Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis (original) (raw)
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The Journal of Clinical Hypertension
With an estimated prevalence of 34%, about 86 million adults in the United States are believed to have high blood pressure (BP), hypertension. 1 Hypertension is a major risk factor for stroke, due to both cerebral infarction and intracerebral hemorrhage, 2 for coronary heart disease, renal impairment, and other end-organ damage. For primary prevention, reduction of BP is generally considered more important than the choice of specific antihypertensive agents, but some classes may offer more protective benefit than others. 3 Extensive meta-analyses and searches have been undertaken to evaluate the effect of antihypertensive treatment classes on morbidity and mortality. Treatment guidelines focus on individual risk factors like comorbidities and age, but do not generally favor one class over another for primary prevention. 4 The most recent update of the Cochrane systematic database review came to the following conclusions: First-line low-dose thiazides reduced morbidity and mortality, first-line ACE inhibitors and calcium channel blockers may be similarly effective, and first-line high-dose thiazides and first-line beta blockers were inferior to first-line low-dose thiazides. 5 Similar recommendations were also put forth by the Eighth Joint National Committee and published by the Journal of the American Medical Association: Initial treatment with a thiazide-type diuretic was more effective than an ACE. 6
Pharmacology : Evidence Meets Practice Making Sense of Hypertension Guidelines
2018
In the United States, one-third of all adults have hypertension (HTN), and 35.8 million of those are uncontrolled. As a leading risk factor, high blood pressure (BP) is a predisposing factor for almost 80% of all cardiovascular chronic illnesses. The risk for major, debilitating cardiovascular disease (CVD) events (heart failure, myocardial infarction [MI], and stroke) drops significantly when BP reaches the guideline-based target (140 mm Hg systolic) or lower. Randomized controlled trials (RCTs) have found that lowering BP by as little as 10 mm Hg in patients with HTN can reduce a person"s lifetime risk for cardiovascular and stroke death by 25% to 40%. Over the last 50 years, extensive effort has been given to determining the optimal BP target for adults with HTN. Despite recent improvements in prescribing practices for evidencebased antihypertensive medication therapy, many diagnosed cases remain ‘‘uncontrolled.’’ Data from the National Health and Nutrition Examination Surve...
Hypertension, 2016
T hiazide-type diuretics are among the first-line agents recommended for use in the treatment of hypertension by multiple clinical practice guidelines published during the past decade. 1-3 The Seventh Report of the Joint National Committee (JNC 7), published in 2003, gave one of the strongest endorsements for thiazide prescription, recommending that they be given as initial therapy for most patients with hypertension. 2 These recommendations were based in large part on the lower incidence of several cardiovascular disease outcomes after treatment with chlorthalidone compared with other antihypertensive agents (ie, the angiotensin-converting enzyme inhibitors [ACEI] lisinopril, the α-blocker doxazosin, or the calcium channel blocker amlodipine) reported in the landmark Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). 4,5 An increase in thiazide prescription was observed after publication of ALLHAT and JNC 7, but the magnitude and duration of this effect was relatively modest and short lived. 6,7 Moreover, reported rates of thiazide prescription remained lower than for other antihypertensive medication classes. 8-10 However, even the most recent of these studies only included patients through 2010, and so may not represent the most upto-date information on the use of thiazides in clinical practice. We therefore sought to examine patterns and correlates of thiazide prescription in a contemporary cohort of patients with hypertension. We conducted a cross-sectional analysis of baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized clinical trial that enrolled persons with hypertension and other cardiovascular risk factors Abstract-Thiazides and thiazide-type diuretics are recommended as first-line agents for the treatment of hypertension, but contemporary information on their use in clinical practice is lacking. We examined patterns and correlates of thiazide prescription in a cross-sectional analysis of baseline data from participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). We examined baseline prescription of thiazides in 7582 participants receiving at least 1 antihypertensive medication by subgroup, and used log-binomial regression to calculate adjusted prevalence ratios for thiazide prescription (versus no thiazide). Forty-three percent of all participants were prescribed a thiazide at baseline, but among participants prescribed a single agent, the proportion was only 16%. The prevalence of thiazide prescription differed significantly by demographic factors, with younger participants, women, and blacks all having higher adjusted prevalence of thiazide prescription than other corresponding subgroups. Participants in the lowest category of kidney function (estimated glomerular filtration rate <30 mL/min per 1.73 m2) were half as likely to be prescribed a thiazide as participants with preserved kidney function. In conclusion, among persons with hypertension and heightened cardiovascular risk, we found that thiazide prescription varied significantly by demographics and kidney disease status, despite limited evidence about relative differences in effectiveness.
