above 140/90 millimeters of mercury), pharmacotherapy is recommended for all patients. When blood pressure is at or above 160/100, combination therapy is typically started from the outset rather than a single drug, because monotherapy rarely achieves target at these levels.

The 2017 American College of Cardiology/American Heart Association guidelines recommend a target below 130/80 millimeters of mercury for patients with established cardiovascular disease or a 10-year cardiovascular risk at or above 10 percent, and consider this target reasonable for most adults treated with pharmacotherapy.

The SPRINT trial (2015) provided the key evidence base for intensive blood pressure control. It compared a systolic target below 120 millimeters of mercury against a standard target below 140 in patients without diabetes. The intensive group had a 25 percent reduction in composite cardiovascular events and a 27 percent reduction in all-cause mortality. This trial reinforced the current guideline target of below 130/80 for high-risk patients.

In patients with diabetes, the target below 130/80 is also recommended, though the evidence for going below 120 is weaker — the ACCORD trial in diabetic patients showed a stroke reduction but no significant benefit on the primary cardiovascular endpoint with intensive control.

The four drug classes with the strongest evidence base for reducing cardiovascular morbidity and mortality in primary hypertension form the foundation of all treatment algorithms: angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers (dihydropyridine class), and thiazide and thiazide-like diuretics. These classes are covered in detail in Modules 3 and 4. Beta-blockers, alpha-blockers, centrally acting agents, and direct vasodilators occupy specific niches addressed in Module 5. Treatment strategy, combination therapy, and resistant hypertension are covered in Module 6.