Clevidipine Rapidly Relieves Acute Heart Failure Symptoms

In acute heart failure (AHF) with hypertension, symptom onset may be abrupt, presenting as profound dyspnea and acute pulmonary edema, say researchers for the PRONTO study (A Study of Blood Pressure Control in Acute Heart Failure—a Pilot Study). For those patients, it is important to control blood pressure (BP) immediately. Usually this would be done with vasodilators; however, the researchers say, safety and efficacy data are lacking, and few comparative trials have been done. Nitrates, hydralazine, and nicardipine, the most commonly used, all have drawbacks, they note. For instance, nitrates can cause variable responses, hydralazine potentially worsens myocardial ischemia, and nicardipine can be challenging to titrate. 

Clevidipine, by contrast, is a rapidly acting IV antihypertensive medication with a 1-minute half-life that allows rapid titration. It lowers BP by selective arteriolar vasodilation and increases cardiac output as peripheral vascular resistance declines, without venous capacitance effects. And because it has no negative inotropic or chronotropic effects, clevidipine might be beneficial in hypertensive AHF, they theorized.

To find out, the researchers examined data from PRONTO. In that study, 44 patients with AHF received clevidipine and 41 received standard-of-care IV antihypertensive therapy (SOC). Most SOC patients were given nitroglycerin IV or nicardipine IV.

Clevidipine patients reached target BP range more often than did SOC patients (71% vs 37%) and sooner. They also required fewer additional IV therapies for BP management (16% vs 51%). Of patients given furosemide, the clevidipine group received lower doses (58 mg vs 78 mg).

When nitroglycerin was removed from the analysis, clevidipine and nicardipine seemed equally effective in reducing BP. When it came to dyspnea, however, clevidipine showed a distinct advantage. Patients in both groups markedly improved in breathing for the first 30 minutes after the study drug was given. At 45 minutes, though, clevidipine patients had greater mean visual analog scale (VAS) dyspnea improvement than did SOC patients, an effect that persisted for 3 hours.

Although clevidipine and SOC patients required similar rates of diagnostic procedures (28% vs 23%), none of the clevidipine patients had therapeutic procedures, whereas 9 SOC patients did. Clevidipine patients also tended to be admitted to the hospital or intensive care unit less often and had shorter hospital stays and fewer readmissions, although the differences were not significant.

The time to treatment proved to be a crucial component of the analysis. The PRONTO study is one of the first randomized studies to enroll patients within 3 hours of arrival at the hospital. Mean door-to-study drug time was 3.2 hours for clevidipine and 2.7 hours for SOC. The marked and rapid improvement in dyspnea seen in both treatment groups suggested that time to treatment may be “an important parameter to consider” in treating patients with AHF, the researchers say, noting that the > 60-mm decrease in the dyspnea VAS “exceeds that of any prior major AHF trial.”

The fact that clevidipine resolved dyspnea faster and for longer than SOC (and seemed to be partially independent of BP reduction) suggests that hemodynamics may be more important than volume removal in hypertensive AHF. Because severity of dyspnea is the root cause of hospitalization in most heart failure admissions, they conclude, “strategies for its relief have potentially valuable implications.”

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.

In acute heart failure (AHF) with hypertension, symptom onset may be abrupt, presenting as profound dyspnea and acute pulmonary edema, say researchers for the PRONTO study (A Study of Blood Pressure Control in Acute Heart Failure—a Pilot Study). For those patients, it is important to control blood pressure (BP) immediately. Usually this would be done with vasodilators; however, the researchers say, safety and efficacy data are lacking, and few comparative trials have been done. Nitrates, hydralazine, and nicardipine, the most commonly used, all have drawbacks, they note. For instance, nitrates can cause variable responses, hydralazine potentially worsens myocardial ischemia, and nicardipine can be challenging to titrate. 

Clevidipine, by contrast, is a rapidly acting IV antihypertensive medication with a 1-minute half-life that allows rapid titration. It lowers BP by selective arteriolar vasodilation and increases cardiac output as peripheral vascular resistance declines, without venous capacitance effects. And because it has no negative inotropic or chronotropic effects, clevidipine might be beneficial in hypertensive AHF, they theorized.

To find out, the researchers examined data from PRONTO. In that study, 44 patients with AHF received clevidipine and 41 received standard-of-care IV antihypertensive therapy (SOC). Most SOC patients were given nitroglycerin IV or nicardipine IV.

Clevidipine patients reached target BP range more often than did SOC patients (71% vs 37%) and sooner. They also required fewer additional IV therapies for BP management (16% vs 51%). Of patients given furosemide, the clevidipine group received lower doses (58 mg vs 78 mg).

