Association of New Use of Antihypertensives That Stimulate vs Inhibit Type 2 and 4 Angiotensin II Receptors With Dementia Among Medicare Beneficiaries.

Importance: Prevalent use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, compared with those that do not stimulate these receptors, has been associated with a lower risk of dementia. However, previous studies were limited by inclusion of individuals with prevalent hypertension and a history of antihypertensive use prior to the start of the study, which can introduce bias. Objective: To examine the association of new use of antihypertensive medication regimens that stimulate vs inhibit type 2 and 4 angiotensin II receptors with Alzheimer disease and related dementias (ADRD) among Medicare beneficiaries. Design, Setting, and Participants: This cohort study was conducted among 57 773 Medicare fee-for-service beneficiaries (January 1, 2006, through December 31, 2018) aged 65 years or older with incident hypertension. Data analysis was conducted from January 1 through June 30, 2022. Exposures: Initiation of antihypertensive medication regimens that stimulate or inhibit type 2 and 4 angiotensin II receptors, or mixed regimens (both stimulating and inhibiting), with the time-dependent measure being each 30-day interval. Main Outcomes and Measures: The primary outcome was time to first occurrence of ADRD (Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse definition). Cox proportional hazards regression modeling with time-dependent variables was performed to estimate the association between time-dependent treatment groups and time to ADRD, after adjusting for sociodemographic and clinical characteristics. Results: The sample included 57 773 Medicare beneficiaries (36 348 women [62.9%]; mean [SD] age, 73.8 [6.3] years; 2954 [5.1%] Black, 1545 [2.7%] Hispanic; 50 184 [86.9%] White, and 3090 [5.4%] Other individuals [the Other category included individuals of American Indian, Asian, other, or unknown race and ethnicity]). During a median of 6.9 years (IQR, 4.7-9.3 years) of follow-up, the unadjusted incidence density rate of ADRD was 2.2 cases per 100 person-years (95% CI, 2.1-2.4 cases per 100 person-years) for the group receiving regimens that stimulate type 2 and 4 angiotensin II receptors compared with 3.1 cases per 100 person-years (95% CI, 3.0-3.2 cases per 100 person-years) for the group receiving regimens that inhibit type 2 and 4 angiotensin II receptors and 2.7 cases per 100 person-years (95% CI, 2.6-2.9 cases per 100 person-years) for the group receiving mixed treatment regimens. In adjusted Cox proportional hazards regression modeling, stimulating treatment was associated with a statistically significant 16% reduction in the hazard of ADRD compared with inhibiting treatment (hazard ratio, 0.84; 95% CI, 0.79-0.90). Mixed regimen use was also associated with reduced hazards of ADRD compared with the inhibiting group (hazard ratio, 0.90; 95% CI, 0.84-0.96). Conclusions and Relevance: This cohort study of Medicare beneficiaries suggests that use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors was associated with lower risk of ADRD compared with antihypertensive medications that inhibit these receptors. Confirmation is needed in a randomized trial.

Angiotensin II for the treatment of distributive shock in the intensive care unit: A US cost-effectiveness analysis.

BACKGROUND: Patients with distributive shock who are unresponsive to traditional vasopressors are commonly considered to have severe distributive shock and are at high mortality risk. Here, we assess the cost-effectiveness of adding angiotensin II to the standard of care (SOC) for severe distributive shock in the US critical care setting from a US payer perspective. METHODS: Short-term mortality outcomes were based on 28-day survival rates from the ATHOS-3 study. Long-term outcomes were extrapolated to lifetime survival using individually estimated life expectancies for survivors. Resource use and adverse event costs were drawn from the published literature. Health outcomes evaluated were lives saved, life-years gained, and quality-adjusted life-years (QALYs) gained using utility estimates for the US adult population weighted for sepsis mortality. Deterministic and probabilistic sensitivity analyses assessed uncertainty around results. We analyzed patients with severe distributive shock from the ATHOS-3 clinical trial. RESULTS: The addition of angiotensin II to the SOC saved .08 lives at Day 28 compared to SOC alone. The cost per life saved was estimated to be $108,884. The addition of angiotensin II to the SOC was projected to result in a gain of .96 life-years and .66 QALYs. This resulted in an incremental cost-effectiveness ratio of $12,843 per QALY. The probability of angiotensin II being cost-effective at a threshold of $50,000 per QALY was 86 percent. CONCLUSIONS: For treatment of severe distributive shock, angiotensin II is cost-effective at acceptable thresholds.

The angiotensin II receptor antagonist losartan: a new advance in the treatment of hypertension.

Losartan is the first of a new class of antihypertensive agents called 'angiotensin II antagonists'. It selectively and completely blocks the binding of angiotensin II at the angiotensin type 1 receptor-a unique mechanism of action different from all the other classes of antihypertensive agents. Losartan is as effective as other commonly used antihypertensive agents, but it permits convenient dosing and is better tolerated. On the strength of current data on its safety and efficacy, losartan should be considered a valuable option for many hypertension patients in whom angiotensin-converting enzyme inhibitors or calcium antagonists would be used. Although the administration of losartan produces beneficial effects and may be cost effective, long term data regarding morbidity and mortality in hypertension are needed.

Transvaginal Doppler ultrasound assessment of intratumoral hemodynamic change before and during hypertensive intra-arterial chemotherapy for uterine cancer.

OBJECTIVE: To evaluate blood flow in malignant uterine tumors during hypertensive intra-arterial chemotherapy. METHODS: Hypertensive intra-arterial chemotherapy (angiotensin II, cisplatin 100 mg, doxorubicin 40 mg) was given to two women with cervical cancer (stage IVA) and seven with endometrial cancer (three stage IA, one stage IB, two stage II, and one stage III). The intratumoral blood flow velocity waveforms were imaged by transvaginal Doppler ultrasound before and during the chemotherapy in six patients. RESULTS: The mean peak systolic velocity during hypertensive intra-arterial chemotherapy (58.9 +/- 29.3 cm/second) was significantly higher than that before chemotherapy (16.0 +/- 6.3 cm/second) (P < .05). There was a significant difference between the end-diastolic velocity before (5.2 +/- 1.8 cm/second) and during chemotherapy (21.2 +/- 6.8 cm/second) (P < .05). The resistance index value during hypertensive intra-arterial chemotherapy (0.607 +/- 0.094) fell significantly from that before therapy (0.644 +/- 0.119) (P < .05). Blood flow velocity waveforms in normal myometrial tissue could be recorded in three cases; in all, the diastolic flow noted before hypertensive intra-arterial chemotherapy disappeared during chemotherapy. CONCLUSION: These results suggest that hypertensive intra-arterial chemotherapy induces a selective marked increase of blood flow in uterine cancer.