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Gordon T McInnes

Publications and source records attributed to Gordon T McInnes.

25 records · Page 2Linked to original sources
PubMed2003

The expanding role of angiotensin receptor blockers in the management of the elderly hypertensive.

The world faces the challenge of an ageing population, and for developed countries, the particular challenge is the increasing number of very old people, over 80 years of age. Hypertension is a condition associated with increasing age, but elderly patients with hypertension are often difficult to manage. Nevertheless, treatment of hypertension is of greatest value in older patients who often have additional risk factors or cardiovascular disease. Older patients have generally tolerated antihypertensive therapy well in randomised, placebo-controlled trials. The tolerability of angiotensin receptor blockers (ARBs) is better than that of many other classes of drugs currently used for the management of hypertension and these drugs have virtually no contraindications. Thus, ARBs have a bright future in the management of hypertension and in the treatment of stroke and cognitive decline in the elderly.

Age Factors↗
PubMed2002

Clinical trials and tribulations.

1. Pharmacologists should be involved in all stages of drug development. Often neglected is the final step, the clinical trials and other studies that determine clinical utility. The present article illustrates how pharmacoepidemiology can facilitate evaluation of the clinical potential of different drugs used to treat hypertension. 2. The evidence base for the drug treatment of hypertension is very strong. Large-scale outcome trials, largely based on diuretics, indicate that stroke events are prevented to the extent expected from blood pressure reduction, but there appears to be a shortfall in the prevention of coronary heart disease events. 3. On theoretical grounds, newer agents may be expected to have benefits in coronary heart disease prevention beyond blood pressure reduction. Recent trials with angiotensin-converting enzyme inhibitors and calcium channel blockers suggest no advantage over conventional drugs, but shortcomings in these studies mean that each is uninformative. 4. Observational studies based on pharmacoepidemiological principles offer an alternative approach to evaluating outcomes in treated hypertensives. 5. Evidence from the Glasgow Blood Pressure Clinic database suggest that there are outcome differences between antihypertensive agents. Angiotensin-converting enzyme inhibitor treatment is associated with a mortality advantage, whereas calcium channel blocker therapy is associated with a poorer prognosis. Preliminary findings from a primary care database support these observations. 6. Long-term follow up of a well-documented high-risk clinical population may allow detection of outcome differences not apparent in relatively short-term clinical trials. 7. Appropriate interpretation of observational data necessitates an understanding of the strengths and limitations of observational data. Clinical pharmacologists have a critical role in design and evaluation of pharmacoepidemiology studies.

Antihypertensive Agents↗
PubMed2001

Debate: does it matter how you lower blood pressure?

The evidence base for drug treatment of hypertension is strong. Early trials using thiazide diuretics suggested a shortfall in prevention of coronary heart disease. The superiority of newer drugs has been widely advocated but trial evidence does not support an advantage of beta-blockers, angiotensin converting enzyme inhibitors, calcium channel blockers or alpha-blockers for this outcome. Even meta-analyses have failed to clarify matters. If this issue is to be settled, bigger and better trials of longer duration in high-risk patients are needed. Meanwhile, the importance of rigorous blood pressure control using multiple drugs has been established. This should be the focus of our attention rather than agonising over differences in cause-specific outcomes that may not be generalisable to all patient populations.

Journal Article↗
PubMedDate not supplied

Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial.