When nitroglycerin was removed from the analysis, clevidipine and nicardipine seemed equally effective in reducing BP. When it came to dyspnea, however, clevidipine showed a distinct advantage. Patients in both groups markedly improved in breathing for the first 30 minutes after the study drug was given. At 45 minutes, though, clevidipine patients had greater mean visual analog scale (VAS) dyspnea improvement than did SOC patients, an effect that persisted for 3 hours.

Although clevidipine and SOC patients required similar rates of diagnostic procedures (28% vs 23%), none of the clevidipine patients had therapeutic procedures, whereas 9 SOC patients did. Clevidipine patients also tended to be admitted to the hospital or intensive care unit less often and had shorter hospital stays and fewer readmissions, although the differences were not significant.

The time to treatment proved to be a crucial component of the analysis. The PRONTO study is one of the first randomized studies to enroll patients within 3 hours of arrival at the hospital. Mean door-to-study drug time was 3.2 hours for clevidipine and 2.7 hours for SOC. The marked and rapid improvement in dyspnea seen in both treatment groups suggested that time to treatment may be “an important parameter to consider” in treating patients with AHF, the researchers say, noting that the > 60-mm decrease in the dyspnea VAS “exceeds that of any prior major AHF trial.”

The fact that clevidipine resolved dyspnea faster and for longer than SOC (and seemed to be partially independent of BP reduction) suggests that hemodynamics may be more important than volume removal in hypertensive AHF. Because severity of dyspnea is the root cause of hospitalization in most heart failure admissions, they conclude, “strategies for its relief have potentially valuable implications.”

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.

In acute heart failure (AHF) with hypertension, symptom onset may be abrupt, presenting as profound dyspnea and acute pulmonary edema, say researchers for the PRONTO study (A Study of Blood Pressure Control in Acute Heart Failure—a Pilot Study). For those patients, it is important to control blood pressure (BP) immediately. Usually this would be done with vasodilators; however, the researchers say, safety and efficacy data are lacking, and few comparative trials have been done. Nitrates, hydralazine, and nicardipine, the most commonly used, all have drawbacks, they note. For instance, nitrates can cause variable responses, hydralazine potentially worsens myocardial ischemia, and nicardipine can be challenging to titrate. 

Clevidipine, by contrast, is a rapidly acting IV antihypertensive medication with a 1-minute half-life that allows rapid titration. It lowers BP by selective arteriolar vasodilation and increases cardiac output as peripheral vascular resistance declines, without venous capacitance effects. And because it has no negative inotropic or chronotropic effects, clevidipine might be beneficial in hypertensive AHF, they theorized.

To find out, the researchers examined data from PRONTO. In that study, 44 patients with AHF received clevidipine and 41 received standard-of-care IV antihypertensive therapy (SOC). Most SOC patients were given nitroglycerin IV or nicardipine IV.

Clevidipine patients reached target BP range more often than did SOC patients (71% vs 37%) and sooner. They also required fewer additional IV therapies for BP management (16% vs 51%). Of patients given furosemide, the clevidipine group received lower doses (58 mg vs 78 mg).

When nitroglycerin was removed from the analysis, clevidipine and nicardipine seemed equally effective in reducing BP. When it came to dyspnea, however, clevidipine showed a distinct advantage. Patients in both groups markedly improved in breathing for the first 30 minutes after the study drug was given. At 45 minutes, though, clevidipine patients had greater mean visual analog scale (VAS) dyspnea improvement than did SOC patients, an effect that persisted for 3 hours.

Although clevidipine and SOC patients required similar rates of diagnostic procedures (28% vs 23%), none of the clevidipine patients had therapeutic procedures, whereas 9 SOC patients did. Clevidipine patients also tended to be admitted to the hospital or intensive care unit less often and had shorter hospital stays and fewer readmissions, although the differences were not significant.

The time to treatment proved to be a crucial component of the analysis. The PRONTO study is one of the first randomized studies to enroll patients within 3 hours of arrival at the hospital. Mean door-to-study drug time was 3.2 hours for clevidipine and 2.7 hours for SOC. The marked and rapid improvement in dyspnea seen in both treatment groups suggested that time to treatment may be “an important parameter to consider” in treating patients with AHF, the researchers say, noting that the > 60-mm decrease in the dyspnea VAS “exceeds that of any prior major AHF trial.”

The fact that clevidipine resolved dyspnea faster and for longer than SOC (and seemed to be partially independent of BP reduction) suggests that hemodynamics may be more important than volume removal in hypertensive AHF. Because severity of dyspnea is the root cause of hospitalization in most heart failure admissions, they conclude, “strategies for its relief have potentially valuable implications.”

Source
Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Ann Intern Med. 2014;160(4):233-242.
doi: 10.7326/M13-1085.