ABSTRACT
Background: Long-term outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH) treated with calcium channel blockers (CCBs) are not well documented. Therefore, this study aimed to determine the long-term response to treatment with CCBs in patients with IPAH. Methods: This retrospective cohort study was performed on 81 patients with IPAH admitted to our center. Vasoreactivity testing with adenosine was performed in all patients. Twenty-five patients showed a positive response to vasoreactivity testing and were included in the analysis. Results: Of 24 patients, 20 (83.3%) were female, and the mean age of the patients was 45.90±10.42 years. Fifteen patients improved after 1 year on CCB therapy (the long-term CCB responders group), and 9 showed no improvement (the CCB failure group). The CCB responders group had a greater proportion of patients in New York Heart Association (NYHA) functional class I or II (93.3%), a longer distance walked, and less severe hemodynamic parameters. At the 1-year evaluation, the long-term CCB responders had more improvements in the mean 6-minute walk test result (437.43±125.32 vs 268.17±130.06; P=0.040), the mixed venous oxygen saturation level (71.84±9.87 vs 59.03±9.95; P=0.041), and the cardiac index (4.76±1.12 vs 3.15±0.90; P=0.012). Additionally, mPAP was lower in the long-term CCB responders group (47.35±12.70 vs 67.23±14.08; P=0.034). Finally, all the CCB responders were in NYHA functional class I or II (P=0.001). Conclusion: Our study illustrated that long-term treatment with oral CCBs was effective in 60% of acute responders and 18.5% of the entire study population.
ABSTRACT
Adjusting the exact warfarin dose has always been challenging since it has a narrow therapeutic window. Numerous factors, including poor drug compliance, drug-drug interactions, and malabsorption syndromes, affect the warfarin plasma concentration, leading to oversensitivity or resistance to warfarin. Patients who need more than 15 mg/d of warfarin for maintained anticoagulant effects are considered warfarin resistant. We describe a 62-year-old man referred to our center with bruising on his feet in June 2021. The patient had a history of valve replacement (mechanical prosthetic valves in 2013), hypothyroidism, and atrial fibrillation. He presented with warfarin resistance (first noticed in 2013) and did not reach the desired warfarin therapeutic effect despite receiving 60 mg of warfarin daily. Upon admission, the patient was on warfarin (100 mg/d) with an international normalized ratio (INR) of 1.5. He underwent laboratory and molecular genetic tests, which showed no mutation in the CYP2C9 and VKORC1, the genes associated with warfarin resistance. A stepwise diagnosis is required to identify the underlying cause. Assessing the patient's compliance, drug history, dietary habits, malabsorption diseases, and genetics may be necessary. We evaluated these possible reasons for resistance and found no correlation. The patient's warfarin intake was monitored closely to reach the INR therapeutic target of 3-3.5. He decided to leave the hospital with personal consent. He was discharged with a cardiologist referral and 24 warfarin tablets daily (120 mg/d) with an INR of 1.8. The patient was followed up 6 months and 2 years after discharge and was on the same daily dose of warfarin as at discharge, with no complications.