BACKGROUND: The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics and beta blockers. Our aim, therefore, was to compare the effect on non-fatal myocardial infarction and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril. METHODS: We did a multicentre, prospective, randomised controlled trial in 19 257 patients with hypertension who were aged 40-79 years and had at least three other cardiovascular risk factors. Patients were assigned either amlodipine 5-10 mg adding perindopril 4-8 mg as required (amlodipine-based regimen; n=9639) or atenolol 50-100 mg adding bendroflumethiazide 1.25-2.5 mg and potassium as required (atenolol-based regimen; n=9618). Our primary endpoint was non-fatal myocardial infarction (including silent myocardial infarction) and fatal CHD. Analysis was by intention to treat. FINDINGS: The study was stopped prematurely after 5.5 years' median follow-up and accumulated in total 106 153 patient-years of observation. Though not significant, compared with the atenolol-based regimen, fewer individuals on the amlodipine-based regimen had a primary endpoint (429 vs 474; unadjusted HR 0.90, 95% CI 0.79-1.02, p=0.1052), fatal and non-fatal stroke (327 vs 422; 0.77, 0.66-0.89, p=0.0003), total cardiovascular events and procedures (1362 vs 1602; 0.84, 0.78-0.90, p<0.0001), and all-cause mortality (738 vs 820; 0.89, 0.81-0.99, p=0.025). The incidence of developing diabetes was less on the amlodipine-based regimen (567 vs 799; 0.70, 0.63-0.78, p<0.0001). INTERPRETATION: The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen. On the basis of previous trial evidence, these effects might not be entirely explained by better control of blood pressure, and this issue is addressed in the accompanying article. Nevertheless, the results have implications with respect to optimum combinations of antihypertensive agents.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA).

BACKGROUND: Results of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) show significantly lower rates of coronary and stroke events in individuals allocated an amlodipine-based combination drug regimen than in those allocated an atenolol-based combination drug regimen (HR 0.86 and 0.77, respectively). Our aim was to assess to what extent these differences were due to significant differences in blood pressures and in other variables noted after randomisation. METHODS: We used data from ASCOT-BPLA (n=19 257) and compared differences in accumulated mean blood pressure levels at sequential times in the trial with sequential differences in coronary and stroke events. Serial mean matching for differences in systolic blood pressure was used to adjust HRs for differences in these events. We used an updated Cox-regression model to assess the effects of differences in accumulated mean levels of various measures of blood pressure, serum HDL-cholesterol, triglycerides and potassium, fasting blood glucose, heart rate, and bodyweight on differences in event rates. FINDINGS: We noted no temporal link between size of differences in blood pressure and different event rates. Serial mean matching for differences in systolic blood-pressure attenuated HRs for coronary and stroke events to a similar extent as did adjustments for systolic blood-pressure differences in Cox-regression analyses. HRs for coronary events and stroke adjusted for blood pressure rose from 0.86 (0.77-0.96) to 0.88 (0.79-0.98) and from 0.77 (0.66-0.89) to 0.83 (0.72-0.96), respectively. Multivariate adjustment gave HRs of 0.94 (0.81-1.08) for coronary events (HDL cholesterol being the largest contributor) and 0.87 (0.73-1.05) for stroke events. INTERPRETATION: Multivariate adjustment accounted for about half of the differences in coronary events and for about 40% of the differences in stroke events between the treatment regimens tested in ASCOT-BPLA, but residual differences were no longer significant. These residual differences could indicate inadequate statistical adjustment, but it remains possible that differential effects of the two treatment regimens on other variables also contributed to the different rates noted, particularly for stroke.

Adult↗
PubMedDate not supplied

The differences between ACE inhibitor-treated and calcium channel blocker-treated hypertensive patients.

Large-scale outcome trials have demonstrated that blood pressure reduction with angiotensin-converting enzyme (ACE) inhibitors or calcium channel blockers (CCBs) is associated with reduced cardiovascular complications in hypertension. Comparative trials against conventional drugs and between ACE inhibitors and CCBs have failed to reveal conclusive differences in cause-specific outcomes. Studies in high-risk patients suggest that ACE inhibitors are superior to CCBs and other drugs in protection against cardiovascular events and renal disease. Very long-term prospectively collected observational data from the Glasgow Blood Pressure Clinic and the UK General Practice Research Database strongly support an advantage of ACE inhibitors over CCBs for cardiovascular morbidity and mortality. Considering all the available information, it can be concluded that the use of CCBs in the routine therapy of hypertension cannot be recommended while wider use of ACE inhibitors, along with low-dose diuretics and beta blockers, appears justified.

Adrenergic beta-Antagonists↗