Carperitide

Congestive heart failure (CHF) represents the severe stage of various cardiovascular diseases. Its core pathophysiological changes involve impaired cardiac pumping function, leading to systemic and pulmonary congestion, and neurohormonal disorders (e.g., overactivation of the renin‑angiotensin‑aldosterone system (RAAS) and sympathetic excitation). These changes ultimately result in a series of clinical symptoms such as dyspnea, edema, and fatigue, posing a serious threat to patients' lives.

In the clinical management of congestive heart failure, it is mainly indicated for acute heart failure and acute decompensation of chronic heart failure, and can also be used as adjuvant therapy for refractory congestive heart failure. It is primarily administered by intravenous infusion, with rapid onset and definite efficacy. Its specific application scenarios and performance are as follows:

Following intravenous infusion, it takes effect within 10–20 minutes. It rapidly vasodilates blood vessels, reduces cardiac load, relieves pulmonary congestion, and alleviates dyspnea. Meanwhile, by inhibiting the RAAS, it reduces sodium and water retention, gradually relieving edema and fatigue.
A multicenter prospective study involving 3,777 patients with acute heart failure showed that 82% of patients achieved clinical improvement after it treatment, including significant benefits in severe patients with Killip class III–IV. The efficacy was more prominent in patients with compensated chronic heart failure (e.g., cardiomyopathy, valvular heart disease, hypertensive heart disease).

In addition, it rapidly improves hemodynamic parameters, including reducing pulmonary capillary wedge pressure and right atrial pressure, increasing cardiac output, and enhancing cardiac pumping function, thereby buying time for subsequent treatment.
In the treatment of refractory congestive heart failure, it demonstrates unique advantages. Patients with refractory congestive heart failure often have uncontrolled symptoms despite conventional therapy with diuretics, vasodilators, and inotropic agents, and are prone to complications such as renal impairment and electrolyte disturbances.

Compared with traditional diuretics, carperitide does not rely on renal filtration function. It can exert natriuretic and diuretic effects even in patients with renal insufficiency, effectively reducing sodium and water retention without aggravating renal damage. Meanwhile, its regulatory effect on the neurohormonal system compensates for the limitations of conventional drugs and breaks the vicious cycle of heart failure.

Clinical cases have shown that a 16‑year‑old male patient with dilated cardiomyopathy and refractory congestive heart failure developed low‑output syndrome and electrolyte disturbances after conventional intensive treatment. After additional intravenous it infusion, his symptoms and hemodynamic parameters improved rapidly and significantly, with the beneficial effect lasting more than 20 days and no obvious drug tolerance.
Furthermore, in refractory heart failure complicated by severe acute myocardial infarction, it rapidly reduces left ventricular filling pressure without causing significant diuresis, hypotension, or reflex tachycardia, showing favorable safety.

In long‑term clinical outcome observations, although a meta‑analysis indicated that it had no significant difference compared with the control group in all‑cause mortality and heart failure‑related hospitalization rates, the study confirmed that it effectively improves acute hemodynamic parameters and clinical symptoms, relieves patient suffering, and enhances short‑term quality of life. Therefore, it still possesses irreplaceable clinical value during acute exacerbation phases.

On one hand, it directly relaxes blood vessels and reduces peripheral vascular resistance.By binding to natriuretic peptide receptor A (NPR‑A) on vascular smooth muscle cells, it activates intracellular guanylate cyclase, elevates cyclic guanosine monophosphate (cGMP) levels, and subsequently relaxes vascular smooth muscle, resulting in vasodilation.

This vasodilatory effect is relatively selective, preferentially acting on peripheral vessels and coronary arteries. It not only reduces peripheral vascular resistance and cardiac afterload, thereby lowering blood pressure, but also dilates coronary arteries, increases myocardial perfusion, and improves myocardial ischemia. This makes it particularly suitable for patients with hypertension complicated by coronary heart disease.

Meanwhile, by inhibiting the secretion of endothelin‑1, it further attenuates vasoconstriction and enhances vasodilation, synergistically maintaining blood pressure homeostasis and preventing excessive elevation or fluctuation.

On the other hand, it regulates the neurohormonal system to stabilize blood pressure indirectly.The pathogenesis of hypertension is closely associated with overactivation of the RAAS and sympathetic nervous system, both of which induce vasoconstriction and sodium‑water retention, thereby elevating blood pressure.

Carperitide suppresses renin secretion and reduces the production of angiotensin II and aldosterone. This not only decreases sodium‑water retention and circulatory volume to lower blood pressure indirectly, but also inhibits vasoconstriction and interrupts the pathological cycle of hypertension.

Furthermore, its inhibitory effect on sympathetic activity reduces norepinephrine release, lowers heart rate and myocardial oxygen consumption, prevents blood pressure elevation caused by sympathetic overactivity, and contributes to long‑term stable blood pressure control.

Clinical studies have demonstrated that it treatment significantly decreases plasma aldosterone levels, gradually normalizes electrolyte profiles, and effectively improves fluid balance.

Clinically, it is indicated for the treatment of sodium‑water retention and edema from various etiologies, including heart failure with edema, cirrhotic ascites, and edema due to renal insufficiency.

In patients with heart failure and edema, its natriuretic and diuretic action effectively reduces excess fluid, relieves edema, lowers cardiac load, and improves cardiac function.In cirrhotic ascites, it promotes the absorption and excretion of ascites, alleviates abdominal distension and dyspnea, without imposing additional hepatic burden.In edema caused by renal insufficiency, its natriuretic and diuretic effect is independent of renal filtration function, thus improving edema to some extent without aggravating renal damage.

it may also be used as an adjuvant in dehydrated patients, but only with strict dose control to avoid worsening dehydration; it is contraindicated in patients with severe dehydration.

It is a polypeptide hormone consisting of 28 amino acids, with a CAS number of 89213-87-6, a molecular formula of C₁₂₇H₂₀₃N₄₅O₃₉S₃, and a molecular weight of approximately 3.08 kDa (3080.44). Its amino acid sequence is abbreviated as SLRRSSCFGGRMDRIGAQSGLGCNSFRY. The cysteine residues at positions 7 and 23 are linked by a disulfide bond, forming a conserved cyclic structure. This cyclic structure is critical for its biological activity and mediates specific binding to natriuretic peptide receptor A; its absence markedly reduces pharmacological activity. Chemically, it is identical to endogenous α‑atrial natriuretic peptide secreted by human atrial cardiomyocytes, ensuring excellent biocompatibility and target specificity.

Carperitide appears as a white or almost white lyophilized powder, odorless and tasteless. Its predicted density is approximately 1.55 ± 0.1 g/cm³, and refractive index is 1.688. It is highly polar, freely soluble in water (solubility about 1 mg/mL), and practically insoluble in organic solvents. The molecule contains multiple charged groups and a suitable isoelectric point, allowing a stable conformation under physiological pH. For clinical use, high purity is required: after purification by reversed‑phase high‑performance liquid chromatography, purity ≥ 98.0%, single impurity ≤ 1.0%, acetate content 5.0%–12.0%, water content ≤ 10.0%, and peptide content ≥ 80.0%.