When we think of Blood Pressure, we often consider its impact in the clinical setting as hypertension, hypotension, and their related risks. But in the realm of drug development, blood pressure isn’t just related to hypo/hypertension; it’s a critical safety parameter that can determine whether a potential therapy moves forward or is stopped in its tracks. Each heartbeat generates a pressure wave that travels through the arterial system, producing a distinct peak (systolic blood pressure [SBP]) followed by a lower value (diastolic blood pressure [DBP]) on the blood pressure trace.

Blood pressure changes can be early warning signs of drug-induced cardiovascular risks, such as arrhythmias, myocardial infarctions, or stroke. Without thorough preclinical evaluations, these risks may go unnoticed until later clinical phases, potentially endangering clinical trial participants and resulting in costly trial failures or market withdrawals.

The High Stakes of Blood Pressure in Drug Development

In nonclinical studies, monitoring blood pressure isn’t just a routine check—it’s a fundamental aspect of evaluating cardiovascular safety. Even though the ICH S7A guidance document emphasizes that BP assessments must be conducted in preclinical evaluations, especially for therapeutics that may affect cardiovascular function, it does not negate a requirement for other therapeutic indications since the cardiovascular system is a major organ system. When new drugs are developed, their effects on the cardiovascular system can be unpredictable. A promising therapeutic can exhibit unintended effects on blood pressure, leading to safety concerns that regulators take seriously. Furthermore, BP and HR variability should be considered when analyzing QT interval data to avoid misleading conclusions on potential QT interval effects.

In addition to pulse pressure changes that occur on blood pressure signals, other parameters such as Heart Rate (HR) can be deduced from a blood pressure signal.HR can be calculated by converting the beat-to beat interval into Beats Per Minute (BPM) = 60/Interval in seconds. Besides calculating the heart rate, analyzing the blood pressure trace can provide information about cardiovascular dynamics and the effectiveness of the heart's contraction. It is noteworthy that BP traces might show a delay between the actual electrical event (the heartbeat) and the mechanical response (the pressure peak). This delay, along with potential artifacts from motion or external interference, can reduce the accuracy of blood pressure-based heart rate calculations.

Understanding the Basics of Pulse Pressure and its Implications

Blood pressure changes in nonclinical models help identify potential risks. Some drugs directly impact blood pressure, while others affect renal function, fluid balance, or neurohormonal pathways. Identifying these risks early improves decision-making before clinical trials.

A decrease in pulse pressure (difference between SBP and DBP) can occur for a several reasons:

Lowered SBP: A drop in the force of heart contractions (stroke volume) can reduce SBP. This is often seen in conditions like heart failure or cardiogenic shock, where the heart isn’t pumping effectively.

Increased DBP: When the DBP rises—possibly due to increased peripheral resistance—the difference between systolic and diastolic pressures narrows.

Clinical Implications: A narrow pulse pressure may indicate reduced cardiac output or underlying hemodynamic instability. It can serve as a warning sign in acute conditions such as cardiac tamponade or severe left ventricular dysfunction.

An increased pulse pressure can occur for several reasons:

Elevated SBP: Conditions such as aortic regurgitation or high cardiac output can cause a higher SBP, widening the gap.

Decreased DBP: Reduced vascular resistance or arterial dilation may lower DBP, also increasing the pulse pressure.

Arterial Stiffness: As arteries age or become stiff due to atherosclerosis, they lose the ability to cushion the pressure wave, leading to higher SBP and lower DBP. This is common in older adults and is associated with increased cardiovascular risk.

Clinical Implications: An increased pulse pressure may signal decreased arterial compliance, left ventricular hypertrophy, myocardial infarction, and stroke.

The Bottom Line: Proactive Safety, Better Outcomes

In summary, a change in pulse pressure when attributed in a dose dependent manner to administration of a test substance, often signals that the heart is not pumping efficiently which can have important implications for cardiovascular health. Neglecting blood pressure pulse monitoring in nonclinical studies poses risks to patient safety and drug approval. Early cardiovascular assessments enable informed decisions, refined dosing strategies, and ensure safer drug development.

Attentive Science: Leading the Way in Cardiovascular Safety Studies

At Attentive Science, we recognize the importance of blood pressure pulse monitoring in drug safety. Our team employs advanced methodologies to ensure comprehensive cardiovascular safety evaluations, supporting regulatory compliance and successful drug development. Advanced techniques, such as implantable telemetry devices, provide real-time, high-precision monitoring. These advancements help detect safety concerns early, minimizing unexpected adverse events.

Partner with Attentive Science to enhance cardiovascular safety strategies and bring safer drugs to market. Contact us today to learn more!