What is the recommended systolic blood pressure target and treatment approach for patients at high risk of cardiovascular events based on the SPRINT (Systolic Blood Pressure Intervention Trial) trial?

SPRINT Trial: Blood Pressure Targets and Treatment Approach

For patients at high cardiovascular risk without diabetes, target a systolic blood pressure <130/80 mmHg using intensive antihypertensive therapy, as this approach reduces major cardiovascular events by 25% and all-cause mortality by 27% compared to standard targets of <140/90 mmHg. 1

Key SPRINT Trial Findings

The SPRINT trial enrolled 9,361 patients aged ≥50 years with systolic blood pressure 130-180 mmHg and elevated cardiovascular risk (but excluding diabetes) and demonstrated:

• 25% reduction in the primary composite outcome (myocardial infarction, acute coronary syndromes, stroke, heart failure, or cardiovascular death) with intensive treatment targeting SBP <120 mmHg versus standard treatment targeting SBP <140 mmHg 1, 2
• 27% reduction in all-cause mortality in the intensive treatment group 1
• 62% reduction in heart failure incidence (HR 0.62; 95% CI 0.45-0.84) 1
• 41% reduction in stroke risk in related trials 1
• Achieved blood pressures were 121 mmHg (intensive) versus 136 mmHg (standard) 1

Recommended Treatment Targets Based on SPRINT

For High-Risk Patients Without Diabetes

Initiate antihypertensive therapy at BP ≥130/80 mmHg and target <130/80 mmHg (not the <120 mmHg used in SPRINT, as this accounts for differences between research and clinical BP measurement methods) 1

For Patients With Diabetes

Target <130/80 mmHg based on combined evidence from SPRINT and ACCORD BP trials, though ACCORD BP showed non-significant reduction in primary composite outcome but significant 41% stroke reduction 1, 3

For Older Adults (≥65 years)

Target <130/80 mmHg for community-dwelling, ambulatory, non-institutionalized older adults, as SPRINT included patients up to age 80+ with demonstrated benefit 1

For those ≥65 years, target 130-139 mmHg systolic if frail or with high comorbidity burden 1, 2

Treatment Approach Algorithm

Step 1: Risk Stratification

Patients qualify for intensive treatment (target <130/80 mmHg) if they have:

• Clinical cardiovascular disease (CHD, heart failure, stroke) 1
• 10-year ASCVD risk ≥10% using ACC/AHA Pooled Cohort Equations 1
• Chronic kidney disease (stage 3 or higher) 1
• Age ≥65 years (automatically ≥10% risk) 1

Step 2: Initial Pharmacologic Therapy

For Stage 1 Hypertension (130-139/80-89 mmHg) with high risk:

• Start single agent: thiazide diuretic (preferably chlorthalidone), calcium channel blocker, ACE inhibitor, or ARB 1
• In Black patients: prefer thiazide diuretic or calcium channel blocker as first-line 1, 4

For Stage 2 Hypertension (≥160/100 mmHg):

• Start two agents from different classes immediately 1, 4
• Preferred combination: ACE inhibitor/ARB + thiazide diuretic or calcium channel blocker 4, 5

Step 3: Medication Selection Based on SPRINT Evidence

The most effective combination in SPRINT analysis was:

• ACE inhibitor or ARB (80% use in intensive arm vs 61% standard) + thiazide diuretic (65% vs 42%), which independently reduced cardiovascular events (HR 0.75; 95% CI 0.61-0.92) 5
• Calcium channel blockers used in 57% (intensive) vs 39% (standard) 5
• Beta-blockers used in 52% (intensive) vs 26% (standard) 5

Step 4: Monitoring and Titration

• Monthly evaluation until BP control achieved 1, 4
• Titrate medications to achieve target <130/80 mmHg 1
• Monitor for adverse events, particularly in older adults 1

Critical Safety Considerations

Avoid Excessive BP Lowering

Do not target <120/80 mmHg in clinical practice, as mean achieved BP below this threshold increases adverse events 1, 3

Maintain diastolic BP ≥60 mmHg, as DBP <60 mmHg independently increases cardiovascular events (HR 1.36; 95% CI 1.07-1.71) even when SBP is controlled 5, 6

Common Adverse Events to Monitor

The intensive treatment arm experienced significantly more:

• Hypotension and syncope 1, 2
• Electrolyte abnormalities (hyperkalemia) 1, 2
• Acute kidney injury 1, 2
• Orthostatic hypotension, particularly in older adults 1, 2

Special Precautions in Older Adults

• Initiate therapy cautiously, especially when starting two drugs 1
• Monitor closely for orthostatic hypotension and falls 1, 2
• SPRINT demonstrated benefit even in frail community-dwelling elderly, but careful titration essential 1

Why Guidelines Recommend <130/80 mmHg Instead of <120 mmHg

The ACC/AHA guidelines pragmatically recommend <130/80 mmHg rather than SPRINT's <120 mmHg target because:

1. SPRINT used standardized automated BP measurement protocols that yield readings approximately 9/6 mmHg lower than typical clinical practice measurements 1
2. Fewer than 50% of SPRINT participants had truly unattended BP measurements, yet achieved similar outcomes 1
3. The <130/80 mmHg target accounts for the difference between research protocols and real-world clinical BP measurement 1

Medication-Specific Recommendations

For Heart Failure with Reduced Ejection Fraction

Use guideline-directed medical therapy: ACE inhibitors/ARBs, beta-blockers (carvedilol, metoprolol succinate, bisoprolol), mineralocorticoid receptor antagonists, and diuretics 1

Avoid non-dihydropyridine calcium channel blockers (verapamil, diltiazem) in HFrEF due to myocardial depressant activity 1

For Chronic Kidney Disease

• ACE inhibitors preferred for CKD stage 3+ or stages 1-2 with albuminuria ≥300 mg/d 1
• ARBs reasonable if ACE inhibitor not tolerated 1
• Target <130/80 mmHg based on SPRINT evidence 1

For Metabolic Syndrome

• First choice: RAAS blocker (ACE inhibitor or ARB) 4
• Second choice: calcium channel blocker or low-dose thiazide diuretic 4
• Avoid traditional beta-blockers due to adverse effects on insulin sensitivity, weight, and lipids (newer vasodilating beta-blockers like carvedilol or nebivolol may be acceptable) 4

Evidence Quality and Nuances

SPRINT provides Level B evidence (randomized controlled trial) for intensive BP lowering in high-risk patients without diabetes 1

The ACCORD BP trial in diabetics showed non-significant primary outcome reduction but significant stroke benefit, interpreted as consistent with SPRINT but underpowered due to less BP-sensitive composite endpoint 1

Meta-analyses confirm that not all SPRINT benefits can be attributed solely to BP reduction; medication choice (particularly ACE inhibitor/ARB + thiazide combinations) contributes independently to outcomes 7, 5

Risk stratification matters: SPRINT subgroup analysis showed intensive treatment benefits patients at intermediate (10-15% Framingham risk) and high risk (≥15%), but not low risk (<10%) 8