Through/Peak Ratios of Once Daily Angiotensin Converting Enzyme Inhibitors and Calcium Antagonists

Abstract

Medications given once daily may increase compliance for treatment of hypertension, if the drugs have a prolonged duration of action. The time-effect profiles for antihypertensive drugs may not depend entirely on pharmacokinetic measurements (plasma levels). Thus, trough/peak effects on blood pressure should be measured. It has been suggested that trough/peak ratios be greater than 50% for optimal 24-h control of pressure. Because very little information is available for many angiotensin converting enzyme (ACE) inhibitors and calcium antagonists concerning their trough/peak ratios and awaiting prospective comparative trials with adequate methodology, we have analyzed the duration of action of blood pressure lowering during long-term therapy with commercially available ACE inhibitors and calcium antagonists in published studies that used ambulatory blood pressure monitoring. Published studies were searched in scientific databases using relevant key words. Twenty-four ACE inhibitor and 34 calcium antagonist studies with comparable methodologies were selected. The mean trough/ peak ratios were computed after reconstruction of the curve of the magnitude of blood pressure changes against time. The results showed that once daily administration of ACE inhibitors produced on average ratios higher than 50% with fosinopril (64%), ramipril (50% to 63%), and trandolapril (50% to 100%). Other studied ACE inhibitors produced ratios on average equal to [enalapril (40% to 64%), cilazapril (10% to 80%), lisinopril (30% to 70%)] or significantly lower than 50% [captopril (25%), benazepril (40%), perindopril (35%), quinapril (10% to 40%), and moexipril (0% to 9%)]. As for once daily calcium antagonists, amlodipine (50% to 100%), lacidipine (40% to 100%), nifedipine Coat-Core (50% to 69%), nifedipine gastrointestinal therapeutic system (GITS) (60% to 94%), as well as various "slow release" formulations of diltiazem (20% to 80%) and verapamil (45% to 100%) had on average ratios higher than 50% whereas felodipine ER (30% to 45%), various slow release formulations of isradipine (10% to 80%), and nitrendipine (10% to 80%) had ratios lower than 50%. Although this retrospective literature analysis may have some theoretical limitations, it suggests that not all once daily ACE inhibitors and calcium antagonists cause trough/peak ratio superior to 50%. This may have important clinical implications.

Masked Hypertension Determined by Self-Measured Blood Pressure at Home and Chronic Kidney Disease in the Japanese General Population: The Ohasama Study

“…It is likely that the early-morning HBP of participants on antihypertensive treatment was affected by an insufficient duration of action of the antihypertensive drugs. Because the trough/peak ratios of most antihypertensive drugs are reported to be < 50% (24), poor BP control late at night and early in the morning could be overlooked in BP measurements performed in the daytime (office BP measurement). This could be a reason why the OR of CKD risk is higher in the MHT group than in the WCHT group.…”

Office blood pressure underestimates ambulatory blood pressure in peripheral arterial disease in comparison to healthy controls

“…This finding, as well as the finding of a higher than expected night BP in treated PAD patients, may reflect the fact that for the majority of patients antihypertensive treatment effect is monitored and guided by OBP, that is, day BP. With most, if not all antihypertensive agents, there is a variation of the BP-lowering effect during the 24-h period, with a peak effect some hours after administration and about 30-80% of the maximum effect still present after 24 h. 24 Therefore, night BP may not be lowered to the same extent as day BP in treated hypertensives if the antihypertensive drug is administered in the morning.…”

Trough to peak ratio of once-daily lisinopril and twice-daily captopril in patients with essential hypertension

“…This may lead to high ratios of no clinical significance because the consequent dilution bias underestimates the magnitude of the BP decrease and therefore overestimates the T:P ratio. 3 For this reason it has been recommended that the T:P ratio should be calculated only in those patients responding to active treatment. 8 In the present study, diastolic T:P ratios calculated in responders to either lisinopril or captopril were similar to those of the total group.…”

“…3 These studies suggested that not all drugs advised for once-daily use comply with the FDA recommendation that T:P ratio should be greater than 0.5. For these agents it appears that a 24-h dosing interval is too long and that they should be given in divided doses.…”