First-line drugs for hypertension (Review
Background Sustained elevated blood pressure, unresponsive to lifestyle measures, leads to a critically important clinical question: What class of drug to use first-line?This review answers that question. Objectives Primary objective: To quantify the benefits and harms of the major first-line anti-hypertensive drug classes: thiazides, beta-blockers, calciumchannel blockers, angiotensin converting enzyme (ACE) inhibitors, alpha-blockers, and angiotensin II receptor blockers (ARB). Search strategy Electronic search ofMEDLINE (Jan. 1966-June 2008), EMBASE, CINAHL, the Cochrane clinical trial register, using standard search strategy of the hypertension review group with additional terms. Selection criteria Randomized trials of at least one year duration comparing one of 6 major drug classes with a placebo or no treatment. More than 70% of people must have BP >140/90 mmHg at baseline. Data collection and analysis The outcomes assessed were mortality, stroke, coronary heart disease (CHD), cardiovascular events (CVS), decrease in systolic and diastolic blood pressure, and withdrawals due to adverse drug effects. Risk ratio (RR) and a fixed effects model were used to combine outcomes across trials. Main results Of 57 trials identified, 24 trials with 28 arms, including 58,040 patients met the inclusion criteria. Thiazides (19 RCTs) reduced mortality (RR 0.89, 95% CI 0.83, 0.96), stroke (RR 0.63, 95% CI 0.57, 0.71), CHD (RR 0.84, 95% CI 0.75, 0.95) and CVS (RR 0.70, 95% CI 0.66, 0.76). Low-dose thiazides (8 RCTs) reduced CHD (RR 0.72, 95% CI 0.61, 0.84), but high-dose thiazides (11 RCTs) did not (RR 1.01, 95% CI 0.85, 1.20). Beta-blockers (5 RCTs) reduced stroke (RR 0.83, 95% CI 0.72, 0.97) and CVS (RR 0.89, 95% CI 0.81, 0.98) but not CHD (RR 0.90, 95% CI 0.78, 1.03) or mortality (RR 0.96, 95% CI 0.86, 1.07). ACE inhibitors (3 RCTs) reduced mortality (RR 0.83, 95% CI 0.72-0.95), stroke (RR 0.65, 95% CI 0.52-0.82), CHD (RR 0.81, 95% CI 0.70-0.94) and CVS (RR 0.76, 95% CI 0.67-0.85). Calcium-channel blocker (1 RCT) reduced stroke (RR 0.58, 95% CI 0.41, 0.84) and CVS (RR 0.71, 95% CI 0.57, 0.87) but not CHD (RR 0.77 95% CI 0.55, 1.09) or mortality (RR 0.86 95% CI 0.68, 1.09). No RCTs were found for ARBs or alpha-blockers. Authors’ conclusions First-line low-dose thiazides reduce all morbidity and mortality outcomes. First-line ACE inhibitors and calcium channel blockers may be similarly effective but the evidence is less robust. First-line high-dose thiazides and first-line beta-blockers are inferior to first-line low-dose thiazides.
American Journal of Hypertension, 1997
The objective of the study was to compare prospectively the impact of study design on drug therapy safety and effectiveness data obtained in hypertension management. The main study was a randomized controlled clinical trial of four different prospective study designs used in postmarketing assessment involving 1008 primary care practices in nine Canadian provinces. Two thousand nine hundred sixty-four patients with mild to moderate hypertension received an angiotensin converting enzyme (ACE) inhibitor daily for 14 weeks in one of four postmarketing studies-a randomized double-blind clinical trial (RCT) (10 to 40 mg fosinopril daily v 5 to 20 mg enalapril daily), two structured open label trials of 10 to 40 mg fosinopril daily (one with free drugs), or an unstructured open label trial of 10 to 40 mg fosinopril daily. Patient demographic and baseline characteristics, systolic and diastolic blood pressures, adverse events reported, and data quality were recorded as the outcome measures. The results showed that the RCT patients were titrated to higher doses of ACE inhibitor than patients in the open studies, P < .008; patients in the open studies were more likely to receive adjuvant diuretic therapy, P < .008. The decrease in blood pressure was similar for patients in all four studies, mean decrease in systolic BP was between 18 and 20 mm Hg, mean decrease in diastolic BP was between 11 and 13 mm Hg. Fewer patients in the unstructured open trial reported adverse events than patients in the RCT; a 55% relative reduction in reported adverse events (P < .008) was associated with the unstructured trial. There were also fewer drug-related adverse events per patient reported in the unstructured study (17 per 100 patients) than in the other studies (27 to 41 per 100 patients), P < .008. Physician preference for rounding off blood pressure measurements to 0 or 5 occurred most often in the unstructured open trial (P < .008). In conclusion, despite differences in dose titration and in the use of adjuvant therapy, antihypertensive drug therapy effectiveness observed in an RCT may be similar to uncontrolled postmarketing studies. Open trials with scheduled follow-up visits are as effective in detecting severe adverse events as RCT, but postmarketing studies with unstructured schedules of follow-up are insufficient in identifying drugrelated adverse events and have poorer quality data.
The Journal of Clinical Hypertension, 2013
Thiazide-type diuretics were first approved in the United States for hypertension in 1957. Chlorthiazide was the first thiazide diuretic used in clinical practice, but today, more than a half-century later, the two most commonly used thiazide-type diuretics in the treatment of hypertension are hydrochlorthiazide (HCTZ) and chlorthalidone. HCTZ is readily available and included in most fixed-dose antihypertensive combinations. At 12.5 mg/d to 25 mg/d, HCTZ is the most widely used thiazide-like diuretic in current practice, despite the fact that chlorthalidone is generally considered to have greater potency and longer duration of action and has been the diuretic most commonly used in major landmark clinical outcome hypertension trials.
Hypertension guidelines, meta-analyses and clinical trials: do we assume too much?
The Medical journal of Australia, 2005
Given fundamental differences in the recommendations in guidelines from major national and international committees, we cannot rely on them unquestioningly. Different antihypertensive agents are known to have differing effects according to age and race. Exchanging (rather than following guideline recommendations of adding to) an ineffective first-line antihypertensive drug can result in control of hypertension with monotherapy. Conclusions about a preferable first-line antihypertensive agent are limited by trial protocols with varying drug doses and questionable drug combinations. Guidelines are often based on meta-analyses of drugs of a particular class, which could ignore important differences between drugs within a class. Trials of 3-5 years cannot determine the long-term effects of drugs which patients often take for decades.