Time to Clinical Benefit of Intensive Blood Pressure Lowering in Patients 60 Years and Older With Hypertension

This secondary analysis of randomized clinical trials estimates the time needed to potentially derive clinical benefit from intensive blood pressure treatment in patients 60 years and older.


eMethods. Detailed description for TTB using frequentist method
Unlike the method implemented by Yourman etal 1 , we calculated TTB and its confidence interval using conventional frequentist method with Monte Carlo simulations instead of the Bayesian approach. We fitted Weibull survival curves using the individual data for the control and intervention groups for each study. The R function "survreg" in the "survival" package was used to estimate the Weibull regression models with argument "strata()" for groups to make both the scale and shape parameters of Weibull distributions to vary for groups. TTB was obtained by numerically solve the equation to make the difference of the Weibull survival curves of groups estimated by the regression model to be the specific absolute risk reduction (ARR) threshold (i.e., 0.002, 0.005, and 0.010). The confidence interval of TTB was calculated based on the simulated sampling distribution of TTB by Monte Carlo method as follows. After the Weibull regression model was estimated, we simulated the Weibull distribution parameters by the estimated asymptotic sampling distribution of them, which was a multivariate normal distribution with the mean vector of parameter estimates and estimated variance covariance matrix. Simulated TTBs were calculated in the same manner described before with simulated Weibull parameters and were treated as the empirical sampling distribution of TTB. Afterwards, the confidence interval of TTB is calculated based on their quantile values. We found the empirical distribution of the logarithm of TTB is single-peaked and approximately symmetric. Therefore, the pivot type bootstrap confidence interval formula 2-4 was also implemented to make TTB's confidence interval more reliable.
In some studies, the calculated TTBs were too large to be practical. Thus, we considered to estimate an overall Weibull regression models for all studies with the study variable as a factor and the "strata()" argument. The overall Weibull survival curves estimated for different groups were based on the weighted averages of the estimated Weibull distribution parameters for each study, normalized by the sample size of each study as weights. The overall TTB and its confidence interval was calculated with the same method as before. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Not treat-to-target design 49 The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Not treat-to-target design 50 Restoration of nocturnal blood pressure dip and reduction of nocturnal blood pressure with evening anti-hypertensive medication administration in pediatric kidney transplant recipients: A pilot randomized clinical trial.
Not treat-to-target design 51  Valsartan, 40 to 80 mg once daily, was administrated as the first-step therapy. If the target BP in each group was not achieved within 1 to 2 months, the dose of valsartan was increased ≤ 160 mg, and/or other antihypertensive agents except other angiotensin II type 1 receptor blockers were added, for example, low-dose diuretics, Ca antagonists, and so on to maintain the target BP.
JATO Untreated subjects initially received efonidipine at a daily dose of 20 to 40 mg (once daily). In subjects who were already receiving antihypertensive medications, a similar dose of efonidipine was added or substituted for one of the drugs being received before study entry without a washout period. The daily dose of efonidipine could be increased to 60 mg (once or twice daily) and antihypertensive drugs other than calcium antagonists were added, if needed.

Cardio-Sis
Antihypertensive drug treatment included various combinations of previous drugs (background therapy) plus drugs made available for the purpose of the study. We dispensed furosemide (25 mg per day), ramipril (5 mg or 10 mg per day), telmisartan (80 mg per day), amlodipine (5 mg or 10 mg per day), bisoprolol (5 mg per day), and transdermal clonidine (2.5 mg or 5.0 mg per day). Ramipril and telmisartan were also available in fixed combinations with hydrochlorothiazide (12.5 mg or 25.0 mg per day for ramipril, and 12.5 mg per day for telmisartan). SPRINT All major classes of antihypertensive agents were included in the formulary and were provided at no cost to the participants. SPRINT investigators could also prescribe other antihypertensive medications (not provided by the study). The protocol encouraged, but did not mandate, the use of drug classes with the strongest evidence for reduction in cardiovascular outcomes, including thiazide-type diuretics (encouraged as the first-line agent), loop diuretics (for participants with advanced chronic kidney disease), and beta-adrenergic blockers (for those with coronary artery disease).Chlorthalidone was encouraged as the primary thiazide-type diuretic, and amlodipine as the preferred calcium-channel blocker. ACCORD All major classes of antihypertensive drugs and many combination medications were provided by the study. All antihypertensive regimens were to include a drug class that had demonstrated reduced cardiovascular events in participants with diabetes: diuretic, beta-blocker, calcium channel blocker (CCB), angiotensin converting-enzyme (ACE) inhibitor, or angiotensin receptor blocker (ARB).For intensive participants, a combination of a diuretic and either an ACE inhibitor or a beta-blocker was recommended as initial therapy. STEP After randomization, all patients were scheduled for follow-up visits at 1, 2, and 3 months and every 3 months thereafter until 48 months. The patients were provided with antihypertensive drugs, including olmesartan (an angiotensin-receptor blocker), amlodipine (a calcium-channel blocker), and hydrochlorothiazide (a diuretic). eTable 4. Results of quality of reporting assessment using risk of bias using the Cochrane tool for assessment of risk of bias